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2020
ANNUAL
REPORT
和
⿈
中
國
醫
藥
科
技
有
限
公
司
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LEAD
INNOVATION
MEET
UNMET NEEDS
HUTCHISON CHINA MEDITECH LIMITED
和 ⿈ 中 國 醫 藥 科 技 有 限 公 司
(INCORPORATED IN THE CAYMAN ISLANDS WITH LIMITED LIABILITY)
BOARD OF DIRECTORS
REMUNERATION COMMITTEE
Paul CARTER (Chairman)
Graeme JACK
Simon TO
TECHNICAL COMMITTEE
Karen FERRANTE (Chairman)
Paul CARTER
Christian HOGG
Tony MOK
Weiguo SU
Simon TO
COMPANY SECRETARY
Edith SHIH
NOMINATED ADVISER
Panmure Gordon (UK) Limited
CORPORATE BROKERS
Panmure Gordon (UK) Limited
HSBC Bank plc
AUDITOR
PricewaterhouseCoopers
Executive Directors
Simon TO, BSc, ACGI, MBA
Chairman
Christian HOGG, BSc, MBA
Chief Executive Officer
Johnny CHENG, BEc, CA
Chief Financial Officer
Weiguo SU, BSc, PhD
Chief Scientific Officer
Non-executive Directors
Dan ELDAR, BA, MA, MA, PhD
Edith SHIH, BSE, MA, MA, EdM, Solicitor,
FCG (CS, CGP), FCS (CS, CGP) (PE)
Independent Non-executive Directors
Paul CARTER, BA, FCMA
Senior Independent Director
Karen FERRANTE, MD, BSc
Graeme JACK, BCom, CA (ANZ), FHKICPA
Tony MOK, BMSc, MD, FRCPC, FHKCP,
FHKAM, FRCP (Edin), FASCO
AUDIT COMMITTEE
Graeme JACK (Chairman)
Paul CARTER
Karen FERRANTE
NOMINATION COMMITTEE
Tony MOK (Chairman) (1)
Simon TO (2)
Paul CARTER (3)
Johnny CHENG (3)
Dan ELDAR (3)
Karen FERRANTE (3)
Christian HOGG (3)
Graeme JACK
Edith SHIH (3)
Weiguo SU (3)
Notes:
(1)
(2)
(3)
Appointed as Chairman on December 11, 2020
Ceased to be Chairman on December 11, 2020
Ceased to be member on December 11, 2020
CORPORATE INFORMATION
Corporate Information
Evolution of Our Corporate Identity
Chairman’s Statement
2020 Full Year Results & Business Updates
Full Year 2020 Financial Results
Financial Summary
Operations Review
Oncology/Immunology
Other Ventures
Use of Non-GAAP Financial Measures and Reconciliation
Biographical Details of Directors
Directors’ Report
Corporate Governance Report
Form 20-F
(with certain items or sub-items highlighted below)
Introduction
Risk Factors
History and Development of the Company
Business Overview
Organizational Structure
Operating and Financial Review and Prospects
Directors, Senior Management and Employees
Major Shareholders and Related Party Transactions
4
5
6
12
14
17
17
31
34
36
41
49
3
7
57
57
147
148
172
186
Consolidated Financial Statements
F-1 to F-118
Information for Shareholders
CONTENTS 2
BUILDING A GLOBAL SCIENCE-FOCUSED BIOPHARMA COMPANY FROM AN ESTABLISHED BASE IN CHINA WORLD CLASS DISCOVERY &
DEVELOPMENT CAPABILITY
• First global-focused novel drug discovery company in
China – established in the early 2000s
• 600+ integrated R&D staff focused on oncology &
immunological diseases
HIGHLY DIFFERENTIATED GLOBAL
PIPELINE
• 10 innovative clinical stage drug candidates
– all discovered in-house by HUTCHMED
• 3 lead assets NDA filed/approved in China – all in late
global development
DEEP PAN-CHINA MARKET ACCESS
CAPABILITY
• 420+ person oncology team – covering 2,300+
oncology hospitals in China
• Highly profitable Other Ventures with 20 years
commercial track-record in China
SEASONED MANAGEMENT
TEAM – STRONG GOVERNANCE
• 11 years – median tenure of 14 person senior
management team
• 0 governance issues during 14 years as a
listed company
Hutchison China MediTech Limited 2020 Annual Report 3
On March 4, 2021 we announced the consolidation
of the two corporate identities that we have used
since our inception. Hutchison China MediTech,
or Chi-Med, has been used as our group identity,
while Hutchison MediPharma has been the
identity of our novel drug research & development
operations under which our oncology products have
been developed and are now being marketed.
The brand HUTCHMED will immediately replace
Chi-Med as our abbreviated name. We plan to
formally change our group company name at our
Annual General Meeting in April 2021, and the
names of our key subsidiary companies over the
balance of 2021. Our ticker symbol, HCM, will remain
unchanged on the Nasdaq Global Select Market and
the AІM market of the London Stock Exchange.
Our vision remains unaltered: to lead innovation
in oncology and immunology drugs, meet
unmet medical needs, and become a global
biopharmaceutical company.
As our pipeline of novel, highly selective
cancer drugs gain approval and advance to the
international stage, we believe now is the right time
to consolidate to a single and ubiquitous corporate
identity that captures the history and brand equity
we have built over the past twenty years. Therefore,
we have chosen to rename ourselves HUTCHMED.
HUTCHMED is a natural combination of the resonant
components from our two separate identities.
Our new brand retains our unique essence, whilst
signaling a new chapter – one brand that helps
patients around the world.
4
EVOLUTION OF OUR CORPORATE IDENTITY “
Our aim is to bring these
internally discovered and
developed innovations to
”
patients the world-over.
SIMON TO, CHAIRMAN
At the heart of HUTCHMED lies a prolific in-house novel drug discovery
and development engine that has produced ten clinical-stage drug
candidates and a further seven late-stage preclinical assets in oncology
and immunology over the past fifteen years.
Our aim is to bring these internally discovered and developed
innovations to patients the world-over.
To support this strategic objective, we have built an oncology and
immunology operation with around 1,200 personnel based mainly
in our two core markets, China and the U.S. In China, supported by
a robust manufacturing infrastructure, our commercial team is now
delivering impressive sales results on our first two oncology drugs,
ELUNATE® in metastatic colorectal cancer and the recently launched
SULANDA® in neuroendocrine tumors. A New Drug Application was also
submitted mid-last year for savolitinib in lung cancer and, subject to
approval, it will be our third approved oncology drug and the
first-in-class selective MET inhibitor on the market in China.
Outside China, our fast expanding international organization, led
mainly from the U.S., is developing six un-partnered oncology
drug candidates. In 2020, it achieved three U.S. Food and Drug
Administration fast track designations and initiated the rolling
submission of surufatinib, our first U.S. New Drug Application filing.
Over the next three years, we will continue to grow our R&D and
commercial organizations globally to support the anticipated launch of
our oncology drugs in China, the U.S. and Europe.
Simon To
Chairman
March 4, 2021
Hutchison China MediTech Limited 2020 Annual Report 5
Hutchison China MediTech Limited 2020 Annual Report 5
CHAIRMAN’S STATEMENT COMMERCIAL OPERATIONS
Full year 2021 Oncology/Immunology consolidated revenues
guidance $110-130 million (2020 actual: $30.2m) with in-house
oncology commercial organization in China now expanded to over
420 personnel (end 2019: about 90) covering over 2,300 oncology
hospitals and over 20,000 oncology physicians;
ELUNATE® (fruquintinib) in-market sales increased 91% to
$33.7 million1 (2019: $17.6m), as provided by Lilly2, during 2020 as a
result of inclusion in the 2020 China NRDL3;
Accelerating sales growth on ELUNATE® since Q4 2020 when
HUTCHMED assumed responsibility for all on-the-ground medical
detailing, promotion and local and regional marketing activities
in China;
•
•
Launched SULANDA® (surufatinib) as a treatment for patients with
advanced non-pancreatic NET4 in China in mid-January 2021 within
three weeks of approval. Unaudited sales of SULANDA® in January-
February 2021, in its first two months on the market, were $4.9
million; and
Established our U.S. commercial organization with the
recruitment of senior leadership team based in New Jersey to
prepare launch readiness for the potential surufatinib U.S. approval
in late 2021 or early 2022.
(Growth vs. Prior Period)
ELUNATE® In-market Sales**
2020
Lilly Sales Team
Q1-Q3 2020
HUTCHMED Sales Team
Q4 2020
Jan-Feb 2021*
$33.7m (+91%)
$23.5m (+37%)
$10.2m (+2,051%)
$14.3m (+116%)
ELUNATE® Revenues consolidated by HUTCHMED***
$20.0m (+85%)
$12.8m (+53%)
$7.2m (+192%)
$10.2m (+269%)
* = Unaudited; ** = Represents total sales to third parties as provided by Lilly;
*** = Represents manufacturing fees, commercial service fees and royalties paid by Lilly to HUTCHMED, and sales to other third parties invoiced by HUTCHMED.
Oncology commercial team covering
2,300+ oncology hospitals and
20,000+ oncology physicians
Over 420-person oncology commercial team
900+
~400
~90
2019
2020
2021e
Management
2023e
2022e
Reps
(cid:31)(cid:30)(cid:29)(cid:28)(cid:27)(cid:28)(cid:26)(cid:25)(cid:24)(cid:29)(cid:28)(cid:23)(cid:23)(cid:22)(cid:21)(cid:29)(cid:20)(cid:19)(cid:27)(cid:24)(cid:18)(cid:22)(cid:19)(cid:23)(cid:24)(cid:17)(cid:20)(cid:16)(cid:22)(cid:24)(cid:19)(cid:18)(cid:24)(cid:25)(cid:22)(cid:19)(cid:21)(cid:24)(cid:22)(cid:30)(cid:15)
See page 33 for all other references and abbreviations
•
•
•
6
2020 FULL YEAR RESULTS & BUSINESS UPDATES REGULATORY ACHIEVEMENTS
CLINICAL DEVELOPMENT ACTIVITIES
China
•
•
•
•
Received China approval for SULANDA® from the China NMPA5
as a treatment for patients with advanced non-pancreatic NET in
December 2020;
Submitted a China NDA6 for savolitinib as a treatment for
patients with MET7 Exon 14 skipping alteration NSCLC8. The NDA was
accepted in May 2020. Priority Review status was granted in July 2020
and review is underway;
Submitted a second China NDA for SULANDA® as a treatment for
patients with advanced pancreatic NET. The NDA was accepted in
September 2020 and review is underway; and
IND9 cleared for HMPL-295, a novel ERK10 inhibitor in the MAPK
pathway11, in late 2020.
United States & Europe
•
•
•
•
•
Initiated surufatinib U.S. FDA12 rolling submission of a NDA for
the treatment of both pancreatic and non-pancreatic NET in December
2020;
Secured U.S. FDA Fast Track Designations for surufatinib for the
treatment of both pancreatic and non-pancreatic NET in April 2020;
Received scientific advice from the EMA13 CHMP14 for surufatinib
for the treatment of both pancreatic and non-pancreatic NET with no
MAA15 filing issues identified;
Secured U.S. FDA Fast Track Designation for fruquintinib for the
treatment of advanced CRC16 in June 2020; and
Cleared two U.S. FDA INDs for HMPL-306 in late 2020, in
hematological malignancies and solid tumors.
Surufatinib (SULANDA® in China), a small molecule inhibitor
of VEGFR17, FGFR18 and CSF-1R19 designed to inhibit tumor
angiogenesis and promote the body’s immune response
against tumor cells via tumor associated macrophage
regulation; approved and launched in China
•
•
•
•
Presented Phase III study in pancreatic NET (SANET-p)
(NCT02589821) at the ESMO20 Congress 2020 and published
simultaneously in The Lancet Oncology. The study met all primary
and secondary endpoints and supported NMPA NDA submission;
Presented preliminary data of U.S. Phase Ib NET cohorts
(NCT02549937) at the ASCO21 Conference 2020 in heavily pretreated
patients with pancreatic or non-pancreatic NET, demonstrating
encouraging efficacy in patients refractory or intolerant to AFINITOR®
and SUTENT®;
Presented pharmacokinetic and safety data of U.S. Phase
Ib NET cohorts (NCT02549937) at the AACR22 Conference 2020,
demonstrating similar profiles of surufatinib between Chinese and
U.S. patients; and
Presented Phase I dose-finding study for surufatinib plus
TUOYI®, Junshi’s23 anti-PD-124 antibody, (NCT04169672) at the AACR
Conference 2020. Data demonstrated that surufatinib plus TUOYI®
were well tolerated with encouraging antitumor activity in patients
with advanced solid tumors. In January 2020, we initiated a Phase II
study in nine solid tumor indications in China.
Potential upcoming clinical and regulatory milestones for Surufatinib:
•
•
•
•
•
•
Complete the U.S. FDA rolling NDA submission for the treatment
of both pancreatic and non-pancreatic NET in the first half of 2021;
Initiate a Phase Ib/II study of surufatinib in combination with
tislelizumab (NCT04579757), BeiGene’s25 PD-1 antibody, in the U.S.
in the first half of 2021;
Submit the EU MAA for the treatment of both pancreatic and
non-pancreatic NET in mid-2021;
Present Phase II data for the SULANDA® plus TUOYI®
combination in select indications in mid-2021;
Receive China approval for patients with advanced pancreatic
NET which may occur as early as the second half of 2021; and
Initiate Phase III pivotal studies for the SULANDA® plus TUOYI®
combination in select indications in the second half of 2021
and beyond.
Hutchison China MediTech Limited 2020 Annual Report 7
Fruquintinib (ELUNATE® in China), a highly selective small
molecule inhibitor of VEGFR 1/2/3 designed to improve kinase
selectivity to minimize off-target toxicity and thereby improve
tolerability; approved and launched in China
Savolitinib, a highly selective small molecule inhibitor of
MET being developed broadly across MET-driven patient
populations in lung and gastric cancer and renal cell carcinoma
•
•
•
•
Initiated a global Phase III registration study (NCT04322539), the
FRESCO-2 study, in refractory metastatic CRC. FRESCO-2 is expected
to enroll over 680 patients from over 150 sites in 14 countries. The
first patient was dosed in September 2020 in the U.S.;
Presented preliminary data of U.S. Phase I/Ib colorectal cancer
cohorts (NCT03251378) at the ESMO Congress 2020 in heavily
pretreated metastatic CRC patients, demonstrating encouraging
efficacy and tolerability in patients refractory or intolerant to
STIVARGA® and LONSURF®;
Completed second planned interim data review for a Phase III
registration study (NCT03223376), the FRUTIGA study, in advanced
gastric cancer. Based on preset criteria the IDMC26 and Joint Steering
Committees recommended that the trial continue with a sample size
increase to ~700 patients; and
Initiated a Phase II study for fruquintinib in combination with
TYVYT®, Innovent’s27 PD-1 antibody, in four solid tumor indications
(NCT03903705) in Q4 2020.
•
•
•
•
Presented Phase II registration study (NCT02897479) for
savolitinib in MET Exon 14 skipping mutation patients at the ASCO
Conference 2020 which met study endpoints and supported NMPA
NDA submission;
Presented Phase II data for the CALYPSO study (NCT02819596)
for savolitinib in combination with IMFINZI®, AstraZeneca’s28 PD-L129
antibody, in PRCC30 patients at the ASCO GU31 Conference 2020
demonstrating encouraging synergy in efficacy and tolerability in line
with single agent safety profiles;
Presented Phase III data for the SAVOIR study (NCT03091192)
for savolitinib in MET positive PRCC patients at the ASCO Conference
2020 showing a clear trend to superiority in efficacy and tolerability
versus SUTENT® in first 60 patient data; and
Presented final Phase II data for TATTON (NCT02143466) at
WCLC32 2020, a global exploratory study in NSCLC aiming to recruit
patients with MET amplification who had progressed after prior
treatment with EGFR33 inhibitors. TATTON clearly confirmed the
importance of the savolitinib plus TAGRISSO® combination.
Potential upcoming clinical and regulatory milestones for Fruquintinib:
Potential upcoming clinical and regulatory milestones for Savolitinib:
Initiate a Phase Ib/II study in the U.S. for fruquintinib in
combination with tislelizumab (NCT04577963) in patients with
advanced, refractory triple negative breast cancer in the first half
of 2021;
Present Phase Ib U.S. expansion data in metastatic CRC
(NCT03251378) in mid-2021;
Present preliminary Phase Ib data for fruquintinib plus
TYVYT® (NCT04179084) and fruquintinib plus geptanolimab
(NCT03977090) in CRC in mid-2021;
Initiate pivotal studies for the ELUNATE® plus anti-PD-1
antibody combination in select indications in the second half
of 2021;
Complete enrollment of the FRESCO-2 study (NCT04322539) in
refractory metastatic CRC in late-2021; and
Complete enrollment of the FRUTIGA study (NCT03223376) in
advanced gastric cancer in late-2021;
•
•
•
•
•
Potential receipt of approval in China for the treatment of
patients with MET Exon 14 skipping alteration NSCLC which may
occur as early as Q2 2021, enabling a $25 million first sale milestone
payment from AstraZeneca. If approved, savolitinib would be the
first-in-class selective MET inhibitor in China;
Initiate global Phase III pivotal studies for the savolitinib plus
IMFINZI® combination in MET positive PRCC in mid-2021;
Initiate Phase II study with potential for registration intent for
savolitinib in metastatic gastric cancer in China in mid-2021;
Conclude the SAVANNAH Phase II study (NCT03778229) for the
savolitinib plus TAGRISSO® combination in NSCLC patients harboring
EGFR mutation and MET amplification or overexpression. SAVANNAH
will inform final regulatory, biomarker and dose regimen strategy for
global Phase III development in the second half of 2021; and
Initiate two further pivotal Phase III studies in China in NSCLC
patients in the second half of 2021.
•
•
•
•
•
•
8
2020 FULL YEAR RESULTS & BUSINESS UPDATES •
•
•
•
HMPL-689, an investigative and highly selective small molecule
inhibitor of PI3Kδ34 designed to address the gastrointestinal
and hepatotoxicity associated with currently approved and
clinical-stage PI3Kδ inhibitors
•
Presented Phase I dose escalation data (NCT03128164) for
HMPL-689 in patients in China with relapsed/refractory lymphoma at
the ASH35 Annual Meeting 2020 demonstrating encouraging efficacy
and tolerability profile.
Potential upcoming clinical and regulatory milestones for HMPL-689:
HMPL-453, an investigative and highly selective small molecule
inhibitor of FGFR 1/2/3
•
Initiated a Phase II study (NCT04353375) in China in patients with
advanced IHCC38 with FGFR239 fusion that had failed at least one line
of systemic therapy.
HMPL-306, an investigative and highly selective small molecule
inhibitor of IDH1/240 designed to address resistance to the
currently marketed IDH inhibitors
Complete Phase Ib expansion study (NCT03128164) and present
interim data in the second half of 2021;
•
Initiated a Phase I dose escalation study (NCT04272957) in China
in patients with relapsed or refractory hematological malignancies
with an IDH1 and/or IDH2 mutation.
Initiate Phase II studies with potential for registration intent
in China in multiple relapsed/refractory non-Hodgkin’s lymphoma
indications during 2021;
Complete Phase I dose escalation in the U.S. and Europe
(NCT03786926) in Q2 2021 and initiate Phase Ib expansion studies in
multiple non-Hodgkin’s lymphoma indications; and
Complete U.S. FDA regulatory discussions in the second half
of 2021 followed by the initiation of registration intent studies in
indolent non-Hodgkin’s lymphoma by the end of 2021.
HMPL-523, an investigative and highly selective small
molecule inhibitor of Syk36, an important component of
the B-cell receptor signaling pathway, for the treatment of
hematological cancers and immune disease
•
•
Completed enrollment of Phase I dose escalation study
(NCT03779113) in the U.S. and Europe; and
Completed enrollment of Phase I/Ib study (NCT03951623) in China
of HMPL-523 in ITP37.
Potential upcoming clinical and regulatory milestones for HMPL-306:
•
•
Initiate a Phase I dose escalation study in the U.S. in patients with
relapsed or refractory hematological malignancies with an IDH1 and/
or IDH2 mutation in the first half of 2021; and
Initiate a Phase I dose escalation study in the U.S. in patients with
solid tumors with an IDH1 and/or IDH2 mutation in the first half of 2021.
HMPL-295, an investigative and highly selective small molecule
inhibitor of ERK in the MAPK pathway with the potential
to address intrinsic or acquired resistance from upstream
mechanisms such as RAS-RAF-MEK
Potential upcoming clinical and regulatory milestones for HMPL-295:
•
Initiate a Phase I study in China in mid-2021.
Discovery, our in-house scientific team has been responsible
for the discovery of all ten of our clinical drug candidates
including our two approved oncology drugs ELUNATE® and
SULANDA®
Potential upcoming clinical and regulatory milestones for HMPL-523:
Potential upcoming discovery milestones:
•
Initiate a Phase III study in ITP in China in the second half of 2021.
•
IND-enabling toxicity studies are underway for three additional
in-house discovered oncology drug candidates, two small
molecules and one antibody. If the outcomes of these studies are as
we anticipate, we will follow with IND submissions during 2021.
Hutchison China MediTech Limited 2020 Annual Report 9
MANUFACTURING OPERATIONS
IMPACT OF COVID-19
•
•
Received surufatinib update to drug manufacturing license at
our Suzhou manufacturing facility, following the NMPA approval in
December 2020; and
Broke ground in December 2020 on our $130 million new
Shanghai manufacturing facility designed to support a five-fold
increase in small molecule drug product manufacturing capacity
relative to our existing Suzhou facilities. We plan also that in
the future the Shanghai facility will also establish scale biologics
manufacturing capability.
The COVID-19 outbreak initially posed some challenges to our operations
in 2020 resulting from restrictions in travel. Our teams adapted quickly
and were able to minimize the effect across our businesses. We will
continue to closely monitor the evolving situation.
OTHER CORPORATE
DEVELOPMENTS
Announced a clinical collaboration agreement with BeiGene
in May 2020 to evaluate combining surufatinib and fruquintinib
with BeiGene’s anti-PD-1 antibody tislelizumab, for the treatment of
various solid tumor cancers, in the U.S., Europe, China and Australia;
Announced a land compensation agreement in June 2020 with
the Guangzhou government for the return of the remaining
34-year land-use rights on an unused plot of land under our HBYS41
joint venture in consideration for cash compensation of up to
approximately $100 million; and
Announced a strategic partnership with Inmagene42 in January
2021 to further develop four novel preclinical drug candidates
discovered by HUTCHMED for the potential treatment of multiple
immunological diseases.
•
•
•
10
2020 FULL YEAR RESULTS & BUSINESS UPDATES Change in Segment Reporting:
As a consequence of our recent commercialization of both ELUNATE® and SULANDA® and the possible approval and launch of savolitinib during 2021, we
have decided to change the manner in which we report segment results in our financial statements. Effective from the year ended December 31, 2020, we
will report two segments, (1) Oncology/Immunology, covering all activities related to oncology/immunology including sales, marketing, manufacturing
and research and development with respect to our drugs and drug candidates; and (2) Other Ventures, which includes all other HUTCHMED businesses.
We have retrospectively revised prior period segment information to conform to current period presentation in the financial information contained in this
annual report.
Oncology/Immunology
Discovery, development, manufacturing & commercialization
of novel oncology & immunology therapeutics
Shanghai
New Jersey
Suzhou
Discovery and
development
Clinical development
& regulatory affairs
GMP-certified
manufacturing
Commercial
HUTCHMED GROUP STRUCTURE
Beijing
Australia
E.U.
Others
Other Ventures
Hutchison Sinopharm
Rx Drug Commercialization
Partner: Sinopharm Group (HCM 51%)
Shanghai Hutchison Pharmaceuticals
Rx Drug Mfg & Commercialization
Partner: Shanghai Pharma (HCM 50%)
Hutchison BYS[1]
Over-the-counter drugs
Partner: Guangzhou Pharma (HCM 40%)
Consumer Healthcare[2]
Notes:
[1] Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited (HUTCHMED holds 50.0% through its 80.0% owned subsidiary Hutchison BYS (Guangzhou) Holding Limited), a JV with
Guangzhou Baiyunshan Pharmaceutical Holdings Co. Limited which holds the other 50.0%.
[2] Mainly Hutchison Hain Organic Holdings Limited, a JV with The Hain Celestial Group, Inc.
Consolidated
Non-Consolidated
12
FULL YEAR 2020 FINANCIAL RESULTS
Cash, Cash Equivalents and Short-Term Investments were
$435.2 million as of December 31, 2020 compared to
$217.2 million as of December 31, 2019.
Net Expenses for the year ended December 31, 2020 were
$353.7 million compared to $310.9 million in 2019.
•
•
Adjusted Group (non-GAAP43) net cash flows excluding financing
activities were -$78.4 million (2019: -$82.3m) mainly due to Oncology/
Immunology R&D44 spending and partially offset by dividends
received from our non-consolidated joint ventures totaling $86.7
million (2019: $28.1m); and
Net cash generated from financing activities in 2020 totaled
$296.4 million (2019: -$1.5m) mainly resulting from a Nasdaq
follow-on offering in January 2020 and two private placements to
General Atlantic45 and CPP Investments46 completed in July and
November 2020 respectively.
Revenues for the year ended December 31, 2020 was
$228.0 million compared to $204.9 million in 2019.
•
•
Oncology/Immunology consolidated revenues were $30.2 million
(2019: $26.8m) comprised of $20.0 million (2019: $10.8m) in
manufacturing revenues, promotion and marketing service revenues
and royalties from the commercial sale of ELUNATE®; and $10.2 million
(2019: $16.0m) in research and development service fee revenues
primarily from AstraZeneca and Lilly; and
Other Ventures consolidated revenues increased 11% (11% at
CER47) to $197.8 million (2019: $178.1m) mainly due to continued
sales growth of third-party prescription drug products.
•
•
•
•
Cost of Sales were $188.5 million (2019: $160.2m), the majority
of which was the cost of third-party prescription drug products
marketed through our profitable Other Ventures;
R&D Expenses were $174.8 million (2019: $138.2m) mainly as a
result of an expansion in the development of our ten novel oncology
drug candidates. With six now in global development, our rapidly
scaling international clinical and regulatory operations in the U.S.
and Europe incurred expenses of $63.3 million (2019: $21.7m) while
R&D expense in China was stable at $111.5 million (2019: $116.5m);
SG&A48 Expenses were $61.3 million (2019: $52.9m) primarily due
to increases in staff costs and share-based compensation to support
expanding operations. This included the build-up of a large-scale
national oncology commercial infrastructure in China to support
the launch of SULANDA® and the assumption of commercial
responsibility on ELUNATE®; and
Other Items49 generated net income of $70.9 million (2019: $40.4m)
resulting primarily from an increase in our share of equity in the
earnings from equity investees under our Other Ventures in China
which delivered solid underlying net income growth of 7% (9% at
CER) in 2020 and also benefited from a one-time land compensation
gain of $28.8 million (2019: nil).
Net Loss attributable to HUTCHMED for the year ended
December 31, 2020 was $125.7 million compared to
$106.0 million in 2019.
•
As a result, the net loss attributable to HUTCHMED in 2020 was
$0.18 per ordinary share / $0.90 per ADS50 compared to net loss
attributable to HUTCHMED of $0.16 per ordinary share / $0.80 per
ADS, in 2019.
Hutchison China MediTech Limited 2020 Annual Report 13
As of December 31,
2020
2019
435,176
47,870
47,694
24,170
139,505
29,703
724,118
31,612
120,882
26,861
25,814
205,169
484,116
34,833
724,118
217,168
43,254
56,600
20,855
98,944
28,301
465,122
23,961
81,624
26,818
19,816
152,219
288,012
24,891
465,122
CONDENSED CONSOLIDATED BALANCE SHEET DATA
(in $’000)
Assets
Cash and cash equivalents and short term investments
Accounts receivable
Other current assets
Property, plant and equipment
Investments in equity investees
Other non-current assets
Total assets
Liabilities and shareholders’ equity
Accounts payable
Other payables, accruals and advance receipts
Long-term bank borrowings
Other liabilities
Total liabilities
Total Company’s shareholders’ equity
Non-controlling interests
Total liabilities and shareholders’ equity
14
FINANCIAL SUMMARY
CONDENSED CONSOLIDATED STATEMENT OF OPERATIONS DATA
(in $’000, except share and per share data)
Revenues:
Oncology/Immunology – Marketed Products
Oncology/Immunology – R&D
Oncology/Immunology consolidated revenues
Other Ventures
Total revenues
Expenses:
Costs of revenues
Research and development expenses
Selling and general administrative expenses
Total expenses
Loss from Operations
Other income
Loss before income taxes and equity in earnings of equity investees
Income tax expense
Equity in earnings of equity investees, net of tax
Net loss
Less: Net income attributable to non-controlling interests
Net loss attributable to HUTCHMED
Losses per share attributable to HUTCHMED - basic and diluted
Number of shares used in per share calculation - basic and diluted
Losses per ADS attributable to HUTCHMED - basic and diluted
Number of ADSs used in per share calculation - basic and diluted
All amounts are expressed in U.S. dollar currency unless otherwise stated.
Year Ended December 31,
2020
2019
19,953
10,262
30,215
197,761
227,976
(188,519)
(174,776)
(61,349)
(424,644)
(196,668)
6,934
(189,734)
(4,829)
79,046
(115,517)
(10,213)
(125,730)
(0.18)
697,931,437
(0.90)
139,586,287
10,766
16,026
26,792
178,098
204,890
(160,152)
(138,190)
(52,934)
(351,276)
(146,386)
5,281
(141,105)
(3,274)
40,700
(103,679)
(2,345)
(106,024)
(0.16)
665,683,145
(0.80)
133,136,629
Hutchison China MediTech Limited 2020 Annual Report 15
CHRISTIAN HOGG,
CHIEF EXECUTIVE OFFICER
We discover, develop, manufacture and market targeted therapies and
immunotherapies for the treatment of cancer and immunological diseases
through a fully integrated team of over 600 scientists and staff (December 31,
2019: ~500), and an in-house oncology commercial organization of over
420 staff (December 31, 2019: ~90).
Currently, we have nine self-discovered oncology drug candidates in
clinical trials in China, with six also in clinical development in the U.S. and
Europe. Our first two drug candidates, fruquintinib and surufatinib, have
been approved and launched by our commercial organization in China.
MARKETED PRODUCT SALES
Fruquintinib (ELUNATE® in China)
ELUNATE® was first commercially launched in China, marketed by our
partner Lilly, starting in November 2018 for the treatment of advanced
CRC. Since launch, Lilly deployed a dedicated team of about 140 oncology
commercial personnel to market ELUNATE® in China. In January 2020,
ELUNATE® was included in the NRDL thereby broadening access by
advanced CRC patients in China.
In July 2020, we reached an agreement with Lilly for HUTCHMED to take
over development and execution of all on-the-ground medical detailing,
promotion and local and regional marketing activities for ELUNATE® in
China. Under the terms of the new agreement, HUTCHMED and Lilly will
share gross profits linked to sales target performance. Subject to meeting
pre-agreed sales targets, Lilly will pay HUTCHMED an estimated total of
70% to 80% of ELUNATE® sales in the form of royalties, manufacturing
costs and service payments.
Since taking on these commercial responsibilities in Q4 2020, HUTCHMED
has deployed its dedicated team of over 420 oncology commercial
personnel to market ELUNATE® with sales now increasing rapidly.
Hutchison China MediTech Limited 2020 Annual Report 17
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY Lilly
Sales Team
Q1-Q3
2020
$23.5m
(+37%)
$12.8m
(+53%)
HUTCHMED
Sales Team
Q4
2020
$10.2m
(+2,051%)
$7.2m
(+192%)
Jan-Feb
2021*
$14.3m
(+116%)
$10.2m
(+269%)
2020
$33.7m
(+91%)
$20.0m
(+85%)
Surufatinib (SULANDA® in China)
SULANDA® was first commercially launched in China in mid-January 2021
for the treatment of advanced non-pancreatic NET. In China, there were
an estimated 67,600 newly diagnosed NET patients in 2018, of which an
estimated 60% were diagnosed with advanced NETs. Considering the
current incidence to prevalence ratio, there may be more than 300,000
patients living with the disease in China.
(Growth vs. Prior Period)
ELUNATE® In-market Sales**
ELUNATE® Revenues
consolidated
by HUTCHMED***
* = Unaudited; ** = Represents total sales to third parties as provided by Lilly;
*** = Represents manufacturing fees, commercial service fees and royalties paid by Lilly to
HUTCHMED, and sales to other third parties invoiced by HUTCHMED.
In 2020, we estimate that ELUNATE® achieved approximately 15%
penetration (patient share), based on our estimation of the size of the
advanced CRC market in China, which would equate to approximately
8,400 patients receiving an average of 4.7 months of treatment (IQVIA).
Driven by inclusion in the NRDL, we are now rapidly expanding hospital
pharmacy listings, one of the most important factors affecting broad-scale
adoption of ELUNATE® in China. In Q4 2020, we increased hospital
listings by over 40% to approximately 280 and target to double this
level of listings in 2021. Our oncology commercial team currently covers
over 2,300 oncology hospitals in China, with ELUNATE® prescriptions in
hospitals without an in-house pharmacy listing being filled in external
retail pharmacies.
We believe that the efficacy and safety benefits of ELUNATE®, combined
with our deep commercial presence and execution, will position us well
to significantly increase our market share in advanced CRC in China in
the future.
More than half of NET patients harbor tumors in the gastrointestinal tract.
As such, there exists major overlap between the oncology physicians and
hospitals in China that treat advanced CRC with ELUNATE® and advanced
gastrointestinal NETs with SULANDA®. We expect that this synergy will
enable us to effectively utilize our full oncology commercial organization
to market both products.
In January-February 2021, the first two months on the market, the total
unaudited sales of SULANDA® were $4.9 million.
A number of factors have contributed to the promising start for SULANDA®
such as, (1) a larger and dedicated oncology commercial team covering
over 300 cities in China; (2) extensive pre- and post-launch marketing
programs to raise awareness among the over 20,000 oncology physicians
in China; and (3) a pricing strategy aimed at maximizing patient access to
SULANDA®.
Our aim is to have SULANDA® included in the 2022 NRDL. Until then we
are implementing a broad-scale, means tested, patient access program
which could materially reduce out-of-pocket costs for patients. We
expect the average duration of treatment for SULANDA® for NET patients
could be similar to the 9.2 months median PFS51 in non-pancreatic NET.
Competition in the advanced non-pancreatic NET market in China is
limited with SULANDA® providing a unique mechanism of action against
the disease.
With the initiation of rolling NDA submissions to the U.S. FDA for
surufatinib in December 2020, we have begun to establish a U.S. oncology
commercial organization with the recruitment of a senior leadership team
based in New Jersey in preparation for a potential surufatinib U.S. launch
in late 2021 or early 2022.
18
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY RESEARCH & DEVELOPMENT
SAVOLITINIB
Savolitinib is an oral, potent, and highly selective small molecule inhibitor
of MET. In global partnership with AstraZeneca, savolitinib has been
studied in NSCLC, PRCC and gastric cancer in over 1,100 patients to date,
both as a monotherapy and in combinations.
Savolitinib – Lung cancer:
MET plays an important role in NSCLC. The table below shows a
summary of the clinical studies for savolitinib in lung cancer patients.
Treatment
Savolitinib
Savolitinib +
TAGRISSO®
Savolitinib +
TAGRISSO®
Savolitinib +
TAGRISSO®
Savolitinib +
TAGRISSO®
Name, Line,
Patient Focus
MET Exon 14
skipping alteration
SAVANNAH: 2L/3L
EGFRm+52;
TAGRISSO®
refractory; MET+
2L/3L EGFRm+;
TAGRISSO®
refractory; MET+
2L EGFR TKI53
refractory
NSCLC; MET+
Naïve patients
with EGFRm &
MET+
Sites
Phase
Status/Plan NCT #
China
II Registration NDA
NCT02897479
accepted
(May 2020)
Ongoing
NCT03778229
Global
II
Registration-
intent
Global
III
In planning
N/A
China
III
In planning
N/A
China
III
In planning
N/A
NDA accepted in MET Exon 14 skipping alterations NSCLC (NCT02897479)
– An estimated 2-3% of NSCLC patients have MET Exon 14 skipping
alterations, which lead to poor prognosis. In late 2019, we completed a
70-patient Phase II registration study that was the basis for NDA, which
was accepted by the China NMPA in May 2020. Priority review status was
granted in July 2020 and, subject to approval, launch is expected in
mid-2021.
Results of the Phase II study were presented at ASCO in June 2020 and
showed that as of the March 31, 2020 data cut-off, ORR54 was 49.2% and
DCR55 was 93.4% in 61 efficacy evaluable patients. Median DoR56 was
9.6 months (95% CI57 5.5–NR58) with maturity of 40%. Median PFS was
6.9 months (95% CI 4.2–19.3) with maturity of 50%. Median OS was 14.0
months (95% CI: 9.7–NR) with maturity of 46%. Clinical data demonstrated
an acceptable safety profile with a low AE59 related discontinuations rate
of 14.3%.
f
o
e
g
n
a
h
C
t
s
e
B
)
%
(
n
o
i
s
e
L
t
e
g
r
a
T
+80%
+60%
+40%
+20%
0%
-20%
-40%
-60%
-80%
-100%
Partial response
Stable disease
Progressive disease
Efficacy Evaluable
Full Analysis
(N=61)
(N=70)
ORR, %[95% CI]
49.2 [36.1, 62.3]
42.9 [31.1, 55.3]
DCR, %[95% CI]
93.4 [84.1, 98.2]
82.9 [71.2, 90.8]
Phase II Study of Savolitinib Monotherapy Showing Effect in MET Exon 14 Alteration
NSCLC Patients
Notes: N= number of patients; ORR = objective response rate; DCR = disease control rate;
CI = confidence interval.
Source: Lu S, Fang J et al. Phase II study of savolitinib in patients (pts) with pulmonary sarcomatoid
carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14
skipping mutations (METex14+). Journal of Clinical Oncology 2020 38:15_suppl, 9519-9519.
Hutchison China MediTech Limited 2020 Annual Report 19
EGFR TKI-resistance in NSCLC – MET-amplification is a major mechanism
for acquired resistance to both first-generation EGFR TKIs, such as IRESSA®
and TARCEVA®, as well as third-generation EGFR TKIs like TAGRISSO®. As
many as 30% of EGFR mutation positive NSCLC patients develop MET
amplification driven resistance to EGFR TKIs. Savolitinib has been studied
extensively in these patients in the TATTON and SAVANNAH studies.
The SAVANNAH study has now fully enrolled the savolitinib 300mg QD60
cohort, and is currently enrolling two additional cohorts of savolitinib 300mg
BID61 and 600mg QD. The SAVANNAH study will also determine optimal
design of the planned global Phase III study regarding optimal biomarker
strategy and dosage regimen. Enrollment is expected to complete in
mid-2021 and planning for the global Phase III study is now underway.
SAVANNAH Phase II study of combination with TAGRISSO® in patients
who have progressed following TAGRISSO® due to MET amplification or
overexpression (NCT03778229) – The SAVANNAH study is a global single-
arm, open-label study. SAVANNAH followed the successful TATTON
study, a Phase Ib/II expansion study of savolitinib in combination with
TAGRISSO® in over 220 EGFR mutation positive TKI refractory NSCLC
patients, with final analysis presented at the virtual 2020 WCLC.
In-Planning – China Phase III study of combination with TAGRISSO® in 2L
EGFR TKI refractory, MET amplified NSCLC patients – We intend to initiate a
Phase III study in China targeting EGFR TKI refractory second-line NSCLC
patient in the second half of 2021.
In-Planning – China Phase III study of combination with TAGRISSO® in EGFR
mutant and MET positive NSCLC patients – We intend to initiate a Phase
III study in China targeting treatment naïve patients who are both EGFR
mutation and MET positive in the second half of 2021.
Part B1 (n=69)
Prior third-generation
EGFR-TKI
TATTON Part B
osimertinib 80 mg +
savolitinib 600 mg [1]
Part B2 (n=51)
No prior third-
generation
EGFR-TKI
(T790M negative)
Part B3 (n=18)
No prior third-
generation
EGFR-TKI
(T790M positive)
TATTON Part D
osimertinib 80 mg +
savolitinib 300 mg
Part D (n=42)
No prior third-
generation
EGFR-TKI
(T790M negative)
Objective response rate*, % [95% CI]
33% [22, 46]
65% [50, 78]
67% [41, 87]
62% [46, 76]
Complete response, %
Partial response, %
Non-response, %
Stable disease (≥ 6 weeks)
Progressive disease
Not evaluable
Disease control rate#, % [95% CI]
Median DoR, months [95% CI]
Median PFS, months [95% CI]
0
33%
42%
12%
13%
0
65%
24%
6%
6%
0
67%
33%
0
0
0
62%
31%
2%
5%
75% [64, 85]
9.5 [4, 15]
5.5 [4.1, 7.7]
88% [76, 96]
10.7 [6, 15]
100% [81, 100]
93% [81, 99]
11.0 [2.8, NR]
9.7 [5, 14]
9.1 [5.5, 12.8]
11.1 [4.1, 22.1]
9.0 [5.6, 12.7]
Savolitinib Plus Tagrisso Combination Showing Effect in EGFR Refractory Patients Who Are Either Tagrisso Refractory (Part B1) or Tagrisso Naïve
(Parts B2, B3, D)
Notes:
[1] Most patients were enrolled to Part B1, B2, B3 on 600 mg savolitinib, prior to weight-based dosing implementation, but following a protocol amendment in response to a
safety signal of hypersensitivity, the final 21 patients enrolled in Part B were dosed with savolitinib by body weight as follows: patients who weighed ≤55 kg (n=8) received 300
mg daily and those weighing >55 kg (n=13) received 600 mg daily; Best response data are for patients who had an opportunity to have two follow-up scans; * Complete or
partial response confirmed at ≥4 weeks. # Disease control rate = confirmed complete response + confirmed partial response + stable disease at ≥5 weeks; CI, confidence interval;
NR, not reached.
Source: Han JY, et al. Osimertinib + savolitinib in patients with EGFRm MET-amplified/overexpressed NSCLC: Phase Ib TATTON Parts B and D final analysis. WCLC January 2021 #FP14.03.
20
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY Savolitinib – Kidney cancer:
MET is a clear genetic driver in RCC62. The table below shows a
summary of the clinical studies for savolitinib in kidney cancer patients.
Treatment
Savolitinib +
IMFINZI®
Savolitinib +
IMFINZI®
Savolitinib +
IMFINZI®
Sites
Phase
Status/Plan NCT #
Global
III
In planning
N/A
Name, Line,
Patient Focus
MET-driven,
unresectable and
locally advanced
or metastatic
PRCC
CALYPSO: PRCC
U.K./Spain II
Interim data
ASCO GU 2020
NCT02819596
U.K./Spain II
Ongoing
NCT02819596
CALYPSO: Clear
cell RCC; VEGFR
TKI refractory
MET+ PRCC – PRCC is the most common of the non-clear cell RCC,
representing approximately 14% of kidney cancer. Approximately 400,000
new cases of kidney cancer were diagnosed globally in 2018, equating
to about 56,500 cases of PRCC, with approximately 40% harboring MET
driven disease. No targeted therapies have been approved specifically for
PRCC.
SAVOIR Phase III in MET-positive PRCC (NCT03091192) – In late 2018,
the SAVOIR study, a global Phase III study of savolitinib monotherapy
compared with SUTENT® (sunitinib) in patients with MET-driven PRCC,
was stopped early with 60 patients randomized at the time, due to
confounding data from a separate, external, retrospective molecular
epidemiology study.
Results from the 60 randomized patients (33 savolitinib, 27 sunitinib) were
promising and data was presented at ASCO in May 2020. In terms of OS,
savolitinib patients had not reached median OS at data cut-off, compared
to 13.2 months for sunitinib patients (HR63 0.51; 95% CI: 0.21–1.17;
p=0.110). Median PFS was 7.0 months for savolitinib patients, compared to
5.6 for sunitinib patients (HR 0.71; 95% CI 0.37–1.36; p=0.313). Responses
were observed in 27% and 7% of savolitinib and sunitinib patients,
respectively. This difference did not reach statistical significance due to
the small sample size. In terms of safety, Grade ≥3 AEs were reported
in 42% of savolitinib patients versus 81% of sunitinib patients, with AEs
leading to dose modification in 30% and 74% of savolitinib and sunitinib
patients, respectively.
S
S
S
O
O
O
f
f
f
o
o
o
y
y
y
t
t
t
i
i
i
l
l
l
i
i
i
b
b
b
a
a
a
b
b
b
o
o
o
r
r
r
P
P
P
1.0
1.01.0
0.8
0.80.8
0.6
0.60.6
0.4
0.40.4
0.2
0.20.2
0.0
0.00.0
0
00
Median,
mo.
Sunitinib
13.2
[7.6, NC]
[95% CI]:
[95% CI]:
[0.21-1.17] P=0.110
[0.21-1.17] P=0.110
Savolitinib (n=33)
Savolitinib (n=33)
Savolitinib (n=33)
Sunitinib (n=27)
Sunitinib (n=27)
Sunitinib (n=27)
Censored observations
Censored observations
Censored observations
++
+
3
33
6
66
9
99
12
1212
15
1515
18
1818
21
2121
24
2424
Time From Randomization (Months)
Time From Randomization (Months)
Time From Randomization (Months)
(%) [95% CI]
Savolitinib (N=33)
Sunitinib (N=27)
ORR*
PFS
9 (27) [13.3, 45.5]
7.0 [2.8, NC]
2 (7) [0.9, 24.3]
5.6 [4.1, 6.9]
Hazard Ratio: 0.71 [0.37, 1.36]
DCR @ 6 months
@ 12 months
16 (48) [30.8, 66.5]
10 (30) [15.6, 48.7]
10 (37) [19.4, 57.6]
6 (22) [8.6, 42.3]
SAVOIR 60-Patient Study of Savolitinib Monotherapy in MET-Driven Papillary Renal
Cell Carcinoma Patients. This Study Demonstrated a Strong Signal of Response and
Potential Survival Benefit Compared to Sunitinib Monotherapy
Notes:
*At data cut-off, all nine savolitinib responders remained in response, while one of two sunitinib
responders remained in response. n = number of patients; CI = confidence interval; DCR = disease
control rate; NC = not calculated; OS = overall survival; PFS = progression-free survival; and
HR = hazard ratio.
Source: Choueiri TK, et al. Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal
Cell Carcinoma: The SAVOIR Phase 3 Randomized Clinical Trial. JAMA Oncol. Published online May
29, 2020. doi:10.1001/jamaoncol.2020.2218.
Savolitinib and Immunotherapy Combinations – Evidence is emerging
demonstrating that MET plays an important role in the tumor
microenvironment, leading to reduced anti-tumor activity of immune cells
in many solid tumors. Therefore, combining immunotherapies with a MET
inhibitor is hypothesized to enhance anti-tumor activity.
CALYPSO Phase II in combination with IMFINZI® PD-L1 inhibitor in RCC
(NCT02819596) – The CALYPSO study is an investigator initiated open-label
Phase I/II study of savolitinib in combination with IMFINZI®. The study is
evaluating the safety and efficacy of the savolitinib/IMFINZI® combination
in patients with PRCC and clear cell RCC at sites in the U.K. and Spain.
CALYPSO PRCC cohort – Interim data for the PRCC cohort of the CALYPSO
Phase II study were presented at ASCO GU 2020 reporting an ORR of
27%, median PFS of 4.9 months (95% CI: 2.5, 12.0) and median OS of 12.3
months (95% CI: 5.8, 21.3). Tolerability was in line with established single
agent safety profiles.
Hutchison China MediTech Limited 2020 Annual Report 21
In-Planning – Phase III in combination with IMFINZI® PD-L1 inhibitor in
MET-driven, unresectable and locally advanced or metastatic PRCC – Based
on the encouraging results of the SAVOIR and CALYPSO studies, we intend
to initiate a global Phase III, open-label, randomized, controlled study of
savolitinib plus IMFINZI® versus sunitinib monotherapy versus IMFINZI®
monotherapy in patients with MET-driven, unresectable and locally
advanced or metastatic PRCC. The study is expected to begin enrollment
by mid-2021.
Savolitinib – Gastric cancer:
MET-driven gastric cancer has a very poor prognosis. Multiple Phase II
studies have been conducted in Asia to study savolitinib in MET-driven
gastric cancer patients. The VIKTORY study is an investigator initiated
Phase II umbrella study in gastric cancer in South Korea in which a total of
715 patients were successfully sequenced into 10 molecular-driven patient
groups. Patients with MET amplification (25/715, or 3.5% of patients) were
treated with savolitinib monotherapy, reporting an ORR of 50% (10/20,
95% CI: 28.0, 71.9), meeting pre-specified 6-week PFS rates and warranting
further study.
In-Planning – China Phase II study with potential for registration intent
in 2L+ gastric cancer with MET amplification – In mid-2021, we intend to
initiate a Phase II registration-intent study in MET-amplified gastric cancer
in China. This is a two-stage, single-arm study which targets advanced
gastric cancer patients who have failed at least one line of treatment. The
primary endpoint is ORR. Subject to the results of the first-stage of this
study we will discuss with the CDE64 of NMPA the appropriate approach
and necessary criteria for registration.
SURUFATINIB
Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively
inhibits the tyrosine kinase activity associated with VEGFR and FGFR,
both shown to be involved in tumor angiogenesis, and CSF-1R, which
plays a key role in regulating tumor-associated macrophages, promoting
the body’s immune response against tumor cells. Surufatinib has been
studied in over 900 patients to date, both as a monotherapy and in
combinations, and is approved in China.
We currently retain all rights to surufatinib worldwide. A summary of the
clinical studies of surufatinib is shown in the table below.
Name, Line,
Patient Focus
Sites
Phase
Status/Plan
NCT #
SANET-ep: Non-
pancreatic NET
China
SANET-p:
Pancreatic NET
China
III
III
NCT02588170
NCT02589821
Approved and
launched
Met primary
endpoint; NDA
accepted (Sept
2020)
Treatment
Surufatinib
monotherapy
Surufatinib
monotherapy
22
Name, Line,
Patient Focus
Sites
Phase
Status/Plan
NCT #
NETs
U.S.
Ib
NCT02549937
NDA rolling
submission
initiated;
est. complete
H1 2021
NETs
Europe
Ib
Expect to file
MAA in mid-2021
N/A
BTC65 and soft
tissue sarcoma
Chemotherapy
refractory BTC
U.S.
Ib
Ongoing
NCT02549937
China
IIb/III
Ongoing
NCT03873532
NENs66
China
BTC
China
Gastric cancer
China
Thyroid cancer
China
SCLC67
China
Soft tissue
sarcoma
Endometrial
cancer
Esophageal
cancer
China
China
China
NSCLC
China
Solid tumors
China
II
II
II
II
II
II
II
II
II
I
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04169672
Ongoing
NCT04427774
Treatment
Surufatinib
monotherapy
Surufatinib
monotherapy
Surufatinib
monotherapy
Surufatinib
monotherapy
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TUOYI® (PD-1)
Surufatinib +
TYVYT® (PD-1)
Surufatinib +
tislelizumab (PD-1)
Solid tumors
U.S./
Europe
Ib/II
In planning
NCT04579757
Surufatinib – NET:
NETs present in the body’s organ system with fragmented epidemiology.
About 55-75% of NETs originate in the GI68 tract and pancreas, 25-30%
in the lung or bronchus, and a further 10-20% in other organs or
unknown origins.
Global development of surufatinib in NET – In June 2020, we held a
pre-NDA meeting with the U.S. FDA for the treatment of patients with
advanced NET and reached an agreement that the completed SANET-ep
(non-pancreatic NET) and SANET-p (pancreatic NET) studies, along
with existing data from surufatinib in U.S. non-pancreatic and pancreatic
NET patients, could form the basis to support a U.S. NDA submission.
The FDA granted Fast Track Designations for our pancreatic and
non-pancreatic NET development programs in April 2020, following
Orphan Drug Designation for pancreatic NET in November 2019.
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY In December 2020, we initiated the filing of a NDA to the U.S. FDA – the
first portion of a rolling submission for surufatinib for the treatment
of pancreatic and non-pancreatic NET. We plan to complete the NDA
submission in the first half of 2021, which would be our first NDA in the
U.S. Filing acceptance of the NDA is subject to FDA review of the
complete application.
We also plan to file a MAA to the EMA in mid-2021, based on scientific
advice from the EMA’s CHMP.
U.S. Phase Ib NET cohorts (NCT02549937) – At ASCO 2020, preliminary data
presented from the two NET cohorts in the ongoing U.S. Phase Ib trial for
surufatinib demonstrated efficacy comparable to China data in heavily
pretreated patients, including AFINITOR® and SUTENT®, with pancreatic
or non-pancreatic NETs. The safety profile was also consistent with the
larger pool of surufatinib safety data. As of April 21, 2020, 16 patients with
pancreatic NET were treated for a median of 7.1 months (range 2.0-17.5)
and 16 patients with non-pancreatic NET were treated for a median of
4.9 months (range of 1.0-10.2). All 32 patients have pretreated progressive
NETs (median prior lines of treatment: 3; range 1-8). Confirmed response
was observed in 18.8% of pancreatic NET patients; all remaining patients
had stable disease (including 1 unconfirmed response), for a DCR of
100%. In the non-pancreatic NET cohort all patients had stable disease
(including 1 unconfirmed response).
Pharmacokinetic and safety data from these cohorts was presented at
AACR 2020, demonstrating similar profiles of surufatinib between Chinese
and U.S. patients, meaning that race had minimal effect on exposure.
surufatinib
everolimus
sunitinib
Other Tx
8
12
10
24
3
3
2
X
15
3
11
2
3
2
5
7
8
36
18
7
8
8
24
X
X
12
4
8
15
10
12
4
7
11
9
18
6
6
3
2
2
2
1
3
6
6
X
X
X
6
14
3
2
1
36
12
24
32
12
3
22
5
12
36
6
18
6
-48
-36
-24
-12
0
24
22
12
12
6
24
PR
Confirmed PR (n=3)
uPR
Unconfirmed PR (n=1)
Treatment ongoing (n=5)
X
X
X
Rx stop – AE (n=1)
Rx stop – PD (n=7)
Rx stop – Other (n=3)
PR
uPR
X
4
12
X
4
13
12
12
PR
X
PR
12
3
24
48
8
X
8
X
36
48
60
72
84
Months since treatment of
everolimus (AFINITOR®) or sunitinib (SUTENT®)
US Phase Ib Study: Encouraging Preliminary Efficacy in Everolimus and Sunitinib
Refractory/Intolerant Neuroendocrine Tumor Patients
Notes: Data cut-off as of April 21, 2020. PR = partial response; AE = adverse event ;
PD = progressive disease, Rx = treatment ; Tx = treatment ; n = number of patients.
Source: Dasari, et al. Efficacy and safety of surufatinib in United States (US) patients (pts) with
neuroendocrine tumors (NETs). Journal of Clinical Oncology 2020 38:15_suppl,
4610-4610.
Surufatinib in SANET-ep (NCT02588170) – In December 2020, surufatinib
was granted approval for drug registration by the NMPA for the treatment
of non-pancreatic NET. The approval was based on results from the
SANET-ep study, a Phase III trial in patients with advanced non-pancreatic
NET conducted in China. The study met the pre-defined primary endpoint
of PFS at a preplanned interim analysis. The results of this trial were
highlighted in an oral presentation at the 2019 ESMO Congress and
published in The Lancet Oncology in September 2020. Median PFS for
patients treated with surufatinib was 9.2 months, compared to 3.8 months
for patients in the placebo group (HR 0.334; 95% CI: 0.223-0.499; p<0.0001).
Surufatinib had an acceptable safety profile, with the most common
treatment-related adverse events of grade 3 or worse being hypertension
(36% of surufatinib patients vs. 13% of placebo patients), proteinuria (19%
vs. 0%) and anemia (5% vs. 3%).
)
%
(
l
a
v
i
v
r
u
s
e
e
r
f
-
n
o
i
s
s
e
r
g
o
r
P
100
90
80
70
60
50
40
30
20
10
0
0
Surufatinib
Placebo
HR 0.334 (95% CI 0.223-0.499); p<0.0001
Surufatinib
Placebo
HR 0.334 (95% CI 0.223–0.499); p<0·0001
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
Number at risk
(number censored)
Time (months)
Surufatinib
Placebo
129 (0)
69 (0)
100 (16)
43 (11)
83 (24)
25 (15)
63 (31)
16 (16)
46 (36)
10 (16)
37 (36)
6 (17)
25 (42)
6 (17)
13 (47)
4 (17)
13 (47)
4 (17)
8 (49)
1 (18)
7 (49)
0 (18)
7 (49)
··
4 (50)
··
3 (50)
··
2 (51)
··
2 (51)
··
0 (52)
··
SANET-ep Clearly Succeeded in Meeting Primary Endpoint of Progression-Free
Survival
Notes:
P-value is obtained from the stratified one-sided log-rank test; Hazard ratio is obtained from
stratified Cox model; CI = confidence interval; and HR = hazard ratio.
Source: Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours
(SANET-ep): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol.
2020;21(11):1500-1512. doi:10.1016/S1470-2045(20)30496-4.
Phase III study of surufatinib in SANET-p (NCT02589821) – The SANET-p study
is a pivotal Phase III study in patients with low- or intermediate-grade,
advanced pancreatic NET in China. In early 2020 it was terminated early as
the pre-defined primary endpoint of PFS was met at a preplanned interim
analysis, leading to a second NDA accepted by the NMPA in September
2020. The results of this study were presented at the ESMO Virtual Congress
2020 and published simultaneously in The Lancet Oncology.
Median PFS was 10.9 months for patients treated with surufatinib, as
compared to 3.7 months for patients in the placebo group (HR 0.491; 95%
CI: 0.319-0.755; p=0.0011). ORRs were 19.2% for the efficacy evaluable
patients in the surufatinib group versus 1.9% for the placebo group, with a
DCR of 80.8% versus 66.0%, respectively. Most patients in the trial had Grade
2 disease with heavy tumor burden, including liver metastasis and multiple
organ involvement. Efficacy was also supported by BIIRC69 assessment,
with a median PFS of 13.9 months for surufatinib as compared to 4.6
months for placebo (HR 0.339; 95% CI 0.209-0.549; p<0.0001). The safety
profile of surufatinib was manageable and consistent with observations
in prior studies. Treatment was well tolerated for most patients, with
discontinuation rates as a result of treatment emergent adverse events of
10.6% in the surufatinib group as compared to 6.8% in the placebo group.
Hutchison China MediTech Limited 2020 Annual Report 23
The positive SANET-ep and SANET-p Phase III studies now position
surufatinib to potentially be approved in the full spectrum of
advanced-NET disease in China. We believe that no other approved
targeted therapy can address and treat all subtypes of NETs.
In the first half of 2021, we expect to start an open-label Phase Ib/II study
in the U.S. of surufatinib in combination with tislelizumab evaluating
the safety, tolerability, pharmacokinetics and efficacy in patients with
advanced solid tumors, including CRC, NET, SCLC, gastric cancer and soft
tissue sarcoma.
Surufatinib
Surufatinib
Placebo
HR for progression or death 0.49 (95% CI 0.32–0.76); p=0·0011
Placebo
HR for progression or death 0.49
(95% CI 0.32-0.76); p=0.0011
In addition, we have expanded our collaboration with Innovent and, in
July 2020, started a Phase I study in China to evaluate the safety and
efficacy of TYVYT® in combination with surufatinib.
RP2D 250mg surufatinib +
toripalimab.
(N=11): ORR = 64%, DCR = 100%.
Anti-tumor signal, particularly in
NEC & NET.
Combination well tolerated, with
no unexpected safety signals.
PDPD
PDPD
PDPD PDPD SDSD SDSD PDPD SDSD
SDSD
SDSD
100%
PD
PD
>160%
>160%
80%
60%
40%
20%
0%
-20%
-40%
-60%
-80%
e
e
n
n
i
i
l
l
e
e
s
s
a
a
b
b
m
m
o
o
r
r
f
f
e
e
g
g
n
n
a
a
h
h
c
c
t
t
n
n
e
e
c
c
r
r
e
e
P
P
-100%
SANET-p Clearly Succeeded in Meeting Primary Endpoint of Progression-Free Survival
Notes:
P-value is obtained from the stratified one-sided log-rank test; Hazard ratio is obtained from
stratified Cox model; CI = confidence interval; and HR = hazard ratio.
Source: Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a
randomised, double-blind, placebocontrolled, phase 3 study. Lancet Oncol. 2020;21(11):1489-1499.
doi:10.1016/S1470-2045(20)30493-9.
Surufatinib – BTC:
Phase IIb/III study of surufatinib monotherapy in second line BTC
(NCT03873532) – In March 2019, based on preliminary Phase Ib/IIa data,
we initiated a registration-intent Phase IIb/III study comparing surufatinib
with capecitabine in patients with unresectable or metastatic BTC whose
disease progressed on first-line chemotherapy. The primary endpoint is
OS. Enrollment for the BTC monotherapy Phase II portion (80 patients)
was completed in 2020, and we expect to conduct an interim analysis
for futility in 2021 when OS data are mature. The interim analysis and
assessment of the current treatment landscape in BTC will inform our
further development strategy.
SDSD SDSD SDSD SDSD SDSD SDSD
SDSD
SDSD
200mg
250mg
300mg
CR = Complete Response
CR = Complete Response
PR = Partial Response
PR = Partial Response
SD = Stable Disease
SD = Stable Disease
PD = Progressive Disease
PD = Progressive Disease
PR = Unconfirmed PR
uu
PRPR
PRPR
uPRuPR
PRPR
uPRuPR
PRPR
PRPR
2
4
C
R
C
1
7
C
R
C
2
5
E
C
0
1
P
a
n
c
r
e
a
t
i
c
N
E
C
2
2
G
C
(
G
E
J
)
0
3
P
N
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T
G
3
2
1
P
N
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T
G
3
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1
3
C
o
o
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1
4
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t
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m
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0
9
G
a
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t
r
i
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N
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G
3
2
6
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C
0
5
R
e
c
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m
N
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0
6
R
e
c
t
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m
N
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C
3
2
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2
7
G
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J
N
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2
0
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a
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t
r
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c
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0
8
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3
0
4
M
A
C
G
2
:
P
N
E
T
G
2
2
8
E
C
1
5
N
E
T
*
1
2
G
E
J
N
E
C
1
1
P
N
E
T
G
2
1
6
G
a
s
t
r
i
c
N
E
C
3
1
A
p
p
e
n
d
i
x
N
E
C
PRPR
PRPR
1
8
C
R
C
3
3
M
S
C
C
2
9
N
E
C
#
1
9
L
A
C
G
2
CRCR
0
2
G
a
s
t
r
i
c
N
E
C
Phase I Dose Finding Study: Encouraging Anti-Tumor Efficacy for Surufatinib
Combined with the Anti-PD-1 Antibody TUOYI in G3 NET/NEC Patients
Notes: NET = neuroendocrine tumor; NEN = neoplasm; NEC = neuroendocrine carcinoma; CRC =
colorectal carcinoma; GC = gastric adenocarcinoma; EC = esophageal squamous cell carcinoma;
GEJ = gastroesophageal junction; MAC G2 = mediastinal atypical carcinoid grade 2; PNET G2
= pancreas NET grade 2; MSCC = metastatic squamous cell carcinoma with unknown primary;
NSCLC = non-small cell lung cancer; LAC = lung atypical carcinoid; * : left supraclavicular lymph
node neuroendocrine tumor; # : Merkel cell carcinoma.
Source: Cao Y, et al. “A phase I trial of surufatinib plus toripalimab in patients with advanced solid
tumors.” Presented at American Association for Cancer Research (AACR) Virtual Annual Meeting I
on April 27, 2020.
Surufatinib – Combinations with Checkpoint Inhibitors:
Surufatinib – Exploratory development:
We are now conducting multiple Phase Ib expansion cohorts in the U.S. to
explore surufatinib use in BTC and soft tissue sarcoma. In China, we intend
to initiate multiple exploratory studies, both as a single agent, and in
combinations, to evaluate efficacy of surufatinib. We are also supporting
dozens of investigator-initiated studies in various tumor settings.
Surufatinib’s ability to inhibit angiogenesis, block the accumulation of
tumor associated macrophages and promote infiltration of effector
T cells into tumors, could help improve the anti-tumor activity of
PD-1 antibodies.
In late 2018, we entered into a global collaboration with Junshi to evaluate
the combination of surufatinib with TUOYI®. We have completed a Phase I
dose-finding study and presented the data at the AACR Conference in April
2020. The data showed that surufatinib plus TUOYI® were well tolerated
with no unexpected safety signals observed. At the RP2D70, a DCR of
100% and ORR of 63.6% were reported for 11 efficacy evaluable patients,
with 2 unconfirmed PRs71. Surufatinib plus TUOYI® showed encouraging
antitumor activity in patients with advanced solid tumors. A Phase II
China study is rapidly enrolling patients in nine solid tumor indications,
including NENs, BTC, gastric cancer, thyroid cancer, SCLC, soft tissue
sarcoma, endometrial cancer, esophageal cancer and NSCLC.
24
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY
Fruquintinib – CRC:
Fruquintinib capsules, sold under the brand name ELUNATE®, are
approved in China for metastatic CRC patients.
Global development of fruquintinib in metastatic CRC – In June 2020,
the U.S. FDA granted Fast Track Designation for the development of
fruquintinib, for the treatment of patients with metastatic CRC who
have been previously treated with fluoropyrimidine-, oxaliplatin-, and
irinotecan-based chemotherapy, a VEGF biological therapy, and, if RAS
wild-type, an anti-EGFR therapy.
In July 2020, we initiated a global Phase III registration study, known as
the FRESCO-2 study, in refractory metastatic CRC which is expected to
enroll over 680 patients from approximately 150 sites in 14 countries. The
first patient was dosed in September 2020 in the U.S. and enrollment is
targeted to complete in late 2021.
The U.S. FDA, EMA and Japanese PMDA76 have all acknowledged the
totality of the fruquintinib clinical data, including the FRESCO-2 study
(if positive), the prior positive Phase III FRESCO study demonstrating
improvement in overall survival that led to fruquintinib approval for
metastatic CRC in China in 2018, and additional completed and ongoing
supporting studies in metastatic CRC, could potentially support an NDA
for the treatment of patients with metastatic CRC in the third-line setting.
Encouraging preliminary results of the U.S. Phase I/Ib study were
presented at ESMO Congress 2020. As of the data cut-off in August 2020,
fruquintinib was generally well-tolerated with preliminary evidence of
anti-tumor activity in patients with heavily penetrated refractory
metastatic CRC. Among 34 total patients, 16 received prior LONSURF®
treatment, 8 received STIVARGA® treatment and 10 received both
LONSURF® and STIVARGA® treatments. The median duration of
fruquintinib treatment was 19.1 weeks, higher than 12.0 weeks of prior
LONSURF® treatment and 9.2 weeks of prior STIVARGA® treatment among
patients in this trial. DCR in 31 evaluable patients was 80.6%. The safety
profile was consistent with that seen in the FRESCO study.
FRUQUINTINIB
Fruquintinib is a novel, selective, oral inhibitor of VEGFR 1/2/3 kinases that
was designed to improve kinase selectivity to minimize off-target toxicity
and thereby improve tolerability. Fruquintinib has been studied in over
2,200 patients to date, both as a monotherapy and in combinations.
We retain all rights to fruquintinib outside of China and are partnered with
Lilly in China. The table below shows a summary of the clinical studies
for fruquintinib.
Treatment
Fruquintinib
monotherapy
Sites
China
Name, Line,
Patient Focus
FRESCO:
≥3L CRC;
chemotherapy
refractory
Fruquintinib
monotherapy
FRESCO-2:
metastatic CRC
U.S./Europe/
Japan
Fruquintinib
monotherapy
U.S.
CRC; TN72 &
HR+73/Her274-
breast cancer
Fruquintinib +
paclitaxel
FRUTIGA: 2L
gastric cancer
China
Phase
Status/Plan NCT #
III
III
Ib
III
Approved and
launched
NCT02314819
Ongoing
NCT04322539
Ongoing
NCT03251378
NCT03223376
Ongoing;
Completed
2nd interim
analysis
Fruquintinib +
TYVYT® (PD-1)
Fruquintinib +
TYVYT® (PD-1)
CRC
China
II
Ongoing
NCT04179084
HCC75
China
Ib/II
Ongoing
NCT03903705
Fruquintinib +
TYVYT® (PD-1)
Endometrial
cancer
China
Ib/II
Ongoing
NCT03903705
RCC
China
Ib/II
Ongoing
NCT03903705
GI tumors
China
Ib/II
Ongoing
NCT03903705
TN breast cancer U.S.
Ib/II
In planning
NCT04577963
Solid tumors
TBD
Ib/II
In planning
NCT04716634
CRC
China
NSCLC
China
Ib
Ib
Ongoing
NCT03977090
Ongoing
NCT03976856
Fruquintinib +
TYVYT® (PD-1)
Fruquintinib +
TYVYT® (PD-1)
Fruquintinib +
tislelizumab
(PD-1)
Fruquintinib +
tislelizumab
(PD-1)
Fruquintinib +
geptanolimab
(PD-1)
Fruquintinib +
geptanolimab
(PD-1)
Hutchison China MediTech Limited 2020 Annual Report 25
Fruquintinib – Gastric Cancer:
Phase III study of fruquintinib in combination with paclitaxel in gastric
cancer (second-line) (NCT03223376) –The FRUTIGA study is a randomized,
double-blind, Phase III study in China to evaluate the efficacy and safety
of fruquintinib combined with paclitaxel compared with paclitaxel
monotherapy, at a 1:1 ratio, for second-line treatment of advanced gastric
cancer. The FRUTIGA study primary endpoint is OS.
In June 2020, the IDMC of the FRUTIGA study completed a second planned
interim data review and, based on the preset criteria, the IDMC and Joint
Steering Committees recommended that the trial continue with a sample
size increase to ~700 patients. We expect to complete enrollment of
FRUTIGA around the year end of 2021.
Fruquintinib – Combinations with Checkpoint Inhibitors:
Phase Ib/II dose expansion study in China of fruquintinib plus TYVYT® is
underway in different tumor types, including HCC, endometrial cancer,
RCC and GI tumors. Moreover, Phase Ib studies of fruquintinib plus
geptanolimab, Genor’s77 anti-PD-1 antibody, in second-line CRC and
NSCLC are also underway.
In the first half of 2021, we expect to start an open-label, multi-center,
non-randomized, Phase Ib/II study in the U.S. to assess the safety and
efficacy of fruquintinib in combination with tislelizumab in patients with
advanced, refractory triple negative breast cancer. Another Phase II study
is being planned to assess the efficacy and safety of the combination in
patients with advanced or metastatic, unresectable gastric cancer
and CRC.
Fruquintinib – Exploratory development:
We are conducting multiple Phase Ib expansion cohorts in the U.S. to
explore fruquintinib in CRC and breast cancer. In China, we are currently
supporting dozens of investigator-initiated studies in various solid
tumor settings.
US Phase Ib study: Encouraging Preliminary Efficacy in STIVARGA and LONSURF
Refractory/Intolerant Metastatic Colorectal Cancer Patients
Notes: Data cut-off as of Aug 20, 2020.
d/c = treatment discontinued; PI = primary inefficacy; N= number of patients ;
Tx = treatment.
Source: Dasari, et al. Phase 1/1b Trial of Fruquintinib in Patients with Advanced Solid Tumors: Preliminary
Results of the Dose Expansion Cohort in Refractory mCRC. ESMO 2020 Abstract #2217.
26
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY
HMPL-689
HMPL-689 is a novel, selective oral inhibitor targeting the isoform PI3Kδ,
a component in the B-cell receptor signaling pathway. HMPL-689’s
pharmacokinetic properties are favorable with good oral absorption,
moderate tissue distribution and low clearance in preclinical studies,
we therefore anticipate low risk of drug accumulation and drug-to-drug
interaction. We currently retain all rights to HMPL-689 worldwide. The
table below shows a summary of the clinical studies for HMPL-689.
Treatment
Name, Line,
Patient Focus Sites
Phase
Status/Plan NCT #
HMPL-689
monotherapy
Healthy
volunteers
HMPL-689
monotherapy
HMPL-689
monotherapy
HMPL-689
monotherapy
HMPL-689
monotherapy
Indolent
non-Hodgkin’s
lymphoma
Indolent
non-Hodgkin’s
lymphoma
Indolent
non-Hodgkin’s
lymphoma
Indolent
non-Hodgkin’s
lymphoma
Australia
I
Completed NCT02631642
U.S./Europe
I/Ib
Ongoing
NCT03786926
U.S./Europe
II
registration-
intent
In planning N/A
China
Ib
Ongoing
NCT03128164
China
II
registration-
intent
In planning N/A
In December 2020, we presented preliminary results from a Phase I dose
escalation study of HMPL-689 in Chinese patients with relapsed/refractory
lymphoma at the ASH Annual Meeting. A total of 56 patients were enrolled
resulting in an ORR of 51.9% (27/52) and complete response rate of 11.5%
(6/52) in efficacy evaluable patients. The median DOR was 9.2 months
(3.9-NR). One patient with follicular lymphoma who achieved complete
response (per post hoc independent radiologic review) was on treatment
for over 19 months. In the nine efficacy evaluable patients treated with
the RP2D of 30mg QD orally in Chinese patients, efficacy was encouraging
with an ORR of 100% (4/4) in follicular lymphoma, 100% in marginal zone
lymphoma (2/2) and 67% (2/3) in diffuse large B cell lymphoma.
HMPL-689 was well tolerated at the RP2D exhibiting dose-proportional
pharmacokinetics and a manageable toxicity profile. The most common
Grade ≥3 non-hematologic TEAEs78 were pneumonia and hypertension.
Grade ≥3 hematologic TEAEs were neutropenia, and no Grade 5 TEAEs
were reported.
The Phase Ib dose expansion study in China is ongoing in multiple
sub-categories of indolent non-Hodgkin’s lymphoma. Based on the
encouraging preliminary results, we are now planning registration
studies in select indolent non-Hodgkin’s lymphoma in China, which are
anticipated to start in mid-2021.
Furthermore, we have initiated a Phase I/Ib study in the U.S. and Europe,
with patient enrollment underway. Dose escalation is near complete and
we expect to be able to engage with regulatory authorities in mid-2021 to
align potential registration pathway with a target to initiate registration
studies in 2021.
CLL/SLL DLBCL
FL
HL
MCL
MZL
Intent-to-treat population (n=56)
e
n
i
l
e
s
a
b
m
o
r
f
e
g
n
a
h
c
t
s
e
B
+80%
+60%
+40%
+20%
0%
-20%
-40%
-60%
-80%
-100%
5mg QD
10mg QD
20mg QD
30mg QD
2.5mg QD
5mg QD
7.5mg QD
10mg QD
40mg QD
Best Response
Complete Response, %
Partial Response, %
% ,esaesiD elbatS
Progressive Disease, %
Overall Response Rate
Clinical Benefit Rate
Time on Treatment
Time to Response
Duration of Response
11 (4-22)
37
43
11
48% (35-62)
82% (70-91)
5.6 months (0.7–23.2)
1.8 months (1.8–1.9)
9.2 months (3.9–NA)
Progression Free Survival
10.1 months (5.5–15.7)
1-year PFS rate
40% (27–57)
PR
Phase I Dose Escalation Study: Promising HMPL-689 Single-Agent Clinical Activity in Relapsed/Refractory B-cell Lymphoma Patients
Notes:
CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; DLBCL = diffuse large B cell lymphoma; FL = follicular lymphoma; HL = Hodgkin’s lymphoma; MCL = mantle cell lymphoma;
MZL = marginal zone lymphoma; BID = twice daily; QD = once daily; PR = partial response; n = number of patients; PFS = progression free survival; NA = not available.
Source: Cao JN, et al. “Results from a Phase 1 Dose Escalation Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta Inhibitor, in Chinese Patients with relapsed/refractory (R/R) Lymphoma” Presented at the
62nd American Society of Hematology (ASH) Annual Meeting and Exposition on December 5, 2020. Abstract #1135.
Hutchison China MediTech Limited 2020 Annual Report 27
HMPL-523
HMPL-453
HMPL-523 is a novel, selective, oral inhibitor targeting Syk, for the
treatment of hematological cancers and immune diseases. Syk is a
component in B-cell receptor signaling pathway. We currently retain all
rights to HMPL-523 worldwide. The table below shows a summary of the
clinical studies for HMPL-523.
HMPL-453 is a novel, selective, oral inhibitor targeting FGFR 1/2/3.
Aberrant FGFR signaling is associated with tumor growth, promotion of
angiogenesis, as well as resistance to anti-tumor therapies. We currently
retain all rights to HMPL-453 worldwide. The table below shows a
summary of the clinical studies for HMPL-453.
Name, Line,
Patient Focus
ITP
Sites
China
Phase
Status/Plan NCT #
Treatment
Name, Line,
Patient Focus
I/Ib
Ongoing
NCT03951623
HMPL-453
monotherapy
Cholangiocarcinoma
(IHCC)
Sites
Phase
Status/Plan NCT #
China
II
Ongoing
NCT04353375
Treatment
HMPL-523
monotherapy
HMPL-523
monotherapy
HMPL-523
monotherapy
HMPL-523
monotherapy
Australia
Ib
Active, not
recruiting
NCT02503033
U.S./Europe
I/Ib
Ongoing
NCT03779113
China
I/Ib
Enrollment
completed
NCT02857998
Indolent
non-Hodgkin’s
lymphoma
Indolent
non-Hodgkin’s
lymphoma
Multiple
sub-types
of B-cell
malignancies
Phase I/Ib dose escalation study of HMPL-523 in patients with ITP
(NCT03951623) – In mid-2019, we started a Phase I study of HMPL-523
for the treatment of ITP, an autoimmune disorder characterized by low
platelet count and an increased bleeding risk. Dose escalation is near
complete with planning and preparation for a Phase III trial in China now
underway.
Phase I/Ib study of HMPL-523 in indolent non-Hodgkin’s lymphoma
(NCT03779113) – We have now initiated a Phase I/Ib study in the U.S. and
Europe. Patient enrollment is underway in 11 sites, multiple dose cohorts
have been completed already and we are close to establishing our Phase
II dose.
Phase I/Ib studies of HMPL-523 in indolent non-Hodgkin’s lymphoma and
multiple subtypes of B-cell malignancies (NCT02503033/NCT02857998) – Our
Phase I/Ib dose escalation and expansion studies in Australia and China
have now enrolled over 200 patients in a broad range of hematological
cancers and have identified indications of interest for future development.
28
In September 2020, we initiated a Phase II, single-arm, multi-center,
open-label study, evaluating the efficacy, safety and pharmacokinetics of
HMPL-453 in patients with advanced IHCC with FGFR2 fusion that
had failed at least one line of systemic therapy. IHCC is a cancer that
develops within the bile ducts, the second most common primary hepatic
malignancy after HCC. Approximately 10-15% of IHCC patients have
tumors that harbor FGFR2 fusion.
HMPL-306
HMPL-306 is a novel small molecule dual-inhibitor of enzymes IDH1 and
IDH2. IDH1 and IDH2 mutations have been implicated as drivers of certain
hematological malignancies, gliomas and solid tumors, particularly
among acute myeloid leukemia patients. We currently retain all rights to
HMPL-306 worldwide. The table below shows a summary of the clinical
studies for HMPL-306.
Treatment
Name, Line,
Patient Focus
HMPL-306
monotherapy
Hematological
malignancies
HMPL-306
monotherapy
Solid tumors &
hematological
malignancies
Sites
Phase
Status/Plan NCT #
China
U.S.
I
I
Ongoing
NCT04272957
In planning
NCT04762602/
NCT04764474
In July 2020, we initiated our Phase I development in China. This
is a multi-center study to evaluate the safety, pharmacokinetics,
pharmacodynamics and efficacy of HMPL-306 in patients of relapsed
or refractory hematological malignancies with an IDH1 and/or IDH2
mutation. Multiple sites have been initiated and we anticipate to be able
to establish the Phase II dose during 2021.
In the U.S., IND applications for solid tumors and hematologic
malignancies were cleared in October 2020. We expect to initiate Phase I
development in the U.S. during the first half of 2021.
OPERATIONS REVIEW – ONCOLOGY/IMMUNOLOGY HMPL-295
HMPL-295, a novel ERK inhibitor, is our 10th in-house discovered small
molecule oncology drug candidate. ERK is a downstream component of
the RAS-RAF-MEK-ERK signaling cascade (MAPK pathway). This is our first
of multiple candidates in discovery targeting the MAPK pathway.
RAS and RAF mutations are present in almost 50% of human cancers,
predict worse clinical prognosis in a wide variety of tumor types, mediate
resistance to targeted therapies, and decrease the response to standard
of care, target therapy and immunotherapy. On the MAPK pathway,
KRAS inhibitors are under clinical evaluation, and acquired resistance
develops for RAF/MEK targeted therapies. ERK inhibition has the potential
to overcome or avoid the intrinsic or acquired resistance from upstream
mechanisms.
We currently retain all rights to HMPL-295 worldwide. Planning for the
Phase I study in China is now underway and set to start in mid-2021.
DISCOVERY RESEARCH &
PRECLINICAL DEVELOPMENT
We strive to create differentiated novel oncology and immunology
treatments with global potential. These include furthering both small
molecule and monoclonal antibody therapies which address aberrant
genetic drivers; cancer cell metabolism; modulate tumor immune
microenvironment; and target immune cell checkpoints. We design
drug candidates with profiles that enable them to be used in innovative
combinations with other therapy, such as chemotherapy, immunotherapy
and other targeted therapy in order to attack disease simultaneously
through multiple modalities and pathways. We believe that this approach
can significantly improve treatment outcomes for patients.
In addition to the ten clinical-stage assets, we have three more novel
oncology drug candidates in late-preclinical stage, including HMPL-653
(targeting solid tumors), HMPL-A83 (targeting solid tumors and
hematological malignancies) and HMPL-760 (targeting hematological
malignancies). We retain all worldwide rights to these assets and are
targeting dual U.S. and China IND submissions during 2021.
NEW MANUFACTURING FACILITY
IN SHANGHAI
In December 2020, we held a ground-breaking ceremony in Zhangjiang
Hi-Tech Park, Shanghai, commencing construction of a large-scale
manufacturing plant for innovative drugs. The $130 million Shanghai
factory will be our largest manufacturing facility, with production capacity
estimated to be five times that of our manufacturing plant in Suzhou.
The Shanghai factory site spans approximately 28,700 square meters.
Constructed in two phases, the buildings will have a total floorplan of
almost 55,000 square meters. The first phase will be primarily for small
molecule production, with production capacity expected to be able to
produce 250 million tablets and capsules per year, five-fold the capacity of
our current Suzhou facility. The second phase will include expansion into
large molecule production.
The current Suzhou site is a GMP79-certified production facility, supplying
drug candidates for clinical trials and the commercialization of ELUNATE®
and SULANDA®. We plan to continue to invest resources in the Suzhou
facility, expanding the production team in phases.
IMMUNOLOGY COLLABORATION
WITH INMAGENE
In January 2021, we entered into a strategic partnership with Inmagene,
a clinical development stage company with a focus on immunological
diseases, to further develop four novel preclinical drug candidates
discovered by us for the potential treatment of multiple immunological
diseases. Funded by Inmagene, we will work together to move the drug
candidates towards IND. If successful, Inmagene will then advance the
drug candidates through global clinical development.
Hutchison China MediTech Limited 2020 Annual Report 29
Our Other Ventures include drug marketing and distribution platforms
covering about 320 cities and towns in China with around 4,800 mainly
manufacturing and commercial personnel. Built over the past 20 years,
it primarily focuses on prescription drug and consumer health products
through several joint ventures and subsidiary companies.
SXBX81 pill: SHPL’s main product is SXBX pill, an oral vasodilator
prescription therapy for coronary artery disease. SXBX pill is the third
largest botanical prescription drug in this indication in China, with a
national market share in 2020 of 18.2% (2019: 18.0%). Sales increased by
4% (6% at CER) to $250.0 million in 2020 (2019: $239.5m).
In 2020, our Other Ventures delivered encouraging growth with
consolidated revenues up 11% (11% at CER) to $197.8 million
(2019: $178.1m). Consolidated net income attributable to HUTCHMED
from our Other Ventures increased by 75% (77% at CER) to $72.8 million
(2019: $41.5m), and excluding the one-time gain of $28.8 million in
2020 (2019: nil) from land compensation, net income attributable to
HUTCHMED grew by 6% (8% at CER) to $44.0 million (2019: $41.5m).
SHPL80
Our own-brand prescription drugs business, operated through our
non-consolidated joint venture SHPL grew sales by 2% (3% at CER) to
$276.4 million (2019: $272.1m). This sales growth and favorable product
mix led to an increase of 9% (12% at CER) in net income attributable to
HUTCHMED to $33.5 million (2019: $30.7m).
The SHPL operation is large-scale, with a commercial team of about 2,200
staff managing the medical detailing and marketing of its products not
just in hospitals in provincial capitals and medium-sized cities, but also
in the majority of county-level hospitals in China. SHPL’s GMP-certified
factory holds 74 drug product manufacturing licenses and is operated by
over 530 manufacturing staff.
SXBX pill is protected by a formulation patent that expires in 2029 and is
one of less than two dozen proprietary prescription drugs represented on
China’s National Essential Medicines List, which means that all Chinese
state-owned health care institutions are required to carry it. SXBX pill is
fully reimbursed in all China.
Hutchison Sinopharm82
Our prescription drugs commercial services business, which in addition
to providing certain commercial services for our own products, provides
services to third-party pharmaceutical companies in China and sales grew
by 15% (15% at CER) to $165.1 million (2019: $143.7m) in 2020.
Hutchison Sinopharm has a dedicated team of over 120 commercial
staff focused on two key areas of operation. First, a team that markets
third-party prescription drug products directly to over 500 public and
private hospitals in the Shanghai region and through a network of over
40 distributors to cover all other provinces in China. Second, a team that
markets HUTCHMED’s science-based infant nutrition products through a
network over 29,000 promoters in China.
Hutchison China MediTech Limited 2020 Annual Report 31
OPERATIONS REVIEW – OTHER VENTURES HBYS
Our own-brand OTC83 drugs business, operated through our
non-consolidated joint venture HBYS grew sales 8% (8% at CER) to $232.4
million (2019: $215.4m), mainly as a result of a 30% increase in sales of
Banlangen, an anti-viral product, in 2020 due to COVID-19. This growth
combined with the land compensation detailed below led to an increase
of 361% (361% at CER) in net income attributable to HUTCHMED to $36.5
million (2019: $7.9m) including a one-time land compensation gain of
$28.8 million (2019: nil).
HBYS’ Bai Yun Shan brand is a market-leading, household name, known
by the majority of Chinese consumers with 185 drug product licenses. In
addition to about 1,000 manufacturing staff in Guangdong and Anhui,
HBYS has a commercial team of about 900 commercial staff that cover the
national retail pharmacy channel in China.
HBYS property update: In June 2020, we entered into an agreement with
the Guangzhou government for the return of HBYS’s remaining 34 years’
land-use rights on its 30,000 square meters unused site in Guangzhou
in return for cash compensation of up to approximately $100 million. In
2020, HBYS received about $40 million and is expected to receive about
$43 million in 2021. In addition, subject to the Guangzhou government’s
confirmation of completion of the remaining administrative procedures
before June 2021, HBYS will be further entitled to receive about $17
million in compensation. The land return had no impact on HBYS
manufacturing operations, which continue to be conducted at larger sites
in Guangzhou and Bozhou, Anhui province.
Other Ventures dividends
The profits of our various Other Ventures businesses are passed to
the HUTCHMED Group through dividend payments primarily from our
non-consolidated joint ventures, SHPL and HBYS. In 2020, dividends of
$86.7 million (2019: $28.1m) were paid from these joint ventures to the
HUTCHMED Group level with aggregate dividends received since inception
of over $300 million.
Christian Hogg
Chief Executive Officer
March 4, 2021
32
OPERATIONS REVIEW – OTHER VENTURES REFERENCES AND ABBREVIATIONS
1
FDA = Food and Drug Administration
EMA = European Medicines Agency
Sales of Elunate® to third parties invoiced by Lilly were $32.7 million
(2019: $17.6m) & invoiced by HUTCHMED were $1.0 million (2019: nil).
Lilly = Eli Lilly and Company
NRDL = National Reimbursement Drug List
NET = Neuroendocrine tumors
NMPA = National Medical Products Administration
NDA = New Drug Application
MET = Mesenchymal epithelial transition receptor
NSCLC = Non-small cell lung cancer
IND = Investigational new drug application
ERK = Extracellular signal-regulated kinase
2
3
4
5
6
7
8
9
10
11 MAPK pathway = RAS-RAF-MEK-ERK signaling cascade
12
13
14 CHMP = Committee for Medicinal Products for Human Use
15 MAA = Marketing Authorisation Application
16 CRC = Colorectal cancer
VEGFR = Vascular endothelial growth factor receptor
17
18
FGFR = Fibroblast growth factor receptor
19 CSF-1R = Colony stimulating factor-1 receptor
20
21
22
23
24
25 BeiGene = BeiGene Ltd.
26
27
28
29
30
31
32 WCLC = World Conference on Lung Cancer
33
34
35
36
37
38
39
40
41 HBYS = Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine
EGFR = Epidermal growth factor receptor
PI3Kδ = Phosphoinositide 3-kinase delta
ASH = American Society of Hematology Annual Meeting
Syk = Spleen tyrosine kinase
ITP = Immune thrombocytopenia purpura
IHCC = Intrahepatic cholangiocarcinoma
FGFR2 = Fibroblast growth factor receptor 2
IDH1/2 = Isocitrate dehydrogenase 1/2
ESMO = European Society for Medical Oncology Annual Congress
ASCO = American Society of Clinical Oncology Annual Meeting
AACR = American Association of Cancer Research Annual Meeting
Junshi = Shanghai Junshi Biosciences Co. Ltd.
PD-1 = Programmed Cell Death Protein-1
IDMC = Independent data monitoring committee
Innovent = Innovent Biologics, Inc.
AstraZeneca = AstraZeneca AB (publ)
PD-L1 = Programmed death-ligand 1
PRCC = Papillary renal cell carcinoma
ASCO GU = American Society of Clinical Oncology Genitourinary Symposium
Company Limited
Inmagene = Inmagene Biopharmaceuticals Co. Ltd.
42
43 GAAP = Generally Accepted Accounting Principles
44
45 General Atlantic = General Atlantic Singapore HCM Pte. Ltd
46 CPP Investments = Canada Pension Plan Investment Board
R&D = Research and development
AE = Adverse event
47 We also report changes in performance at constant exchange rate (“CER”)
which is a non-GAAP measure. Please refer to “Use of Non-GAAP Financial
Measures and Reconciliation” below for further information relevant to
the interpretation of these financial measures and reconciliations of these
financial measures to the most comparable GAAP measures.
SG&A = Selling, general and administrative
48
49 Other items = includes other income, income tax expense, equity in earnings
of equity investees, net of tax and net income attributable to non-controlling
interests
ADS = American depositary share
PFS = Progression-free survival
EGFRm = Epidermal growth factor receptor mutation
EGFR TKI = Epidermal growth factor receptor tyrosine kinase inhibitor
50
51
52
53
54 ORR = Objective response rate
55 DCR = Disease control rate
56 DoR = Duration of response
57 CI = Confidence interval
58 NR = Not reached
59
60 QD = Once daily dose
61 BID = Twice daily dose
RCC = Renal cell cancer
62
63 HR = Hazard ratio
64 CDE = Center for Drug Evaluation
65 BTC = Biliary tract cancer
66 NENs = Neuroendocrine neoplasms
SCLC = Small cell lung cancer
67
68 GI = Gastrointestinal
69 BIIRC = Blinded Independent Image Review Committee
70
71
72
73 HR+ = Hormone receptor-positive
74 Her2 = Human epidermal growth factor receptor 2
75 HCC = Hepatocellular carcinoma
76
77 Genor = Genor Biopharma Co. Ltd.
78
79 GMP = Good Manufacturing Practice
80
81
82 Hutchison Sinopharm = Hutchison Whampoa Sinopharm Pharmaceuticals
RP2D = Recommended Phase II Dose
PR = Partial Response
TN = Triple-negative
SHPL = Shanghai Hutchison Pharmaceuticals Limited
SXBX = She Xiang Bao Xin
PMDA = Pharmaceuticals and Medical Devices Agency
TEAEs = Treatment emergent adverse events
(Shanghai) Company Limited
83 OTC = Over-the-counter
Hutchison China MediTech Limited 2020 Annual Report 33
used for translation may have a significant effect on our reported results.
We believe the presentation at CER provides useful and meaningful
information because it facilitates year-to-year comparisons of our results
and increases the transparency of our underlying performance.
Reconciliation of GAAP change in cash and cash equivalents
and short-term investments to Adjusted Group net cash
flows excluding financing activities:
$’millions
2020
2019
Cash and cash equivalents and short-term
investments at end of year
435.2
217.2
Excludes: Cash and cash equivalents and
short-term investments at beginning of year
(217.2)
(301.0)
Excludes: Net cash (generated from)/used in
financing activities for the year
(296.4)
1.5
Adjusted Group net cash flows excluding
financing activities
(78.4)
(82.3)
In addition to financial information prepared in accordance with U.S.
GAAP, this annual report also contains certain non-GAAP financial
measures based on management’s view of performance including:
•
•
Adjusted Group net cash flows excluding financing activities
CER
Management uses such measures internally for planning and forecasting
purposes and to measure the HUTCHMED Group’s overall performance.
We believe these adjusted financial measures provide useful and
meaningful information to us and investors because they enhance
investors’ understanding of the continuing operating performance of our
business and facilitate the comparison of performance between past and
future periods. These adjusted financial measures are non-GAAP measures
and should be considered in addition to, but not as a substitute for, the
information prepared in accordance with U.S. GAAP. Other companies
may define these measures in different ways.
Adjusted Group net cash flows excluding financing activities: We include
the change in short-term investments for the period to the change in
cash and cash equivalents for the period, and exclude the net cash
(generated from)/used in financing activities for the period to derive our
adjusted Group net cash flows excluding financing activities. We believe
the presentation of adjusted Group net cash flows excluding financing
activities provides useful and meaningful information about the change
in our cash resources excluding those from financing activities which may
present significant period-to-period differences.
CER: We remove the effects of currency movements from year-to-year
comparisons by retranslating the current year’s performance at
previous year’s foreign currency exchange rates. Because we have
significant operations in China, the RMB to U.S. dollar exchange rates
34
USE OF NON-GAAP FINANCIAL MEASURES AND RECONCILIATION
Reconciliation of GAAP revenues, net income attributable to HUTCHMED from Other Ventures to CER:
$’millions (except %)
Year Ended
Change Amount
Change %
December
December
Exchange
Exchange
31, 2020
31, 2019
Actual
CER
effect
Actual
CER
effect
Consolidated revenues
Other Ventures^
197.8
178.1
19.7
20.5
(0.8)
11%
11%
0%
165.1
143.7
21.4
22.1
(0.7)
15%
15%
0%
^ Includes:
— Hutchison Sinopharm
– prescription drugs
Non-consolidated joint venture
revenues
— SHPL
— HBYS
Consolidated net income attributable
to HUTCHMED
Other Ventures
— Consolidated entities
— Equity investees
— SHPL
— HBYS
Excluding one-time HBYS land
compensation gain
Other Ventures
— Consolidated entities
— Equity investees
— SHPL
— HBYS
Land compensation gain
— HBYS
Revenue of Key Product of SHPL
508.8
276.4
232.4
487.5
272.1
215.4
72.8
2.8
70.0
33.5
36.5
44.0
2.8
41.2
33.5
7.7
41.5
2.9
38.6
30.7
7.9
41.5
2.9
38.6
30.7
7.9
28.8
–
— SXBX pill
250.0
239.5
21.3
4.3
17.0
31.3
(0.1)
31.4
2.8
28.6
2.5
(0.1)
2.6
2.8
(0.2)
28.8
10.5
25.9
7.6
18.3
32.2
(0.1)
32.3
3.7
28.6
3.3
(0.1)
3.4
3.7
(0.3)
28.8
13.7
(4.6)
(3.3)
(1.3)
(0.9)
–
(0.9)
(0.9)
–
(0.8)
–
(0.8)
(0.9)
0.1
–
(3.2)
4%
2%
8%
75%
-5%
82%
9%
361%
6%
-5%
7%
9%
-2%
–
4%
5%
3%
8%
77%
-5%
84%
12%
361%
8%
-5%
9%
12%
-3%
–
6%
-1%
-1%
0%
-2%
0%
-2%
-3%
0%
-2%
0%
-2%
-3%
1%
–
-2%
Hutchison China MediTech Limited 2020 Annual Report 35
Simon TO
Christian HOGG
Executive Director and Chairman
Executive Director and Chief Executive Officer
Mr To, aged 69, has been a Director since
2000 and an Executive Director and Chairman
of Hutchison China MediTech Limited (the
“Company”) since 2006. He is also a member of
the Nomination Committee, Remuneration Committee
and Technical Committee of the Company. He is managing director
of Hutchison Whampoa (China) Limited (“Hutchison China”) and has
been with Hutchison China for over 40 years, building its business from
a small trading company to a multi-billion dollar investment group. He
has negotiated major transactions with multinationals such as Procter &
Gamble (“P&G”), Lockheed, Pirelli, Beiersdorf, United Airlines and British
Airways. He is currently the chairman of Gama Aviation Plc and formerly
served as independent non-executive director on the boards of China
Southern Airlines Company Limited and Air China Limited.
Mr To’s career in China spans more than 45 years. He is the original
founder of the China healthcare business of Hutchison Whampoa
Limited (“HWL”) (currently a subsidiary of CK Hutchison Holdings Limited
(“CKHH”)) and has been instrumental in the acquisitions made to date.
He received a Bachelor’s Degree in Mechanical Engineering from Imperial
College, London and a Master in Business Administration from Stanford
University’s Graduate School of Business.
Mr Hogg, aged 55, has been the Chief Executive
Officer and an Executive Director of the Company
since 2006. He is also a member of the Technical
Committee of the Company. He was a member of
the Nomination Committee of the Company from April
2019 to December 2020. He joined the business in 2000, as its first
employee, and has since led all aspects of the creation, implementation
and management of the Company’s strategy, business and listings. This
includes the establishment of the Oncology/Immunology operations
which now have an organization of about 1,200 scientific and commercial
personnel involved in the launch of its first two oncology drugs, ELUNATE®
and SULANDA® in China, as well as the management of global clinical
development activities on the Company’s portfolio of ten in-house
discovered novel oncology drug candidates. Furthermore, Mr Hogg
oversaw the acquisition and operational integration of assets led to
the formation of the Company’s Other Ventures operations, which
manufacture, market and distribute prescription drugs and consumer
health products, covering an extensive network of hospitals across China.
Prior to joining the Company, Mr Hogg spent ten years with P&G, starting
in the United States in Finance and then Brand Management in the
Laundry and Cleaning Products Division. Mr Hogg then moved to China to
manage P&G’s detergent business, followed by a move to Brussels to run
P&G’s global bleach business.
Mr Hogg received a Bachelor’s degree in Civil Engineering from the
University of Edinburgh and a Master in Business Administration from the
University of Tennessee.
36
BIOGRAPHICAL DETAILS OF DIRECTORS Johnny CHENG
Dan ELDAR
Executive Director and Chief Financial Officer
Non-executive Director
Mr Cheng, aged 54, has been an Executive Director
since 2011 and Chief Financial Officer of the
Company since 2008. He was a member of the
Nomination Committee of the Company from April
2019 to December 2020.
Prior to joining the Company, Mr Cheng was Vice President, Finance
of Bristol Myers Squibb in China and was a director of Sino-American
Shanghai Squibb Pharmaceuticals Ltd. and Bristol-Myers Squibb (China)
Investment Co. Ltd. in Shanghai between late 2006 and 2008.
Mr Cheng started his career as an auditor with Price Waterhouse (currently
PricewaterhouseCoopers) in Australia and then KPMG in Beijing before
spending eight years with Nestlé China where he was in charge of a
number of finance and control functions in various operations. Mr Cheng
received a Bachelor of Economics, Accounting Major from the University
of Adelaide and is a member of Chartered Accountants Australia and New
Zealand.
Dr Eldar, aged 67, has been a Non-executive
Director of the Company since 2016. He was a
member of the Nomination Committee of the
Company from April 2019 to December 2020. He has
more than 30 years of experience as a senior executive,
leading global operations in telecommunications, water, biotech and
healthcare. He is an executive director of Hutchison Water Israel Ltd
which focuses on large scale projects including desalination, wastewater
treatment and water reuse. He was formerly an independent
non-executive director of Leumi Card Ltd., a subsidiary of Bank Leumi
Le-Israel B.M., one of Israel’s leading credit card companies.
Dr Eldar holds a Doctor of Philosophy degree in Government from Harvard
University, Master of Arts degree in Government from Harvard University,
Master of Arts degree in Political Science and Public Administration from
the Hebrew University of Jerusalem and a Bachelor of Arts degree in
Political Science from the Hebrew University of Jerusalem.
Weiguo SU
Executive Director and Chief Scientific Officer
Dr Su, aged 63, has been an Executive Director
of the Company since 2017. He is also a member
of the Technical Committee of the Company. He
was a member of the Nomination Committee of the
Company from April 2019 to December 2020. He has been
the Executive Vice President and Chief Scientific Officer of the Company
since 2012. Dr Su has headed all drug discovery and research since he
joined the Company, including master-minding the Company’s scientific
strategy, being a key leader of the Oncology/Immunology operations,
and responsible for the discovery of each and every small molecule
drug candidate in the Company’s product pipeline. Prior to joining
the Company in 2005, Dr Su spent 15 years with the U.S. Research and
Development Department of Pfizer, Inc. with his last position as director of
the Medicinal Chemistry Department.
In March 2017, Dr Su was granted the prestigious award by the China
Pharmaceutical Innovation and Research Development Association
(PhIRDA) as one of the Most Influential Drug R&D Leaders in China.
Dr Su received a Bachelor of Science degree in Chemistry from Fudan
University in Shanghai. He completed a PhD and Post-doctoral Fellowship
in Chemistry at Harvard University under the guidance of Nobel Laureate
Professor E. J. Corey.
Hutchison China MediTech Limited 2020 Annual Report 37
Edith SHIH
Paul CARTER
Non-executive Director and Company Secretary
Senior Independent Non-executive Director
Mr Carter, aged 60, has been the Senior
Independent Non-executive Director of the
Company since 2017. He is also Chairman of the
Remuneration Committee and a member of the Audit
Committee and Technical Committee of the Company. He
was a member of the Nomination Committee of the Company from April
2019 to December 2020. He has more than 26 years of experience in the
pharmaceutical industry. From 2006 to 2016, Mr Carter served in various
senior executive roles at Gilead Sciences, Inc. (“Gilead”), a
research-based biopharmaceutical company, with the last position
as Executive Vice President, Commercial Operations. In this role, Mr
Carter headed the worldwide commercial organization responsible for
the launch and commercialization of all of Gilead’s products. Prior to
joining Gilead, he spent 14 years with GlaxoSmithKline plc (GSK) and
its group companies, with the last position as Regional Head of the
International Business in Asia. He is currently a director of Mallinckrodt
plc and Immatics N.V. He is chairman of Evox Therapeutics and a retained
advisor to several firms active in the life sciences sector. He was formerly a
director of Alder Biopharmaceuticals, Inc.
Mr Carter holds a degree in Business Studies from the Ealing School of
Business and Management (now merged into University of West London)
and is a Fellow of the Chartered Institute of Management Accountants in
the United Kingdom.
Ms Shih, aged 69, has been a Non-executive
Director and Company Secretary of the Company
since 2006 and company secretary of Group
companies since 2000. She was a member of the
Nomination Committee of the Company from April 2019 to December
2020. She is also executive director and company secretary of CKHH.
She has been with the Cheung Kong (Holdings) Limited (“CKH”) group
since 1989 and with HWL from 1991 to 2015. Both CKH and HWL became
wholly-owned subsidiaries of CKHH in 2015. She has acted in various
capacities within the HWL group, including head group general counsel
and company secretary of HWL as well as director and company secretary
of HWL subsidiaries and associated companies. Ms Shih is in addition
a non-executive director of Hutchison Telecommunications Hong Kong
Holdings Limited as well as Hutchison Port Holdings Management
Pte. Limited as the trustee-manager of Hutchison Port Holdings Trust
and a member of Board of Commissioners of PT Duta Intidaya Tbk.
The aforementioned companies are either subsidiaries or associated
companies of CKHH of which Ms Shih has oversight. She has over 35
years of experience in legal, regulatory, corporate finance, compliance
and corporate governance fields. She is the immediate past International
President and current member of the Executive Committee of The
Chartered Governance Institute (“CGI”) as well as a past President and
current chairperson or member of various committees and panels of
The Hong Kong Institute of Chartered Secretaries (“HKICS”). She is also
chairman of the Process Review Panel for the Financial Reporting Council,
a panel member of the Securities and Futures Appeals Tribunal and the
immediate past chairman of the Governance Committee of the Hong
Kong Institute of Certified Public Accountants.
Ms Shih is a solicitor qualified in England and Wales, Hong Kong and
Victoria, Australia and a Fellow of both the CGI and HKICS, holding
Chartered Secretary and Chartered Governance Professional dual
designations. Ms Shih holds a Bachelor of Science degree in Education
and a Master of Arts degree from the University of the Philippines as
well as a Master of Arts degree and a Master of Education degree from
Columbia University, New York.
38
BIOGRAPHICAL DETAILS OF DIRECTORS Karen FERRANTE
Graeme JACK
Independent Non-executive Director
Independent Non-executive Director
Dr Ferrante, aged 63, has been an Independent
Non-executive Director of the Company since
2017. She is also the Chairman of the Technical
Committee and a member of the Audit Committee
of the Company. She was a member of the Nomination
Committee of the Company from April 2019 to December 2020. She has
more than 26 years of experience in the pharmaceutical industry. She was
the former Chief Medical Officer and Head of Research and Development
of Tokai Pharmaceuticals, Inc., a biopharmaceutical company focused on
developing and commercializing innovative therapies for prostate cancer
and other hormonally driven diseases. From September 2007 to July 2013,
Dr Ferrante held senior positions at Millennium Pharmaceuticals, Inc. and
its parent company, Takeda Pharmaceutical Company Limited, including
Chief Medical Officer and most recently as Oncology Therapeutic Area and
Cambridge USA Site Head. From 1999 to 2007, she held positions of increasing
responsibility at Pfizer, Inc., with the last position as Vice President, Oncology
Development. Dr Ferrante is currently a member of the board of directors of
MacroGenics, Inc. and Cogent Biosciences, Inc. (formerly Unum Therapeutics
Inc.). She was previously a director of Baxalta Incorporated until it was
acquired by Shire plc in 2016 and a director of Progenics Pharmaceuticals,
Inc. until it was acquired by Lantheus Holdings, Inc. in 2020.
Dr Ferrante has been an author of a number of papers in the field of
oncology, an active participant in academic and professional associations
and symposia and holder of several patents. Dr Ferrante holds a Bachelor
of Science degree in Chemistry and Biology from Providence College and
a Doctor of Medicine from Georgetown University.
Mr Jack, aged 70, has been an Independent
Non-executive Director of the Company since 2017.
He is also the Chairman of the Audit Committee
and a member of the Nomination Committee and
Remuneration Committee of the Company. He has more
than 40 years of experience in finance and audit. He retired as partner of
PricewaterhouseCoopers in 2006 after a distinguished career with the firm
for over 33 years. He is currently an independent non-executive director of
The Greenbrier Companies, Inc. (an international supplier of equipment
and services to the freight rail transportation markets), Hutchison Port
Holdings Management Pte. Limited as the trustee-manager of Hutchison
Port Holdings Trust (a developer and operator of deep water container
terminals) and of COSCO SHIPPING Development Co., Ltd., formerly
known as “China Shipping Container Lines Company Limited” (an
integrated financial services platform principally engaged in vessel and
container leasing).
He holds a Bachelor of Commerce degree from the University of New
South Wales, Australia and is a Fellow of the Hong Kong Institute of
Certified Public Accountants and an Associate of Chartered Accountants
Australia and New Zealand.
Hutchison China MediTech Limited 2020 Annual Report 39
Tony MOK
Independent Non-executive Director
Professor Mok, aged 60, has been an Independent
Non-executive Director of the Company since
2017. He is also the Chairman of the Nomination
Committee and a member of the Technical
Committee of the Company. He has more than 31 years of
experience in clinical oncology with his main research interest focusing on
biomarker and molecular targeted therapy in lung cancer. He is currently
Li Shu Fan Medical Foundation Named Professor and Chairman of
Department of Clinical Oncology at The Chinese University of Hong Kong.
He has contributed to over 250 articles in international peer-reviewed
journals, as well as multiple editorials and textbooks.
In October 2018, Professor Mok was the first Chinese to be bestowed with
the European Society for Medical Oncology (ESMO) Lifetime Achievement
Award, one of the most prestigious international honours and recognitions
given to cancer researchers, for his contribution to and leadership in lung
cancer research worldwide.
Professor Mok is a Non-executive Director of AstraZeneca PLC, a board
director of the American Society of Clinical Oncology (“ASCO”) and
Steering Committee Member of the Chinese Society of Clinical Oncology
(CSCO). He is also Past President of International Association for the Study
of Lung Cancer (IASLC), and co-founder of Sanomics Limited and Aurora
Tele-Oncology Limited.
Professor Mok is also closely affiliated with the oncology community in
China and has been awarded an Honorary Professorship at Guangdong
Province People's Hospital, Guest Professorship at Peking Union Medical
College Hospital and Visiting Professorship at Shanghai Jiao Tong
University.
Professor Mok received his Bachelor of Medical Science degree and Doctor
of Medicine from University of Alberta, Canada. He is also a Fellow of Royal
College of Physicians and Surgeons of Canada, Hong Kong College of
Physicians, Hong Kong Academy of Medicine, Royal College of Physicians
of Edinburgh and ASCO.
From left: Johnny Cheng, Tony Mok, Graeme Jack, Karen Ferrante, Christian Hogg, Simon To, Paul Carter, Edith Shih, Dan Eldar, Weiguo Su.
40
BIOGRAPHICAL DETAILS OF DIRECTORS The Directors have pleasure in submitting to shareholders their report and
the audited financial statements for the year ended December 31, 2020.
DIVIDENDS
PRINCIPAL ACTIVITIES
The principal activity of the Company is that of a holding company of a
biopharmaceutical group with operations in China, the U.S. and Europe. It
is focused on the research, development, manufacture and marketing of
pharmaceutical products.
BUSINESS REVIEW
No interim dividend for the year ended December 31, 2020 was declared
and the Directors do not recommend the payment of a final dividend for
the year ended December 31, 2020.
RESERVES
Movements in the reserves of the Group during the year are set out in the
Consolidated Statements of Changes in Shareholders’ Equity on page F-7
of Form 20-F.
A detailed review of the performance, business activities and future
development of the Company and its subsidiaries (the “Group”) is set out
in the Chairman’s Statement and the Operations Review.
PROPERTY, PLANT AND
EQUIPMENT
RESULTS
The Consolidated Statements of Operations are set out on page F-5 of
Form 20-F and show the Group’s results for the year ended December 31,
2020.
Particulars of the movements of property, plant and equipment of the
Group are set out in note 10 to the Consolidated Financial Statements on
page F-22 of Form 20-F.
SHARE CAPITAL
The share capital of the Company is set out in the Consolidated Balance
Sheets on page F-4 of Form 20-F. Details of the ordinary shares of the
Company are set out in note 18 to the Consolidated Financial Statements
on page F-28 of Form 20-F.
Hutchison China MediTech Limited 2020 Annual Report 41
DIRECTORS’ REPORT DIRECTORS
The Directors of the Company as of December 31, 2020 were:
DIRECTORS’ INTERESTS IN
SHARES
As of December 31, 2020, the interests in the shares of the Company held
by the Directors and their families were as follows:
Name of Director
Christian Hogg
Johnny Cheng
Simon To
Edith Shih
Weiguo Su
Dan Eldar
Tony Mok
Paul Carter
Karen Ferrante
Graeme Jack
Number of
Number of
American
ordinary
depositary
shares held
shares held
10,938,020
2,561,460
1,800,000
700,000
–
19,000
–
35,240
–
–
68,035
14,401
133,237
100,000
71,661
8,993
10,002
–
5,785
3,000
Executive Directors:
Simon To
Christian Hogg
Johnny Cheng
Weiguo Su
Non-executive Directors:
Dan Eldar
Edith Shih
Independent Non-executive Directors:
Paul Carter
Karen Ferrante
Graeme Jack
Tony Mok
Pursuant to the UK Corporate Governance Code, the Directors, being
Mr Simon To, Mr Christian Hogg, Mr Johnny Cheng, Dr Weiguo Su, Dr Dan
Eldar, Ms Edith Shih, Mr Paul Carter, Dr Karen Ferrante, Mr Graeme Jack
and Professor Tony Mok will all retire at the annual general meeting
(the “AGM”) and, being eligible, will offer themselves for re-election by
shareholders.
The Directors’ biographical details are set out on pages 36 to 40.
42
DIRECTORS’ REPORT
SHARE OPTION SCHEMES AND DIRECTORS’ RIGHTS TO ACQUIRE
SHARES
(i)
Share option scheme adopted in 2005 by the Company
The Company conditionally adopted a share option scheme on June 4, 2005 which was amended on March 21, 2007 (the “2005 Share Option
Scheme”). Pursuant to the 2005 Share Option Scheme, the Board of Directors of the Company may, at its discretion, offer any employees and
directors (including Executive and Non-executive Directors but excluding Independent Non-executive Directors) of the Company, holding
companies of the Company and any of their subsidiaries or affiliates, and subsidiaries or affiliates of the Company share options to subscribe for
shares of the Company. The 2005 Share Option Scheme has a term of 10 years. It expired in 2016 and no further share option can be granted.
The following share options were outstanding under the 2005 Share Option Scheme during the year ended December 31, 2020:
Name or category
of participants
Date of
grant of
share
options
Number of
share options
Granted
Exercised
held at
January 1, 2020 (3)
during
2020 (3)
during
2020 (3)
Expired/
lapsed/
canceled
during
2020 (3)
Number of
share options
held at
December 31,
2020 (3)
Employees in aggregate
24.6.2011 (1)
20.12.2013 (1)
750,000
766,180
1,516,180
–
–
–
(350,000)
(50,000)
(400,000)
–
–
–
400,000
716,180
1,116,180
Exercise
price of
share
options (2)
£
0.4405
0.6100
Exercise
period of
share options
24.6.2011 to
23.6.2021
20.12.2013 to
19.12.2023
The share options granted are exercisable subject to, amongst other relevant vesting criteria, the vesting schedule of 25% on each of the first, second, third and
fourth anniversaries of the effective date of grant.
(2)
The stated prices were the adjusted prices as a result of the share subdivision mentioned in note (3) below.
(3)
Effective from May 30, 2019, each ordinary share of US$1.00 each of the Company was subdivided into 10 new ordinary shares of US$0.10 each. Accordingly,
adjustments have been made to the number of share options by multiplying the number by 10 and to the share price and exercise price by dividing the price
by 10 pursuant to the terms of the 2005 Share Option Scheme.
(ii) Share option scheme adopted in 2015 by the Company
The Company conditionally adopted a share option scheme on April 24, 2015 which was amended on April 27, 2020 (the “2015 Share Option
Scheme”). Pursuant to the 2015 Share Option Scheme, the Board of Directors of the Company may, at its discretion, offer any employees and
directors (including Executive and Non-executive Directors but excluding Independent Non-executive Directors) of the Company, holding
companies of the Company and any of their subsidiaries or affiliates, and subsidiaries or affiliates of the Company share options to subscribe for
shares of the Company.
On April 27, 2020, the shareholders of the Company approved the refreshment of the maximum number of shares which may be issued upon
the exercise of all options to be granted (the “Scheme Limit”) under the 2015 Share Option Scheme. The Scheme Limit as refreshed is 34,528,738
shares, representing about 5% of the shares in issue as at April 27, 2020.
Hutchison China MediTech Limited 2020 Annual Report 43
Total:
Note:
(1)
The following share options were outstanding under the 2015 Share Option Scheme during the year ended December 31, 2020:
Name or category
of participants
Executive Director
Christian Hogg
Date of
grant of
share
options
28.4.2020 (2)
14.12.2020 (2)
Johnny Cheng
28.4.2020 (2)
Weiguo Su
Employees in aggregate
15.6.2016 (1)
27.3.2017 (2)
19.3.2018 (2)
28.4.2020 (2)
14.12.2020 (2)
15.6.2016 (1)
20.4.2018 (2)
6.6.2018 (2)
6.8.2018 (2)
19.10.2018 (2)
21.5.2019 (2)
9.10.2019 (2)
11.12.2019 (2)
20.4.2020 (2)
28.4.2020 (2)
11.8.2020 (2)
14.12.2020 (2)
Number of
share options
Granted
Exercised
held at
January 1, 2020 (4)
during
2020 (4)
during
2020 (4)
Expired/
lapsed/
canceled
Number of
share options
during
2020 (4)
held at
December 31, 2020 (4)
Exercise
period of
share options
–
–
–
1,291,700 (5)
39,610 (5)
401,900 (5)
3,000,000
1,000,000
1,000,000
–
–
2,936,860
6,440,160
369,360
680,000
255,000
100,000
1,735,000
400,000
–
–
–
789,700 (5)
18,960(5)
–
–
–
–
–
–
–
–
–
–
–
–
2,855,000
7,408,200 (5)
1,155,000 (5)
1,477,010 (5)
–
–
–
–
–
–
–
–
–
–
(30,780)
–
–
–
–
–
–
–
–
–
–
–
–
(1,904,940)
(176,130)
–
–
–
1,291,700
28.4.2020 to 27.4.2030
39,610
14.12.2020 to 13.12.2030
401,900
28.4.2020 to 27.4.2030
$22.090
3,000,000
1,000,000
1,000,000
789,700
15.6.2016 to 19.12.2023
27.3.2017 to 26.3.2027
19.3.2018 to 18.3.2028
28.4.2020 to 27.4.2030
18,960
14.12.2020 to 13.12.2030
2,936,860
4,535,220
162,450
680,000
255,000
100,000
15.6.2016 to 19.12.2023
20.4.2018 to 19.4.2028
6.6.2018 to 5.6.2028
6.8.2018 to 5.8.2028
19.10.2018 to 18.10.2028
21.5.2019 to 20.5.2029
(50,000)
(395,000)
1,290,000
9.10.2019 to 8.10.2029
–
–
–
–
–
–
(2,080,000)
(261,800)
(410,000)
–
400,000
775,000
7,146,400
745,000
11.12.2019 to 10.12.2029
20.4.2020 to 19.4.2030
28.4.2020 to 27.4.2030
11.8.2020 to 10.8.2030
1,477,010
14.12.2020 to 13.12.2030
Exercise
price of
share
options (3)
$22.090
$29.000
£1.970
£3.105
£4.974
$22.090
$29.000
£1.970
£4.645
£4.166
£4.860
£4.610
£4.220
£2.978
£3.592
£3.340
$22.090
$32.820
$29.000
Total:
Notes:
(1)
(2)
17,916,380
15,437,080
(80,780)
(5,227,870)
28,044,810
The share options granted are exercisable subject to, amongst other relevant vesting criteria, the vesting schedule of approximately 50% on the day after the
acceptance of the offer, approximately 25% on December 20, 2016 and approximately 25% on December 20, 2017.
The share options granted are exercisable subject to, amongst other relevant vesting criteria, the vesting schedule of 25% on each of the first, second, third and
fourth anniversaries of the date of grant.
(3)
The stated prices were the adjusted prices as a result of the share subdivision mentioned in note (4) below.
(4)
Effective from May 30, 2019, each ordinary share of US$1.00 each of the Company was subdivided into 10 new ordinary shares of US$0.10 each. Accordingly,
adjustments have been made to the number of share options by multiplying the number by 10 and to the share price and exercise price by dividing the price
by 10 pursuant to the terms of the 2015 Share Option Scheme.
(5)
The share options were granted in the form of America depositary shares and the relevant exercise prices were in US dollars.
44
DIRECTORS’ REPORT
LONG TERM INCENTIVE PLAN
The Company adopted a Long Term Incentive Plan on April 24, 2015
(the “LTIP”). The Directors (including Executive Directors, Non-executive
Directors and Independent Non-executive Directors), the directors of
the Company’s subsidiaries and the employees of the Company and its
subsidiaries and affiliates are eligible to participate in the LTIP. The LTIP
awards grant participating directors or employees a conditional right
to receive ordinary shares of the Company or the equivalent American
depositary shares (collectively the “Awarded Shares”), to be purchased
by an independent third party trustee (the “Trustee”) according to the
predetermined awards or up to a maximum cash amount depending
upon the achievement of annual performance targets for each financial
year of the Company stipulated in the LTIP awards.
(i) Grant of LTIP
On April 20, 2020, the Company granted:
(1)
awards under the LTIP to three Directors and 331 employees,
giving a conditional right to cash amounts which are
used by the Trustee to purchase Awarded Shares in the
Company, on market up to a maximum total cash amount
of US$37,352,846 depending upon the achievement of the
performance targets in 2020. Details of the grants are as
follows:
Maximum amount
per annum for
the LTIP period
stipulated in
Name or category of participants
the LTIP awards
Executive Directors
Christian Hogg
Johnny Cheng
Weiguo Su
US$1,580,193
US$640,443
US$1,407,120
Senior managers and executives in
US$33,725,090
aggregate
Total:
US$37,352,846
Vesting will occur two business days after the date of
announcement of the annual results for the financial year
2022;
(2)
(3)
non-performance based LTIP award of US$650,000 to two
employees. It is a one-off cash amount to be allocated to
the grantees and used by the Trustee to purchase Awarded
Shares, out of which US$150,000 awards will be vested one
year after grant and US$500,000 awards will be vested 25%
per year over four years;
non-performance based LTIP awards of US$200,000 each to
seven Directors. It is a one-off cash amount to be allocated to
the grantees and used by the Trustee to purchase Awarded
Shares which will be subject to a vesting schedule of 25% per
year over four years. Details of the grants are as follows:
Amount for
the LTIP period
stipulated in
Name or category of participants
the LTIP awards
Executive Director
Simon To
Non-executive Directors
Dan Eldar
Edith Shih
Independent Non-executive Directors
Paul Carter
Karen Ferrante
Graeme Jack
Tony Mok
Total:
US$200,000
US$200,000
US$200,000
US$200,000
US$200,000
US$200,000
US$200,000
US$1,400,000
On August 12, 2020, the Company granted:
(1)
awards under the LTIP to 39 employees, giving a
conditional right to cash amounts which are used
by the Trustee to purchase Awarded Shares in
the Company, on market up to a maximum total
cash amount of US$2,058,974 depending upon the
achievement of the performance targets in 2020.
Vesting will occur two business days after the date of
announcement of the annual results for the financial
year 2022; and
Hutchison China MediTech Limited 2020 Annual Report 45
(2)
non-performance based LTIP award of US$300,000 to an
employee. It is a one-off cash amount to be allocated to
the grantee and used by the Trustee to purchase Awarded
Shares which will be subject to a vesting schedule of 25% per
year over four years.
SIGNIFICANT SHAREHOLDINGS
As of February 26, 2021, according to the records of the Company, the
following holders held interests in 3% or more of the issued share capital
of the Company:
Any Awarded Shares purchased on behalf of a LTIP grantee are
to be held by the Trustee until they are vested. Vesting will also
depend upon the continued employment of the award holder and
will otherwise be at the discretion of the Board.
(ii) Vesting of LTIP
On March 6, 2020, awards granted under the LTIP on March 15, 2017
in respect of the annual performance targets for the financial year
2017 were vested. Details of the vesting are as follows:
Number of
Number of
American
ordinary
depositary
Name or category of participants
shares
shares
Executive Directors
Christian Hogg
Johnny Cheng
Weiguo Su
–
–
–
14,975
5,857
10,475
Senior managers and executives
460,660
16,524
in aggregate
Total:
460,660
47,831
Number of
Number of
ordinary
American
Approximate
shares
depositary
% of issued
held
shares held
share capital
332,478,770
–
45.69%
2,651,060
6,183,155
4.61%
10,899,950
20,000,000(3)
4,485,069
–
4.58%
2.75%
Name
Hutchison Healthcare
Holdings Limited (1)
(“HHHL”)
The Capital Group
Companies, Inc. (2)
Prudential plc group (2)
General Atlantic Singapore
HCM Pte. Ltd. (2)
(“General Atlantic”)
Notes:
(1)
(2)
(3)
HHHL is a private company registered in the British Virgin Islands and carries
on business as a holding company. HHHL is an indirect wholly-owned
subsidiary of CK Hutchison Holdings Limited which is a Cayman Islands
company registered and listed in Hong Kong.
Major interests in shares of the Company notified to the Company under the
provisions of rule 5 of the Disclosure Rules and Transparency Rules of the UK
Financial Conduct Authority which have been incorporated by reference into
the Company’s Articles of Association.
General Atlantic is entitled to further subscribe for up to 16,666,670 ordinary
shares by exercising a warrant, in part or whole, at any time after July 2, 2020
and ending on January 3, 2022.
46
DIRECTORS’ REPORT
AUDITOR
The financial statements have been audited by PricewaterhouseCoopers
who will retire and, being eligible, will offer themselves for re-appointment.
ANNUAL GENERAL MEETING
The AGM of the Company will be held on Wednesday, April 28, 2021 at
6:00 pm at the Conference Room, 18th Floor, Hutchison Telecom Tower,
99 Cheung Fai Road, Tsing Yi, Hong Kong. Details of the resolutions
proposed are set out in the Notice of the AGM.
By Order of the Board
Edith Shih
Director and Company Secretary
March 4, 2021
Hutchison China MediTech Limited 2020 Annual Report 47
The Board is responsible for directing the strategic objectives of the
Company and overseeing the management of the business. Directors
are charged with the task of promoting the success of the Company
and making decisions in the best interests of the Company, taking into
account the views of its stakeholders.
The Board, led by the Chairman, Mr Simon To, determines and monitors
the Group’s long term objectives and commercial strategies, annual
operating and capital expenditure budgets and business plans, evaluates
the performance of the Company, and supervises the Management of the
Company (the “Management”). Management is responsible for the
day-to-day operations of the Group under the leadership of the Chief
Executive Officer (the “CEO”).
As of December 31, 2020 and up to the date of this report, the Board
comprised ten Directors, including the Chairman, CEO, Chief Financial
Officer (the “CFO”), Chief Scientific Officer, two Non-executive Directors
and four Independent Non-executive Directors (one of whom is the Senior
Independent Non-executive Director). Biographical details of the Directors
are set out in the “Biographical Details of Directors” section on pages 36 to
40 and on the website of the Company (www.hutch-med.com). Although
the composition of the Board did not follow the recommendation
under the Code which states that at least half the board, excluding the
chairman, should comprise non-executive directors determined by the
board to be independent, the Nomination Committee has considered the
structure, size, diversity profile and skill set matrix of the current Board
and confirmed it considers that each Director will continue possessing the
character, experience, integrity and the levels of skills, care and diligence
required as a Director of the Company in respect of all decisions taken at
both Board and, where applicable, Committee level to ensure the long
term sustainable success of the Company.
The Company strives to attain and maintain high standards of corporate
governance best suited to the needs and interests of the Company
and its subsidiaries (the “Group”) as it believes that effective corporate
governance practices are fundamental to safeguarding shareholder
interests and enhancing shareholder value. Accordingly, the Company
has adopted corporate governance principles that emphasize a quality
board of Directors (the “Board”), effective risk management, internal
controls, stringent disclosure practices, transparency and accountability.
It is, in addition, committed to continuously improving these practices
and inculcating an ethical corporate culture. In respect of the financial
year ended December 31, 2020, the Company adopted the principles
of the 2018 UK Corporate Governance Code (the “Code”) applicable to
companies listed on the London Stock Exchange with a premium listing,
despite its shares being traded on AIM and hence not required to comply
with the Code. Although the American depositary shares of the Company
are listed on NASDAQ Global Select Market (“Nasdaq”), being a foreign
private issuer, it is permitted to follow Cayman Islands law for certain
corporate governance practices. In addition, the Company is subject to
and complies with certain applicable requirements of the Sarbanes-Oxley
Act (the “SOX”).
Set out below are the corporate governance practices adopted by the
Company.
THE BOARD
The primary objective of the Company is to become a fully integrated
global leader in the discovery, development and commercialization of
targeted therapies and immunotherapies for the treatment of cancer
and immunological diseases. The strategy of the Company is to leverage
the highly specialized expertise of the drug discovery division, known as
the Oncology/Immunology operations, to develop and expand our drug
candidate portfolio for the global market while also building on the
first-mover advantage in the development and launch of novel cancer
drugs in China. The Chairman’s Statement and the Operations Review
contain discussions and analyses of the Group’s opportunities,
performance and the basis on which the Group generates or preserves
value over the longer term and the basis on which the Group will execute
its strategy for delivering the objective of the Group.
Hutchison China MediTech Limited 2020 Annual Report 49
CORPORATE GOVERNANCE REPORT Mr To has served as the Chairman of the Company for more than nine
years. Notwithstanding the length of his service, Mr To continues to
demonstrate his commitment as Chairman, providing direction on
Company strategy, assisting generally on business operations. With his
in-depth knowledge, business experience in China and extensive network
of relationships, the Board took the view that it is in the best interests of
the Company that Mr To continues to act as the Chairman.
The role of the Chairman is separate from that of the CEO. Such division
of responsibilities reinforces the independence and accountability of
these executives. Mr To being the Chairman of the Company is not an
independent director. Given Mr To’s knowledge and experience of the
Company’s business, the Board took the view that it is in the best interests
of the Company that Mr To acts as the Chairman.
The Chairman is responsible for the effective conduct of the Board,
ensuring that it as a whole plays an effective role in the development and
determination of the Group’s strategy and overall commercial objectives
and acts as the guardian of the Board’s decision-making processes. He
is responsible for setting the agenda for each Board meeting, taking into
account, where appropriate, matters proposed by Directors. He also
ensures that the Board receives accurate, timely and clear information
on the Group’s performance, issues, challenges and opportunities facing
the Group and matters reserved to it for decision. With the support of
the Executive Directors and the Company Secretary, the Chairman seeks
to ensure that the Board complies with approved procedures, including
the schedule of Reserved Matters to the Board for its decision and the
Terms of Reference of all Board Committees. The Board, under the
leadership of the Chairman, has adopted good corporate governance
practices and procedures and taken appropriate steps to provide effective
communication with shareholders, as outlined later in this report.
The CEO, Mr Christian Hogg, is responsible for managing the businesses
of the Group, formulating and developing the Group’s strategy and
overall commercial objectives in close consultation with the Chairman
and the Board. With the executive management team of each core
business division, the CEO implements the decisions of the Board and
its Committees. He maintains an ongoing dialogue with the Chairman to
keep him fully informed of all major business development and issues.
He is also responsible for ensuring that the development needs of senior
management reporting to him are identified and met as well as leading
the communication program with shareholders.
The Board meets regularly. Between scheduled meetings, senior
management of the Group provides information to Directors on a
regular basis with respect to the activities and development of the
Group. Throughout the year, Directors participate in the deliberation and
approval of routine and operational matters of the Company by way of
written resolutions with supporting explanatory materials, supplemented
by additional verbal and/or written information from the Company
Secretary or other executives as and when required. Whenever warranted,
additional Board meetings are held. In addition, Directors have full access
to information on the Group and independent professional advice at all
times whenever deemed necessary by the Directors and they are at liberty
to propose appropriate matters for inclusion in Board agendas.
With respect to regular meetings of the Board, Directors receive written
notice of the meetings generally about a month in advance and an
agenda with supporting Board papers no less than three days prior to
the meetings. With respect to other meetings, Directors are given as
much notice as is reasonable and practicable in the circumstances.
Except for those circumstances permitted by the Articles of Association
of the Company, a Director who has a material interest in any contract,
transaction, arrangement or any other kind of proposal put forward to the
Board for consideration abstains from voting on the relevant resolution
and such Director is not counted for quorum determination purposes.
The Company held six Board meetings in 2020 with overall attendance of
approximately 98%.
Position
Chairman:
Executive Directors:
Non-executive Directors:
Name of
Director
Simon To
Christian Hogg
Johnny Cheng
Weiguo Su
Dan Eldar
Edith Shih
Independent Non-executive
Paul Carter
Directors:
Karen Ferrante
Graeme Jack
Tony Mok
Attended/
Eligible to
attend
6/6
6/6
6/6
6/6
6/6
6/6
6/6
6/6
6/6
5/6
50
CORPORATE GOVERNANCE REPORT
In addition to Board meetings, the Chairman held two meetings with
Non-executive Directors without the presence of the Executive Directors,
with full attendance. Such meetings provide an effective forum for the
Chairman to listen to the views of the Non-executive Directors including
corporate governance improvement, effectiveness of the Board, and
any other issues they may wish to raise in the absence of other Directors
and senior management of the Company. The Senior Independent
Non-executive Director, Mr Paul Carter, also held a meeting with all
Non-executive Directors without the presence of the Chairman, with full
attendance, for the appraisal of the Chairman’s performance.
In addition, evaluation of the performance of the Board and its
Committees together with the Chairman of each Committee was
conducted by questionnaire. The results of the evaluation were reviewed
by the Nomination Committee with the objective of ensuring the Board,
its Committees and the Chairman of each Committee continue to act
effectively in fulfilling the duties and responsibilities expected of them.
The Board believes that its internally-led evaluation has been effective and
resulted in a number of recommendations that have improved the way
the Board and the Committees function. For this reason, an externally led
evaluation (as recommended by the Code) was not thought necessary but
the Board will consider the engagement of an external service provider at
an appropriate juncture.
All Non-executive Directors are engaged on service contracts which
are automatically renewed for successive 12-month periods unless
terminated by written notice given by either party. The Chairman of the
Board is of the view that the performance of each of the Non-executive
Directors continues to be effective and they all demonstrate commitment
to their role as a Non-executive Director. Under the Articles of Association
of the Company, all Directors are subject to re-election by shareholders at
annual general meetings (the “AGM”) and at least once every three years
on a rotation basis. A retiring Director is eligible for re-election and
re-election of retiring Directors at general meetings is dealt with by separate
individual resolutions. In the interests of good corporate governance and
pursuant to the Code, the Directors and the Board have resolved that
all Directors will retire at the upcoming AGM of the Company and, being
eligible, will offer themselves for re-election by shareholders. This practice
complies with the recommendation under the Code. Save as mentioned
herein, there are no existing or proposed service contracts between any
of the Directors and the Company which cannot be terminated by the
Company within 12 months and without payment of compensation.
Where vacancies arise at the Board, candidates are proposed and put
forward to the Board for consideration and approval, with the objective
of appointing to the Board individuals with expertise in the businesses
of the Group and leadership qualities to complement the capabilities of
the existing Directors thereby enabling the Company to retain as well as
improve its competitive position.
Upon appointment to the Board, Directors receive a package
of orientation materials on the Group and are provided with a
comprehensive induction to the Group’s businesses by senior executives.
Continuing education and relevant reading materials are provided to
Directors regularly to help ensure that they are apprised of the latest
changes in the commercial, legal and regulatory environment in which the
Group conducts its businesses.
BOARD COMMITTEES
The Company has established four permanent board committees: Audit
Committee, Nomination Committee, Remuneration Committee and
Technical Committee, details of which are described later in this report.
Other board committees are established by the Board as and when
warranted to take charge of specific duties.
COMPANY SECRETARY
The Company Secretary, Ms Edith Shih, is accountable to the Board
for ensuring that Board procedures are followed and Board activities
are efficiently and effectively conducted. These objectives are achieved
through adherence to proper Board processes and the timely preparation
and dissemination to Directors of comprehensive Board agendas and
papers.
The Company Secretary is responsible for ensuring that the Board is fully
apprised of the relevant legislative, regulatory and corporate governance
developments of relevance to the Group and that it takes these in to
consideration when making decisions for the Group. From time to time,
she organizes seminars on specific topics of importance and interest
and disseminates relevant reference materials to Directors for their
information.
The Company Secretary is also directly responsible for the Group’s
compliance with all obligations of the AIM Rules for Companies and
applicable Nasdaq listing rules (collectively, the “Rules”), including the
preparation, publication and dispatch of annual and interim reports
within the time limits laid down in the Rules, the timely dissemination
to shareholders and the market of announcements, press releases and
information relating to the Group and assisting in the notification of
Directors’ dealings in securities of the Group.
Hutchison China MediTech Limited 2020 Annual Report 51
Furthermore, the Company Secretary advises the Directors on related
party transactions and price-sensitive/inside information, and Directors’
obligations for disclosure of interests and dealings in the Company’s
securities, to ensure that the standards and disclosures requirements
of the Rules are complied with and, where required, reported in the
annual and interim reports of the Company. In relation to related party
transactions, detailed analysis is performed on all potential related party
transactions to ensure full compliance and for Directors’ consideration.
The Company Secretary also serves a crucial conduit of communications
internally and externally. The Company Secretary facilitates information
flow and communication among Directors and also conveys the Board’s
decisions to the Management from time to time and ensures a good
channel of communication with shareholders. All Directors have access to
the Company Secretary advice where they consider necessary.
ACCOUNTABILITY AND AUDIT
Financial Reporting
The responsibility of Directors in relation to the financial statements is
set out below. This should be read in conjunction with, but distinguished
from, the Report of Independent Auditor on pages F-2 to F-3 of Form 20-F
which acknowledges the reporting responsibility of the Group’s Auditor.
Annual Report and Financial Statements
The Directors acknowledge their responsibility for the preparation of
the annual report and financial statements of the Company, ensuring
that the financial statements, taken as a whole, is fair, balanced and
understandable and provide the information necessary for shareholders
to assess the Company’s position, performance, business model and
strategy in accordance with the Code, Cayman Islands Companies Law
and the applicable accounting standards.
Accounting Policies
The Directors consider that in preparing the financial statements, the
Group has applied appropriate accounting policies that are consistently
adopted and made judgments and estimates that are reasonable in
accordance with the applicable accounting standards.
Accounting Records
The Directors are responsible for ensuring that the Group keeps
accounting records which disclose the financial position of the Group,
upon which financial statements of the Group could be prepared in
accordance with the Group’s accounting policies.
Safeguarding Assets
The Directors are responsible for taking all reasonable and necessary
steps to safeguard the assets of the Group and to prevent and detect
fraud and other irregularities within the Group.
Going Concern
The Directors, having made appropriate inquiries, are of the view that the
Group has adequate resources to continue in operational existence for the
foreseeable future and that, for this reason, it is appropriate for the Group
to adopt the going concern basis in preparing the financial statements.
Audit Committee
Under the Terms of Reference of the Audit Committee, the Audit
Committee is required to review the Group’s annual and interim results,
and annual and interim financial statements, oversee the relationship
between the Company and its external auditor, monitor and review the
effectiveness of the Company’s internal audit function in the context of
the Company’s overall risk management systems giving due consideration
to laws and regulations and the provisions of the Code. The Committee
is authorized to obtain, at the Company’s expense, external legal or other
professional advice on any matters within its Terms of Reference.
In addition, the Audit Committee assists the Board in meeting its
responsibilities for maintaining effective risk management and internal
control systems. It reviews the process by which the Group evaluates
its control environment and risk assessment process, and the way in
which business and control risks are managed. It receives and considers
the presentations of Management in relation to the reviews on the
effectiveness of the Group’s risk management and internal control
systems and the adequacy of resources, qualifications and experience of
staff in the Group’s accounting and financial reporting function, and their
training programs and budget. In addition, the Audit Committee reviews
with the internal auditor of CK Hutchison Holdings Limited (“CKHH”, being
the largest shareholder of the Company) the work plans for its audits
for the Group together with its resource requirements and deliberates
on the reports of the internal auditor of CKHH to the Audit Committee
on the effectiveness of risk management and internal controls in the
Group business operations. Further, it also considers the reports from the
Company Secretary on the Group’s material litigation proceedings and
compliance status on legal and regulatory requirements. These reviews
and reports were taken into consideration by the Audit Committee when it
makes its recommendation to the Board for approval of the consolidated
financial statements for the year.
52
CORPORATE GOVERNANCE REPORT The Terms of Reference for the Audit Committee and the Complaints
Procedures adopted by the Board are published on the website of the
Company.
The Group’s policy regarding the engagement of its external auditor for
the various services listed below is as follows:
•
•
•
•
•
Audit services – include audit services provided in connection with
the audit of the consolidated financial statements. All such services
are to be provided by the external auditor.
Audit related services – include services that would normally be
provided by an external auditor but not generally included in the
audit fees, for example, audits of the Group’s pension plans, due
diligence and accounting advice related to mergers and acquisitions,
internal control reviews of systems and/or processes, and issuance of
special audit reports for tax or other purposes. The external auditor
is to be invited to undertake those services that it must, or is best
placed to, undertake in its capacity as an auditor.
Taxation related services – include all tax compliance and tax
planning services, except for those services which are provided
in connection with the audit. The Group uses the services of the
external auditor where it is best suited. All other significant taxation
related work is undertaken by other parties as appropriate.
Other services – include, for example, risk management diagnostics
and assessments, and non-financial systems consultations. The
external auditor is also permitted to assist Management and the
internal auditor of CKHH with internal investigations and fact-finding
into alleged improprieties. These services are subject to specific
approval by the Audit Committee.
General consulting services – the external auditor is not eligible to
provide services involving general consulting work.
For the year ended December 31, 2020, fees of US$4.4 million charged by
PwC in total were for both audit and non-audit services. The non-audit
services, which amounted to approximately US$0.1 million, were mainly
related to the provision of tax advices and IT system and security review.
These non-audit services had been reviewed prior to the engagement
by the Audit Committee, which considered such services not having an
impairing effect on the independence of the auditor.
The Audit Committee comprises three Independent Non-executive
Directors who possess the relevant business and financial management
experience and skills to understand financial statements and contribute
to the financial governance, internal controls and risk management of
the Company. It is chaired by Mr Graeme Jack with Mr Paul Carter and
Dr Karen Ferrante as members. None of the Committee Members is
related to the Company’s external auditor.
The Audit Committee held four meetings in 2020 with 100% attendance of
its members.
Name of Member
Graeme Jack (Chairman)
Paul Carter
Karen Ferrante
Attended/
Eligible to
attend
4/4
4/4
4/4
The Audit Committee meets with the CFO and other senior management
of the Company from time to time for the purposes of reviewing the
annual and interim results, the annual and interim reports and other
financial, internal control and risk management matters of the Company.
It considers and discusses the reports and presentations of Management
and the Group’s internal and external auditors, with a view to ensuring
that the Group’s consolidated financial statements are prepared in
accordance with generally accepted accounting principles in the
United States. It also meets with the Group’s principal external auditor,
PricewaterhouseCoopers (“PwC”), to consider the reports of PwC on the
scope, strategy, progress and outcome of its independent review of the
interim financial report and annual audit of the consolidated financial
statements. In addition, the Audit Committee holds regular private
meetings with the external auditor, the CFO and the internal auditor of
CKHH separately without the presence of Management.
External Auditor
The Audit Committee reviews and monitors the external auditor’s
independence, objectivity and effectiveness of the audit process. Each
year, the Audit Committee receives a letter from the external auditor
confirming its independence and objectivity. It holds meetings with
representatives of the external auditor to consider the scope of its audit,
and approves its fees and the scope and appropriateness of non-audit
services, if any, to be provided by it. The Audit Committee also makes
recommendation to the Board on the appointment and retention of the
external auditor.
Hutchison China MediTech Limited 2020 Annual Report 53
RISK MANAGEMENT, INTERNAL
CONTROL AND LEGAL &
REGULATORY COMPLIANCE
The Board has overall responsibility for the Group’s systems of risk
management, internal control and legal and regulatory compliance.
In meeting its responsibility, the Board seeks to inculcate risk awareness
across the Group’s business operations and has put in place policies
and procedures, including parameters of delegated authority, which
provide a framework for the identification and management of risks. The
Board evaluates and determines the nature and extent of the risks that
the Company is willing to accept in pursuit of the Group’s strategic and
business objectives. It also reviews and monitors the effectiveness of the
systems of risk management and internal control on an ongoing basis.
Reporting and review activities include review by the Executive Directors
and the Board and approval of detailed operational and financial
reports, budgets and plans provided by management of the business
operations, review by the Board of actual results against budget, review
by the Audit Committee of the ongoing work of the internal audit and risk
management functions of CKHH, as well as regular business reviews by
the Executive Directors and the executive management team of each core
business division.
Whilst these procedures are designed to identify and manage risks
that could adversely impact the achievement of the Group’s business
objectives, they do not provide absolute assurance against material
mis-statement, errors, losses or fraud.
To ensure compliance with the requirements of section 404 of SOX, the
Company conducted a SOX compliance project, which assessed the
management of internal controls and procedures, and the evaluation
of the internal control systems relating to financial reporting of the
Company.
Risk Management
Risk management is integrated into the day-to-day operations of the
Group, and is a continuous and proactive process carried out at all
levels. Coupled with a strong internal control environment, the Group is
committed to effectively managing the risks it faces, be they strategic,
financial, operational or compliance, by adopting an Enterprise Risk
Management (ERM) framework based on the COSO (the Committee of
Sponsoring Organizations of the Treadway Commission) model.
The ERM framework facilitates a systematic approach in identifying,
assessing and managing risks within the Group. There are ongoing
dialogues between the Executive Directors and the management team of
each core business division to assess the plausible impact of current and
emerging risks and their mitigation measures so as to institute additional
controls and deploy appropriate insurance instruments, such as Directors
and Officers Liability Insurance, in minimizing or eliminating potential
financial, compliance or other risks to the Group’s businesses.
The Group adopts a “top-down and bottom-up” approach with respect
to formal risk review and reporting. Such approach involves regular input
from each core business unit as well as discussions and reviews by the
Executive Directors. On a half-yearly basis, each core business unit is
responsible for formally identifying the significant risks their business
faces and considering the likelihood of occurrence and potential impact
to the business, whilst the Executive Directors provide input after taking
a holistic assessment of all the significant risks that the Group faces.
Relevant risk information including key mitigation measures and plans are
recorded in a risk register to facilitate the ongoing review and tracking of
progress.
The review of the risk management system is overseen by the Board
through the Audit Committee. The Audit Committee reviews the
composite Risk Register together with the related risk assessment report
every six months, and provides input as and where appropriate so as
to ensure the effectiveness of the Group’s risk management system.
The following table summarizes the principal risks of the Group and the
related mitigation actions.
54
CORPORATE GOVERNANCE REPORT Risk Management Overview
Risk Factor
Risk Description
Management Actions
Risks Related to the Financial Position and Need for Capital
Funding for product development
The research and development of drug candidates, as
• Active monitoring of available cash resources against
programs and commercialization
well as commercialization in the areas of manufacturing,
future cash requirements
efforts
marketing, sales and distribution of such drug candidates,
• Diversified sources of funding
requires significant expenditures. Failure to raise capital
o Cash inflows from commercial operations
on attractive terms may compromise the Group’s ability to
o Sharing of clinical development costs with and
execute its business plans.
receipt of milestone income from partners through
collaborations
o Ready access to capital markets as listed on AIM and
Nasdaq
o Bank borrowing facilities
o Proceeds from private placements of shares and
possible issuance pursuant to any exercise of other
instruments, e.g. warrants
Risks Related to Oncology/Immunology Operations and Development of the Group’s Drug Candidates
The Group’s future profitability
The Group does not expect to be significantly profitable
• Regularly evaluating the research and development
is dependent on the successful
unless and until it successfully completes its clinical trials,
development and commercialization
receives relevant regulatory approval and generates
of the drug candidates
substantial sales of approved innovative drugs in
developments.
strategy of the Group in light of unmet medical
needs. Two oncology drugs, ELUNATE® in metastatic
colorectal cancer and SULANDA® in non-pancreatic
neuroendocrine tumors, were approved and launched
Competition in discovering,
The development and commercialization of new drugs
• Targeting potential markets with high unmet demands
developing and commercializing
is highly competitive. The competition from other
in drug discovery process
drugs
pharmaceutical companies with respect to current drug
• Formation of strategic partnerships and collaborations
candidates, as well as any future drug candidates, is always
with other companies
present given market dynamics.
• Expanding our clinical and regulatory operations
worldwide including the U.S. and Europe
Attract, retain and motivate key
Attracting, retaining and motivating key executives
• Benchmarking salary and compensation structure
executives and qualified personnel
and personnel is critical to an organization’s success,
against peer groups
particularly in the innovative pharmaceutical industry.
• Share-based compensation provided to incentivize key
The loss of key executives and personnel could impede
management/talent
the achievement of research, development and
• Establishing key performance measurement and talent
commercialization initiatives.
development schemes
Commercial strategy for newly
Following the commercial launches of the Group’s pipeline
• Building a large-scale global production facility in
approved drug products
products, a comprehensive strategy is required to be
Shanghai
formulated to secure manufacturing and commercialization
• Setting up commercial infrastructure to perform
capacity.
commercialization activities of developed drug
products in China and the U.S.
Hutchison China MediTech Limited 2020 Annual Report 55
Risk Factor
Risk Description
Management Actions
Risks Related to Sales of the Group’s Internally Developed Drugs and Other Drugs
Compliance with extensive regulatory
The regulatory framework in China governs and addresses
• Setting up compliance team and implementing internal
requirements for pharmaceutical
all aspects of operations within the pharmaceutical
policies and procedures to monitor compliance
companies in China
industry, including licensing and certification requirements,
• Benchmarking against regulatory reviews of industry
periodic renewal and reassessment processes, and
groups and best practices of peers
registration of new drugs, interactions with healthcare
professionals and organizations among others. Violations
of such requirements may adversely affect the Group’s
businesses.
Product liability claims
The Group’s businesses face an inherent risk of product
liability exposure related to sales of products or the
• Establishing measures to ensure product safety
o
Independent laboratory testing
products licensed from third parties. If the Group cannot
o Compliance with relevant quality practices
successfully defend against product liability claims, if any,
o Sourcing from well-established suppliers
product reputation and financial results could be materially
• Procuring product liability insurance
Risks Related to the Group’s Dependence on Third Parties
affected.
Relationships with collaboration
Poor relationships with collaboration partners could lead
• Establishing joint steering committees to make key
partners
to disagreement regarding clinical development and
decisions and resolve any differences
commercialization, and termination or expiration of the
• Ongoing dialogue and regular meetings at executive
collaboration. Any such matters would cause adverse
levels to facilitate strategic alignment and planning
impacts to business reputation and financial results.
Sourcing of materials for clinical trials
The development and commercialization of drug
• Active monitoring of the supply of materials and
and commercial products
candidates requires sufficient supplies for clinical
inventory levels
testing and commercial demand. Development and
• Sourcing from well-established clinical suppliers with
commercialization could be interrupted if suppliers fail to
long-term relationships
provide a stable supply of necessary materials.
Compliance with clinical trial
The regulatory approval process for clinical trials may be
•
Implementation of measures to ensure compliance
regulatory requirements of
delayed or subject the Group to enforcement action in
o Sourcing from well-established clinical suppliers
collaboration with partner/clinical
cases where clinical research organizations or collaboration
o Maintaining relevant liability insurance
research organization
partners fail to comply with clinical trial regulations. Any
non-compliance may require clinical trials to be repeated
and delay regulatory approval.
Other Risks and Risks Related to Doing Business in China
Compliance with anti-bribery and
Within the pharmaceutical and drug distribution industry,
• Establishing Anti-Bribery and Anti-Corruption Policy
anti-corruption regulations
employees are in contact with healthcare professionals
and other related policies and procedures with relevant
and organizations and persons who may be considered
compliance requirements
government officials and are therefore subject to risks of
• Setting up compliance teams to closely monitor
violations under the U.S. Foreign Corrupt Practices Act, the
activities
Bribery Act 2010 of the Parliament of the United Kingdom,
• Reinforcing employees’ ethical, personal and
Chinese anti-corruption laws and other laws in the
professional standards through regular training and
countries where the Group conducts business. Violations
annual declarations
could result in criminal or civil sanctions and other material
adverse impacts to the business.
56
CORPORATE GOVERNANCE REPORT Risk Factor
Risk Description
Management Actions
The COVID-19 pandemic and other
As of the date of this annual report, the Group do not
• The COVID-19 outbreak initially posed some challenges
adverse public health developments
expect any material impact on the long-term activity, the
to the Group’s operations in 2020 resulting from
could materially and adversely affect
Group do not yet know the full extent of potential delays
restrictions in travel
the Group’s business
or impacts on the business, the clinical trials, the research
• The Group adapted quickly and was able to minimize
programs, healthcare systems or the global economy as a
the effect across the businesses
whole, which could have a material adverse effect on the
• The Group will continue to closely monitor the evolving
business, financial condition and results of operations and
situation
cash flows.
Uncertainties with respect to the
The implementation of laws and regulations in China may
• Close monitoring of the pharmaceutical regulatory
legal system and changes in laws and
be in part based on government policies and internal
environment in China
regulations in China
rules that are subject to the interpretation and discretion
• Benchmarking against regulatory reviews of industry
of different government agencies. Unexpected changes
groups and best practices of peers
to laws and regulations can materially affect business
operations and financial results.
Adverse information technology
Pharmaceutical companies which develop and
• Setting up of information technology systems security
incidents
commercialize new drugs rely significantly on information
subject to regular reviews internally and by external
technology for storing clinical and financial data.
experts
Information technology systems could be vulnerable
• Regular maintenance and upgrade of information
to damage from external or internal security incidents,
technology systems security
breakdowns, malicious intrusions and cybercrimes,
• Compliance with best-practice cybersecurity guidelines
which may cause significant interruptions or losses to the
published by the National Institute of Standards and
business.
Technology (NIST)
Foreign currency fluctuations
The value of the Renminbi against the U.S. dollar and
• Active cash management to mitigate foreign currency
other currencies may fluctuate and is affected by changes
exposure
in political and economic conditions. Appreciation or
o Active monitoring of China operations and its
depreciation in the value of the Renminbi relative to U.S.
funding requirements to plan remittances and
dollars would affect financial results reported in U.S. dollar
timely conversion to address exposure to currency
terms regardless of any underlying change in the business
exchange rate variations
or results of operations.
Compliance with data protection and
The business is subject to data protection and privacy
• Establishing Information Security Policy and other
privacy regulations
laws at the local, state, national and international levels
related policies and procedures with relevant
where applicable. Legal requirements regarding data
compliance requirements
protection and privacy continue to evolve and may result
• Closely monitoring the development in the relevant
in ever-increasing public security and escalating levels of
regulatory regime to ensure compliance with the
enforcement action.
requirements
Risks Related to Intellectual Property
Protect product intellectual property
The discovery and development of innovative
• Active management and tracking of intellectual
rights
medicines require significant investment of resources. A
property rights
pharmaceutical company’s success depends in part on
• Frequent consultations with external counsel
its ability to protect such investments, products and drug
• Establishing protection mechanisms including
candidates from competition by establishing and enforcing
execution of confidentiality and non-competition
intellectual property rights. Failure could cause additional
agreements, registration of intellectual property rights
competition to harm the business.
and defense of any intellectual property related claims
Pages 7 to 56 of Form 20-F provide a further discussion of these and other important risk factors which could affect the Group’s financial condition or
results of operations that differ materially from expected or historical results.
Hutchison China MediTech Limited 2020 Annual Report 57
Internal Control Environment
Group structures covering all subsidiaries, associated companies and
joint ventures are maintained and updated on a timely and regular
basis. Executive Directors are appointed to the boards of all material
operating subsidiaries and associates for overseeing and monitoring
those companies, including attendance at board meetings, review and
approval of budgets, plans and business strategies with associated risks
identified and setting of key business performance targets. The executive
management team of each core business division is accountable for
the conduct and performance of each business in the division within
the agreed strategies and similarly management of each business is
accountable for its conduct and performance.
The internal control procedures of the Group include a comprehensive
system for reporting information to the executive management team of
each core business division and the Executive Directors.
Business plans and budgets are prepared annually by management of
individual businesses and subject to review and approval by both the
executive management team and Executive Directors as part of the
Group’s five-year corporate planning cycle. Reforecasts for the current
year are prepared on a quarterly basis and reviewed for variances to
the budget and for approval. When setting budgets and reforecasts,
Management identifies, evaluates and reports on the likelihood and
potential financial impact of significant business risks.
Executive Directors review monthly management reports on the financial
results and key operating statistics of each business division and
discuss with the executive management team and senior management
of business operations to review these reports, business performance
against budgets, forecasts, significant business risk sensitivities and
strategies. In addition, financial controllers of the executive management
team of each core business division discuss with the representatives of
the Finance Department to review monthly performance against budget
and forecast, and to address accounting and finance related matters.
The Finance Department has established guidelines and procedures for
the approval and control of expenditures. Operating expenditures are
subject to overall budget control and are controlled within each business
with approval levels set by reference to the level of responsibility of each
executive and officer. Capital expenditures are subject to overall control
within the annual budget review and approval process, and more specific
control and approval prior to commitment by the Finance Department
or Executive Directors are required for unbudgeted expenditures and
material expenditures within the approved budget. Quarterly reports of
actual versus budgeted and approved expenditures are also reviewed.
The Group’s internal audit activity continues to be outsourced to CKHH,
which appoints a General Manager with responsibility for the internal
audit to report directly to the Audit Committee. The Audit Committee
believes that outsourcing offers the Group access to the range of skills and
resources required and endorsed its continuing use. The Audit Committee
monitors and reviews the internal audit relationship with CKHH and
the procedures used, as described in further detail below, to ensure the
effectiveness of the internal audit process.
The General Manager of the internal audit function of CKHH, reporting
directly to the Audit Committee, provides independent assurance as to
the existence and effectiveness of the risk management activities and
controls in the Group’s business operations in various countries. Using
risk assessment methodology and taking into account the dynamics of
the Group’s activities, internal audit derives its yearly audit plan which
is reviewed by the Audit Committee, and reassessed during the year as
needed to ensure that adequate resources are deployed and the plan’s
objectives are met. Internal audit function of CKHH is responsible for
assessing the Group’s risk management and internal control systems,
formulating an impartial opinion on the systems, and reporting its findings
to the Audit Committee, the CEO, the CFO and the senior management
concerned as well as following up on all reports to ensure that all
issues have been satisfactorily resolved. In addition, a regular dialogue
is maintained with the external auditor so that both are aware of the
significant factors which may affect their respective scope of work.
Depending on the nature of business and risk exposure of individual
business units, the scope of work performed by the internal audit function
includes financial, IT and operations reviews, recurring and surprise
audits, fraud investigations and productivity efficiency reviews.
Reports from the external auditor on internal controls and relevant
financial reporting matters are presented to the General Manager of the
internal audit function of CKHH and, as appropriate, to the CFO. These
reports are reviewed and appropriate actions are taken.
The Board, through the Audit Committee, has monitored the Group’s risk
management and internal control systems for the year ended December
31, 2020 covering all material financial, operational and compliance
controls, has conducted a review of their effectiveness, and is satisfied that
such systems are effective and adequate. In addition, it has reviewed and
is satisfied with the adequacy of resources, qualifications and experience
of the staff of the Group’s accounting and financial reporting and internal
audit functions, and their training programs and budget.
58
CORPORATE GOVERNANCE REPORT Legal and Regulatory Control Compliance
Nomination Process
The Group is committed to ensuring its businesses are operated in
compliance with local and international laws, rules and regulations. The
Legal Department has the responsibility of safeguarding the legal interests
of the Group, including preparing, reviewing and approving all legal and
corporate secretarial documentation of Group companies, working in
conjunction with finance, tax, treasury, corporate secretarial and business
unit personnel on the review and co-ordination process, and advising
Management of legal and commercial issues of concern. In addition,
the Legal Department is also responsible for overseeing regulatory
compliance matters of all Group companies. It analyzes and monitors
the regulatory frameworks within which the Group operates, including
reviewing applicable laws and regulations and preparing and submitting
responses or filings to relevant regulatory and/or government authorities
on regulatory issues and consultations. In addition, the Legal Department
prepares and updates internal policies where necessary so as to
strengthen the internal controls and compliance procedures of the Group.
The Legal Department also determines and approves the engagement of
external legal advisors, ensuring the requisite professional standards are
adhered to as well as most cost effective services are rendered. Further,
the Legal Department organizes and holds from time to time continuing
education on legal and regulatory matters of relevance to the Group for
Directors and the business executives.
NOMINATION COMMITTEE
The current Nomination Committee, chaired by Professor Tony Mok,
an Independent Non-executive Director and with the Chairman Mr To
and Independent Non-executive Director Mr Jack as members, is in
compliance with the code provision of the Code. Prior to December 11,
2020, the Nomination Committee comprised all Directors as members
with a sub-committee comprising members in compliance with the code
provision requirements under the Code established, on an ad hoc basis,
to facilitate the selection and nomination process.
The responsibilities of the Nomination Committee are to review the
structure, size, diversity profile and skills set of the Board against its
needs and make recommendations on the composition of the Board to
achieve the Group corporate strategy as well as promote shareholder
value. It identifies suitable director and senior management candidates
and selects or makes recommendations to the Board on the appointment
or re-appointment of Directors, succession planning for Directors
and selection of individuals to be nominated as senior management.
Furthermore, it also assesses the independence of Independent
Non-executive Directors having regard to the criteria under the Code and
reviews the Director Nomination Policy and Board Diversity Policy
periodically with a view of making recommendation on any proposed
revisions to the Board.
The nomination process has been, and will continue to be, conducted
in accordance with the Director Nomination Policy and Board Diversity
Policy, which were adopted and updated in December 2020 respectively.
They are available on the website of the Company. The Board will from
time to time review these policies and monitor their implementation
to ensure continued effectiveness and compliance with regulatory
requirements and good corporate governance practices.
Board candidates are selected based on merit and the contribution
such candidate can bring to the Board to complement and expand the
competencies, experience and perspectives of the Board as a whole,
taking into account the corporate strategy of the Group and the benefits
of various aspects of diversity, including gender, age, culture, ethnicity,
educational background, professional experience and other factors that
the Nomination Committee may consider relevant from time to time
towards achieving a diversified Board.
In the determination of the suitability of a candidate, the Nomination
Committee will have due regard to the benefits of various aspects of
diversity in accordance with the Board Diversity Policy. If the Board
determines that an additional or replacement Director is required, the
Nomination Committee will deploy multiple channels for identifying
suitable director candidates, including referral from Directors,
shareholders, management, advisors of the Company and external
executive search firms. Where a retiring Director, being eligible, offers
himself/herself for re-election, the Nomination Committee will consider
and, if appropriate, recommend such retiring Director to stand for
re-election. A circular containing the requisite information on retiring
Directors will be sent to shareholders prior to a general meeting in
accordance with the Code.
Shareholders of the Company may also nominate a person to stand for
election as a Director at a general meeting in accordance with the Articles
of Association of the Company and applicable laws and regulations.
The Terms of Reference for the Nomination Committee adopted by the
Board are published on the website of the Company.
The Nomination Committee held one meeting in 2020 with 100%
attendance of its members. During 2020, the Nomination Committee
reviewed the structure, size and composition (including skills set,
knowledge and experience) of the Board, ensuring that it has a balanced
composition of skills and experience appropriate for the requirements
of the businesses of the Group and that appropriate individuals with
relevant expertise and leadership qualities are appointed to the Board to
complement the capabilities of existing Directors.
Hutchison China MediTech Limited 2020 Annual Report 59
The Nomination Committee also assessed the independence of all the
Independent Non-executive Directors and considered all of them being
independent having regard to the annual independence confirmation
provided by the Independent Non-executive Directors, the assessment
of the Nomination Committee of their independence with reference
to the independence criteria set out in the Code; and in particular, the
Independent Non-Executive Directors continue to provide a balanced
and independent view to the Board and play a leading role in the Board
committees and bring independent and external dimension as well
as constructive and informed comments on issues of the Company’s
strategy, policy, performance, accountability, resources, key appointments
and standards of conduct. In addition, none of the Independent
Non-executive Directors have any involvement in the daily management of
the Company, or any financial or other interests or relationships in the
business of the Company or there exist any circumstances which would
materially interfere with their exercise of independent judgment. It also
discussed the succession planning for Directors and Senior Management.
The Remuneration Committee meets towards the end of each year to
determine the remuneration package of Executive Directors and senior
management of the Group and during the year to consider grants of share
options and long term incentive plan awards and other remuneration
related matters. Remuneration matters are also considered and approved
by way of written resolutions and additional meetings where warranted.
The Remuneration Committee held six meetings in 2020. All members
attended the meetings except for one Independent Non-executive Director
who was not able to attend two of the meetings due to illness.
Name of Member
Paul Carter (Chairman)
Graeme Jack
Simon To
Attended/
Eligible to
attend
4/6
6/6
6/6
In March 2021, the Nomination Committee reviewed again the structure,
skills set, expertise and competencies of the Board, affirmed the
independence of the Independent Non-executive Directors, deliberated
and selected Directors for retirement and re-election at the 2021 annual
general meeting and recommended to the Board for consideration. In
addition, the Committee reviewed the results of assessment of the Board
and its Committees for the year 2020.
During the year, the Remuneration Committee reviewed background
information on market data (including economic indicators, statistics and
the Remuneration Bulletin), headcount and staff costs. It also reviewed
and approved the proposed 2021 directors’ fees, year-end bonus and 2021
remuneration package of Executive Directors and senior executives of the
Company. Executive Directors do not participate in the determination of
their own remuneration.
Remuneration Policy
The remuneration of Mr Hogg, Mr Johnny Cheng and Dr Weiguo Su,
the Executive Directors, and senior executives is determined by the
Remuneration Committee with reference to the expertise and experience
of those individuals in the industry, the performance and profitability
of the Group and remuneration benchmarks from other local and
international companies as well as prevailing market conditions.
Senior management also participates in bonus arrangements which
are determined in accordance with the performance of the Group and
of the individual. The Chairman, Mr To, does not receive performance
related remuneration from the Company and is remunerated through his
service agreement. All Non-executive Directors have entered into service
agreements with the Company and are remunerated with fixed fees as
determined by the Board.
REMUNERATION OF DIRECTORS
AND SENIOR MANAGEMENT
Remuneration Committee
The responsibilities of the Remuneration Committee are to assist the
Board in achieving its objectives of attracting, retaining and motivating
employees of the highest caliber and experience needed to shape and
execute strategy across the Group’s substantial, diverse and international
business operations. It assists the Group in the administration of a fair
and transparent procedure for setting remuneration policies including
assessing the performance of Executive Directors and senior executives of
the Group and determining their remuneration packages.
The Terms of Reference for the Remuneration Committee adopted by the
Board are published on the website of the Company.
The Remuneration Committee comprises three members and is chaired
by Mr Carter, an Independent Non-executive Director, with the Chairman
Mr To and Independent Non-executive Director Mr Jack, as members. The
composition is not in compliance with the Code which stipulates that the
Remuneration Committee should comprise at least three Independent
Non-executive Directors. Given Mr To’s knowledge on the remuneration
and specialized market conditions of the Company’s business, the Board
took the view that it was in the best interests of the Company that Mr To
acts as a member of the Remuneration Committee.
60
CORPORATE GOVERNANCE REPORT
Directors’ emoluments comprise payments to Directors from the Company and its subsidiaries. The emoluments of each of the Directors disclosed in the
below table exclude amounts received by certain Directors from the subsidiaries of the Company but which were not retained and were paid onward by
the respective Directors to a subsidiary of the Company or subsidiaries of CKHH. The amounts paid to each Director for 2020 are as below:
Name of Director
Executive Directors:
Simon To
Christian Hogg
Johnny Cheng
Weiguo Su
Non-executive Directors:
Dan Eldar
Edith Shih
Independent Non-executive Directors:
Paul Carter
Karen Ferrante
Graeme Jack
Tony Mok
Salary
and fees
US$
80,000 (1) (5)
458,076 (2) (5)
380,141 (3)
420,894 (2)
70,000
70,000 (4) (5)
117,000
102,500
104,000
84,000
Bonus
US$
–
897,435
371,794
735,930
–
–
–
–
–
–
Benefits-
in-kind
US$
Taxable
benefits
US$
Pension
contributions
US$
–
9,936
9,936
6,471
–
–
–
–
–
–
–
17,820
–
10,000
–
29,369
27,091
32,229
–
–
–
–
–
–
–
–
–
–
–
–
Total
US$
80,000
1,412,636
788,962
1,205,524
70,000
70,000
117,000
102,500
104,000
84,000
Aggregate emoluments
1,886,611
2,005,159
26,343
27,820
88,689
4,034,622
Notes:
(1)
Such Director’s fees were paid to Hutchison Whampoa (China) Limited.
(2)
Emoluments paid include Director’s fees of US$75,000.
(3)
Emoluments paid include Director’s fees of US$70,000.
(4)
Such Director’s fees were paid to Hutchison International Limited.
(5)
(6)
(7)
(8)
Director’s fees received from the subsidiaries of the Company during the year he/she served as director that were paid to a subsidiary of the Company or subsidiaries
of CKHH are not included in the amounts above.
The fair value of share options granted is calculated in accordance with the methodology disclosed on page F-13 of Form 20-F. This methodology does not take
into account the actual share price at the date of exercise or whether any vested share options would be exercised. The significant inputs to the valuation model are
disclosed on page F-29 of Form 20-F and the details of the share options granted are set out in the “Directors’ Report” section on pages 41 to 47. The fair value of the
granted options, if any, is not included in the amounts above.
For the year ended December 31, 2020, the Group accrued US$0.3 million, US$0.1 million and US$0.5 million with respect to the awards of Long Term Incentive Plan of
the Company granted to Mr Hogg, Mr Cheng and Dr Su respectively, for which such amounts are not included in the table above.
For the year ended December 31, 2020, the Group accrued US$0.1 million with respect to the non-performance based awards of Long Term Incentive Plan of the
Company granted to each of Mr To, Dr Eldar, Ms Shih, Mr Carter, Dr Ferrante, Mr Jack and Professor Mok, for which such amounts are not included in the table above.
Hutchison China MediTech Limited 2020 Annual Report 61
In 2020, the Remuneration Committee has reviewed the approach
to remuneration and reporting on executive remuneration in detail,
with particular reference to the Code and associated guidance. Aimed
at attracting and retaining top talent, the Remuneration Committee
appointed an independent advisor, Aon Hewitt Consulting (Shanghai) Co.,
Ltd. (“Aon”) to conduct a compensation benchmarking research on peer
group U.S. and China biotech companies. Aon has no other connection
with the Company or individual Directors. The Remuneration Committee
comprehensively reviewed the Group’s compensation and share-based
incentives policies, performed benchmarking research on peer group
U.S. and China biotech companies and established an attractive policy
to ensure the Group is able to recruit and retain top talent. Vesting of
share-based awards under the policy is in line with that peer group. The
Committee takes seriously its responsibility to ensure that the executive
remuneration practices of the Group drive strong performance, are aligned
with the strategy and sustainability of the Group and are appropriate in
the context of the external regulatory environment and the expectations
of our stakeholders.
The Committee consulted with the Group’s largest shareholder when
developing its remuneration policy. In reviewing and setting remuneration,
including that of Executive Directors, the Committee receives updates on
investors’ views from time to time. These lines of communication ensure
that emerging best-practice principles are factored into the Committee’s
decision-making.
TECHNICAL COMMITTEE
The Technical Committee was chaired by Dr Ferrante with the Chairman
Mr To, Mr Hogg and Dr Su, Executive Directors, Mr Carter and Professor
Mok, both Independent Non-executive Directors, as members. The
Committee considers from time to time matters relating to the technical
aspects of the business and research and development. It also invites
such executives as it thinks fit to attend meetings as and when required.
The Terms of Reference for the Technical Committee adopted by the
Board are published on the website of the Company.
The Technical Committee held four meetings in 2020 with 100%
attendance of its members.
CODE OF ETHICS
The Group places utmost importance on employees’ ethical, personal
and professional standards. Every employee is provided with the Group’s
Code of Ethics booklet, and all employees are expected to achieve the
highest standards set out in the Code of Ethics including avoiding
conflicts of interest, discrimination or harassment and bribery etc.
Employees are required to report any non-compliance with the Code of
Ethics to Management.
62
In addition, the Group expects its business partners (suppliers, vendors,
customers, agents, contractors, joint venture partners and representatives,
etc.) who work with the Group to work to the same high ethical standards
as set out in the Group’s Code of Ethics for Business Partners. This Code
of Ethics is designed to deter wrongdoing and to promote (i) honest and
ethical conduct, including the ethical handling of actual or apparent
conflicts of interest between personal and professional relationships; (ii)
respect of confidentiality and intellectual property; (iii) compliance with
applicable laws, rules, codes and regulations; (iv) prompt reporting of any
violations of this Code of Ethics to the Company Compliance Officer; and
(v) accountability for adherence to this Code of Ethics.
STAKEHOLDER ENGAGEMENT
The Code emphasizes the importance of section 172 of the UK Companies
Act 2006, which requires directors to promote the success of the Company
for the benefit of its shareholders as a whole, having regard to the
following matters:
•
•
•
•
•
the likely consequence of any decision in the long term;
the interests of the Company’s employees;
the need to foster the Company’s business relationships with
suppliers, customers and others;
the impact of the Company’s operations on the community and the
environment;
the desirability of the Company maintaining a reputation for high
standards of business conduct; and
the need to act fairly as between members of the Company
•
(collectively, “section 172 Matters”).
Provision 5 of the Code requires the Board to understand the views of
the Company’s key stakeholders and to describe how their interests and
the section 172 Matters have been considered in Board discussions and
decision-making. The Board received an induction session regarding
the Code and the section 172 Matters in 2019. The importance to
the Company of giving due consideration to our stakeholders is well
understood by the Board. The Company welcomes the emphasis placed
on the section 172 Matters under the Code.
In order to comply with Provision 5 of the Code, the Company has
identified the following key stakeholders including those who are material
to the long term success of the Company:
•
•
•
•
•
Shareholders
Customers
Suppliers – including collaboration partners and joint venture
partners
Employees
Community and the environment
CORPORATE GOVERNANCE REPORT Below is the information on how the Board has had regard to the section 172 Matters.
1.
Shareholders
Engagement
Result of engagement
Investor relations and communication
Investor relations and communication
The Company devotes significant senior resource to ongoing investor
Collaboration with our current shareholders, and the attraction of new
engagement. Through its Chairman, CEO and senior executives, the
prospective investors, is important for the Company. Through frequent
Company communicates regularly with the investment community,
engagement we ascertain what is important to our shareholders, both
including shareholders, analysts and media, holding regular briefing
in terms of their investment profile and where they may benefit from
meetings, conference calls and presentations and making announcements
additional knowledge or explanation.
and press releases.
The Chairman and the CEO are assisted in these activities by members of
understanding of their investment principles.
the management team, including the CFO, the Senior Vice President of
Corporate Finance and Development and the Group General Counsel.
Through these activities the Company is better able to articulate its position
Similarly, such engagement with our prospective investors affords a greater
and strategy, its understanding of its industry environment and the rationale
The Directors develop an understanding of the views of investors about
for Board decisions regarding the business operations of the Company and
the Company by periodic meetings with the Chairman and the CEO.
its financial management.
The Board is committed to providing transparent and detailed
The Board believes that appropriate steps have been taken during the
information on the Company to shareholders through the publication
year so that all members of the Board have an understanding of the views
of notices, announcements, press releases, annual and interim reports.
of major shareholders on a range of matters which are material to the
Regularly updated financial, business, scientific and other information
development of the business of the Company in the short, medium and
on the progress of the Company’s operations are made available on
longer term.
www.hutch-med.com.
Direct communication with investors include in-person presentations
hosted by the Company, industry and investment conferences and
meetings with individual fund managers and fund analysts.
Hutchison China MediTech Limited 2020 Annual Report 63
Engagement
Result of engagement
AGM, Company website and feedback
AGM, Company website and feedback
Shareholders are encouraged to attend general meetings of the Company,
The most recent AGM of the Company, held on April 27, 2020, had a good
including the AGM at which the Chairman and Directors are available
level of participation and engagement by shareholders and provided
to answer questions relating to the Company and its business. The
shareholders with the opportunity to put questions to the Chairman, the
AGM is regarded as an especially important opportunity to engage with
CEO and other Directors. All members of the Board attended the AGM. In
shareholders. All shareholders have statutory rights to call for general
accordance with best practice, votes on all resolutions were taken on a poll.
meetings by sending a written request and proposed agenda to the
In this way, all votes were counted, including votes of shareholders unable
Company Secretary.
to attend the meeting in person utilizing a proxy to vote on their behalf.
Votes were cast in relation to approximately 90% of the issued share capital.
The Company website www.hutch-med.com includes detailed information
All resolutions were passed by over 80% of votes cast.
about the Company. It also hosts a comprehensive ‘Shareholder
Information’ page which provides a large amount of information that
The Company has received many inquiries over the course of the year
any current shareholder or prospective investor may seek – including
through our website and other investor communication channels, which
frequently asked questions, share price details and details of past and
have allowed us to answer investors’ questions.
upcoming events, as well as an archive of all announcements and financial
reports. Furthermore, investors are encouraged to provide comments,
How engagement with Shareholders influenced the Board’s
feedback and suggestions directly to the Company Secretary or to the
decision-making
Company by email to ir@hutch-med.com.
Views of shareholders are taken into consideration by the Board in designing
the Company’s strategy and remuneration policy and in appraising its
operational performance.
2.
Customers
Engagement
Result of engagement
Shanghai Hutchison Pharmaceuticals Limited (“SHPL”) has developed a
In 2019, the “Guideline for Diagnosis and Treatment of Chinese Medicine in
diversified marketing activity model to respond to the needs of customers,
Stable Angina Coronary Artery Disease” was published, and before that 12
including key opinion leaders (“KOLs”), physicians and patients. SHPL
other relative guidelines were published, helping physicians to understand
delivers different programs for different customer segments, including
and implement clinical guidelines in order to make better choices. In 2016
cooperating in clinical research with KOLs and assisting KOLs to establish
SHPL launched and remains committed to “The Belt and Road Initiative"
clinical guidelines or consensus.
project with the Cardiovascular Disease Committee of Chinese Association
of Integrative Medicine. The project promotes the development of
SHPL has established multiple channels to listen to customer feedback,
prevention and treatment of chronic cardiovascular diseases in primary care
such as face-to-face visiting, post-conference research and social media
units, including the creation of an online/offline patient education program.
platforms.
64
From 2006 to the present, SHPL has also established “Yihe Special Fund for
Moral Construction” with the Chinese Medical Doctor Association and has
carried out a series of "Promote the Professionalism of Physicians – Chinese
Physicians’ Declaration Initiative" activities to build a harmonious
doctor-patient relationship.
From 2017 to the present, after signing a strategic cooperation framework
agreement with the China Cardiovascular Health Association, SHPL
has enhanced its contribution to Chest Pain Centers by promoting the
construction and certification of Chest Pain Centers within about 1,500
hospitals in China.
CORPORATE GOVERNANCE REPORT
Engagement
Result of engagement
The revenue of Hutchison MediPharma (“HMPL”) is derived primarily
HMPL and its partners have jointly planned, executed and completed several
from its drug development and commercialization partners, AstraZeneca
clinical trials and a new drug product regulatory approval. This includes
plc and Eli Lilly and Company, in the form of milestone payments,
creating clinical trial protocols, working jointly with medical institutions,
development cost contributions, royalties on product sales, service
regulators in China, U.S. and Europe, gathering and managing clinical data,
fees for detailing and promotion of products and manufacturing sales.
and building documentation for all files. Products have been manufactured,
Engagement with these partners occurs across the Company through
delivered and sold across China through these collaborations.
regularly scheduled and ad hoc communication, including weekly,
bi-weekly, monthly and quarterly meetings of Joint Steering Committees,
How engagement with Customers influenced the Board’s
Joint Development Committees, Joint Manufacturing Committees and
decision-making
Joint Commercialization Committees, amongst others. HMPL will also
be receiving revenues on the sales of its unpartnered drug candidates
including SULANDA®.
The Board has sought to ensure that customers’ requirements/views are
taken into account as part of its decision-making process.
3.
Suppliers – including collaboration partners and joint venture partners
Engagement
Result of engagement
We want to be valued not only for our medicines but also for the way we
Handbook of standards
work. We seek to operate in a transparent and ethical way and expect
the same high standards from our suppliers and partners. Whether it
We are committed to upholding the Code of Ethics and the Code of Ethics
is investing in technological alternatives in science for our research or
for our Business Partners – taking measures to ensure that there is no
refusing to tolerate bribery or any other form of corruption, we aim to go
violation of the Code of Ethics in any of our businesses or in those of our
beyond what is required of us to be an example of how good business is
partners and suppliers. The principles articulated within our Code of Ethics
done.
are communicated to all our people through regular staff training.
We work responsibly with our suppliers, collaboration partners and joint
Regular supplier engagement program & Ethical audits
venture partners. The Board aims for continuous improvement in our
business and supply chains, and during the year the Board has taken the
In 2019, apart from annual feedback, we also visited our suppliers and
following steps with that in mind.
•
•
•
•
•
Supply chain risk management
Handbook of standards
Regular supplier engagement program
Ethical audits
Supplier scorecards
Supply chain risk management
partners more than 50 times. We also conduct regular audits to assess Code
of Ethics compliance for major suppliers, and maintain a zero-tolerance
policy towards violations of its principles.
Supplier scorecards & Continuous improvement
Not only product quality, delivery and responsiveness of our suppliers are
taken into account in our supplier scorecards, but also their commitment to
social responsibility and ethical compliance. We have a strong commitment
to continuous improvement together with our suppliers and partners.
Our ethical standards are integral to our procurement and partnering
activities and we monitor compliance through regular supplier
HMPL has maintained high quality and timely supply of finished goods to its
engagement, ethical audits and improvement programs. We work only
customers. There have been no interruptions in either commercial product
with those suppliers and partners whose standards of ethical behavior are
supply to customers, nor to clinical trial centers, that have adversely
consistent with our own. We will not use suppliers who are unable to meet
affected normal operations.
our standards.
HMPL’s commercial products, ELUNATE® and SULANDA®, are formulated
and packaged through its own production facility in Suzhou. The active
decision-making
pharmaceutical ingredients are manufactured by suppliers with extensive
The Board routinely considers the interests of our suppliers, including
know-how and experience. HMPL has regular interaction with the
collaboration partners and joint venture partners, in its decision-making
suppliers’ teams, including persons specifically assigned to HMPL. An
excess inventory of both active pharmaceutical ingredient and finished
and to ensure that they are aligned with the Company’s practices, values
and behaviors.
How engagement with Suppliers influenced the Board’s
goods are kept at a secure location. Regular Quality Assurance and Quality
Control testing on the products and ingredients is conducted.
Hutchison China MediTech Limited 2020 Annual Report 65
4.
Employees
Engagement
Workplace Safety
Result of engagement
Workplace Safety
The health, safety and wellbeing of employees are priorities for the
We regularly review and, where necessary, improve our safety measures,
Company. We continue to provide employees with the right environment
facility equipment and overall infrastructure so we can ensure the safety of
and the skills and education regarding their responsibilities for achieving
our employees in our office work setting. In 2020, we had zero work related
the best health and safety outcomes for themselves and the Company as
incident reports and we will continue to keep our work environment safe.
a whole.
We have established an Employee Health and Safety unit to provide
regular communication, training, and necessary infrastructures to ensure
we engage with employees on occupational health and safety issues.
Employee Engagement Activities
Employee Engagement Activities
There are multiple platforms and channels for our employees to
•
Major large scale Town Hall meetings were arranged with employees
engage with internal and external stakeholders so as to reinforce their
from various functions and departments of the Company’s entities.
commitment to the Company’s objective and mission.
•
•
•
Senior Leaders Town Hall Meetings – twice a year event where
senior management discusses company strategy, provides milestone
more than 750 participants present, including employees and their
family members. Due to the COVID-19 pandemic, it was not possible to
progress reports and hosts employee Q&A sessions.
host this event in 2020.
•
A Hutchison MediPharma Family Day was hosted in October 2019 with
Team Building and Community Development – cross functional
team building and community service where employees engage
through charity and sport events.
•
The Company communicated a compensation strategy to promote
the recruitment and retention of key talent in critical roles within the
Company and instigated a benchmark exercise of employee rewards/
Rewards, Recognitions and Learning and Development – we
provide several reward and recognition opportunities throughout
•
In 2020, there were 126 awards and recognitions made to employees
the performance period and also enhanced on-line learning and
with 166 promotions.
benefits to ensure market competitiveness.
development.
•
The Company launched major modern on-line learning platform for all
employees to enhance learning and development capabilities.
Employee Engagement Survey
Employee Engagement Survey
•
The Company carried out an employee engagement survey as part of
•
The survey returned a 96% response rate and overall high level
an ongoing engagement process with employees.
of satisfaction with the Company’s outlook, strategy and senior
management team with a number of recommendations regarding
rewards/benefits and increasing opportunities for learning and
development which were actioned upon as described above regarding
the rewards/benefits benchmark exercise and the launch of the on-line
learning platform.
66
CORPORATE GOVERNANCE REPORT
5.
Community and the environment
Engagement
Result of engagement
The Company endorses and supports the proposition that "enterprises
should give back to society and bear social responsibility". The following
activities have been conducted:
(1)
Shanghai Hutchison Pharmaceuticals Limited School
Bookroom
With the theme of "passing knowledge and lighting hope", the
Since the start of the project, 75 bookrooms have been built, including 5
"SHPL bookroom" activity is a national public welfare project
new bookrooms in 2019. Beyond the establishment of bookrooms, SHPL
launched by SHPL in 2010. It aims to provide books for primary and
secondary schools in remote areas, ethnic minority areas and rural
encourages children’s comprehension of books through reading activities
such as essay and story contests. In addition, through various activities such
areas.
(2)
I donate books when you walk
as study tours and summer camps, children in China are helped to walk
out of the mountains into modern cities, to broaden their horizons and to
experience the world.
This is a derivative project designed and launched by SHPL in 2018
This project promotes the combination of a healthy lifestyle with reading
and is based on the SHPL bookroom model.
by teenagers, encouraging practical action to improve education in remote
areas of China and to embrace the concept of "walking for love".
(3)
Hope Primary School
In 2008, SHPL aided the construction of Hope primary school in
Since 2008, SHPL has provided continuous support to the school, including
Zaoyang Township, Hanbin District, Ankang City, Shaanxi Province.
the award of scholarships and bursaries, the construction of a bookroom,
the organization of student summer camps, selection of outstanding
teachers for further education and staff support activities.
(4)
Volunteer activities
SHPL actively encourages employees to participate in social
In 2019, employees from Shanghai organized and participated in 44
volunteer service and organizes various volunteer activities on a
volunteer activities.
regular basis.
(5)
Coronavirus-related contributions
The Company engaged with several government and
In 2020, SHPL and HMPL jointly donated RMB3.5 million to the Shanghai
non-government entities to support activities aimed at minimizing
Charity Foundation to support frontline work towards epidemic prevention
infection of the general public with COVID-19.
and control in Hubei province, particularly in the city of Wuhan.
In addition, the funds will also go towards the purchase of protective
clothing, surgical gowns and urgently needed medical supplies such as
goggles, masks, and disinfectants.
SHPL also donated 240 imported infrared ear thermometers and 500 silver
mercury thermometers to Fengxian District, Shanghai, where the company's
factory is located, through the Red Cross Society, to support the smooth
implementation of local COVID-19 prevention work.
Hutchison China MediTech Limited 2020 Annual Report 67
Engagement
Result of engagement
SHPL’s ShengMai Injection (“SM Injection”) was recommended in the
“Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia”
jointly issued by the National Health Commission & National Administration
of Traditional Chinese Medicine. SHPL donated more than 36,000 boxes
of SM Injection to the Red Cross Society and hospitals in 13 provinces
and cities including Hubei, Anhui, Inner Mongolia and Tianjin, with a total
estimated value of around RMB1.8 million.
How engagement with Community and the Environment influenced
the Board’s decision-making
The Board encourages the Company’s business units to contribute to the
welfare of the local communities in which its businesses operate.
The 2020 AGM was held on April 27, 2020 at 47th Floor, Cheung Kong Center, 2 Queen’s Road Central, Hong Kong attended by all Directors and
representatives of PwC.
The Group values feedback from shareholders on its efforts to promote transparency and foster investor relationship. Comments and suggestions
to the Board or the Company are welcome and can be addressed to the Company Secretary by mail/e-mail or to the Company by e-mail at
info@hutch-med.com.
By Order of the Board
Edith Shih
Director and Company Secretary
March 4, 2021
68
CORPORATE GOVERNANCE REPORT
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 20-F
(Mark one)
☐
☒
REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2020
OR
OR
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to
OR
SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
☐
Date of event requiring this shell company report
Commission file number 001-37710
HUTCHISON CHINA MEDITECH LIMITED
(Exact name of Registrant as specified in its charter)
N/A
(Translation of Registrant’s name into English)
Cayman Islands
(Jurisdiction of incorporation or organization)
48th Floor, Cheung Kong Center
2 Queen’s Road Central
Hong Kong
+852 2121 8200
(Address of principal executive offices)
Christian Hogg
Chief Executive Officer
Level 18, The Metropolis Tower
10 Metropolis Drive
Hunghom, Kowloon
Hong Kong
Telephone: +852 2121 8200
Facsimile: +852 2121 8281
(Name, telephone, email and/or facsimile number and address of Company contact person)
Securities registered or to be registered pursuant to Section 12(b) of the Act:
Title of each class
American depositary shares, each representing five ordinary shares,
par value $0.10 per share
Securities registered or to be registered pursuant to Section 12(g) of the Act:
Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act:
Trading Symbol(s)
HCM
Name of each exchange on which registered
Nasdaq Global Select Market
None
(Title of Class)
None
(Title of Class)
Indicate the number of outstanding shares of each of the issuer’s classes of capital or common stock as of the close of the period covered by the Annual Report:
727,722,215 ordinary shares were issued and outstanding as of December 31, 2020.
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.
If this report is an annual or transition report, indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. Note
Yes No
Yes No
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the
registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes No
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months
(or for such shorter period that the registrant was required to submit such files).
Yes No
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or an emerging growth company. See definition of “large accelerated filer,” “accelerated filer,” and “emerging
growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer
Emerging growth company ☐
If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new
or revised financial accounting standards† provided pursuant to Section 13(a) of the Exchange Act. ☐
†The term “new or revised financial accounting standard” refers to any update issued by the Financial Accounting Standards Board to its Accounting Standards Codification after April 5, 2012.
Non-accelerated filer
Accelerated filer
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley
Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepare or issued its audit report.
Indicate by check mark which basis of accounting the registrant has used to prepare the financial statements included in this filing:
U.S. GAAP
International Financial Reporting Standards as issued
by the International Accounting Standards Board
Other
If “Other” has been checked in response to the previous question, indicate by check mark which financial statement item the registrant has elected to follow.
If this is an Annual Report, indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).
Item 17 Item 18
☐ Yes ☒ No
(APPLICABLE ONLY TO ISSUERS INVOLVED IN BANKRUPTCY PROCEEDINGS DURING THE PAST FIVE YEARS)
Indicate by check mark whether the registrant has filed all documents and reports required to be filed by Sections 12, 13 or 15(d) of the Securities Exchange Act of 1934 subsequent to the distribution of securities under a plan
confirmed by a court.
Yes No
Hutchison China MediTech Limited
Table of Contents
Introduction
Cautionary Statement Regarding Forward-Looking Statements
PART I
Item 1.
Item 2.
Item 3.
Item 4.
Identity of Directors, Senior Management and Advisers
Offer Statistics and Expected Timetable
Key Information
Information on the Company
Item 4A.
Unresolved Staff Comments
Item 5.
Item 6.
Item 7.
Item 8.
Item 9.
Operating and Financial Review and Prospects
Directors, Senior Management and Employees
Major Shareholders and Related Party Transactions
Financial Information
The Offer and Listing
Item 10.
Additional Information
Item 11.
Quantitative and Qualitative Disclosures About Market Risk
Item 12.
Description of Securities Other Than Equity Securities
PART II
Item 13.
Defaults, Dividend Arrearages and Delinquencies
Item 14. Material Modifications to the Rights of Security Holders and Use Of Proceeds
Item 15.
Controls and Procedures
Item 16.
Reserved
Item 16A. Audit Committee Financial Experts
Item 16B. Code of Ethics
Item 16C. Principal Accountant Fees and Services
Item 16D. Exemptions From The Listing Standards For Audit Committees
Item 16E. Purchases of Equity Securities by the Issuer and Affiliated Purchasers
Item 16F. Change In Registrant’s Certifying Accountant
Item 16G. Corporate Governance
Item 16H. Mine Safety Disclosure
PART III
Item 17.
Financial Statements
Item 18.
Financial Statements
Item 19.
Exhibits
SIGNATURES
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INTRODUCTION
This annual report on Form 20-F contains our audited consolidated statements of operations data for the years ended December 31,
2020, 2019 and 2018 and our audited consolidated balance sheet data as of December 31, 2020 and 2019. Our consolidated financial
statements have been prepared in accordance with U.S. generally accepted accounting principles, or U.S. GAAP.
This annual report also includes audited consolidated income statement data for the years ended December 31, 2020, 2019 and 2018
and the audited consolidated statements of financial position data as of December 31, 2020 and 2019 for each of our two non-
consolidated joint ventures, Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan, which are accounted for using the equity
accounting method. This annual report also includes audited consolidated income statement data for the period ended December 9,
2019 and the year ended December 31, 2018 and the audited consolidated statement of financial position data as of December 9, 2019
of Nutrition Science Partners when it was our non-consolidated joint venture. On December 9, 2019, we acquired our joint venture
partner’s 50% shareholding in Nutrition Science Partners, after which Nutrition Science Partners became our consolidated subsidiary.
The financial statements of each of Shanghai Hutchison Pharmaceuticals, Hutchison Baiyunshan and Nutrition Science Partners have
been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting
Standard Board, or IASB.
Unless the context requires otherwise, references herein to the “company,” “Hutchmed,” “we,” “us” and “our” refer to Hutchison
China MediTech Limited and its consolidated subsidiaries and joint ventures.
Unless otherwise indicated, references in this annual report to:
Conventions Used in this Annual Report
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“ADRs” are to the American depositary receipts, which evidence our ADSs;
“ADSs” are to our American depositary shares, each of which represents five ordinary shares;
“China” or “PRC” are to the People’s Republic of China, excluding, for the purposes of this annual report only, Taiwan and
the special administrative regions of Hong Kong and Macau;
“CK Hutchison” are to CK Hutchison Holdings Limited, a company incorporated in the Cayman Islands and listed on The
Stock Exchange of Hong Kong Limited, or the Hong Kong Stock Exchange, and the ultimate parent company of our largest
shareholder, Hutchison Healthcare Holdings Limited;
“E.U.” are to the European Union;
“Guangzhou Baiyunshan” are to Guangzhou Baiyunshan Pharmaceutical Holdings Company Limited, a leading China-based
pharmaceutical company listed on the Shanghai Stock Exchange and the Hong Kong Stock Exchange;
“Hain Celestial” are to The Hain Celestial Group, Inc., a Nasdaq-listed, natural and organic food and personal care products
company;
“HK$” or “HK dollar” are to the legal currency of the Hong Kong Special Administrative Region;
“Hutchison Baiyunshan” are to Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited, our
non-consolidated joint venture with Guangzhou Baiyunshan in which we have a 50% interest through a holding company in
which we have a 80% interest;
“Hutchison Consumer Products” are to Hutchison Consumer Products Limited, our wholly owned subsidiary;
“Hutchison Hain Organic” are to Hutchison Hain Organic Holdings Limited, our joint venture with Hain Celestial in which we
have a 50% interest;
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“Hutchison Healthcare” are to Hutchison Healthcare Limited, our wholly owned subsidiary;
“Hutchison MediPharma” are to Hutchison MediPharma Limited, our subsidiary through which we operate our
Oncology/Immunology operations in which we have a 99.8% interest;
“Hutchison MediPharma Holdings” are to Hutchison MediPharma Holdings Limited, our subsidiary in which we have a 99.8%
interest and which is the indirect holding company of Hutchison MediPharma;
“Hutchison Sinopharm” are to Hutchison Whampoa Sinopharm Pharmaceuticals (Shanghai) Company Limited, our joint
venture with Sinopharm in which we have a 50.9% interest;
“Nutrition Science Partners” are to Nutrition Science Partners Limited, our subsidiary in which we have a 99.8% interest and
formerly our non-consolidated joint venture with Nestlé Health Science S.A.;
“ordinary shares” or “shares” are to our ordinary shares, par value $0.10 per share;
“RMB” or “renminbi” are to the legal currency of the PRC;
“Shanghai Hutchison Pharmaceuticals” are to Shanghai Hutchison Pharmaceuticals Limited, our non-consolidated joint venture
with Shanghai Pharmaceuticals in which we have a 50% interest;
“Shanghai Pharmaceuticals” are to Shanghai Pharmaceuticals Holding Co., Ltd., a leading pharmaceutical company in China
listed on the Shanghai Stock Exchange and the Hong Kong Stock Exchange;
“Sinopharm” are to Sinopharm Group Co. Ltd., a leading distributor of pharmaceutical and healthcare products and a leading
supply chain service provider in China listed on the Hong Kong Stock Exchange;
“United States” or “U.S.” are to the United States of America;
“$” or “U.S. dollars” are to the legal currency of the United States; and
“£” or “pound sterling” are to the legal currency of the United Kingdom.
References in this annual report to our “Oncology/Immunology” operations are to all activities related to oncology/immunology,
including sales, marketing, manufacturing and research and development with respect to our drugs and drug candidates, and references
to our “Other Ventures” are to all of our other businesses.
Our reporting currency is the U.S. dollar. In addition, this annual report also contains translations of certain foreign currency
amounts into dollars for the convenience of the reader. Unless otherwise stated, all translations of pound sterling into U.S. dollars were
made at £1.00 to $1.35, all translations of RMB into U.S. dollars were made at RMB6.55 to $1.00 and all translations of HK dollars into
U.S. dollars were made at HK$7.80 to $1.00, which are the exchange rates used in our audited consolidated financial statements as of
December 31, 2020. We make no representation that the pound sterling, HK dollar or U.S. dollar amounts referred to in this annual
report could have been or could be converted into U.S. dollars, pounds sterling or HK dollars, as the case may be, at any particular rate
or at all.
Trademarks and Service Marks
We own or have been licensed rights to trademarks, service marks and trade names for use in connection with the operation of our
business, including, but not limited to, our trademarks “Hutchison”, “Chi-Med”, “Hutchison China MediTech”, “Hutchmed”,
“Elunate”, “Sulanda” and the logo used by Hutchison MediPharma. All other trademarks, service marks or trade names appearing in
this annual report that are not identified as marks owned by us are the property of their respective owners.
4
Solely for convenience, the trademarks, service marks and trade names referred to in this annual report are listed without the ®,
(TM) and (sm) symbols, but we will assert, to the fullest extent under applicable law, our applicable rights in these trademarks, service
marks and trade names.
CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS
This annual report contains forward-looking statements made under the “safe harbor” provisions of the U.S. Private Securities
Litigation Reform Act of 1995. These statements relate to future events or to our future financial performance and involve known and
unknown risks, uncertainties and other factors which may cause our actual results, performance or achievements to be materially
different from any future results, performance or achievements expressed or implied by the forward-looking statements. The words
“anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “goal,” “intend,” “may,” “might,”
“objective,” “plan,” “potential,” “predict,” “project,” “positioned,” “seek,” “should,” “target,” “will,” “would,” or the negative of these
terms or other similar expressions are intended to identify forward-looking statements, although not all forward-looking statements
contain these identifying words. These forward-looking statements are based on current expectations, estimates, forecasts and
projections about our business and the industry in which we operate and management’s beliefs and assumptions, are not guarantees of
future performance or development and involve known and unknown risks, uncertainties and other factors. These forward-looking
statements include statements regarding:
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•
•
•
•
•
•
•
•
•
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•
•
•
the initiation, timing, progress and results of our or our collaboration partners’ pre-clinical and clinical studies, and our research
and development programs;
our or our collaboration partners’ ability to advance our drug candidates into, and/or successfully complete, clinical studies;
the timing of regulatory filings and the likelihood of favorable regulatory outcomes and approvals;
regulatory developments in China, the United States and other countries;
the establishment of an oncology drug sales team to support the marketing and sales of our approved drug candidates;
the pricing and reimbursement of our and our joint ventures’ products and our approved drug candidates;
our ability to contract on commercially reasonable terms with contract research organizations, or CROs, third-party suppliers
and manufacturers;
the scope of protection we are able to establish and maintain for intellectual property rights covering our or our joint ventures’
products and our drug candidates;
the ability of third parties with whom we contract to successfully conduct, supervise and monitor clinical studies for our drug
candidates;
estimates of our expenses, future revenues, capital requirements and our needs for additional financing;
our ability to obtain additional funding for our operations;
the potential benefits of our collaborations and our ability to enter into future collaboration arrangements;
the ability and willingness of our collaborators to actively pursue development activities under our collaboration agreements;
our receipt of milestone or royalty payments pursuant to our strategic alliances with AstraZeneca AB (publ), or AstraZeneca,
and Lilly (Shanghai) Management Company Limited, or Eli Lilly;
the rate and degree of market acceptance of our drug candidates;
our financial performance;
5
•
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•
•
•
our ability to attract and retain key scientific and management personnel;
our relationship with our joint venture and collaboration partners;
developments relating to our competitors and our industry, including competing drug products;
changes in our tax status or the tax laws in the jurisdictions that we operate;
developments in our business strategies and business plans; and
the extent of the impact of the COVID-19 pandemic, including the duration, spread, severity, and any recurrence of the COVID-
19 pandemic, the duration and scope of related government orders and restrictions and the extent of the impact of the COVID-
19 pandemic on the global economy.
Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking
statements we make. As a result, any or all of our forward-looking statements in this annual report may turn out to be inaccurate. We
have included important factors in the cautionary statements included in this annual report on Form 20-F, particularly in the section of
this annual report on Form 20-F titled “Risk Factors,” that we believe could cause actual results or events to differ materially from the
forward-looking statements that we make. We may not actually achieve the plans, intentions or expectations disclosed in our
forward-looking statements, and you should not place undue reliance on our forward-looking statements. Moreover, we operate in a
highly competitive and rapidly changing environment in which new risks often emerge. It is not possible for our management to predict
all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may
cause actual results to differ materially from those contained in any forward-looking statements we may make.
You should read this annual report and the documents that we reference herein and have filed as exhibits hereto completely and
with the understanding that our actual future results may be materially different from what we expect. The forward-looking statements
contained herein are made as of the date of the filing of this annual report, and we do not assume any obligation to update any
forward-looking statements except as required by applicable law.
In addition, this annual report contains statistical data and estimates that we have obtained from industry publications and reports
generated by third-party market research firms. Although we believe that the publications, reports and surveys are reliable, we have not
independently verified the data and cannot guarantee the accuracy or completeness of such data. You are cautioned not to give undue
weight to this data. Such data involves risks and uncertainties and are subject to change based on various factors, including those
discussed above.
6
PART I
ITEM 1. IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS
Not applicable.
ITEM 2. OFFER STATISTICS AND EXPECTED TIMETABLE
Not applicable.
ITEM 3. KEY INFORMATION
A. [Reserved]
B. Capitalization and Indebtedness.
Not applicable.
C. Reasons for the Offer and Use of Proceeds.
Not applicable.
D. Risk Factors.
The following summarizes some, but not all, of the risks provided below. Please carefully consider all of the information
discussed in this Item 3.D. “Risk Factors” in this annual report for a more thorough description of these and other risks.
Risks Relating to Our Financial Position and Need for Capital
• Risks relating to our need for additional funding
• Risks relating to our existing and future indebtedness
Risks Relating to Our Oncology/Immunology Operations and Development of Our Drug Candidates
• Risks relating to our approach to the discovery and development of drug candidates and the lengthy, expensive and
uncertain clinical development process
• Risks relating to expediting regulatory review, obtaining and maintaining regulatory approval and ongoing regulatory
review for our drug candidates
• Risks relating to the commercialization of our drug candidates
• Risks relating to undesirable side effects of our drug candidates
• Risks relating to competition in discovering, developing and commercializing drugs
• Risks relating to our collaboration partners with respect to clinical trials, marketing and distribution
• Risks relating to the expansion of our international operations
7
Risks Relating to Sales of Our Internally Developed Drugs and Other Drugs
• Risks relating to obtaining and maintaining permits and licenses for our and our joint ventures' pharmaceutical operations
in China
• Risks relating to leveraging our Other Ventures’ prescription drug business to commercialize our internally developed
drug candidates
• Risks relating to competition in selling our approved, internally developed drugs and drugs of our Other Ventures
• Risks relating to maintaining and enhancing the brand recognition of our drugs
• Risks relating to the availability of reimbursement of our drugs, the lack of which could diminish our sales or profitability
• Risks relating to counterfeit products in China
• Risks relating to rapid changes in the pharmaceutical industry rendering our products obsolete
• Risks relating to cultivating or sourcing raw materials
• Risks relating to adverse publicity of us, our joint ventures or our products
Risks Relating to Our Dependence on Third Parties
• Risks relating to disagreements with current or future collaboration partners which we rely on for certain drug development
activities including the conducting of clinical trials
• Risks relating to relying on third party suppliers for the active pharmaceutical ingredients in our drug candidate and drug
products
• Risks relating to our, our collaboration partners or our CROs’ failure to comply with regulatory requirements pertaining
to clinical trials
• Risks relating to relying on third parties to construct our new manufacturing facility in Shanghai
• Risks relating to relying on distributors for logistics and distributions services
• Risks relating to the availability of benefits currently enjoyed by virtue of our association with CK Hutchison
Other Risks and Risks Relating to Doing Business in China
• Risks relating to COVID-19
• Risks relating to compliance with privacy laws, information security policies and contractual obligations related to data
privacy and security and any information technology or data security failures
• Risks relating to product liability claims or lawsuits
• Risks relating to liabilities under anti-corruption laws, environmental, health and safety laws and laws relating to equity
incentive plans
• Risks relating to uncertainties with respect to the PRC legal system, China’s currency exchange limits and PRC government
tax incentives or treatment
8
Risks Relating to Intellectual Property
• Risks relating to our, our joint ventures and our collaboration partners’ abilities to protect and enforce intellectual property
rights and maintain confidentiality of trade secrets
• Risks relating to infringing upon third parties’ intellectual property rights
Risks Relating to our ADSs
• Risks relating to being delisted from the Nasdaq if the PCAOB continues to be unable to inspect our independent registered
public accounting firm for three consecutive years
• Risks relating to our largest shareholder which may limit the ability of other shareholders to influence corporate matters
You should carefully consider the following risk factors in addition to the other information set forth in this annual report. If
any of the following risks were actually to occur, our company’s business, financial condition and results of operations prospects could
be adversely affected and the value of our ADSs would likely suffer.
Risks Relating to Our Financial Position and Need for Capital
We may need substantial additional funding for our product development programs and commercialization efforts. If we are unable
to raise capital on acceptable terms when needed, we could incur losses and be forced to delay, reduce or eliminate such efforts.
We expect our expenses to increase significantly in connection with our ongoing activities, particularly as we or our collaboration
partners advance the clinical development of our clinical drug candidates which are currently in active or completed clinical studies in
various countries. We will incur significant expenses as we continue research and development and initiate additional clinical trials of,
and seek regulatory approval for, these and other future drug candidates. In addition, we expect to incur significant commercialization
expenses related to product manufacturing, marketing, sales and distribution in China for surufatinib, our unpartnered drug candidate
approved in China in December 2020, and any of our other unpartnered drug candidates that may be approved in the future. In particular,
the costs that may be required for the manufacture of any drug candidate that receives regulatory approval may be substantial as we may
have to modify or increase the production capacity at our current manufacturing facilities or contract with third-party manufacturers.
We may also incur expenses as we create additional infrastructure, such as our new manufacturing facility under construction in
Shanghai, and expand our U.S.-based clinical and commercial team to support our operations at our U.S. subsidiary, Hutchison
MediPharma International Inc. Accordingly, we may need to obtain substantial funding in connection with our continuing operations
through public or private equity offerings, debt financings, collaborations or licensing arrangements or other sources. If we are unable
to raise capital when needed or on attractive terms, we could incur losses and be forced to delay, reduce or eliminate our research and
development programs or any future commercialization efforts.
Our net cash used in operating activities was $32.8 million, $80.9 million and $62.1 million for the years ended December 31, 2018,
2019 and 2020, respectively. We believe, however, that our expected cash flow from operations, including dividends from our Other
Ventures and milestone and other payments from our collaboration partners, our cash and cash equivalents and short-term investments
as well as our unutilized bank facilities as of December 31, 2020, including: (i) the aggregate HK$424.0 million ($54.4 million) revolving
credit facilities with The Hongkong and Shanghai Banking Corporation Limited, or HSBC, and (ii) the HK$117.0 million ($15.0 million)
revolving credit facility with Deutsche Bank AG, Hong Kong Branch, or Deutsche Bank AG, will enable us to fund our operating
expenses, debt service and capital expenditure requirements for at least the next 12 months. We have based this estimate on assumptions
that may prove to be wrong, and we could use our capital resources sooner than we currently expect. Our future capital requirements
will depend on many factors, including:
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the number and development requirements of the drug candidates we pursue;
the scope, progress, timing, results and costs of researching and developing our drug candidates, and conducting pre-clinical
and clinical trials;
the cost, timing and outcome of regulatory review of our drug candidates;
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the cost and timing of commercialization activities, including product manufacturing, marketing, sales and distribution, for our
drug candidates for which we receive regulatory approval;
the amount and timing of any milestone payments from our collaboration partners, with whom we cooperate with respect to
the development and potential commercialization of certain of our drug candidates;
the cash received from commercial sales of drug candidates for which we have received regulatory approval;
our ability to establish and maintain strategic partnerships, collaboration, licensing or other arrangements and the financial
terms of such agreements;
the cost, timing and outcome of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual
property rights and defending any intellectual property-related claims;
our headcount growth and associated costs, particularly as we expand our clinical activities in the United States and Europe;
and
the costs of operating as a public company listed in the United States and United Kingdom.
Identifying potential drug candidates and conducting pre-clinical testing and clinical trials is a time-consuming, expensive and
uncertain process that may take years to complete, and our commercial revenue will be derived from sales of products that will not be
commercially available unless and until we receive regulatory approval. We may never generate the necessary data or results required
for certain drug candidates to obtain regulatory approval, and even if approved, they may not achieve commercial success. Accordingly,
we will need to continue to rely on financing to achieve our business objectives. Adequate financing may not be available to us on
acceptable terms, or at all.
Raising capital may cause dilution to our shareholders, restrict our operations or require us to relinquish rights to technologies or
drug candidates.
We expect to finance our cash needs in part through cash flow from our operations, including dividends from our Other Ventures,
and we may also rely on raising capital through a combination of public or private equity offerings, debt financings and/or license and
development agreements with collaboration partners. In addition, we may seek capital due to favorable market conditions or strategic
considerations, even if we believe we have sufficient funds for our current or future operating plans. To the extent that we raise capital
through the sale of equity or convertible debt securities, the ownership interest of our shareholders may be materially diluted, and the
terms of such securities could include liquidation or other preferences that adversely affect the rights of our existing shareholders. Debt
financing and preferred equity financing, if available, may involve agreements that include restrictive covenants that limit our ability to
take specified actions, such as incurring additional debt, making capital expenditures or declaring dividends. Additional debt financing
would also result in increased fixed payment obligations.
In addition, if we raise funds through collaborations, strategic partnerships or marketing, distribution or licensing arrangements with
third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or drug candidates
or grant licenses on terms that may not be favorable to us. We may also lose control of the development of drug candidates, such as the
pace and scope of clinical trials, as a result of such third-party arrangements. If we are unable to raise funds through equity or debt
financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization
efforts or grant rights to develop and market drug candidates that we would otherwise prefer to develop and market ourselves.
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Our existing and any future indebtedness could adversely affect our ability to operate our business.
Our outstanding indebtedness combined with current and future financial obligations and contractual commitments, including any
additional indebtedness beyond our current facilities with HSBC and Deutsche Bank AG could have significant adverse consequences,
including:
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requiring us to dedicate a portion of our cash resources to the payment of interest and principal, and prepayment and repayment
fees and penalties, thereby reducing money available to fund working capital, capital expenditures, product development and
other general corporate purposes;
increasing our vulnerability to adverse changes in general economic, industry and market conditions;
subjecting us to restrictive covenants that may reduce our ability to take certain corporate actions or obtain further debt or
equity financing;
limiting our flexibility in planning for, or reacting to, changes in our business and the industry in which we compete; and
placing us at a competitive disadvantage compared to our competitors that have less debt or better debt servicing options.
We intend to satisfy our current and future debt service obligations with our existing cash and cash equivalents and short-term
investments. Nevertheless, we may not have sufficient funds, and may be unable to arrange for financing, to pay the amounts due under
our existing debt. Failure to make payments or comply with other covenants under our existing debt instruments could result in an event
of default and acceleration of amounts due.
We are subject to liquidity risk with respect to our investments in our joint ventures.
Our interests in our joint ventures are subject to liquidity risk. Such investments are not as liquid as other investment products as
there is no cash flow until dividends are declared and received by us even if such joint ventures are profitable. Furthermore, our ability
to promptly sell one or more of our interests in our joint ventures in response to changing corporate strategy or economic, financial and
investment conditions is limited. The market for such investments can be affected by various factors, such as general economic and
market conditions, availability of financing, interest rates and investor demand, many of which are beyond our control. If we determine
to sell any of our joint venture investments, we cannot predict if we will be successful or whether any price or other terms offered by a
prospective purchaser would be acceptable to us.
Risks Relating to Our Oncology/Immunology Operations and Development of Our Drug Candidates
Historically, our in-house research and development division, which is included in our Oncology/Immunology operations, has not
generated significant profits or has operated at a net loss. Our future profitability is dependent on the successful commercialization
of our drug candidates.
To date, fruquintinib and surufatinib are our only drug candidates that have been approved for sale. We do not expect to be
significantly profitable unless and until we generate substantial revenues from fruquintinib and/or successfully commercialize
surufatinib and/or our other drug candidates. We expect to incur significant sales and marketing costs as we prepare to commercialize
our drug candidates.
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Successful commercialization of our drug candidates is subject to many risks. Fruquintinib is marketed in collaboration with our
partner, Eli Lilly. Beginning in October 2020, we assumed responsibility for the development and execution of all on-the-ground
medical detailing, promotion and local and regional marketing activities for fruquintinib in China. Surufatinib is marketed by us without
the support of a collaboration partner. Fruquintinib and surufatinib are the first innovative oncology drugs we, as an organization, have
commercialized, and there is no guarantee that we will be able to successfully commercialize fruquintinib, surufatinib or any of our
other drug candidates for their approved indications. There are numerous examples of failures to meet expectations of market potential,
including by pharmaceutical companies with more experience and resources than us. There are many factors that could cause the
commercialization of fruquintinib, surufatinib or our other drug candidates to be unsuccessful, including a number of factors that are
outside our control. In the case of fruquintinib, for example, the third-line metastatic colorectal cancer, or mCRC, patient population in
China may be smaller than we estimate or physicians may be unwilling to prescribe, or patients may be unwilling to take, fruquintinib
for a variety of reasons. Additionally, any negative development for fruquintinib or surufatinib in clinical development in additional
indications, or in regulatory processes in other jurisdictions, may adversely impact the commercial results and potential of fruquintinib
or surufatinib in China and globally. Thus, significant uncertainty remains regarding the commercial potential of fruquintinib and
surufatinib.
We may not achieve profitability after generating revenues from fruquintinib and/or sales from surufatinib or our other drug
candidates, if ever. If the commercialization of fruquintinib, surufatinib and/or our other drug candidates is unsuccessful or perceived
as disappointing, our stock price could decline significantly and the long-term success of the product and our company could be harmed.
All of our drug candidates, other than fruquintinib and surufatinib in China, are still in development. If we are unable to obtain
regulatory approval and ultimately commercialize our drug candidates, or if we experience significant delays in doing so, our
business will be materially harmed.
All of our drug candidates are still in development, including fruquintinib and surufatinib which have been approved in China for
the treatment of third-line mCRC and non-pancreatic neuroendocrine tumors (NET), respectively, but are still in development in the
United States and other jurisdictions for these and other indications.
Although we receive certain payments from our collaboration partners, including upfront payments and payments for achieving
certain development, regulatory or commercial milestones, for certain of our drug candidates, our ability to generate revenue from our
drug candidates is dependent on their receipt of regulatory approval for and successful commercialization of such products, which may
never occur. Each of our drug candidates in development will require additional pre-clinical and/or clinical trials, regulatory approval
in multiple jurisdictions, manufacturing supply, substantial investment and significant marketing efforts before we generate any revenue
from product sales. The success of our drug candidates will depend on several factors, including the following:
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successful completion of pre-clinical and/or clinical trials;
successful enrollment in, and completion of, clinical trials;
receipt of regulatory approvals from applicable regulatory authorities for planned clinical trials, future clinical trials, drug
registrations or post-approval trials;
successful completion of all safety studies required to obtain regulatory approval and/or fulfillment of post-approval
requirements in the United States, China and other jurisdictions for our drug candidates;
adapting our commercial manufacturing capabilities to the specifications for our drug candidates for clinical supply and
commercial manufacturing;
obtaining and maintaining patent and trade secret protection or regulatory exclusivity for our drug candidates;
launching commercial sales of our drug candidates, if and when approved, whether alone or in collaboration with others;
acceptance of the drug candidates, if and when approved, by patients, the medical community and third-party payors;
effectively competing with other therapies;
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obtaining and maintaining healthcare coverage and adequate reimbursement;
enforcing and defending intellectual property rights and claims; and
• maintaining a continued acceptable safety profile of the drug candidates following approval.
If we do not achieve one or more of these factors in a timely manner or at all, we could experience significant delays or an inability
to successfully commercialize our drug candidates, which would materially harm our business.
Our primary approach to the discovery and development of drug candidates focuses on the inhibition of kinases, some of which are
unproven.
A primary focus of our research and development efforts is on identifying kinase targets for which drug compounds previously
developed by others affecting those targets have been unsuccessful due to limited selectivity, off-target toxicity and other problems. We
then work to engineer drug candidates which have the potential to have superior efficacy, safety and other features as compared to such
prior drug compounds. We also focus on developing drug compounds with the potential to be global best-in-class/next-generation
therapies for validated kinase targets.
Even if we are able to develop compounds that successfully target the relevant kinases in pre-clinical studies, we may not succeed
in demonstrating safety and efficacy of the drug candidates in clinical trials. Even if we are able to demonstrate safety and efficacy of
compounds in certain indications in certain jurisdictions, we may not succeed in demonstrating the same in other indications or same
indications in other jurisdictions. As a result, our efforts may not result in the discovery or development of drugs that are commercially
viable or are superior to existing drugs or other therapies on the market. While the results of pre-clinical studies, early-stage clinical
trials as well as clinical trials in certain indications have suggested that certain of our drug candidates may successfully inhibit kinases
and may have significant utility in several cancer indications, potentially in combination with other cancer drugs, chemotherapy and
immunotherapies, we have not yet demonstrated efficacy and safety for many of our drug candidates in later stage clinical trials.
We may expend our limited resources to pursue a particular drug candidate or indication and fail to capitalize on drug candidates
or indications that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we must limit our research programs to specific drug candidates that
we identify for specific indications. As a result, we may forego or delay pursuit of opportunities with other drug candidates or for other
indications that later prove to have greater commercial potential. Our resource allocation decisions may cause us to fail to capitalize on
viable commercial drugs or profitable market opportunities. In addition, if we do not accurately evaluate the commercial potential or
target market for a particular drug candidate, we may relinquish valuable rights to that drug candidate through collaboration, licensing
or other royalty arrangements when it would have been more advantageous for us to retain sole development and commercialization
rights to such drug candidate.
The regulatory approval processes of the U.S. Food and Drug Administration, or FDA, National Medical Products Administration
of China, or NMPA, and comparable authorities are lengthy, time consuming and inherently unpredictable, and if we are ultimately
unable to obtain regulatory approval for our drug candidates, our ability to generate revenue will be materially impaired.
Our drug candidates and the activities associated with their development and commercialization, including their design, testing,
manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale, distribution, import and export,
are subject to comprehensive regulation by the FDA, NMPA and other regulatory agencies in the United States and China and by
comparable authorities in other countries. Securing regulatory approval requires the submission of extensive pre-clinical and clinical
data and supporting information to the various regulatory authorities for each therapeutic indication to establish the drug candidate’s
safety and efficacy. Securing regulatory approval also requires the submission of information about the drug manufacturing process to,
and inspection of manufacturing facilities by, the relevant regulatory authority. Our drug candidates may not be effective, may be only
moderately effective or may prove to have undesirable or unintended side effects, toxicities or other characteristics that may preclude
our obtaining regulatory approval or prevent or limit commercial use.
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The process of obtaining regulatory approvals in the United States, China and other countries is expensive, may take many years if
additional clinical trials are required, if approval is obtained at all, and can vary substantially based upon a variety of factors, including
the type, complexity and novelty of the drug candidates involved. Changes in regulatory approval policies during the development
period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted New Drug
Application, or NDA, pre-market approval or equivalent application types, may cause delays in the approval or rejection of an
application. The FDA, NMPA and comparable authorities in other countries have substantial discretion in the approval process and may
refuse to accept any application or may decide that our data are insufficient for approval and require additional pre-clinical, clinical or
other studies. Our drug candidates could be delayed in receiving, or fail to receive, regulatory approval for many reasons, including the
following:
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the FDA, NMPA or comparable regulatory authorities may disagree with the number, design, size, conduct or implementation
of our clinical trials;
• we may be unable to demonstrate to the satisfaction of the FDA, NMPA or comparable regulatory authorities that a drug
candidate is safe and effective for its proposed indication;
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the results of clinical trials may not meet the level of statistical significance required by the FDA, NMPA or comparable
regulatory authorities for approval;
• we may be unable to demonstrate that a drug candidate’s clinical and other benefits outweigh its safety risks;
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the FDA, NMPA or comparable regulatory authorities may disagree with our interpretation of data from pre-clinical studies or
clinical trials;
the data collected from clinical trials of our drug candidates may not be sufficient to support the submission of an NDA or other
submission or to obtain regulatory approval in the United States or elsewhere;
the FDA, NMPA or comparable regulatory authorities may fail to approve the manufacturing processes for our clinical and
commercial supplies;
the approval policies or regulations of the FDA, NMPA or comparable regulatory authorities may significantly change in a
manner rendering our clinical data insufficient for approval;
the FDA, NMPA or comparable regulatory authority may prioritize treatments for emerging health crises, such as COVID-19,
resulting in delays for our drug candidates;
the FDA, NMPA or comparable regulatory authorities may restrict the use of our products to a narrow population; and
our collaboration partners or CROs that are retained to conduct the clinical trials of our drug candidates may take actions that
materially and adversely impact the clinical trials.
In addition, even if we were to obtain approval, regulatory authorities may approve any of our drug candidates for fewer or more
limited indications than we request, may not approve the price we intend to charge for our drugs, may grant approval contingent on the
performance of costly post-marketing clinical trials, or may approve a drug candidate with a label that does not include the labeling
claims necessary or desirable for the successful commercialization of that drug candidate. Any of the foregoing scenarios could
materially harm the commercial prospects for our drug candidates.
Furthermore, even though the NMPA has granted approval for fruquintinib and surufatinib for use in third-line mCRC patients and
for NET, respectively, we are still subject to substantial, ongoing regulatory requirements. See “—Even if we receive regulatory approval
for our drug candidates, we are subject to ongoing obligations and continued regulatory review, which may result in significant additional
expense.”
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If the FDA, NMPA or another regulatory agency revokes its approval of, or if safety, efficacy, manufacturing or supply issues arise
with, any therapeutic that we use in combination with our drug candidates, we may be unable to market such drug candidate or may
experience significant regulatory delays or supply shortages, and our business could be materially harmed.
We are currently focusing on the clinical development of savolitinib as both a monotherapy and in combination with immunotherapy
(Imfinzi) and targeted therapy (Tagrisso). We are also focusing on the clinical development of our drug candidate fruquintinib as both
a monotherapy and in combination with immunotherapies (Tyvyt and genolimzumab), chemotherapy (Taxol) and an anti-PD-1 antibody
(tislelizumab). In addition, we are currently focusing on the clinical development of surufatinib as a monotherapy and in combination
with immunotherapies (Tuoyi, Tyvyt and tislelizumab). However, we did not develop and we do not manufacture or sell Tagrisso,
Taxol, Imfinzi, Tyvyt, genolimzumab, Tuoyi, tislelizumab or any other therapeutic we use in combination with our drug candidates.
We may also seek to develop our drug candidates in combination with other therapeutics in the future.
If the FDA, NMPA or another regulatory agency revokes its approval, or does not grant approval, of any of these and other
therapeutics we use in combination with our drug candidates, we will not be able to market our drug candidates in combination with
such therapeutics. If safety or efficacy issues arise with these or other therapeutics that we seek to combine with our drug candidates in
the future, we may experience significant regulatory delays, and we may be required to redesign or terminate the applicable clinical
trials. In addition, if manufacturing or other issues result in a supply shortage of these or any other combination therapeutics, we may
not be able to complete clinical development of savolitinib, fruquintinib, surufatinib and/or any other of our drug candidates on our
current timeline or at all.
Even if one or more of our drug candidates were to receive regulatory approval for use in combination with a therapeutic, we would
continue to be subject to the risk that the FDA, NMPA or another regulatory agency could revoke its approval of the combination
therapeutic, or that safety, efficacy, manufacturing or supply issues could arise with one of these combination therapeutics. This could
result in savolitinib, fruquintinib, surufatinib or one of our other products being removed from the market or being less successful
commercially.
We face substantial competition, which may result in others discovering, developing or commercializing drugs before or more
successfully than we do.
The development and commercialization of new drugs is highly competitive. We face competition with respect to our current drug
candidates, and will face competition with respect to any drug candidates that we may seek to develop or commercialize in the future,
from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies worldwide. There are a
number of large pharmaceutical and biotechnology companies that currently market drugs or are pursuing the development of therapies
in the field of kinase inhibition for cancer and other diseases. Some of these competitive drugs and therapies are based on scientific
approaches that are the same as or similar to our approach, and others are based on entirely different approaches. Potential competitors
also include academic institutions, government agencies and other public and private research organizations that conduct research, seek
patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization.
Specifically, there are a large number of companies developing or marketing treatments for cancer and immunological diseases,
including many major pharmaceutical and biotechnology companies.
Many of the companies against which we are competing or against which we may compete in the future have significantly greater
financial resources and expertise in research and development, manufacturing, pre-clinical testing, conducting clinical trials, obtaining
regulatory approvals and marketing approved drugs than we do. Mergers and acquisitions in the pharmaceutical, biotechnology and
diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or
early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and
established companies. These competitors also compete with us in recruiting and retaining qualified scientific and management
personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies
complementary to, or necessary for, our programs.
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Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize drugs that are safer,
more effective, have fewer or less severe side effects, are more convenient or are less expensive than any drugs that we or our
collaborators may develop. Our competitors also may obtain FDA, NMPA or other regulatory approval for their drugs more rapidly than
we may obtain approval for ours, which could result in our competitors establishing a strong market position before we or our
collaborators are able to enter the market. The key competitive factors affecting the success of all of our drug candidates, if approved,
are likely to be their efficacy, safety, convenience, price, the level of generic competition and the availability of reimbursement from
government and other third-party payors.
Clinical development involves a lengthy and expensive process with an uncertain outcome.
There is a risk of failure for each of our drug candidates. It is difficult to predict when or if any of our drug candidates will prove
effective and safe in humans or will receive regulatory approval. Before obtaining regulatory approval from regulatory authorities for
the sale of any drug candidate, we or our collaboration partners must complete pre-clinical studies and then conduct extensive clinical
trials to demonstrate the safety and efficacy of our drug candidates in humans. Clinical testing is expensive, difficult to design and
implement and can take many years to complete. The outcomes of pre-clinical development testing and early clinical trials may not be
predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. Moreover,
pre-clinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their
drug candidates performed satisfactorily in pre-clinical studies and clinical trials have nonetheless failed to obtain regulatory approval
of their drug candidates. Our current or future clinical trials may not be successful.
Commencing each of our clinical trials is subject to finalizing the trial design based on ongoing discussions with the FDA, NMPA
or other regulatory authorities. The FDA, NMPA and other regulatory authorities could change their position on the acceptability of our
trial designs or clinical endpoints, which could require us to complete additional clinical trials or impose approval conditions that we do
not currently expect. Successful completion of our clinical trials is a prerequisite to submitting an NDA or analogous filing to the FDA,
NMPA or other regulatory authorities for each drug candidate and, consequently, the ultimate approval and commercial marketing of
our drug candidates. We do not know whether any of our clinical trials will begin or be completed on schedule, if at all.
We and our collaboration partners may incur additional costs or experience delays in completing our pre-clinical or clinical trials,
or ultimately be unable to complete the development and commercialization of our drug candidates.
We and our collaboration partners, including AstraZeneca, Eli Lilly, BeiGene Ltd., or BeiGene, Inmagene Biopharmaceuticals Co.
Ltd., or Inmagene, Innovent Biologics (Suzhou) Co., Inc., or Innovent, Genor Biopharma Co. Ltd., or Genor, and Shanghai Junshi
Biosciences Co. Ltd., or Junshi, may experience delays in completing our pre-clinical or clinical trials, and numerous unforeseen events
could arise during, or as a result of, future clinical trials, which could delay or prevent us from receiving regulatory approval, including:
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regulators or institutional review boards, or IRBs, or ethics committees or the China Human Genetic Resources Administration
Office may not authorize us or our investigators to commence or conduct a clinical trial at a prospective trial site;
• we may experience delays in reaching, or we may fail to reach, agreement on acceptable terms with prospective trial sites and
prospective CROs, who conduct clinical trials on behalf of us and our collaboration partners, the terms of which can be subject
to extensive negotiation and may vary significantly among different CROs and trial sites;
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clinical trials may produce negative or inconclusive results, and we or our collaboration partners may decide, or regulators may
require us or them, to conduct additional clinical trials or we may decide to abandon drug development programs;
the number of patients required for clinical trials of our drug candidates may be larger than we anticipate, enrollment in these
clinical trials may be slower than we anticipate or participants may drop out of these clinical trials or fail to return for
post-treatment follow-up at a higher rate than we anticipate;
third-party contractors used in our clinical trials may fail to comply with regulatory requirements or meet their contractual
obligations in a timely manner, or at all, or may deviate from the clinical trial protocol or drop out of the trial, which may
require that we or our collaboration partners add new clinical trial sites or investigators;
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• we or our collaboration partners may elect to, or regulators, IRBs or ethics committees may require that we or our investigators,
suspend or terminate clinical research for various reasons, including non-compliance with regulatory requirements or a finding
that the participants are being exposed to unacceptable health risks;
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the cost of clinical trials of our drug candidates may be greater than we anticipate;
the supply or quality of our drug candidates, companion diagnostics, if any, or other materials necessary to conduct clinical
trials of our drug candidates may be insufficient or inadequate; and
our drug candidates may have undesirable side effects or unexpected characteristics, causing us or our investigators, regulators,
IRBs or ethics committees to suspend or terminate the trials, or reports may arise from pre-clinical or clinical testing of other
cancer therapies that raise safety or efficacy concerns about our drug candidates.
We could encounter regulatory delays if a clinical trial is suspended or terminated by us or our collaboration partners, by, as
applicable, the IRBs of the institutions in which such trials are being conducted, by the Data Safety Monitoring Board, which is an
independent group of experts that is formed to monitor clinical trials while ongoing, or by the FDA, NMPA or other regulatory
authorities. Such authorities may impose a suspension or termination due to a number of factors, including: a failure to conduct the
clinical trial in accordance with regulatory requirements or the applicable clinical protocols, inspection of the clinical trial operations or
trial site by the FDA, NMPA or other regulatory authorities that results in the imposition of a clinical hold, unforeseen safety issues or
adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative actions
or lack of adequate funding to continue the clinical trial. Many of the factors that cause a delay in the commencement or completion of
clinical trials may also ultimately lead to the denial of regulatory approval of our drug candidates. Further, the FDA, NMPA or other
regulatory authorities may disagree with our clinical trial design and our interpretation of data from clinical trials, or may change the
requirements for approval even after it has reviewed and commented on the design for our clinical trials.
If we or our collaboration partners are required to conduct additional clinical trials or other testing of our drug candidates beyond
those that are currently contemplated, if we or our collaboration partners are unable to successfully complete clinical trials of our drug
candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety
concerns, we may:
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be delayed in obtaining regulatory approval for our drug candidates;
not obtain regulatory approval at all;
obtain approval for indications or patient populations that are not as broad as intended or desired;
be subject to post-marketing testing requirements; or
have the drug removed from the market after obtaining regulatory approval.
Our drug development costs will also increase if we experience delays in testing or regulatory approvals. We do not know whether
any of our clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Significant
pre-clinical study or clinical trial delays also could allow our competitors to bring products to market before we do and impair our ability
to successfully commercialize our drug candidates and may harm our business and results of operations. Any delays in our clinical
development programs may harm our business, financial condition and prospects significantly.
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If we or our collaboration partners experience delays or difficulties in the enrollment of patients in clinical trials, the progress of
such clinical trials and our receipt of necessary regulatory approvals could be delayed or prevented.
We or our collaboration partners may not be able to initiate or continue clinical trials for our drug candidates if we or our
collaboration partners are unable to locate and enroll a sufficient number of eligible patients to participate in these trials as required by
the FDA, NMPA or similar regulatory authorities. In particular, we and our collaboration partners have designed many of our clinical
trials, and expect to design future trials, to include some patients with the applicable genomic alteration that causes the disease with a
view to assessing possible early evidence of potential therapeutic effect. Genomically defined diseases, however, may have relatively
low prevalence, and it may be difficult to identify patients with the applicable genomic alteration. In addition, for many of our trials, we
focus on enrolling patients who have failed their first or second-line treatments, which limits the total size of the patient population
available for such trials. The inability to enroll a sufficient number of patients with the applicable genomic alteration or that meet other
applicable criteria for our clinical trials would result in significant delays and could require us or our collaboration partners to abandon
one or more clinical trials altogether.
In addition, some of our competitors have ongoing clinical trials for drug candidates that treat the same indications as our drug
candidates, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’
drug candidates.
Patient enrollment may be affected by other factors including:
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the severity of the disease under investigation;
the total size and nature of the relevant patient population;
the design and eligibility criteria for the clinical trial in question;
the availability of an appropriate genomic screening test/companion diagnostic;
the perceived risks and benefits of the drug candidate under study;
the efforts to facilitate timely enrollment in clinical trials;
the patient referral practices of physicians;
the availability of competing therapies which are undergoing clinical trials;
the ability to monitor patients adequately during and after treatment; and
the proximity and availability of clinical trial sites for prospective patients.
Enrollment delays in our clinical trials may result in increased development costs for our drug candidates, which could cause the
value of our company to decline and limit our ability to obtain financing.
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Our drug candidates may cause undesirable side effects that could delay or prevent their regulatory approval, limit the commercial
profile of an approved label, or result in significant negative consequences following regulatory approval, if any.
Undesirable side effects caused by our drug candidates could cause us or our collaboration partners to interrupt, delay or halt clinical
trials or could cause regulatory authorities to interrupt, delay or halt our clinical trials and could result in a more restrictive label or the
delay or denial of regulatory approval by the FDA, NMPA or other regulatory authorities. In particular, as is the case with all oncology
drugs, it is likely that there may be side effects, for example, hand-foot syndrome, associated with the use of certain of our drug
candidates. Results of our trials could reveal a high and unacceptable severity and prevalence of these or other side effects. In such an
event, our trials could be suspended or terminated and the FDA, NMPA or comparable regulatory authorities could order us to cease
further development of or deny approval of our drug candidates for some or all targeted indications. The drug-related side effects could
affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims. Any of
these occurrences may harm our business, financial condition and prospects significantly.
Further, our drug candidates could cause undesirable side effects related to off-target toxicity. Many of the currently approved
tyrosine kinase inhibitors have been associated with off-target toxicities because they affect multiple kinases. While we believe that the
kinase selectivity of our drug candidates has the potential to significantly improve the unfavorable adverse off-target toxicity issues, if
patients were to experience off-target toxicity, we may not be able to achieve an effective dosage level, receive approval to market, or
achieve the commercial success we anticipate with respect to any of our drug candidates, which could prevent us from ever generating
revenue or achieving profitability. Many compounds that initially showed promise in early-stage testing for treating cancer have later
been found to cause side effects that prevented further development of the compound.
Clinical trials assess a sample of the potential patient population. With a limited number of patients and duration of exposure, rare
and severe side effects of our drug candidates may only be uncovered with a significantly larger number of patients exposed to the drug
candidate. If our drug candidates receive regulatory approval and we or others identify undesirable side effects caused by such drug
candidates (or any other similar drugs) after such approval, a number of potentially significant negative consequences could result,
including:
•
•
regulatory authorities may withdraw or limit their approval of such drug candidates;
regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contra-indication;
• we may be required to create a medication guide outlining the risks of such side effects for distribution to patients;
• we may be required to change the way such drug candidates are distributed or administered, conduct additional clinical trials
or change the labeling of the drug candidates;
•
regulatory authorities may require a Risk Evaluation and Mitigation Strategy, or REMS, plan to mitigate risks, which could
include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution
methods, patient registries and other risk minimization tools;
• we may be subject to regulatory investigations and government enforcement actions;
• we may decide to remove such drug candidates from the marketplace;
• we could be sued and held liable for injury caused to individuals exposed to or taking our drug candidates; and
•
our reputation may suffer.
Any of these events could prevent us from achieving or maintaining market acceptance of the affected drug candidates and could
substantially increase the costs of commercializing our drug candidates, if approved, and significantly impact our ability to successfully
commercialize our drug candidates and generate revenue.
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We and our collaboration partners have conducted and intend to conduct additional clinical trials for certain of our drug candidates
at sites outside the United States, and the FDA may not accept data from trials conducted in such locations or may require additional
U.S.-based trials.
We and our collaboration partners have conducted, currently are conducting and intend in the future to conduct, clinical trials
outside the United States, particularly in China where our Oncology/Immunology operations are headquartered as well as in other
jurisdictions such as Australia, Japan, South Korea, the U.K, and various European countries.
Although the FDA may accept data from clinical trials conducted outside the United States, acceptance of these data is subject to
certain conditions imposed by the FDA. For example, the clinical trial must be well designed and conducted by qualified investigators
in accordance with current good clinical practices, or GCPs, including review and approval by an independent ethics committee and
receipt of informed consent from trial patients. The trial population must also adequately represent the U.S. population, and the data
must be applicable to the U.S. population and U.S. medical practice in ways that the FDA deems clinically meaningful. Generally, the
patient population for any clinical trial conducted outside of the United States must be representative of the population for which we
intend to seek approval in the United States. In addition, while these clinical trials are subject to applicable local laws, FDA acceptance
of the data will be dependent upon its determination that the trials also comply with all applicable U.S. laws and regulations. There can
be no assurance that the FDA will accept data from trials conducted outside of the United States. If the FDA does not accept the data
from our clinical trials conducted outside the United States, it would likely result in the need for additional clinical trials, which would
be costly and time-consuming and delay or permanently halt our ability to develop and market these or other drug candidates in the
United States.
In addition, there are risks inherent in conducting clinical trials in jurisdictions outside the United States including:
•
regulatory and administrative requirements of the jurisdiction where the trial is conducted that could burden or limit our ability
to conduct our clinical trials;
•
foreign exchange fluctuations;
• manufacturing, customs, shipment and storage requirements;
•
•
cultural differences in medical practice and clinical research; and
the risk that patient populations in such trials are not considered representative as compared to patient populations in the United
States and other markets.
If we are unable to obtain and/or maintain priority review by the NMPA, fast track designation by the FDA, or another expedited
registration pathway for our drug candidates, the time and cost we incur to obtain regulatory approvals may increase. Even if we
receive such approvals, they may not lead to a faster development, review or approval process.
Under the Opinions on Priority Review and Approval for Encouraging Drug Innovation, the NMPA may grant priority review
approval to (i) certain drugs with distinctive clinical value, including innovative drugs not sold within or outside China, (ii) new drugs
with clinical treatment advantages for AIDS and other rare diseases, and (iii) drugs which have been concurrently filed with the
competent drug approval authorities in the United States or E.U. for marketing authorization and passed such authorities’ onsite
inspections and are manufactured using the same production line in China. Priority review provides a fast track process for drug
registration. We have received priority review status for three of our drug candidates—fruquintinib for the treatment of advanced
colorectal cancer, or CRC, savolitinib for the treatment of non-small cell lung cancer, or NSCLC and surufatinib for the treatment of
advanced NET. We anticipate that we may seek priority review for certain of our other drug candidates in the future.
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In the United States, if a drug is intended for the treatment of a serious or life-threatening condition and the drug demonstrates the
potential to address unmet medical needs for this condition, we may apply for fast track designation by the FDA. The FDA has broad
discretion whether or not to grant this designation, so even if we believe a particular drug candidate is eligible for this designation, we
cannot be sure that the FDA would decide to grant it. We have sought and will likely continue to seek fast track designation for some
of our drug candidates. For example, in April 2020, the FDA granted fast track designation to surufatinib for both the non-pancreatic
and pancreatic neuroendocrine tumor development programs. Even if we receive fast track designation for a drug candidate, we may
not experience a faster development process, review or approval compared to conventional FDA procedures. The FDA may withdraw
fast track designation if it believes that the designation is no longer supported by data from our clinical development program.
A failure to obtain and/or maintain priority review, fast track designation or any other form of expedited development, review or
approval for our drug candidates would result in a longer time period to commercialization of such drug candidate, could increase the
cost of development of such drug candidate and could harm our competitive position in the marketplace. In addition, even if we obtain
priority review, there is no guarantee that we will experience a faster review or approval compared to non-accelerated registration
pathways or that a drug candidate will ultimately be approved for sale.
Although we have obtained orphan drug designation for surufatinib for the treatment of pancreatic neuroendocrine tumors in the
United States, we may not be able to obtain or maintain the benefits associated with orphan drug status, including market exclusivity.
Under the Orphan Drug Act, the FDA may designate a drug as an orphan drug if it is intended to treat a rare disease or condition,
which is generally defined as affecting fewer than 200,000 individuals in the United States. We have obtained orphan drug designation
from the FDA for surufatinib for the treatment of pancreatic neuroendocrine tumors. Generally, if a drug with an orphan drug designation
subsequently receives the first marketing approval for the indication for which it has such designation, the drug may be entitled to a
seven-year period of marketing exclusivity, which precludes the FDA from approving another marketing application for the same
molecule for the same indication for that time period. We can provide no assurance that another drug will not receive marketing approval
prior to our product candidates. Orphan drug exclusivity may be lost if the FDA determines that the request for designation was
materially defective or if the manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare
disease or condition. In addition, even after a drug is granted orphan exclusivity and approved, the FDA can subsequently approve
another drug for the same condition before the expiration of the seven-year exclusivity period if the FDA concludes that the later drug
is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.
Even if we receive regulatory approval for our drug candidates, we are subject to ongoing obligations and continued regulatory
review, which may result in significant additional expense.
If the FDA, NMPA or a comparable regulatory authority approves any of our drug candidates, we will continue to be subject to
extensive and ongoing regulatory requirements. For example, even though the NMPA has granted approval of fruquintinib, the
manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping
for fruquintinib continue to be subject to the NMPA’s oversight. These requirements include submissions of safety and other
post-marketing information and reports, registration, as well as continued compliance with current good manufacturing processes.
Any regulatory approvals that we receive for our drug candidates may also be subject to limitations on the approved indicated uses
for which the drug may be marketed or to the conditions of approval, or contain requirements for potentially costly post-marketing
testing, including Phase IV clinical trials, and surveillance to monitor the safety and efficacy of the drug. In addition, regulatory policies
may change or additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our drug
candidates. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if
we are not able to maintain regulatory compliance, we may lose any regulatory approval that we may have obtained, which would
adversely affect our business, prospects and ability to achieve or sustain profitability.
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We may be subject to penalties if we fail to comply with regulatory requirements or experience unanticipated problems with any of
our drugs that receive regulatory approval.
Once a drug is approved by the FDA, NMPA or a comparable regulatory authority for marketing, it is possible that there could be
a subsequent discovery of previously unknown problems with the drug, including problems with third-party manufacturers or
manufacturing processes, or failure to comply with regulatory requirements. If any of the foregoing occurs with respect to our drug
products, it may result in, among other things:
•
•
•
•
•
restrictions on the marketing or manufacturing of the drug, withdrawal of the drug from the market, or drug recalls;
fines, warning letters or holds on clinical trials;
refusal by the FDA, NMPA or comparable regulatory authority to approve pending applications or supplements to approved
applications filed by us, or suspension or revocation of drug license approvals;
drug seizure or detention, or refusal to permit the import or export of drugs; and
injunctions or the imposition of civil or criminal penalties.
Any government investigation of alleged violations of law could require us to expend significant time and resources and could
generate negative publicity. If we or our collaborators are not able to maintain regulatory compliance, regulatory approval that has been
obtained may be lost and we may not achieve or sustain profitability, which would adversely affect our business, prospects, financial
condition and results of operations.
The incidence and prevalence for target patient populations of our drug candidates are based on estimates and third-party sources.
If the market opportunities for our drug candidates are smaller than we estimate or if any approval that we obtain is based on a
narrower definition of the patient population, our revenue and ability to achieve profitability will be adversely affected, possibly
materially.
Periodically, we make estimates regarding the incidence and prevalence of target patient populations for particular diseases based
on various third-party sources and internally generated analysis and use such estimates in making decisions regarding our drug
development strategy, including determining indications on which to focus in pre-clinical or clinical trials.
These estimates may be inaccurate or based on imprecise data. For example, the total addressable market opportunity will depend
on, among other things, their acceptance by the medical community and patient access, drug pricing and reimbursement. The number
of patients in the addressable markets may turn out to be lower than expected, patients may not be otherwise amenable to treatment with
our drugs, or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results
of operations and our business.
Our future success depends on our ability to retain key executives and to attract, retain and motivate qualified personnel.
We are highly dependent on the expertise of the members of our research and development team, as well as the other principal
members of our management, including Christian Hogg, our Chief Executive Officer and director, and Weiguo Su, Ph.D., our Chief
Scientific Officer and director. Although we have entered into employment agreements with our executive officers, each of them may
terminate their employment with us at any time with three months’ prior written notice. We do not maintain “key person” insurance for
any of our executives or other employees.
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Recruiting and retaining qualified management, scientific, clinical, manufacturing and sales and marketing personnel will also be
critical to our success. The loss of the services of our executive officers or other key employees could impede the achievement of our
research, development and commercialization objectives and seriously harm our ability to successfully implement our business strategy.
Furthermore, replacing executive officers and key employees may be difficult and may take an extended period of time because of the
limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain regulatory
approval of and commercialize drugs. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain
or motivate these key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology
companies for similar personnel. We also experience competition for the hiring of scientific and clinical personnel from universities and
research institutions. Failure to succeed in clinical trials may make it more challenging to recruit and retain qualified scientific personnel.
We have expanded our footprint and operations in the United States, and we intend to expand our international operations further
in the future, but we may not achieve the results that we expect.
In early 2018, we opened our first office in the United States. While we have been involved in clinical and non-clinical development
in North America and Europe for over a decade, the activities conducted by our new U.S. office will significantly broaden and scale our
non-Asian clinical development and international operations. We have significantly expanded, and intend to continue to expand, our
U.S. clinical team to support our increasing clinical activities in the United States, Europe, Japan and Australia. In preparation for a
potential launch of surufatinib in the U.S., we have established a U.S. commercial organization with the recruitment of a senior
leadership team based in New Jersey. Conducting our business in multiple countries subjects us to a variety of risks and complexities
that may materially and adversely affect our business, results of operations, financial condition and growth prospects, including, among
other things:
•
•
•
•
•
•
•
the increased complexity and costs inherent in managing international operations;
diverse regulatory, financial and legal requirements, and any future changes to such requirements, in one or more countries
where we are located or do business;
country-specific tax, labor and employment laws and regulations;
applicable trade laws, tariffs, export quotas, custom duties or other trade restrictions and any changes to them;
challenges inherent in efficiently managing employees in diverse geographies, including the need to adapt systems, policies,
benefits and compliance programs to differing labor and other regulations;
changes in currency rates; and
regulations relating to data security and the unauthorized use of, or access to, commercial and personal information.
As a result of our growth, our business and corporate structure has become more complex. There can be no assurance that we will
effectively manage the increased complexity without experiencing operating inefficiencies or control deficiencies. Significant
management time and effort is required to effectively manage the increased complexity of our company, and our failure to successfully
do so could have a material adverse effect on our business, financial condition, results of operations and growth prospects.
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We may be restricted from transferring our scientific data abroad.
On March 17, 2018, the General Office of the State Council promulgated the Measures for the Management of Scientific Data, or
the Scientific Data Measures, which provides a broad definition of scientific data and relevant rules for the management of scientific
data. According to the Scientific Data Measures, enterprises in China must seek governmental approval before any scientific data
involving a state secret may be transferred abroad or to foreign parties. Further, any researcher conducting research funded at least in
part by the Chinese government is required to submit relevant scientific data for management by the entity to which such researcher is
affiliated before such data may be published in any foreign academic journal. Given that the term state secret is not clearly defined in
the Scientific Data Measures, if and to the extent our research and development of drug candidates will be subject to the Scientific Data
Measures and any subsequent laws as required by the relevant government authorities, we cannot assure you that we can always obtain
relevant approvals for sending scientific data (such as the results of our pre-clinical studies or clinical trials conducted within China)
abroad or to our foreign partners in China. If we are unable to obtain necessary approvals in a timely manner, or at all, our research and
development of drug candidates may be hindered, which may materially and adversely affect our business, results of operations, financial
conditions and prospects. If the relevant government authorities consider the transmission of our scientific data to be in violation of the
requirements under the Scientific Data Measures, we may be subject to fines and other administrative penalties imposed by those
government authorities.
If we participate in compassionate-use programs, discrepancies among the regulations in different countries may lead to increased
risk of adverse drug reactions and serious adverse events arising from the use of our drug candidates.
Compassionate-use programs are regulatory programs that facilitate access to investigational drugs for the treatment of patients
with serious or immediately life-threatening diseases or conditions that lack therapeutic alternatives. Currently, there is no unified
approach or standard practice to regulate compassionate-use programs or access to investigational drugs across countries. In China,
currently there is no officially approved regulation to oversee compassionate-use programs. In the United States, compassionate-use
programs are limited to patients who have a life-threatening disease or serious disease or condition, who may gain access to an
investigational medical product for treatment outside of clinical trials when no comparable or satisfactory alternative therapy options
are available. Additionally, the U.S. Right to Try Act provides a separate pathway for patients with a life-threatening disease or condition
who have exhausted all other treatment options and who are unable to participate in clinical trials to access investigational drugs that
have passed Phase I clinical trials under a more expedited process.
The regulatory discrepancy for compassionate-use programs among countries may lead to uneven patient entry criteria and protocols
for compassionate use programs. This may create increased risk of serious adverse events because of enrolled patients’ advanced disease
or comorbidities. In addition, because the products in compassionate-use programs are investigational drugs, many of which are still in
experimental stages and have not received marketing approval, patients in compassionate-use program may exhibit adverse drug
reactions from using these products. If we participate in compassionate-use programs, we may be subject to the risk of enrolled patients
exhibiting adverse drug reactions or serious adverse events being produced from the use of our future drug products. Such occurrences
can potentially lead to clinical holds of our ongoing clinical trials or complicate the determination of the safety profile of a drug candidate
under regulatory review for commercial marketing, or expose us to tort liability. Changes in government regulations or in practices
relating to the pharmaceutical and biopharmaceutical industries, including healthcare reform in China, and compliance with new
regulations may result in additional costs.
Risks Relating to Sales of Our Internally Developed Drugs and Other Drugs
Pharmaceutical companies in China are required to comply with extensive regulations and hold a number of permits and licenses
to carry on their business. Our and our joint ventures’ ability to obtain and maintain these regulatory approvals is uncertain, and
future government regulation may impose additional burdens on our operations.
The pharmaceutical industry in China is subject to extensive government regulation and supervision. The regulatory framework
addresses all aspects of operating in the pharmaceutical industry, including approval, production, distribution, advertising, licensing and
certification requirements and procedures, periodic renewal and reassessment processes, registration of new drugs and environmental
protection. Violation of applicable laws and regulations may materially and adversely affect our business. In order to manufacture and
distribute pharmaceutical products in China, we and our joint ventures are required to:
•
obtain a pharmaceutical manufacturing permit for each production facility from the relevant food and drug administrative
authority;
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•
•
•
obtain a drug registration certificate, which includes a drug approval number, from the NMPA for each drug manufactured by
us;
obtain a pharmaceutical distribution permit from the NMPA; and
renew the pharmaceutical manufacturing permits, the pharmaceutical distribution permits, drug registration certificates, among
other requirements.
If we or our joint ventures are unable to obtain or renew such permits or any other permits or licenses required for our or their
operations, we will not be able to engage in the manufacture and distribution of our products and our business may be adversely affected.
The regulatory framework regarding the pharmaceutical industry in China is subject to change and amendment from time to time.
Any such change or amendment could materially and adversely impact our business, financial condition and results of operations. The
PRC government has introduced various reforms to the Chinese healthcare system in recent years and may continue to do so, with an
overall objective to expand basic medical insurance coverage and improve the quality and reliability of healthcare services. The specific
regulatory changes under the reform still remain uncertain. The implementing measures to be issued may not be sufficiently effective
to achieve the stated goals and, as a result, we may not be able to benefit from such reform to the level we expect, if at all. Moreover,
the reform could give rise to regulatory developments, such as more burdensome administrative procedures, which may have an adverse
effect on our business and prospects.
For further information regarding government regulation in China and other jurisdictions, see Item 4.B. “Business Overview—
Regulation—Government Regulation of Pharmaceutical Product Development and Approval,” “Business Overview—Regulation—
Coverage and Reimbursement” and “Business Overview—Regulation—Other Healthcare Laws.”
As a significant portion of the operations of our Other Ventures is conducted through joint ventures, we are largely dependent on
the success of our joint ventures and our receipt of dividends or other payments from our joint ventures for cash to fund our
operations.
We are party to joint venture agreements with Shanghai Pharmaceuticals and Guangzhou Baiyunshan, relating to our non-
consolidated joint ventures, which together form part of the operations of our Other Ventures. Our equity in the earnings of these non-
consolidated joint ventures, net of tax, was $38.3 million, $40.6 million and $79.1 million for the years ended December 31, 2018, 2019
and 2020, respectively, as recorded in our consolidated financial statements. As such, our results of operations and financial performance
have been, and will continue to be, affected by the financial performance of these joint ventures as well as any other equity investees
we have or may have in the future. Furthermore, we have consolidated joint ventures with each of Sinopharm and Hain Celestial which
accounted for substantially all of our Other Ventures’ consolidated revenue for the years ended December 31, 2018, 2019 and 2020.
As a result, our ability to fund our operations and pay our expenses or to make future dividend payments, if any, is largely dependent
on the earnings of our joint ventures and the payment of those earnings to us in the form of dividends. Payments to us by our joint
ventures will be contingent upon our joint ventures’ earnings and other business considerations and may be subject to statutory or
contractual restrictions. Each joint venture’s ability to distribute dividends to us is subject to approval by their respective boards of
directors, which in the case of Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan are comprised of an equal number of
representatives from each party.
Operationally, our joint venture partners have certain responsibilities and/or certain rights to exercise control or influence over
operations and decision-making under the joint venture arrangements. Therefore, the success of our joint ventures depends on the efforts
and abilities of our joint venture parties to varying degrees. For example, we share the ability to appoint the general manager of our joint
venture with Guangzhou Baiyunshan, with each of us having a rotating four-year right, and therefore, our ability to manage the day-to-
day operations of this joint venture is more limited. On the other hand, we appoint the general managers of Hutchison Sinopharm and
Shanghai Hutchison Pharmaceuticals pursuant to the respective joint venture agreements governing these entities and therefore oversee
the day-to-day management of these joint ventures. However, we still rely on our joint venture partners Sinopharm and Shanghai
Pharmaceuticals to provide certain distribution and logistics services. See “—Risks Relating to Our Dependence on Third Parties—Joint
ventures form an important part of our Other Ventures, and our ability to manage and develop the businesses conducted by these joint
ventures depends in part on our relationship with our joint venture partners” for more information.
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We intend to leverage the know-how and infrastructure of our Other Ventures’ prescription drug business to commercialize our
internally developed drug candidates, but we may not be successful in building a commercial sales team to successfully manufacture,
sell and market our approved drugs, and we may not be able to generate any revenue from such products.
Our Other Ventures include a prescription drugs business that manufactures, markets, distributes and sells proprietary and third
party drugs, as well as a consumer health business involved in over-the-counter pharmaceutical products. Our prescription drugs business
is primarily operated by our Shanghai Hutchison Pharmaceuticals and Hutchison Sinopharm joint ventures. We intend to leverage our
experience operating our prescription drugs business to commercialize certain of our approved, internally developed drug candidates in
China. However, to do so, we must adapt our know-how to build a specific oncology and/or immunology focused sales and marketing
team. As of December 31, 2020, we have a oncology commercial team with about 390 staff in China to support the commercialization
of fruquintinib, surufatinib and our other drug candidates, if approved. There are risks involved with leveraging the experience from our
current business to establish an in-house oncology commercial team. For example, recruiting and/or training a sales force to detail our
approved drug candidates is time consuming and could delay any drug launch. Factors that may inhibit our efforts to commercialize our
drug candidates include:
•
•
•
•
our inability to recruit and retain adequate numbers of effective sales and marketing personnel;
our inability to effectively manage the expansion of our operations and train additional qualified personnel in the relevant areas
of oncology and/or immunology;
the inability of our sales personnel to obtain access to physicians or educate adequate numbers of physicians who then prescribe
any future drugs; and
the lack of complementary drugs to be offered by our sales personnel, which may put us at a competitive disadvantage relative
to companies with more extensive product lines.
In such case, our business, results of operations, financial condition and prospects will be materially and adversely affected.
We face substantial competition in selling our approved, internally developed drugs and the drugs of our Other Ventures.
The marketed drugs developed and sold by our Oncology/Immunology operations and the prescription drugs business which is part
of our Other Ventures’ operations face substantial competition in the pharmaceutical industry in China, which is characterized by a
number of established, large pharmaceutical companies, as well as smaller emerging pharmaceutical companies, engaged in the
development, production, marketing or sales of prescription drugs, in particular cardiovascular drugs. The identities of the key
competitors with respect to drugs sold by our Oncology/Immunology and Other Ventures operations vary by product and, in certain
cases, competitors have greater financial resources than us and may elect to focus these resources on developing, importing or in-
licensing and marketing products in the PRC that are substitutes for our products and may have broader sales and marketing
infrastructure with which to do so.
Such drugs may compete against products that have lower prices, superior performance, greater ease of administration or other
advantages compared to our products. In some circumstances, price competition may drive our competitors to conduct illegal
manufacturing processes to lower their manufacturing costs. Increased competition may result in price reductions, reduced margins and
loss of market share, whether achieved by either legal or illegal means, any of which could materially and adversely affect our profit
margins. We and our joint ventures may not be able to compete effectively against current and future competitors.
26
If we are not able to maintain and enhance brand recognition of our drugs to maintain a competitive advantage, our reputation,
business and operating results may be harmed.
We believe that market awareness of our products sold through our Oncology/Immunology and Other Ventures operations, which
include our joint ventures’ branded products, such as Baiyunshan and Shang Yao, and the brands of third-party products which are
distributed through our joint ventures, has contributed significantly to our success. We also believe that maintaining and enhancing
such brands is critical to maintaining our competitive advantage. Although the sales and marketing staff of such businesses will continue
to further promote such brands to remain competitive, they may not be successful. If we or our joint ventures are unable to further
enhance brand recognition and increase awareness of such products, or are compelled to incur excessive marketing and promotion
expenses in order to maintain brand awareness, our business and results of operations may be materially and adversely affected.
Furthermore, our results of operations could be adversely affected if the Baiyunshan and Shang Yao brands, or the brands of any other
products, or our reputation, are impaired by certain actions taken by our joint venture partners, distributors, competitors or relevant
regulatory authorities.
Reimbursement may not be available for the products currently sold through our Oncology/Immunology and Other Ventures
operations or our drug candidates in China, the United States or other countries, which could diminish our sales or affect our
profitability.
The regulations that govern pricing and reimbursement for pharmaceuticals vary widely from country to country. Some countries
require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins after regulatory
approval is granted. In some foreign markets, pharmaceutical pricing remains subject to continuing governmental control even after
initial approval is granted. Furthermore, once marketed and sold, government authorities and third-party payors, such as private health
insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. Adverse
pricing reimbursement levels may hinder market acceptance of our drug candidates or other products sold by us.
In China, for example, the Ministry of Human Resources and Social Security of the PRC or provincial or local human resources
and social security authorities, together with other government authorities, review the inclusion or removal of drugs from the Medicines
Catalogue for the National Basic Medical Insurance, Labor Injury Insurance and Childbirth System in China, or the National
Reimbursement Drug List, or NRDL, or provincial or local medical insurance catalogues for the National Medical Insurance Program,
and the category under which a drug will be classified, both of which affect the amounts reimbursable to program participants for their
purchases of those medicines. These determinations are made based on a number of factors, including price and efficacy. Depending on
the category under which a drug is classified in the provincial medicine catalogue, a National Medical Insurance Program participant
residing in that province can be reimbursed for the full cost of Category A medicine and for the majority of the cost of a Category B
medicine. In some instances, if the price range designated by the local or provincial government decreases, it may adversely affect our
business and could reduce our total revenue, and if our revenue falls below production costs, we may stop manufacturing certain
products. In November 2019, fruquintinib was added to China’s NRDL as a Category B medicine.
In addition, in order to access certain local or provincial-level markets, our joint ventures are periodically required to enter into
competitive bidding processes for She Xiang Bao Xin pills (the best-selling product of our Shanghai Hutchison Pharmaceuticals joint
venture), Fu Fang Dan Shen tablets (one of the best-selling products of our Hutchison Baiyunshan joint venture) and other products with
a pre-defined price range. The competitive bidding in effect sets price ceilings for those products, thereby limiting our profitability.
In the United States, there have been and continue to be a number of legislative initiatives to contain healthcare costs which may
affect reimbursement rates of our drug candidates if approved. For example, in March 2010, the Patient Protection and Affordable Care
Act, as amended by the Health Care and Education Reconciliation Act, or the Affordable Care Act, was passed, which substantially
changes the way health care is financed by both governmental and private insurers. The Affordable Care Act, among other things,
establishes a new Medicare Part D coverage gap discount program, in which, effective 2019, manufacturers must agree to offer 70%
point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period as a
condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D. In addition, other legislative changes have been
proposed and adopted in the United States since the Affordable Care Act was enacted.
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Modifications to or repeal of all or certain provisions of the Affordable Care Act had been expected based on statements made by
former President Trump and certain members of Congress. However, President Biden has indicated that his healthcare policy will build
on the Affordable Care Act. We cannot predict the ultimate content, timing or effect of any changes to the Affordable Care Act or other
federal and state reform efforts. There is no assurance that federal or state health care reform will not adversely affect our future business
and financial results. We expect that additional U.S. state and federal healthcare reform measures will be adopted in the future, any of
which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in
reduced demand for our drug candidates or additional pricing pressures. We expect that the pharmaceutical industry will experience
pricing pressures due to the increasing influence of managed care (and related implementation of managed care strategies to control
utilization), additional federal and state legislative and regulatory proposals to regulate pricing of drugs, limit coverage of drugs or
reduce reimbursement for drugs, public scrutiny and recent regulatory initiatives to control the price of pharmaceuticals through
government negotiations of drug prices in Medicare Part D and importation of cheaper products from abroad.
Moreover, eligibility for reimbursement in the United States does not imply that any drug will be paid for in all cases or at a rate
that covers our costs, including research, development, manufacture, sale and distribution. Interim U.S. reimbursement levels for new
drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary
according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower
cost drugs and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory
discounts or rebates required by U.S. government healthcare programs or private payors and by any future relaxation of laws that
presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States. Third-party payors
in the United States often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our
inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for any approved
drugs that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize
drugs and our overall financial condition.
Sales of our generic prescription drugs rely on the ability to win tender bids for the medicine purchases of hospitals in China.
Our prescription drugs business markets to hospitals in China who may make bulk purchases of a medicine only if that medicine is
selected under a government-administered tender process that was initiated in 2018 and aimed at driving consolidation in the fragmented
generic prescription drug market in China. Pursuant to this process, major cities bulk-buy certain generic drugs together, forcing
companies to bid for contracts and driving down prices. The process was expanded nationwide to cover more cities and drugs in 2019
and 2020. This process, which only applies to generic prescription drugs, may reduce our Other Ventures’ product portfolio as some of
our third-party generic drug partners may fail to win bids.
Periodically, a bidding process is organized on a provincial or municipal basis. Whether a drug manufacturer is invited to participate
in the tender depends on the level of interest that hospitals have in purchasing this drug. The interest of a hospital in a medicine is
evidenced by:
•
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the inclusion of this medicine on the hospital’s formulary, which establishes the scope of drug physicians at this hospital may
prescribe to their patients, and
the willingness of physicians at this hospital to prescribe a particular drug to their patients.
We believe that effective marketing efforts are critical in making and keeping hospitals interested in purchasing the prescription
drugs sold through our Other Ventures so that we and our joint ventures are invited to submit the products to the tender. Even if we and
our joint ventures are invited to do so, competitors may be able to substantially reduce the price of their products or services. If
competitors are able to offer lower prices, our and our joint ventures’ ability to win tender bids during the hospital tender process will
be materially affected, and could reduce our total revenue or decrease our profit.
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Counterfeit products in China could negatively impact our revenue, brand reputation, business and results of operations.
Our products are subject to competition from counterfeit products, especially counterfeit pharmaceuticals which are manufactured
without proper licenses or approvals and are fraudulently mislabeled with respect to their content and/or manufacturer. Counterfeiters
may illegally manufacture and market products under our or our joint venture’s brand names, the brand names of the third-party products
we or they sell, or those of our or their competitors. Counterfeit pharmaceuticals are generally sold at lower prices than the authentic
products due to their low production costs, and in some cases are very similar in appearance to the authentic products. Counterfeit
pharmaceuticals may or may not have the same chemical content as their authentic counterparts. If counterfeit pharmaceuticals illegally
sold under our or our joint ventures’ brand names or the brand names of third-party products we or they sell result in adverse side effects
to consumers, we or our joint ventures may be associated with any negative publicity resulting from such incidents. In addition,
consumers may buy counterfeit pharmaceuticals that are in direct competition with products sold through our Oncology/Immunology
and Other Ventures operations, which could have an adverse impact on our revenue, business and results of operations. The proliferation
of counterfeit pharmaceuticals in China and globally may grow in the future. Any such increase in the sales and production of counterfeit
pharmaceuticals in China, or the technological capabilities of the counterfeiters, could negatively impact our revenue, brand reputation,
business and results of operations.
Rapid changes in the pharmaceutical industry may render our Other Ventures’ products or our internally developed drugs and drug
candidates obsolete.
Future technological improvements by our competitors and continual product developments in the pharmaceutical market may
render our and our joint ventures’ existing products, our or their third-party licensed products or our drug candidates obsolete or affect
our viability and competitiveness. Therefore, our future success will largely depend on our and our joint ventures’ ability to:
•
•
•
•
•
improve existing products;
develop innovative drug candidates;
diversify the product and drug candidate portfolio;
license diverse third-party products; and
develop new and competitively priced products which meet the requirements of the constantly changing market.
If we or our joint ventures fail to respond to this environment by improving our existing products, licensing new third-party products
or developing new drug candidates in a timely fashion, or if such new or improved products do not achieve adequate market acceptance,
our business and profitability may be materially and adversely affected.
Certain of our joint ventures’ principal products involve the cultivation or sourcing of key raw materials including botanical
products, and any quality control or supply failure or price fluctuations could adversely affect our ability to manufacture our products
and/or could materially and adversely affect our operating results.
The key raw materials used in the manufacturing process of certain of our joint ventures’ principal products are medicinal herbs
whose properties are related to the regions and climatic conditions in which they are grown. Access to quality raw materials and products
necessary for the manufacture of our products is not guaranteed. We rely on a combination of materials grown by our or our joint
ventures’ entities and materials sourced from third-party growers and suppliers. The availability, quality and prices of these raw materials
are dependent on and closely affected by weather conditions and other seasonal factors which have an impact on the yields of the harvests
each year. The quality, in some instances, also depends on the operations of third-party growers or suppliers. There is a risk that such
growers or suppliers sell or attempt to sell us or our joint ventures raw materials which are not authentic. If there is any supply
interruption for an indeterminate period of time, our joint ventures may not be able to identify and obtain alternative supplies that comply
with our quality standards in a timely manner. Any supply disruption could adversely affect our ability to satisfy demand for our
products, and materially and adversely affect our product sales and operating results. Moreover, any use by us or our joint ventures of
unauthentic materials illegally sold to us by third-party growers or suppliers in our or our joint ventures’ products may result in adverse
side effects to the consumers, negative publicity, or product liability claims against us or our joint ventures, any of which may materially
and adversely affect our operating results.
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The prices of necessary raw materials and products may be subject to price fluctuations according to market conditions, and any
sudden increases in demand in the case of a widespread illness such as COVID-19, SARS, MERS or avian flu may impact the costs of
production. For example, the market price of Banlangen, the main natural raw material in Hutchison Baiyunshan’s Banlangen granules,
fluctuated significantly in the first two quarters of 2020. We source Banlangen and other necessary raw materials on a purchase order
basis and do not have long-term supply contracts in place so that inventory levels can be managed to reduce its risk to price fluctuations;
however, we cannot guarantee that we or our joint ventures will be successful in doing so. Raw material price fluctuations could increase
the cost to manufacture our products and adversely affect our operating results.
Adverse publicity associated with our company, our joint ventures or our or their products or third-party licensed products or similar
products manufactured by our competitors could have a material adverse effect on our results of operations.
Sales of our and our joint ventures’ products are highly dependent upon market perceptions of the safety and quality of such
products, including proprietary products and third-party products we and they distribute. Concerns over the safety of biopharmaceutical
products manufactured in China could have an adverse effect on the reputation of our industry and the sale of such products, including
products manufactured or distributed by us and our joint ventures.
We and our joint ventures could be adversely affected if any of our or our joint ventures’ products, third-party licensed products or
any similar products manufactured by other companies prove to be, or are alleged to be, harmful to patients. Any negative publicity
associated with severe adverse reactions or other adverse effects resulting from patients’ use or misuse of our and our joint ventures’
products or any similar products manufactured by other companies could also have a material adverse impact on our results of operations.
We and our joint ventures have not, to date, experienced any significant quality control or safety problems. If in the future we or our
joint ventures become involved in incidents of the type described above, such problems could severely and adversely impact our financial
position and reputation.
We are dependent on our joint ventures’ production facilities in Shanghai, Guangzhou and Bozhou, China and our manufacturing
facility in Suzhou, China for the manufacture of the principal products of our joint ventures and our own drug candidates and
products.
The principal products sold by our Other Ventures are mainly produced or expected to be produced at our joint ventures’
manufacturing facilities in Shanghai, Guangzhou and Bozhou, China. Our commercial supplies of Elunate (the brand name of
fruquintinib in China) and Sulanda (the brand name of surufatinib in China) sold by our Oncology/Immunology operations are
manufactured at our manufacturing facility in Suzhou. Until construction of our new manufacturing facility in Shanghai is completed
and it receives the requisite government approvals, we have no back-up manufacturing facility for fruquintinib and surufatinib, and our
ability to produce such drugs will be negatively impacted if we experience any significant production problems at our Suzhou facility.
A significant disruption at our and/or our joint ventures’ facilities, even on a short-term basis, could impair our and/or our joint ventures’
ability to timely produce and ship products, which could have a material adverse effect on our business, financial position and results of
operations.
Our and our joint ventures’ manufacturing operations are vulnerable to interruption and damage from natural and other types of
disasters, including earthquake, fire, floods, environmental accidents, power loss, communications failures and similar events. If any
disaster were to occur, our ability to operate our or our joint ventures’ business at these facilities would be materially impaired. In
addition, the nature of our production and research activities could cause significant delays in our programs and make it difficult for us
to recover from a disaster. We and our joint ventures maintain insurance for business interruptions to cover some of our potential losses;
however, such disasters could still disrupt our operations and thereby result in substantial costs and diversion of resources.
In addition, our and our joint ventures’ production process requires a continuous supply of electricity. We and they have encountered
power shortages historically due to restricted power supply to industrial users during summers when the usage of electricity is high and
supply is limited or as a result of damage to the electricity supply network. Because the duration of those power shortages was brief,
they had no material impact on our or their operations. Interruptions of electricity supply could result in lengthy production shutdowns,
increased costs associated with restarting production and the loss of production in progress. Any major suspension or termination of
electricity or other unexpected business interruptions could have a material adverse impact on our business, financial condition and
results of operations.
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Risks Relating to Our Dependence on Third Parties
Disagreements with our current or future collaboration partners, the amendment of any collaboration agreement or the termination
of any collaboration arrangement, could cause delays in our product development and materially and adversely affect our business.
Our collaborations, including those with our oncology drug partners AstraZeneca and Eli Lilly, and any future collaborations that
we enter into may not be successful. Disagreements between parties to a collaboration arrangement regarding clinical development and
commercialization matters can lead to delays in the development process or commercializing the applicable drug candidate and, in some
cases, termination of the collaboration arrangement. In addition, we or our partners may seek to amend the terms of one or more our
collaboration agreements to adjust, among other things, the respective roles of our company and our collaboration partner as
circumstances change. Our interests may not always be aligned with those of our collaboration partners, for instance, we are much
smaller than our collaboration partners and because they or their affiliates may sell competing products. This may result in potential
conflicts between our collaborators and us on matters that we may not be able to resolve on favorable terms or at all.
Collaborations with pharmaceutical or biotechnology companies and other third parties, including our existing agreements with
AstraZeneca and Eli Lilly, are often terminable by the other party for any reason with certain advance notice. Any such termination or
expiration would adversely affect us financially and could harm our business reputation. For instance, in the event one of the strategic
alliances with a current collaborator is terminated, we may require significant time and resources to secure a new collaboration partner,
if we are able to secure such an arrangement at all. As noted in the following risk factor, establishing new collaboration arrangements
can be challenging and time-consuming. The loss of existing or future collaboration arrangements would not only delay or potentially
terminate the possible development or commercialization of products we may derive from our technologies, but it may also delay or
terminate our ability to test specific target candidates.
We rely on our collaborations with third parties for certain of our drug development activities, and, if we are unable to establish new
collaborations when desired on commercially attractive terms or at all, we may have to alter our development and commercialization
plans.
Certain of our drug development programs and the potential commercialization of certain drug candidates rely on collaborations,
such as savolitinib with AstraZeneca and fruquintinib with Eli Lilly. In addition, we recently entered into collaborations with BeiGene
and Inmagene. In the future, we may decide to collaborate with additional pharmaceutical and biotechnology companies for the
development and potential commercialization of our other drug candidates.
We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for collaboration
will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the
proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results
of clinical trials, the likelihood of approval by the FDA, NMPA or similar regulatory authorities outside the United States and China,
the potential market for the subject drug candidate, the costs and complexities of manufacturing and delivering such drug candidate to
patients, the potential of competing drugs, the existence of uncertainty with respect to our ownership of technology, which can exist if
there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally. The
collaborator may also consider alternative drug candidates or technologies for similar indications that may be available to collaborate
on and whether such collaboration could be more attractive than the one with us for our drug candidate. The terms of any additional
collaboration or other arrangements that we may establish may not be favorable to us.
We may also be restricted under existing collaboration agreements from entering into future agreements on certain terms with
potential collaborators. Collaborations are complex and time-consuming to negotiate and document. In addition, there have been a
significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of
potential future collaborators.
We may not be able to negotiate additional collaborations on a timely basis, on acceptable terms, or at all. If we are unable to do
so, we may have to curtail the development of the drug candidate for which we are seeking to collaborate, reduce or delay its development
program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or
marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we
elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional
capital, which may not be available to us on acceptable terms or at all. If we do not have sufficient funds, we may not be able to further
develop our drug candidates or bring them to market and generate drug revenue.
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The third-party vendors upon whom we rely for the supply of the active pharmaceutical ingredient used in some of our drug
candidates and drug products are our sole source of supply, and the loss of any of these suppliers could significantly harm our
business.
The active pharmaceutical ingredients used in some of our drug candidates and products are supplied to us from third-party vendors.
Our ability to successfully develop our drug candidates, and to supply our commercial drugs in quantities sufficient to meet the market
demand, depends in part on our ability to obtain the active pharmaceutical ingredients for these drugs in accordance with regulatory
requirements and in sufficient quantities for commercialization and clinical testing. We contract with a single supplier to manufacture
and supply us with the active pharmaceutical ingredient for fruquintinib for clinical and commercial purposes and are in the process of
engaging a second supplier. We have already validated the second supplier’s current good manufacturing practice, or cGMP, production
processes and submitted an application for its approval to the NMPA. We also contract with a single supplier to manufacture and supply
us with the active pharmaceutical ingredient for surufatinib for clinical and commercial purposes. Other than the foregoing, we do not
currently have arrangements in place for a contingent or second-source supply of the active pharmaceutical ingredients for fruquintinib
or surufatinib or any other active pharmaceutical ingredients used in our drug candidates in the event any of our current suppliers of
such active pharmaceutical ingredient cease operations for any reason, which may lead to an interruption in our production and supply
of the product.
For all of our drug candidates and products, we aim to identify and qualify a manufacturer to provide such active pharmaceutical
ingredient prior to submission of an NDA to the FDA and/or NMPA. We are not certain, however, that our current supply arrangements
will be able to meet our demand, either because of the nature of our agreements with third party suppliers, our limited experience with
third party suppliers or our relative importance as a customer to those suppliers. It may be difficult for us to assess third party vendors’
ability to timely meet our demand in the future based on past performance. While our suppliers have generally met our demand on a
timely basis in the past, they may subordinate our needs in the future to their other customers.
Establishing additional or replacement suppliers for the active pharmaceutical ingredients used in our drug candidates, if required,
may not be accomplished quickly. If we are able to find a replacement supplier, such alternative arrangements would need to be qualified
and may require additional regulatory approval, which could result in further delay. While we seek to maintain adequate inventory of
the active pharmaceutical ingredients used in our drug candidates, any interruption or delay in the supply of components or materials,
or our inability to obtain such active pharmaceutical ingredient from alternate sources at acceptable prices in a timely manner could
impede, delay, limit or prevent our development efforts, which could harm our business, results of operations, financial condition and
prospects.
We and our collaborators rely, and expect to continue to rely, on third parties to conduct certain of our clinical trials for our drug
candidates. If these third parties do not successfully carry out their contractual duties, comply with regulatory requirements or meet
expected deadlines, we may not be able to obtain regulatory approval for or commercialize our drug candidates and our business
could be harmed.
We do not have the ability to independently conduct large-scale clinical trials. We and our collaboration partners rely, and expect
to continue to rely, on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, to conduct
or otherwise support certain clinical trials for our drug candidates. Nevertheless, we and our collaboration partners (as applicable) will
be responsible for ensuring that each clinical trial is conducted in accordance with the applicable protocol, legal and regulatory
requirements and scientific standards, and reliance on CROs will not relieve us of our regulatory responsibilities. For any violations of
laws and regulations during the conduct of clinical trials for our drug candidates, we could be subject to warning letters or enforcement
action that may include civil penalties up to and including criminal prosecution.
Although we or our collaboration partners design the clinical trials for our drug candidates, CROs conduct most of the clinical trials.
As a result, many important aspects of our development programs, including their conduct and timing, are outside of our direct control.
Our reliance on third parties to conduct clinical trials results in less control over the management of data developed through clinical
trials than would be the case if we were relying entirely upon our own staff. Communicating with outside parties can also be challenging,
potentially leading to mistakes as well as difficulties in coordinating activities. Outside parties may:
•
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have staffing difficulties;
fail to comply with contractual obligations;
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•
•
•
experience regulatory compliance issues;
undergo changes in priorities or become financially distressed; or
form relationships with other entities, some of which may be our competitors.
These factors may materially and adversely affect the willingness or ability of third parties to conduct our and our collaboration
partners’ clinical trials and may subject us or them to unexpected cost increases that are beyond our or their control.
If any of our and our collaboration partners’ relationships with these third-party CROs terminate, we or they may not be able to
enter into arrangements with alternative CROs on reasonable terms or at all. If CROs do not successfully carry out their contractual
duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain
is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, any clinical trials
such CROs are associated with may be extended, delayed or terminated, and we may not be able to obtain regulatory approval for or
successfully commercialize our drug candidates. As a result, we believe that our financial results and the commercial prospects for our
drug candidates in the subject indication would be harmed, our costs could increase and our ability to generate revenue could be delayed.
We, our collaboration partners or our CROs may fail to comply with the regulatory requirements pertaining to clinical trials, which
could result in fines, adverse publicity and civil or criminal sanctions.
We, our collaboration partners and our CROs are required to comply with regulations for conducting, monitoring, recording and
reporting the results of clinical trials to ensure that the data and results are scientifically credible and accurate, and that the trial patients
are adequately informed of the potential risks of participating in clinical trials and their rights are protected. These regulations are
enforced by the FDA, the NMPA and comparable foreign regulatory authorities for any drugs in clinical development. In the United
States, the FDA regulates GCP through periodic inspections of clinical trial sponsors, principal investigators and trial sites. If we, our
collaboration partners or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed
unreliable and the FDA or comparable foreign regulatory authorities may require additional clinical trials before approving the marketing
applications for the relevant drug candidate. We cannot assure you that, upon inspection, the FDA or other applicable regulatory
authority will determine that any of the future clinical trials for our drug candidates will comply with GCPs. In addition, clinical trials
must be conducted with drug candidates produced under applicable manufacturing regulations. Our failure or the failure of our
collaboration partners or CROs to comply with these regulations may require us or them to repeat clinical trials, which would delay the
regulatory approval process and could also subject us to enforcement action. We are also required to register applicable clinical trials
and post certain results of completed clinical trials on a U.S. government-sponsored database, ClinicalTrials.gov, within certain
timeframes. Failure to do so can result in fines, adverse publicity and civil sanctions.
Joint ventures form an important part of our Other Ventures, and our ability to manage and develop the businesses conducted by
these joint ventures depends in part on our relationship with our joint venture partners.
We are party to joint venture agreements with each of Shanghai Pharmaceuticals, Guangzhou Baiyunshan, Sinopharm and Hain
Celestial, which together form an important part of our Other Ventures. Under these arrangements, our joint venture partners have
certain operational responsibilities and/or certain rights to exercise control or influence over operations and decision-making.
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Our equity interests in these operating companies do not provide us with the ability to control actions which require shareholder
approval. In addition, under the joint venture contracts for these entities, the consent of the directors nominated by our joint venture
partners is required for the passing of resolutions in relation to certain matters concerning the operations of these companies. As a result,
although we participate in the management, and in the case of Hutchison Sinopharm, Hutchison Hain Organic and Shanghai Hutchison
Pharmaceuticals nominate the management and run the day-to-day operations, we may not be able to secure the consent of our joint
venture partners to pursue activities or strategic objectives that are beneficial to or that facilitate our overall business strategies. With
respect to Hutchison Baiyunshan, which is a jointly controlled and managed joint venture where we share the ability to appoint the
general manager with our partner Guangzhou Baiyunshan, with each of us having a rotating four-year right, we rely on our relationship
with our partner, and our ability to manage the day-to-day operations of this joint venture is more limited. To the extent Guangzhou
Baiyunshan does not, for example, diligently perform its responsibilities with respect to any aspect of Hutchison Baiyunshan’s
operations, agree with or cooperate in the implementation of any plans we may have for Hutchison Baiyunshan’s business in the future
or take steps to ensure that Hutchison Baiyunshan is in compliance with applicable laws and regulations, our business and ability to
comply with legal, regulatory and financial reporting requirements which will apply to us as a public company, as well as the results of
this joint venture, could be materially and adversely affected. Furthermore, disagreements or disputes which arise between us and our
joint venture partners may potentially require legal action to resolve and hinder the smooth operation of our Other Ventures or adversely
affect our financial condition, results of operations and prospects.
We are relying on third parties to construct our new manufacturing facility in Shanghai. Any delays in completing and receiving
regulatory approvals for our new Shanghai facility, or any disruptions to the third parties’ performance of their obligations, could
reduce or restrict our production capacity for the drug candidates used in our clinical trials or our commercial supply for any drug
candidates which are approved.
We are contracting with third parties to construct our new manufacturing facility in Shanghai. The new facility is expected to be a
55,000 square meter large-scale facility with a production capacity estimated to be five times that of our existing manufacturing plant
in Suzhou. The first phase will be primarily for small molecule production, with production capacity expected to be able to produce
250 million tablets and capsules per year. The second phase is expected to include expansion into large molecule production. Third
parties will be responsible for the construction of the buildings, including the production lines and other production facilities within such
buildings.
We cannot assure you that we will not experience any disruptions to the third parties’ performance of their obligations, and there
could be delays in completing and receiving regulatory approvals for our new manufacturing facility. If the construction of our
manufacturing facility or our production lines encounter unanticipated delays or incur additional expenses than expected, if regulatory
evaluation and/or approval of our new manufacturing facility is delayed, or if our third party contracts are terminated or adversely
affected, our manufacturing capacity of our drug candidates may be limited, which would delay or limit our development and
commercialization activities and our opportunities for growth. Cost overruns associated with constructing or maintaining our Shanghai
facility could also require us to raise additional funds from other sources. Any disruption that impedes our ability to manufacture our
drug candidates in a timely manner could materially adversely affect our business, financial condition, results of operations and
prospects.
We and our joint ventures rely on our distributors for logistics and distribution services.
We and our joint ventures rely on distributors to perform certain operational activities, including invoicing, logistics and delivery
of the products we and they market to the end customers. Because we and our joint ventures rely on third-party distributors, we have
less control than if we handled distribution logistics directly and can be adversely impacted by the actions of our distributors. Any
disruption of our distribution network, including failure to renew existing distribution agreements with desired distributors, could
negatively affect our ability to effectively sell our products and materially and adversely affect the business, financial condition and
results of operations of us and our joint ventures.
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There is no assurance that the benefits currently enjoyed by virtue of our association with CK Hutchison will continue to be available.
Historically, we have relied on the reputation and experience of, and support provided by, our founding shareholder, a wholly owned
subsidiary of CK Hutchison, to advance our joint ventures and collaborations in China and elsewhere. CK Hutchison is a Hong Kong-
based, multinational conglomerate with operations in over 50 countries. CK Hutchison is the ultimate parent company of Hutchison
Healthcare Holdings Limited, which as of March 1, 2021, owns 45.69% of our total outstanding share capital. We believe that CK
Hutchison group’s reputation in China has given us an advantage in negotiating collaborations and obtaining opportunities.
We also benefit from sharing certain services with the CK Hutchison group including, among others, legal and regulatory services,
company secretarial support services, tax and internal audit services, shared use of accounting software system and related services,
participation in the CK Hutchison group’s pension, medical and insurance plans, participation in the CK Hutchison group’s procurement
projects with third-party vendors/suppliers, other staff benefits and staff training services, company functions and activities and operation
advisory and support services. We pay a management fee to an affiliate of CK Hutchison for the provision of such services. In each of
the years ended December 31, 2018, 2019 and 2020, we paid a management fee of approximately $0.9 million, $0.9 million and $1.0
million respectively. In addition, we benefit from the fact that two retail chains affiliated with the CK Hutchison group, PARKnSHOP
and Watsons, sell certain of our Other Ventures’ products in their stores throughout Hong Kong and in other Asian countries. For the
years ended December 31, 2018, 2019 and 2020, sales of our products to members of the CK Hutchison group amounted to $8.3 million,
$7.6 million and $5.5 million, respectively.
Our business also depends on certain intellectual property rights licensed to us by the CK Hutchison group. See “—Risks Relating
to Intellectual Property—We and our joint ventures are dependent on trademark and other intellectual property rights licensed from
others. If we lose our licenses for any of our products, we or our joint ventures may not be able to continue developing such products or
may be required to change the way we market such products” for more information on risks associated with such intellectual property
licensed to us.
There can be no assurance the CK Hutchison group will continue to provide the same benefits or support that they have provided
to our business historically. Such benefit or support may no longer be available to us, in particular, if CK Hutchison’s ownership interest
in our company significantly decreases in the future.
Other Risks and Risks Relating to Doing Business in China
The COVID-19 pandemic and other adverse public health developments could materially and adversely affect our business.
In December 2019, an outbreak of a novel strain of coronavirus (COVID-19) was reported and has since spread around the world.
In March 2020, the World Health Organization declared the COVID-19 outbreak a global pandemic. In response to the pandemic, many
governments around the world have implemented a variety of measures to reduce the spread of COVID-19, including travel restrictions
and bans, instructions to residents to practice social distancing, quarantine advisories, shelter-in-place orders and required closures of
non-essential businesses. The COVID-19 pandemic has negatively impacted the global economy, disrupted global supply chains, and
created significant volatility and disruption of financial markets.
The continued COVID-19 pandemic and other adverse public health developments could adversely impact our operations, given
the impact they may have on the manufacturing and supply chain, our sales and marketing and clinical trial operations and those of our
collaboration partners, and the ability to advance our research and development activities and pursue development of any of our drug
candidates, each of which could have an adverse impact on our business and our financial results. For instance, our clinical studies have
encountered some limitations to patient visits for screening, treatment and clinical assessment. In addition, our prescription drug sales
teams have seen some short-term limitations on conducting normal operations. The ultimate impact of the current COVID-19 pandemic,
or any other adverse public health development, is highly uncertain and will depend on future developments that cannot be predicted
with confidence, such as the duration of the outbreak and the effectiveness of actions to contain and treat COVID-19. Although, as of
the date of this annual report, we do not expect any material impact on our long-term activity, we do not yet know the full extent of
potential delays or impacts on our business, our clinical trials, our research programs, healthcare systems or the global economy as a
whole, which could have a material adverse effect on our business, financial condition and results of operations and cash flows.
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We are subject to stringent privacy laws, information security policies and contractual obligations related to data privacy and security,
and we may be exposed to risks related to our management of the medical data of subjects enrolled in our clinical trials and other
personal or sensitive information.
We routinely receive, collect, generate, store, process, transmit and maintain medical data, treatment records and other personal
details of the subjects enrolled in our clinical trials, along with other personal or sensitive information. As such, we are subject to the
relevant local, state, national and international data protection and privacy laws, directives regulations, and standards that apply to the
collection, use, retention, protection, disclosure, transfer and other processing of personal data in the various jurisdictions in which we
operate and conduct our clinical trials. We are also subject to contractual obligations regarding the processing of personal data. Legal
requirements regarding data protection and privacy continue to evolve and may result in ever-increasing public scrutiny and escalating
levels of enforcement and sanctions and increased costs of compliance. Failure to comply with any of these laws could result in
enforcement action against us, including investigations, civil and criminal enforcement action, fines, imprisonment of company officers
and public censure, claims for damages by customers and other affected individuals, damage to our reputation and loss of goodwill, any
of which could have a material adverse effect on our business, financial condition, results of operations or prospects.
Data protection and privacy laws and regulations generally require clinical trial sponsors and operators and their personnel to protect
the privacy of their enrolled subjects and prohibit unauthorized disclosure of personal information. While we have adopted security
policies and measures to protect our proprietary data and patients’ privacy, personal patient information could be subject to leaks caused
by hacking activities, human error, employee misconduct or negligence or system breakdown. We also cooperate with third parties
including collaboration partners, principal investigators, hospitals, CROs and other third-party contractor and consultants for our clinical
trials and operations. Any leakage or abuse of patient data by our third-party partners may be perceived by the patients as a result of our
failure. Furthermore, any change in applicable laws and regulations could affect our ability to use medical data and subject us to liability
for the use of such data for previously permitted purposes. Any failure or perceived failure by us to prevent information security breaches
or to comply with privacy policies or privacy-related legal obligations, or any compromise of information security that results in the
unauthorized release or transfer of personally identifiable information or other patient data, could cause our customers to lose trust in us
and could expose us to legal claims.
There are numerous U.S. federal and state laws and regulations related to the privacy and security of personal information. In
particular, regulations promulgated pursuant to the Health Insurance Portability and Accountability Act of 1996, or HIPAA, establish
privacy and security standards that limit the use and disclosure of individually identifiable health information (known as “protected
health information”) and require the implementation of administrative, physical and technological safeguards to protect the privacy of
protected health information and ensure the confidentiality, integrity and availability of electronic protected health information.
Determining whether protected health information has been handled in compliance with applicable privacy standards and our contractual
obligations can require complex factual and statistical analyses and may be subject to changing interpretations. Although we take
measures to protect sensitive data from unauthorized access, use or disclosure, and whenever possible contractually require third-party
partners to do the same, our information technology and infrastructure and those of our third-party partners may be vulnerable to attacks
by hackers or viruses or breached due to employee error, malfeasance or other malicious or inadvertent disruptions. Any such breach or
interruption could compromise those networks and the information stored there could be accessed by unauthorized parties, manipulated,
publicly disclosed, lost or stolen. Any such access, breach, or other loss of information relating to our information technology and
infrastructure or that of our third-party partners may subject us to liability including legal claims or proceedings and liability under
federal or state laws that protect the privacy of personal information, such as the HIPAA, the Health Information Technology for
Economic and Clinical Health Act, and regulatory penalties. If we or a third-party partner suffers a breach, we may need to send breach
notifications to affected individuals and, if 500 or more individuals were affected, to the Secretary of the Department of Health and
Human Services. Breach notifications may separately be required under applicable state breach notification laws, which may include
notifications to affected individuals, and for extensive breaches, to the media, credit reporting agencies, and/or State Attorneys General.
Such notices could harm our reputation and our ability to compete and could potentially attract enforcement scrutiny from governmental
authorities.
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Regulatory authorities in China have implemented and are considering a number of legislative and regulatory proposals concerning
data protection. For example, the PRC Cyber Security Law, which became effective in June 2017, created China’s first national-level
data protection for “network operators”, which may include all organizations in China that provide services over the internet or another
information network. Drafts of some of these measures have now been published, including the Data Security Management Measures
published in May 2019, and Measures on Security Assessment for Individual Information Cross-border Transfer (Draft for Comments)
in June 2019, which may, upon enactment, require security review before transferring human health-related data out of China. On
October 21, 2020, the full text of the draft Law on Personal Information Protection was released, which applies to any processing of
personal information of a natural person within the territory of the PRC, regardless of nationality, and which is accompanied by hefty
fines for non-compliance. The draft law applies extraterritorially in certain contexts, including where the processing of personal
information is intended to serve the purpose of providing products or services to individuals residing within the PRC or of analyzing
and assessing the behaviors of individuals residing within the territory of the PRC. In addition, certain industry-specific laws and
regulations affect the collection and transfer of personal data in China. The Interim Measures for the Administration of Human Genetic
Resources and implementation guidelines issued by the Ministry of Science and Technology and Ministry of Health, for example, require
approval from the Human Genetic Resources Administration of China before entering into a definitive contract where human genetic
resources, or HGR, are involved in any international collaborative project and additional approval for any export or cross-border transfer
of the HGR samples or associated data. The Regulations of the PRC on the Administration of Human Genetic Resources, which became
effective and implemented on July 1, 2019, further stipulate, however, that no approval is required for “international collaboration in
clinical trials” that do not involve the export of HGR materials. However, the two parties shall file the type, quantity and usage of the
HGR to be used with the administrative department of science and technology under the State Council before clinical trials. It is possible
that these laws may be interpreted and applied in a manner that is inconsistent with our practices, potentially resulting in confiscation
of HGR samples and associated data and administrative fines.
Our clinical trial programs may implicate European data privacy laws, including the General Data Protection Regulation, or the
GDPR, and local laws further implementing or supplementing the GDPR. The GDPR implements more stringent operational
requirements for processors and controllers of personal data including requirements for such companies to be able to ensure and be able
to demonstrate compliance with the GDPR. If our or our third-party partners’ privacy or data security measures fail to comply with the
GDPR requirements, we may be subject to litigation, regulatory investigations, enforcement notices requiring us to change the way we
use personal data and/or fines of up to 20 million Euros or up to 4% of the total worldwide annual turnover of the preceding financial
year, whichever is higher. In addition to statutory enforcement, non-compliance can lead to compensation claims by affected individuals,
negative publicity and a potential loss of business. We are also subject to European laws on personal data export, as we may transfer
personal data from the E.U. to other jurisdictions which are not considered by the European Commission to offer “adequate” protection
of personal data (such as Hong Kong or the United States). Such transfers need to be legitimized by a valid transfer mechanism under
the GDPR. On July 16, 2020, the Court of Justice of the E.U., or CJEU, unexpectedly declared that the EU-US Privacy Shield Framework
is no longer a valid mechanism to transfer personal data from the EU to the United States. It also concluded that the European
Commission’s Standard Contractual Clauses for the transfer of personal data to data processors outside of the EU remain valid, but that
companies must carry out assessments of the laws of the third countries to which personal data is exported, and (where an adequate level
of protection cannot be assured) may need to supplement the Standard Contractual Clauses with additional protective measures. This
decision has created uncertainty around how organizations can comply with the GDPR when transferring EU data to the United States
as well as other third countries. These changes could require us to make operational changes and could increase costs and may lead to
governmental enforcement actions, litigation, fines and penalties or adverse publicity that could have an adverse effect on our business.
Complying with all applicable laws, regulations, standards and obligations relating to data privacy, security, and transfers may
cause us to incur substantial operational costs or require us to modify our data processing practices and processes. Non-compliance
could result in proceedings against us by data protection authorities, governmental entities or others, including class action privacy
litigation in certain jurisdictions, which would subject us to significant fines, penalties, judgments and negative publicity. In addition, if
our practices are not consistent or viewed as not consistent with legal and regulatory requirements, including changes in laws, regulations
and standards or new interpretations or applications of existing laws, regulations and standards, we may become subject to audits,
inquiries, whistleblower complaints, adverse media coverage, investigations, loss of export privileges, severe criminal or civil sanctions
and reputational damage. Any of the foregoing could have a material adverse effect on our competitive position, business, financial
conditions, results of operations and prospects.
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Product liability claims or lawsuits could cause us, our collaborators or our joint ventures to incur substantial liabilities.
We, our collaborators and our joint ventures face an inherent risk of product liability exposure related to the use of our drug
candidates in clinical trials, sales of our or our joint ventures’ products or the products we or they license from third parties. If we, our
collaborators and our joint ventures cannot successfully defend against claims that the use of such drug candidates in our clinical trials
or any products sold by us or our joint ventures, including fruquintinib, surufatinib and/or any of our drug candidates which receive
regulatory approval, caused injuries, we, our collaborators and our joint ventures could incur substantial liabilities. Regardless of merit
or eventual outcome, liability claims may result in:
•
•
decreased demand for our and our joint ventures’ products;
significant negative media attention and reputational damage;
• withdrawal of clinical trial participants;
•
•
•
•
significant costs to defend the related litigation;
substantial monetary awards to trial participants or patients;
loss of revenue; and
the inability to commercialize any drug candidates that we may develop.
Our principal insurance policies cover product liability for fruquintinib and surufatinib, property loss due to accidents or natural
disasters and adverse events in clinical trials. Existing PRC laws and regulations do not require us, our collaborators or our joint ventures
to have, nor do we or they, maintain liability insurance to cover product liability claims except with respect to fruquintinib and surufatinib
and liability with respect to our oncology and immunology clinical trials. Any litigation might result in substantial costs and diversion
of resources. While we maintain liability insurance for clinical trials and products, this insurance may not fully cover our potential
liabilities. Inability to obtain sufficient insurance coverage at an acceptable cost or otherwise to protect against potential product liability
claims could prevent or inhibit the commercialization of products that we or our collaborators develop.
We and our joint ventures may be exposed to liabilities under the U.S. Foreign Corrupt Practices Act, or FCPA, the Bribery Act
2010 of the United Kingdom, or U.K. Bribery Act, and Chinese anti-corruption laws, and any determination that we have violated
these laws could have a material adverse effect on our business or our reputation.
In the day-to-day conduct of our business, we and our joint ventures are in frequent contact with persons who may be considered
government officials under applicable anti-corruption, anti-bribery and anti-kickback laws, which include doctors at public hospitals in
China and elsewhere. Therefore, we and our joint ventures are subject to risk of violations under the FCPA, the U.K. Bribery Act, and
other laws in the countries where we do business. We and our joint ventures have operations, agreements with third parties and we and
our joint ventures make most of our sales in China. The PRC also strictly prohibits bribery of government officials. Our and our joint
ventures’ activities in China create the risk of unauthorized payments or offers of payments by the directors, employees, representatives,
distributors, consultants or agents of our company or our joint ventures, even though they may not always be subject to our control. It
is our policy to implement safeguards to discourage these practices by our and our joint ventures’ employees. We have implemented
and adopted policies designed by the R&D-based Pharmaceutical Association Committee, an industry association representing
approximately 40 global biopharmaceutical companies, to ensure compliance by us and our joint ventures and our and their directors,
officers, employees, representatives, distributors, consultants and agents with the anti-corruption laws and regulations. We cannot assure
you, however, that our existing safeguards are sufficient or that our or our joint ventures’ directors, officers, employees, representatives,
distributors, consultants and agents have not engaged and will not engage in conduct for which we may be held responsible, nor can we
assure you that our business partners have not engaged and will not engage in conduct that could materially affect their ability to perform
their contractual obligations to us or even result in our being held liable for such conduct. Violations of the FCPA, the U.K. Bribery Act
or Chinese anti-corruption laws may result in severe criminal or civil sanctions, and we may be subject to other liabilities, which could
have a material adverse effect on our business, reputation, financial condition, cash flows and results of operations.
38
Ensuring that our and our joint ventures’ future business arrangements with third parties comply with applicable laws could also
involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current
or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our or our
joint ventures’ operations were found to be in violation of any of these laws or any other governmental regulations that may apply to us,
we may be subject to significant civil, criminal and administrative penalties, damages, fines, disgorgement, individual imprisonment
and exclusion from government funded healthcare programs, any of which could substantially disrupt our operations. If the physicians,
hospitals or other providers or entities with whom we and our joint ventures do business are found not to be in compliance with applicable
laws, they may also be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare
programs.
If we or our joint ventures fail to comply with environmental, health and safety laws and regulations, we or they could become subject
to fines or penalties or incur costs that could have a material adverse effect on the success of our business.
We and our joint ventures are subject to numerous environmental, health and safety laws and regulations, including those governing
laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our operations involve
the use of hazardous and flammable materials, including chemical materials. Our operations also produce hazardous waste products.
We and our joint ventures are therefore subject to PRC laws and regulations concerning the discharge of waste water, gaseous waste
and solid waste during our manufacturing processes. We and our joint ventures are required to establish and maintain facilities to dispose
of waste and report the volume of waste to the relevant government authorities, which conduct scheduled or unscheduled inspections of
our facilities and treatment of such discharge. We and our joint ventures may not at all times comply fully with environmental
regulations. Any violation of these regulations may result in substantial fines, criminal sanctions, revocations of operating permits,
shutdown of our facilities and obligation to take corrective measures. We and our joint ventures generally contract with third parties for
the disposal of these materials and waste. We and our joint ventures cannot eliminate the risk of contamination or injury from these
materials. In the event of contamination or injury resulting from the use of hazardous materials, we and/or our joint ventures could be
held liable for any resulting damages, and any liability could exceed our resources. We and/or our joint ventures also could incur
significant costs associated with civil or criminal fines and penalties.
Although we and our joint ventures maintain workers’ compensation insurance to cover costs and expenses incurred due to
on-the-job injuries to our employees and third-party liability insurance for injuries caused by unexpected seepage, pollution or
contamination, this insurance may not provide adequate coverage against potential liabilities. Furthermore, the PRC government may
take steps towards the adoption of more stringent environmental regulations. Due to the possibility of unanticipated regulatory or other
developments, the amount and timing of future environmental expenditures may vary substantially from those currently anticipated. If
there is any unanticipated change in the environmental regulations, we and our joint ventures may need to incur substantial capital
expenditures to install, replace, upgrade or supplement our equipment or make operational changes to limit any adverse impact or
potential adverse impact on the environment in order to comply with new environmental protection laws and regulations. If such costs
become prohibitively expensive, we may be forced to cease certain aspects of our or our joint ventures’ business operations.
We rely significantly on information technology and any failure, inadequacy, interruption or security lapse of that technology,
including any cybersecurity incidents, could harm our ability to operate our business effectively.
We are heavily dependent on critical, complex and interdependent information technology systems, including internet-based
systems, to support our business processes. Our information technology system security is continuously reviewed, maintained and
upgraded in response to possible security breach incidents. Despite the implementation of these measures, our information technology
systems and those of third parties with which we contract are vulnerable to damage from external or internal security incidents,
breakdowns, malicious intrusions, cybercrimes, including State-sponsored cybercrimes, malware, misplaced or lost data, programming
or human errors or other similar events. System failures, accidents or security breaches could cause interruptions in our operations and
could result in inappropriately accessed, tampered with, modified or stolen scientific data or a material disruption of our clinical activities
and business operations, in addition to possibly requiring substantial expenditures of resources to remedy. Such event could significantly
harm our Oncology/Immunology operations, including resulting in the loss of clinical trial data which could result in delays in our
regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Such events could also lead to the loss
of important information such as trade secrets or other intellectual property and could accelerate the development or manufacturing of
competing products by third parties. To the extent that any disruption or security breach were to result in a loss of, or damage to, our
data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and our research and
development programs and the development of our drug candidates could be delayed.
39
The PRC’s economic, political and social conditions, as well as governmental policies, could affect the business environment and
financial markets in China, our ability to operate our business, our liquidity and our access to capital.
Substantially all of our and our joint ventures’ business operations are conducted in China. Accordingly, our results of operations,
financial condition and prospects are subject to a significant degree to economic, political and legal developments in China. China’s
economy differs from the economies of developed countries in many respects, including with respect to the amount of government
involvement, level of development, growth rate, control of foreign exchange and allocation of resources. While the PRC economy has
experienced significant growth in the past 30 years, growth has been uneven across different regions and among various economic
sectors of China. The PRC government has implemented various measures to encourage economic development and guide the allocation
of resources. Some of these measures benefit the overall PRC economy, but may have a negative effect on us or our joint ventures. For
example, our financial condition and results of operations may be adversely affected by government control over capital investments or
changes in tax regulations that are applicable to us or our joint ventures. More generally, if the business environment in China deteriorates
from the perspective of domestic or international investors, our or our joint ventures’ business in China may also be adversely affected.
Uncertainties with respect to the PRC legal system and changes in laws, regulations and policies in China could materially and
adversely affect us.
We conduct a substantial portion of our business through our subsidiaries and joint ventures in China. PRC laws and regulations
govern our and their operations in China. Our subsidiaries and joint ventures are generally subject to laws and regulations applicable to
foreign investments in China, which may not sufficiently cover all of the aspects of our or their economic activities in China. In
particular, some laws, particularly with respect to drug price reimbursement, are relatively new, and because of the limited volume of
published judicial decisions and their non-binding nature, the interpretation and enforcement of these laws and regulations are uncertain.
Furthermore, recent regulatory reform in the China pharmaceutical industry will limit the number of distributors allowed between a
manufacturer and each hospital to one, which may limit the rate of sales growth of Hutchison Sinopharm in future periods. In addition,
the implementation of laws and regulations may be in part based on government policies and internal rules that are subject to the
interpretation and discretion of different government agencies (some of which are not published on a timely basis or at all) that may
have a retroactive effect. As a result, we may not be aware of our, our collaboration partners’ or our joint ventures’ violation of these
policies and rules until sometime after the violation. In addition, any litigation in China, regardless of outcome, may be protracted and
result in substantial costs and diversion of resources and management attention.
For further information regarding government regulation in China and other jurisdictions, see Item 4.B. “Business Overview—
Regulation—Government Regulation of Pharmaceutical Product Development and Approval—PRC Regulation of Pharmaceutical
Product Development and Approval,” “Business Overview—Regulation—Coverage and Reimbursement—PRC Coverage and
Reimbursement” and “Business Overview—Regulation—Other Healthcare Laws—Other PRC Healthcare Laws.”
Restrictions on currency exchange may limit our ability to receive and use our revenue effectively.
Substantially all of our revenue is denominated in renminbi, which currently is not a freely convertible currency. A portion of our
revenue may be converted into other currencies to meet our foreign currency obligations, including, among others, payments of dividends
declared, if any, in respect of our ordinary shares or ADSs. Under China’s existing foreign exchange regulations, our subsidiaries and
joint ventures are able to pay dividends in foreign currencies or convert renminbi into other currencies for use in operations without
prior approval from the PRC State Administration of Foreign Exchange, or the SAFE, by complying with certain procedural
requirements. However, we cannot assure you that the PRC government will not take future measures to restrict access to foreign
currencies for current account transactions.
Our PRC subsidiaries’ and joint ventures’ ability to obtain foreign exchange is subject to significant foreign exchange controls and,
in the case of amounts under the capital account, requires the approval of and/or registration with PRC government authorities, including
the SAFE. In particular, if we finance our PRC subsidiaries or joint ventures by means of foreign debt from us or other foreign lenders,
the amount is not allowed to exceed either the cross-border financing risk weighted balance calculated based on a formula by the PBOC
or the difference between the amount of total investment and the amount of the registered capital as acknowledged by the Ministry of
Commerce, or MOFCOM, and the SAFE. Further, such loans must be filed with and registered with the SAFE or their local branches
and the National Development and Reform Commission (if applicable). If we finance our PRC subsidiaries or joint ventures by means
of additional capital contributions, the amount of these capital contributions must first be filed with the relevant government approval
authority. These limitations could affect the ability of our PRC subsidiaries and joint ventures to obtain foreign exchange through debt
or equity financing.
40
Our business benefits from certain PRC government tax incentives. The expiration of, changes to, or our PRC subsidiaries/joint
ventures failing to continuously meet the criteria for these incentives could have a material adverse effect on our operating results
by significantly increasing our tax expenses.
Certain of our PRC subsidiaries and joint ventures have been granted High and New Technology Enterprise, or HNTE, status by
the relevant PRC authorities. This status allows the relevant enterprise to enjoy a reduced Enterprise Income Tax, or EIT, rate at 15%
on its taxable profits. For the duration of its HNTE grant, the relevant PRC enterprise must continue to meet the relevant HNTE criteria
or else the 25% standard EIT rate will be applied from the beginning of the calendar year when the enterprise fails to meet the relevant
criteria. We are preparing to renew the HNTE status which expired at the end of 2020 for one of our PRC subsidiaries. It is unclear
whether the HNTE status and tax incentives under the current policy will continue to be granted after the expiration dates. If the rules
for such incentives are amended or the status is not renewed, higher EIT rates may apply resulting in increased tax burden which will
impact our business, financial condition, results of operations and growth prospects.
We may be treated as a resident enterprise for PRC Tax purposes under China’s Enterprise Income Tax Law and Implementation
Rules, effective as of January 1, 2008, or the EIT Law, and our global income may therefore be subject to PRC income tax.
China’s EIT Law defines the term “de facto management bodies” as “bodies that substantially carry out comprehensive management
and control on the business operation, employees, accounts and assets of enterprises.” Under the EIT Law, an enterprise incorporated
outside of China whose “de facto management bodies” are located in China is considered a “resident enterprise” and will be subject to
a uniform 25% EIT rate on its global income. On April 22, 2009, China’s State Administration of Taxation, or the SAT, in the Notice
Regarding the Determination of Chinese-Controlled Offshore-Incorporated Enterprises as PRC Tax Resident Enterprises on the Basis
of De Facto Management Bodies, or Circular 82, further specified certain criteria for the determination of what constitutes “de facto
management bodies.” If all of these criteria are met, the relevant foreign enterprise may be regarded to have its “de facto management
bodies” located in China and therefore be considered a resident enterprise in China. These criteria include: (i) the enterprise’s day-to-day
operational management is primarily exercised in China; decisions relating to the enterprise’s financial and human resource matters are
made or subject to approval by organizations or personnel in China; (ii) the enterprise’s primary assets, accounting books and records,
company seals, and board and shareholders’ meeting minutes are located or maintained in China; and (iii) 50% or more of voting board
members or senior executives of the enterprise habitually reside in China. Although Circular 82 only applies to foreign enterprises that
are majority-owned and controlled by PRC enterprises, not those owned and controlled by foreign enterprises or individuals, the
determining criteria set forth in Circular 82 may be adopted by the PRC tax authorities as the test for determining whether the enterprises
are PRC tax residents, regardless of whether they are majority-owned and controlled by PRC enterprises.
Except for our PRC subsidiaries and joint ventures incorporated in China, we believe that none of our entities incorporated outside
of China is a PRC resident enterprise for PRC tax purposes. However, the tax resident status of an enterprise is subject to determination
by the PRC tax authorities, and uncertainties remain with respect to the interpretation of the term “de facto management body.”
If we are treated as a PRC tax resident, dividends distributed by us to our non-PRC shareholders and ADS holders or any gains
realized by non-PRC shareholders and ADS holders from the transfer of our shares or ADSs may be subject to PRC tax.
Under the EIT Law, dividends payable by a PRC enterprise to its foreign investor who is a non-PRC resident enterprise, as well as
gains on transfers of shares of a PRC enterprise by such a foreign investor will generally be subject to a 10% withholding tax, unless
such non-PRC resident enterprise’s jurisdiction of tax residency has an applicable tax treaty with the PRC that provides for an exemption
or a reduced rate of withholding tax.
If the PRC tax authorities determine that we should be considered a PRC resident enterprise for EIT purposes, any dividends payable
by us to our non-PRC resident enterprise shareholders or ADS holders, as well as gains realized by such investors from the transfer of
our shares or ADSs may be subject to a 10% withholding tax, unless an exemption or reduced rate is available under an applicable tax
treaty. Furthermore, if we are considered a PRC resident enterprise for EIT purposes, it is unclear whether our non-PRC individual
shareholders (including our ADS holders) would be subject to any PRC tax on dividends or gains obtained by such non-PRC individual
shareholders. If any PRC tax were to apply to dividends or gains realized by non-PRC individuals, it would generally apply at a rate of
up to 20% unless a reduced rate is available under an applicable tax treaty. If dividends payable to our non-PRC resident shareholders,
or gains from the transfer of our shares or ADSs by such shareholders are subject to PRC tax, the value of your investment in our shares
or ADSs may decline significantly.
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There is uncertainty regarding the PRC withholding tax rate that will be applied to distributions from our PRC subsidiaries and joint
ventures to their respective Hong Kong immediate holding companies, which could have a negative impact on our business.
The EIT Law provides that a withholding tax at the rate of 10% is applicable to dividends payable by a PRC resident enterprise to
investors who are “non-resident enterprises” (i.e., that do not have an establishment or place of business in the PRC or that have such
establishment or place of business but the relevant dividend is not effectively connected with the establishment or place of business).
However, pursuant to the Arrangement between the Mainland of China and the Hong Kong Special Administrative Region for the
Avoidance of Double Taxation and the Prevention of Fiscal Evasion with respect to Taxes on Income, or the Arrangement, withholding
tax at a reduced rate of 5% may be applicable to dividends payable by PRC resident enterprises to beneficial owners of the dividends
that are Hong Kong tax residents if certain requirements are met. There is uncertainty regarding whether the PRC tax authorities will
consider us to be eligible to the reduced tax rate. If the Arrangement is deemed not to apply to dividends payable by our PRC subsidiaries
and joint ventures to their respective Hong Kong immediate holding companies that are ultimately owned by us, the withholding tax
rate applicable to us will be the statutory rate of 10% instead of 5% which may potentially impact our business, financial condition,
results of operations and growth prospects.
We may be treated as a resident enterprise for U.K. corporate tax purposes, and our global income may therefore be subject to U.K.
corporation tax.
U.K. resident companies are taxable in the United Kingdom on their worldwide profits. A company incorporated outside of the
United Kingdom would be regarded as a resident if its central management and control resides in the United Kingdom. The place of
central management and control generally means the place where the high-level strategic decisions of a company are made.
We are an investment holding company incorporated in the Cayman Islands and are admitted to trading on the AIM market of the
London Stock Exchange. Our central management and control resides in Hong Kong, and therefore we believe that we are not a U.K.
resident for corporate tax purposes. However, the tax resident status of a non-resident entity could be challenged by the U.K. tax
authorities.
If the U.K. tax authorities determine that we are a U.K. tax resident, our profits will be subject to U.K. Corporation Tax rate at 19%,
subject to the potential availability of certain exemptions related to dividend income and capital gains. This may have a material adverse
effect on our financial condition and results of operations.
Any failure to comply with PRC regulations regarding our employee equity incentive plans may subject the PRC plan participants
or us to fines and other legal or administrative sanctions, which could adversely affect our business, financial condition and results
of operations.
In February 2012, the SAFE promulgated the Notices on Issues Concerning the Foreign Exchange Administration for Domestic
Individuals Participating in Stock Incentive Plans of Overseas Publicly Listed Companies. Based on this regulation, PRC residents who
are granted shares or share options by a company listed on an overseas stock market under its employee share option or share incentive
plan are required to register with the SAFE or its local counterparts by following certain procedures. We and our employees who are
PRC residents and individual beneficial owners who have been granted shares or share options have been subject to these rules due to
our listing on the AIM market of the London Stock Exchange and Nasdaq. We have registered the option schemes and the share incentive
plan and will continue to assist our employees to register their share options or shares. However, any failure of our PRC individual
beneficial owners and holders of share options or shares to comply with the SAFE registration requirements in the future may subject
them to fines and legal sanctions and may, in rare instances, limit the ability of our PRC subsidiaries to distribute dividends to us.
In addition, the SAT has issued circulars concerning employee share options or restricted shares. Under these circulars, employees
working in the PRC who exercise share options, or whose restricted shares vest, will be subject to PRC individual income tax, or IIT.
The PRC subsidiaries of an overseas listed company have obligations to file documents related to employee share options or restricted
shares with relevant tax authorities and to withhold IIT of those employees related to their share options or restricted shares. Although
the PRC subsidiaries currently withhold IIT from the PRC employees in connection with their exercise of share options, if they fail to
report and pay the tax withheld according to relevant laws, rules and regulations, the PRC subsidiaries may face sanctions imposed by
the tax authorities or other PRC government authorities.
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We may be involved in litigation, legal disputes, claims or administrative proceedings which could be costly and time-consuming to
resolve.
We may become subject, from time to time, to legal proceedings and claims that arise in the ordinary course of business or pursuant
to governmental or regulatory enforcement activity. Any litigation or proceeding to which we become a party might result in substantial
costs and divert management’s attention and resources. Furthermore, any litigation, legal disputes, claims or administrative proceedings
which are initially not of material importance may escalate and become important to us due to a variety of factors, such as changes in
the facts and circumstances of the cases, the likelihood of loss, the monetary amount at stake and the parties involved. Our insurance
might not cover claims brought against us, provide sufficient payments to financially cover all of the costs to resolve such claims or
continue to be available on terms acceptable to us.
The political relationships between China and other countries may affect our business operations.
We conduct our business primarily through our subsidiaries and joint ventures in China, but we also have significant clinical
operations in the United States and other foreign jurisdictions. As a result, China’s political relationships with the United States and
other jurisdictions may affect our business operations. There can be no assurance that our clinical trial participants or customers will not
alter their perception of us or their preferences as a result of adverse changes to the state of political relationships between China and
the relevant foreign jurisdictions. Any tensions and political concerns between China and the relevant foreign jurisdictions may adversely
affect our business, financial condition, results of operations, cash flows and prospects.
Risks Relating to Intellectual Property
If we, our joint ventures or our collaboration partners are unable to protect our or their products and drug candidates through
intellectual property rights, our competitors may compete directly against us or them.
Our success depends, in part, on our, our joint venture partners’ and our collaboration partners’ ability to protect our and our joint
ventures’ and our collaboration partners’ products and drug candidates from competition by establishing, maintaining and enforcing our
or their intellectual property rights. We, our joint ventures and our collaboration partners seek to protect the products and technology
that we and they consider commercially important by filing PRC and international patent applications, relying on trade secrets or
pharmaceutical regulatory protection or employing a combination of these methods. As of December 31, 2020, we had 235 issued
patents, including 19 Chinese patents, 22 U.S. patents and 13 European patents, 155 patent applications pending in the above major
market jurisdictions, and six pending Patent Cooperation Treaty, or PCT, patent applications relating to the drug candidates of our
Oncology/Immunology operations. For more details, see Item 4.B. “Business Overview—Patents and Other Intellectual Property.”
Patents may become invalid and patent applications may not be granted for a number of reasons, including known or unknown prior art,
deficiencies in the patent application or the lack of originality of the technology. In addition, the PRC and the United States have adopted
the “first-to-file” system under which whoever first files an invention patent application will be awarded the patent. Under the first-to-
file system, third parties may be granted a patent relating to a technology which we invented. Furthermore, the terms of patents are
finite. The patents we hold and patents to be issued from our currently pending patent applications generally have a twenty-year
protection period starting from the date of application.
We, our joint ventures and/or our collaboration partners may become involved in patent litigation against third parties to enforce
our or their patent rights, to invalidate patents held by such third parties, or to defend against such claims. A court may refuse to stop
the other party from using the technology at issue on the grounds that our or our joint ventures’ patents do not cover the third-party
technology in question. Further, such third parties could counterclaim that we or our joint ventures infringe their intellectual property or
that a patent we, our joint ventures or our collaboration partners have asserted against them is invalid or unenforceable. In patent
litigation, defendant counterclaims challenging the validity, enforceability or scope of asserted patents are commonplace. In addition,
third parties may initiate legal proceedings against us or our intellectual property to assert such challenges to our intellectual property
rights.
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The outcome of any such proceeding is generally unpredictable. Grounds for a validity challenge could be an alleged failure to meet
any of several statutory requirements, including lack of novelty, obviousness or non-enablement. Patents may be unenforceable if
someone connected with prosecution of the patent withheld relevant information or made a misleading statement during prosecution. It
is possible that prior art of which we, our joint ventures or our collaboration partners and the patent examiner were unaware during
prosecution exists, which could render our or their patents invalid. Moreover, it is also possible that prior art may exist that we, our joint
ventures or our collaboration partners are aware of but do not believe is relevant to our or their current or future patents, but that could
nevertheless be determined to render our patents invalid. The cost to us or our joint ventures of any patent litigation or similar proceeding
could be substantial, and it may consume significant management time. We and our joint ventures do not maintain insurance to cover
intellectual property infringement.
An adverse result in any litigation proceeding could put one or more of our or our joint ventures’ patents at risk of being invalidated
or interpreted narrowly. If a defendant were to prevail on a legal assertion of invalidity or unenforceability of our patents covering one
of our or our joint ventures’ products or our drug candidates, we could lose at least part, and perhaps all, of the patent protection covering
such product or drug candidate. Competing drugs may also be sold in other countries in which our or our joint ventures’ patent coverage
might not exist or be as strong. If we lose a foreign patent lawsuit, alleging our or our joint ventures’ infringement of a competitor’s
patents, we could be prevented from marketing our drugs in one or more foreign countries. Any of these outcomes would have a
materially adverse effect on our business.
Intellectual property and confidentiality legal regimes in China may not afford protection to the same extent as in the United States
or other countries. Implementation and enforcement of PRC intellectual property laws may be deficient and ineffective. Policing
unauthorized use of proprietary technology is difficult and expensive, and we or our joint ventures may need to resort to litigation to
enforce or defend patents issued to us or them or to determine the enforceability, scope and validity of our proprietary rights or those of
others. The experience and capabilities of PRC courts in handling intellectual property litigation varies, and outcomes are unpredictable.
Further, such litigation may require a significant expenditure of cash and may divert management’s attention from our or our joint
ventures’ operations, which could harm our business, financial condition and results of operations. An adverse determination in any
such litigation could materially impair our or our joint ventures’ intellectual property rights and may harm our business, prospects and
reputation.
Developments in patent law could have a negative impact on our business.
From time to time, authorities in the United States, China and other government authorities may change the standards of
patentability, and any such changes could have a negative impact on our business.
For example, in the United States, the Leahy-Smith America Invents Act, or the America Invents Act, which was signed into law
in 2011, includes a number of significant changes to U.S. patent law. These changes include a transition from a “first-to-invent” system
to a “first-to-file” system, changes to the way issued patents are challenged, and changes to the way patent applications are disputed
during the examination process. As a result of these changes, patent law in the United States may favor larger and more established
companies that have greater resources to devote to patent application filing and prosecution. The U.S. Patent and Trademark Office, or
USPTO, has developed new and untested regulations and procedures to govern the full implementation of the America Invents Act, and
many of the substantive changes to patent law associated with the America Invents Act, and, in particular, the first-to-file provisions
became effective on March 16, 2013. Substantive changes to patent law associated with the America Invents Act may affect our ability
to obtain patents, and if obtained, to enforce or defend them. Accordingly, it is not clear what, if any, impact the America Invents Act
will have on the cost of prosecuting our or our joint ventures’ patent applications and our or their ability to obtain patents based on our
or our joint ventures’ discoveries and to enforce or defend any patents that may issue from our or their patent applications, all of which
could have a material adverse effect on our business.
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If we are unable to maintain the confidentiality of our and our joint ventures’ trade secrets, the business and competitive position of
ourselves and our joint ventures may be harmed.
In addition to the protection afforded by patents and the PRC’s State Secret certification, we and our joint ventures rely upon
unpatented trade secret protection, unpatented know-how and continuing technological innovation to develop and maintain our
competitive position. We seek to protect our and our joint ventures’ proprietary technology and processes, in part, by entering into
confidentiality agreements with our and their collaborators, scientific advisors, employees and consultants, and invention assignment
agreements with our and their consultants and employees. We and our joint ventures may not be able to prevent the unauthorized
disclosure or use of our or their technical know-how or other trade secrets by the parties to these agreements, however, despite the
existence generally of confidentiality agreements and other contractual restrictions. If any of the collaborators, scientific advisors,
employees and consultants who are parties to these agreements breaches or violates the terms of any of these agreements, we and our
joint ventures may not have adequate remedies for any such breach or violation, and we could lose our trade secrets as a result. Enforcing
a claim that a third-party illegally obtained and is using our or our joint ventures’ trade secrets, like patent litigation, is expensive and
time consuming, and the outcome is unpredictable. In addition, courts in China and other jurisdictions outside the United States are
sometimes less prepared or willing to protect trade secrets.
Our and our joint ventures’ trade secrets could otherwise become known or be independently discovered by our or their competitors.
For example, competitors could purchase our drugs and attempt to replicate some or all of the competitive advantages we derive from
our development efforts, willfully infringe our intellectual property rights, design around our protected technology or develop their own
competitive technologies that fall outside of our intellectual property rights. If any of our or our joint ventures’ trade secrets were to be
lawfully obtained or independently developed by a competitor, we and our joint ventures would have no right to prevent them, or others
to whom they communicate it, from using that technology or information to compete against us or our joint ventures. If our or our joint
ventures’ trade secrets are unable to adequately protect our business against competitors’ drugs, our competitive position could be
adversely affected, as could our business.
We and our joint ventures are dependent on trademark and other intellectual property rights licensed from others. If we lose our
licenses for any of our products, we or our joint ventures may not be able to continue developing such products or may be required
to change the way we market such products.
We and our joint ventures are parties to licenses that give us or them rights to third-party intellectual property that are necessary
or useful for our or our joint ventures’ businesses. In particular, the “Hutchison,” “Chi-Med”, “Hutchison China MediTech”
and “Hutchmed” brands, among others, have been licensed to us by Hutchison Whampoa Enterprises Limited, an affiliate of our
largest shareholder, Hutchison Healthcare Holdings Limited. Hutchison Whampoa Enterprises Limited grants us a royalty-free,
worldwide license to such brands. Under the terms of our brand license agreement, Hutchison Whampoa Enterprises Limited
has the right to terminate the license if, among other things, we commit a material breach of the agreement, or within any twelve-
month period the aggregate direct or indirect shareholding in our company held by CK Hutchison is reduced to less than 40%, 30% or
20%. Furthermore, the Elunate trademark is licensed to us in China by our collaboration partner Eli Lilly.
In addition, the “Baiyunshan” brand, which is a key brand used by Hutchison Baiyunshan on its products, has been licensed to
Hutchison Baiyunshan by our joint venture partner, Guangzhou Baiyunshan, for use during the 50-year joint venture period; however,
Guangzhou Baiyunshan has the right to terminate the license if its interest in Hutchison Baiyunshan falls below 50%. If any such license
is terminated, our or Hutchison Baiyunshan’s business, and our or their positioning in the Chinese market and our financial condition,
results of operations and prospects may be materially and adversely affected.
In some cases, our licensors have retained the right to prosecute and defend the intellectual property rights licensed to us or our
joint ventures. We depend in part on the ability of our licensors to obtain, maintain and enforce intellectual property protection for such
licensed intellectual property. Such licensors may not successfully maintain their intellectual property, may determine not to pursue
litigation against other companies that are infringing on such intellectual property, or may pursue litigation less aggressively than we or
our joint ventures would. Without protection for the intellectual property we or our joint ventures license, other companies might be
able to offer substantially identical products or branding, which could adversely affect our competitive business position and harm our
business prospects.
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If our or our joint ventures’ products or drug candidates infringe the intellectual property rights of third parties, we and they may
incur substantial liabilities, and we and they may be unable to sell these products.
Our commercial success depends significantly on our and our joint ventures’ ability to operate without infringing the patents and
other proprietary rights of third parties. In the PRC, invention patent applications are generally maintained in confidence until their
publication 18 months from the filing date. The publication of discoveries in the scientific or patent literature frequently occurs
substantially later than the date on which the underlying discoveries were made and invention patent applications are filed. Even after
reasonable investigation, we may not know with certainty whether any third-party may have filed a patent application without our
knowledge while we or our joint ventures are still developing or producing that product. While the success of pending patent applications
and applicability of any of them to our or our joint ventures’ programs are uncertain, if asserted against us or them, we could incur
substantial costs and we or they may have to:
•
•
•
obtain licenses, which may not be available on commercially reasonable terms, if at all;
redesign products or processes to avoid infringement; and
stop producing products using the patents held by others, which could cause us or them to lose the use of one or more of our or
their products.
To date, we and our joint ventures have not received any material claims of infringement by any third parties. If a third-party claims
that we or our joint ventures infringe its proprietary rights, any of the following may occur:
• we or our joint ventures may have to defend litigation or administrative proceedings that may be costly whether we or they win
or lose, and which could result in a substantial diversion of management resources;
• we or our joint ventures may become liable for substantial damages for past infringement if a court decides that our technology
infringes a third-party’s intellectual property rights;
•
a court may prohibit us or our joint ventures from producing and selling our or their product(s) without a license from the
holder of the intellectual property rights, which may not be available on commercially acceptable terms, if at all; and
• we or our joint ventures may have to reformulate product(s) so that it does not infringe the intellectual property rights of others,
which may not be possible or could be very expensive and time consuming.
Any costs incurred in connection with such events or the inability to sell our or our joint ventures’ products may have a material
adverse effect on our business and results of operations.
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We, our joint ventures and our collaboration partners may not be able to effectively enforce our intellectual property rights
throughout the world.
Filing, prosecuting and defending patents on our or our joint venture’s products or drug candidates in all countries throughout the
world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly in developing
countries. Moreover, our, our joint ventures’ or our collaboration partners’ ability to protect and enforce our or their intellectual property
rights may be adversely affected by unforeseen changes in foreign intellectual property laws. Additionally, the patent laws of some
foreign countries do not afford intellectual property protection to the same extent as the laws of the United States. Many companies have
encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal
systems of some countries, particularly developing countries, may not favor the enforcement of patents and other intellectual property
rights. This could make it difficult for us or our joint ventures to stop the infringement of our or their patents or the misappropriation of
our or their other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent
owner must grant licenses to third parties. Consequently, we may not be able to prevent third parties from practicing our or our joint
ventures’ inventions throughout the world. Competitors may use our or our joint ventures’ technologies in jurisdictions where we or
they have not obtained patent protection to develop their own drugs and, further, may export otherwise infringing drugs to territories
where we or our joint ventures have patent protection, if our, our joint ventures’ or our collaboration partners’ ability to enforce our or
their patents to stop infringing activities is inadequate. These drugs may compete with our drug candidates, and our patents or other
intellectual property rights may not be effective or sufficient to prevent them from competing.
Proceedings to enforce our or our joint ventures’ patent rights in foreign jurisdictions, whether or not successful, could result in
substantial costs and divert our or their efforts and resources from other aspects of our and their businesses. While we intend to protect
our intellectual property rights in the major markets for our drug candidates, we cannot ensure that we will be able to initiate or maintain
similar efforts in all jurisdictions in which we may wish to market our drug candidates. Furthermore, as AstraZeneca is responsible for
enforcing our intellectual property rights with respect to savolitinib on our behalf, we may be unable to ensure that such rights are
enforced or maintained in all jurisdictions. Accordingly, our efforts to protect the intellectual property rights of our drug candidates in
such countries may be inadequate.
We and our joint ventures may be subject to damages resulting from claims that we or they, or our or their employees, have wrongfully
used or disclosed alleged trade secrets of competitors or are in breach of non-competition or non-solicitation agreements with
competitors.
We and our joint ventures could in the future be subject to claims that we or they, or our or their employees, have inadvertently or
otherwise used or disclosed alleged trade secrets or other proprietary information of former employers or competitors. Although we try
to ensure that our and our joint ventures’ employees and consultants do not improperly use the intellectual property, proprietary
information, know-how or trade secrets of others in their work for us or our joint ventures, we or our joint ventures may in the future be
subject to claims that we or they caused an employee to breach the terms of his or her non-competition or non-solicitation agreement,
or that we, our joint ventures, or these individuals have, inadvertently or otherwise, used or disclosed the alleged trade secrets or other
proprietary information of a former employer or competitor. Litigation may be necessary to defend against these claims. Even if we and
our joint ventures are successful in defending against these claims, litigation could result in substantial costs and could be a distraction
to management. If our or our joint ventures’ defenses to these claims fail, in addition to requiring us and them to pay monetary damages,
a court could prohibit us or our joint ventures from using technologies or features that are essential to our or their products or our drug
candidates, if such technologies or features are found to incorporate or be derived from the trade secrets or other proprietary information
of the former employers. An inability to incorporate such technologies or features would have a material adverse effect on our business,
and may prevent us from successfully commercializing our drug candidates. In addition, we or our joint ventures may lose valuable
intellectual property rights or personnel as a result of such claims. Moreover, any such litigation or the threat thereof may adversely
affect our or our joint ventures’ ability to hire employees or contract with independent sales representatives. A loss of key personnel or
their work product could hamper or prevent our ability to commercialize our drug candidates, which would have an adverse effect on
our business, results of operations and financial condition.
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Patent terms may be inadequate to protect the competitive position of our drug candidates for an adequate amount of time, and the
absence of patent linkage, patent term extension and data and market exclusivity for NMPA-approved pharmaceutical products
could increase the risk of early generic competition for our drug candidates in China.
In the United States, the Drug Price Competition and Patent Term Restoration Act of 1984, generally referred to as the Hatch-
Waxman Amendments, and similar legislation in the E.U. and certain other countries, provides the opportunity for limited patent term
extension. The Hatch-Waxman Amendments permit a patent-term extension of up to five years to reflect patent term lost during certain
portions of product development and the FDA regulatory review process. However, a patent term extension cannot extend the remaining
term of a patent beyond a total of 14 years from the date of drug approval; only one patent may be extended and only those claims
covering the approved drug, a method for using it, or a method for manufacturing it may be extended. The application for the extension
must be submitted prior to the expiration of the patent for which extension is sought. A patent that covers multiple products for which
approval is sought can only be extended in connection with one of the approvals. Depending upon the timing, duration and specifics of
any FDA marketing approval process for any drug candidates we may develop, one or more of our U.S. patents may be eligible for
limited patent term extension under the Hatch-Waxman Amendments. However, we may not be granted an extension because of, for
example, failing to exercise due diligence during the testing phase or regulatory review process, failing to apply within applicable
deadlines, failing to apply prior to expiration of relevant patents, or otherwise failing to satisfy applicable requirements. Moreover, the
applicable period or the scope of patent protection afforded could be less than we request. In addition, to the extent we wish to pursue
patent term extension based on a patent that we in-license from a third party, we would need the cooperation of that third party. If we
fail to obtain patent term extensions or if the term of any such extension is less than we request, our competitors may obtain approval of
competing products following our patent expiration, and thus our revenue could be reduced. Further, if this occurs, our competitors may
take advantage of our investment in development and trials by referencing our clinical and preclinical data and launch their product
earlier than might otherwise be expected, and our competitive position, business, financial condition, results of operations and prospects
could be materially adversely affected.
The Hatch-Waxman Amendments also include a process for patent linkage, pursuant to which the FDA will stay approval of certain
follow-on applications during the pendency of litigation between the follow-on applicant and the patent holder or licensee, generally for
a period of 30 months. Moreover, the Hatch-Waxman Amendments provide for statutory exclusivities that can prevent submission or
approval of certain follow-on marketing applications. For example, federal law provides a five-year period of exclusivity within the
United States to the first applicant to obtain approval of a new chemical entity and three years of exclusivity protecting certain
innovations to previously approved active ingredients where the applicant was required to conduct new clinical investigations to obtain
approval for the modification. Similarly, the U.S. Orphan Drug Act provides seven years of market exclusivity for certain drugs to treat
rare diseases, where the FDA designates the drug candidate as an orphan drug and the drug is approved for the designated orphan
indication. See “Risks Relating to Our Oncology/Immunology Operations and Development of Our Drug Candidates—Although we
have obtained orphan drug designation for surufatinib for the treatment of pancreatic neuroendocrine tumors in the United States, we
may not be able to obtain or maintain the benefits associated with orphan drug status, including market exclusivity.”
In China, however, there is no currently effective law or regulation providing patent term extension, patent linkage, or data
exclusivity (referred to as regulatory data protection). Therefore, a lower-cost generic drug can emerge onto the market much more
quickly. Chinese regulators have set forth a framework for integrating patent linkage and data exclusivity into the Chinese regulatory
regime, as well as for establishing a pilot program for patent term extension. To be implemented, this framework will require adoption
of regulations. On October 17, 2020, the Standing Committee of the National People’s Congress published the Patent Law of PRC
(Amended in 2020), which will come into effect on June 1, 2021, or the Amended Patent Law. The Amended Patent Law provides that,
among other things, the owner of the patent for an innovative new drug that has been granted the marketing authorization in China is
entitled to request the Patent Administration Department under the State Council to grant a patent term extension of up to five years, in
order to compensate the time required for the regulatory approval for the commercialization of such innovative new drug, provided that
the patent term of such innovative new drug shall not exceed a total of 14 years. Furthermore, the PRC government entered into the
Economic and Trade Agreement Between the Government of the People’s Republic of China and the Government of the United States
of America with the U.S. government in January 2020 which provides that the owner of the patent for an innovative new drug that has
been granted the marketing authorization in China is entitled to request a patent term extension of up to five years, provided that, the
patent term of such innovative new drug shall not exceed a total of 14 years from the date of marketing approval in China. If we are
unable to obtain patent term extension, or the term of any such extension is less than that we request, our competitors or other third
parties may obtain approval of competing products following our patent expiration. Any of the foregoing could have a material adverse
effect on our competitive position, business, financial condition, results of operations and prospects.
48
Risks Relating to Our ADSs
Our audit report and the audit reports of our non-consolidated joint ventures included in this annual report are prepared by auditors
who are not inspected by the PCAOB. As such, you are deprived of the benefits of a PCAOB inspection. In addition, various legislative
and regulatory developments related to U.S.-listed China-based companies due to lack of PCAOB inspection and other developments
may have a material adverse impact on our listing and trading in the U.S. and the trading prices of our ADSs. We could be delisted
from the Nasdaq if the PCAOB continues to be unable to inspect our independent registered public accounting firm for three
consecutive years.
Our auditor and the auditors for our non-consolidated joint ventures are registered with the PCAOB. Pursuant to laws in the United
States, the PCAOB has authority to conduct regular inspections over independent registered public accounting firms registered with the
PCAOB to assess their compliance with the applicable professional standards. Our auditor is located in Hong Kong, a special
administrative region of China, a jurisdiction where the PCAOB is currently unable to conduct full inspections without the approval of
the Chinese authorities. The auditors of our non-consolidated joint ventures are located in mainland China. As a result, we understand
that our auditor and the auditors for our non-consolidated joint ventures are not currently inspected by the PCAOB.
This lack of PCAOB inspections in China prevents the PCAOB from fully evaluating audits and quality control procedures of our
auditor and the auditors of our non-consolidated joint ventures. As a result, we and investors in our securities are deprived of the benefits
of such PCAOB inspections. The inability of the PCAOB to conduct inspections of auditors in China makes it more difficult to evaluate
the effectiveness of the audit procedures or quality control procedures of our auditor and the auditors of our non-consolidated joint
ventures as compared to auditors outside of China that are subject to the PCAOB inspections, which could cause investors and potential
investors in our securities to lose confidence in our audit procedures and reported financial information and the quality of our financial
statements.
In May 2013, the PCAOB announced that it had entered into a Memorandum of Understanding on Enforcement Cooperation with
the China Securities Regulatory Commission, or the CSRC, and the PRC Ministry of Finance, which established a cooperative
framework between the parties for the production and exchange of audit documents relevant to investigations undertaken by the PCAOB,
the CSRC or the PRC Ministry of Finance in the United States and the PRC. The PCAOB continued to discuss with the CSRC and the
PRC Ministry of Finance on joint inspections in the PRC of PCAOB-registered audit firms that provide auditing services to Chinese
companies that trade on U.S. stock exchanges. In December 2018, the SEC and the PCAOB issued a joint statement on regulatory access
to audit and other information internationally that cites the ongoing challenges faced by them in overseeing the financial reporting of
companies listed in the United States with operations in China, the absence of satisfactory progress in discussions on these issues with
Chinese authorities and the potential for remedial action if significant information barriers persist. In April 2020, the SEC and the
PCAOB issued another joint statement reiterating the greater risks of insufficient disclosures from companies in many emerging markets,
including China, compared to those from U.S. domestic companies. In discussing the specific issues related to these risks, the statement
again highlighted the PCAOB’s inability to inspect audit work and practices of accounting firms in China with respect to U.S. reporting
companies. In June 2020, the U.S. President issued a memorandum ordering the President’s Working Group on Financial Markets, or
the PWG, to submit a report to the President within 60 days of the memorandum that includes recommendations for actions that can be
taken by the executive branch and by the SEC or the PCAOB on Chinese companies listed on U.S. stock exchanges and their audit
firms. In August 2020, the PWG released the report. In particular, with respect to jurisdictions that do not grant the PCAOB sufficient
access to fulfill its statutory mandate, or NCJs, the PWG recommended that enhanced listing standards be applied to companies from
NCJs for seeking initial listing and remaining listed on U.S. stock exchanges. Under the enhanced listing standards, if the PCAOB does
not have access to work papers of the principal audit firm located in a NCJ for the audit of a U.S.-listed company as a result of
governmental restrictions, the U.S.-listed company may satisfy this standard by providing a co-audit from an audit firm with comparable
resources and experience where the PCAOB determines that it has sufficient access to the firm’s audit work papers and practices to
inspect the co-audit; there is currently no legal framework under which such a co-audit may be conducted for China-based companies.
The report recommended a transition period until January 1, 2022 before the new listing standards apply to companies already listed on
U.S. stock exchanges. Under the PWG recommendations, if we fail to meet the enhanced listing standards before January 1, 2022, we
could face de-listing from the Nasdaq, deregistration from the SEC and/or other risks, which may materially and adversely affect, or
effectively terminate, our ADS trading in the United States. There were recent media reports about the SEC’s proposed rulemaking in
this regard. It is uncertain whether the PWG recommendations will be adopted, in whole or in part, and the impact of any new rule on
us cannot be estimated at this time.
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As part of a continued regulatory focus in the United States on access to audit and other information currently protected by national
law, in particular China’s, in June 2019, a bipartisan group of lawmakers introduced bills in both houses of Congress that would require
the SEC to maintain a list of issuers for which the PCAOB is not able to inspect or investigate an auditor’s report issued by a foreign
public accounting firm. The Ensuring Quality Information and Transparency for Abroad-Based Listings on our Exchanges Act, or
EQUITABLE, prescribes increased disclosure requirements for such issuers and, beginning in 2025, the delisting from national
securities exchanges such as Nasdaq of issuers included for three consecutive years on the SEC’s list. On May 20, 2020, the U.S. Senate
passed S. 945, the Holding Foreign Companies Accountable Act, or the Act. The Act was approved by the U.S. House of Representatives
on December 2, 2020. The Act was signed into law by the president of the United States on December 18, 2020. In essence, the Act
requires the SEC to prohibit foreign companies from listing securities on U.S. securities exchanges if a company retains a foreign
accounting firm that cannot be inspected by the PCAOB for three consecutive years, beginning in 2021. The enactment of the Act and
any additional rulemaking efforts to increase U.S. regulatory access to audit information in China could cause investor uncertainty for
affected SEC registrants, including us, the market price of our securities could be materially adversely affected, and we could be delisted
from Nasdaq if we are unable to meet the PCAOB inspection requirement in time.
Our largest shareholder owns a significant percentage of our ordinary shares, which may limit the ability of other shareholders to
influence corporate matters.
As of March 1, 2021, Hutchison Healthcare Holdings Limited owned approximately 45.69% of our ordinary shares. Accordingly,
Hutchison Healthcare Holdings Limited can influence the outcome of any corporate transaction or other matter submitted to shareholders
for approval and the interests of Hutchison Healthcare Holdings Limited may differ from the interests of our other shareholders. Under
our Articles of Association, certain matters, such as amendments to our amended and restated Memorandum and Articles of Association,
require the approval of not less than three-fourths of votes cast by such shareholders as, being entitled so to do, vote in person (or, in the
case of such shareholders as are corporations, by their respective duly authorized representative) or by proxy. Therefore, Hutchison
Healthcare Holdings Limited’s approval will be required to achieve any such threshold. In addition, Hutchison Healthcare Holdings
Limited has and will continue to have a significant influence over the management and the strategic direction of our company.
Substantial future sales or perceived potential sales of our ADSs, ordinary shares or other equity or equity-linked securities in the
public market could cause the price of our ADSs to decline significantly.
Sales of our ADSs, ordinary shares or other equity or equity-linked securities in the public market, or the perception that these sales
could occur, could cause the market price of our ADSs to decline significantly. All of our ordinary shares represented by ADSs are
freely transferable by persons other than our affiliates without restriction or additional registration under the Securities Act of 1933, or
the Securities Act. The ordinary shares held by our affiliates are also available for sale, subject to volume and other restrictions as
applicable under Rules 144 and 701 under the Securities Act, under sales plans adopted pursuant to Rule 10b5-1 or otherwise.
We have filed with the SEC registration statements on Form F-3, commonly referred to as a “shelf registration,” that permit us to
sell any number of ADSs in a registered offering at our discretion. We have completed registered offerings raising aggregate gross
proceeds of approximately $537.9 million under such shelf registration statements. In addition, our largest shareholder has completed
registered secondary offerings raising aggregate gross proceeds of approximately $310.4 million for it as a selling shareholder under a
shelf registration statement. We may decide to conduct future offerings from time to time, and such sales could cause the price of our
ADSs to decline significantly.
In connection with the issuance of ordinary shares in private placements in 2020, we agreed to provide two shareholders Form F-3
registration rights. Registration of the ordinary shares held by such shareholders may result in these shares becoming freely tradable
without restriction under the Securities Act immediately upon the effectiveness of the registration. Sales of these shares, or the perception
that such sales could occur, could cause the price of our ADSs to decline. In addition, any changes in the investment strategies or
philosophies of our major shareholders may lead to the sale of our ADSs and other securities, which could cause the price of our ADSs
to decline.
We may be at a risk of securities litigation.
Historically, securities litigation, particularly class action lawsuits brought in the United States, have often been brought against a
company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology and
biopharmaceutical companies have experienced significant share price volatility in recent years. If we were to be sued, it could result in
substantial costs and a diversion of management’s attention and resources, which could harm our business.
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If securities analysts do not publish research or reports about our business or if they publish negative evaluations of our business,
the price of our ADSs could decline.
The trading market for our ADSs will rely in part on the research and reports that industry or financial analysts publish about us or
our business. We may not be able to maintain continuous research coverage by industry or financial analysts. If one or more of the
analysts covering our business downgrade their evaluations of our stock, the price of our stock could decline. If one or more of these
analysts cease to cover our stock, we could lose visibility in the market for our stock, which in turn could cause our stock price to decline.
As a foreign private issuer, we are not subject to certain U.S. securities law disclosure requirements that apply to a domestic U.S.
issuer, which may limit the information publicly available to our shareholders.
As a foreign private issuer we are not required to comply with all of the periodic disclosure and current reporting requirements of
the Exchange Act and therefore there may be less publicly available information about us than if we were a U.S. domestic issuer. For
example, we are not subject to the proxy rules in the United States and disclosure with respect to our annual general meetings will be
governed by the AIM Rules for Companies, or the AIM Rules, and Cayman Islands requirements. In addition, our officers, directors
and principal shareholders are exempt from the reporting and “short-swing” profit recovery provisions of Section 16 of the Exchange
Act and the rules thereunder. Therefore, our shareholders may not know on a timely basis when our officers, directors and principal
shareholders purchase or sell our ordinary shares or ADSs.
As a foreign private issuer, we are permitted to adopt certain home country practices in relation to corporate governance matters
that differ significantly from Nasdaq corporate governance listing standards. These practices may afford less protection to
shareholders than they would enjoy if we complied fully with corporate governance listing standards.
As a foreign private issuer, we are permitted to take advantage of certain provisions in the Nasdaq listing rules that allow us to
follow Cayman Islands law for certain governance matters. Certain corporate governance practices in the Cayman Islands may differ
significantly from corporate governance listing standards as, except for general fiduciary duties and duties of care, Cayman Islands law
has no corporate governance regime which prescribes specific corporate governance standards. We intend to continue to follow Cayman
Islands corporate governance practices in lieu of the corporate governance requirements of the Nasdaq Global Select Market in respect
of the following: (i) the majority independent director requirement under Section 5605(b)(1) of the Nasdaq listing rules, (ii) the
requirement under Section 5605(d) of the Nasdaq listing rules that a remuneration committee comprised solely of independent directors
governed by a remuneration committee charter oversee executive compensation and (iii) the requirement under Section 5605(e) of the
Nasdaq listing rules that director nominees be selected or recommended for selection by either a majority of the independent directors
or a nominations committee comprised solely of independent directors. Cayman Islands law does not impose a requirement that our
board of directors consist of a majority of independent directors. Nor does Cayman Islands law impose specific requirements on the
establishment of a remuneration committee or nominating committee or nominating process. Therefore, our shareholders may be
afforded less protection than they otherwise would have under corporate governance listing standards applicable to U.S. domestic
issuers. We have voluntarily complied with many of the principles of the U.K. published by the U.K. Financial Reporting Council which
guides certain of our other corporate governance practices. See Item 6.C. “Board Practice—U.K. Corporate Governance Code” for more
details.
Fluctuations in the value of the renminbi may have a material adverse effect on your investment.
The value of the renminbi against the U.S. dollar and other currencies fluctuates and is affected by, among other things, changes in
China’s and international political and economic conditions and the PRC government’s fiscal and currency policies. Since 1994, the
conversion of renminbi into foreign currencies, including U.S. dollars, has been based on rates set by the PBOC, which are set daily
based on the previous business day’s inter-bank foreign exchange market rates and current exchange rates on the world financial markets.
It is expected that China may further reform its exchange rate system in the future.
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Significant revaluation of the renminbi may have a material adverse effect on your investment. For example, to the extent that we
need to convert U.S. dollars into renminbi for our operations, appreciation of the renminbi against the U.S. dollar would have an adverse
effect on the renminbi amount we would receive from the conversion. Conversely, if we decide to convert our renminbi into U.S. dollars,
appreciation of the U.S. dollar against the renminbi would have a negative effect on the U.S. dollar amount available to us. Appreciation
or depreciation in the value of the renminbi relative to the U.S. dollar would affect our financial results reported in U.S. dollar terms
regardless of any underlying change in our business or results of operations. In addition, our operating transactions and assets and
liabilities in the PRC are mainly denominated in renminbi. Such amounts are translated into U.S. dollars for purpose of preparing our
consolidated financial statements, with translation adjustments reflected in accumulated other comprehensive income/(loss) in
shareholders’ equity. We recorded a foreign currency translation loss of $6.6 million and $4.3 million and a foreign currency translation
gain of $9.5 million for the years ended December 31, 2018, 2019 and 2020, respectively.
Very limited hedging options are available in China to reduce our exposure to exchange rate fluctuations. To date, we have not
entered into any hedging transactions in an effort to reduce our exposure to foreign currency exchange risk. While we may decide to
enter into hedging transactions in the future, the availability and effectiveness of these hedges may be limited and we may not be able
to adequately hedge our exposure or at all. In addition, our currency exchange losses may be magnified by PRC exchange control
regulations that restrict our ability to convert renminbi into foreign currency.
We may in the future lose our foreign private issuer status under U.S. securities laws, which could result in significant additional
costs and expenses.
We are a foreign private issuer as defined in the Securities Act, and therefore, we are not required to comply with all of the periodic
disclosure and current reporting requirements of the Exchange Act. The determination of foreign private issuer status is made annually
on the last business day of an issuer’s most recently completed second fiscal quarter, and, accordingly, the next determination will be
made with respect to us on June 30, 2021. We would lose our foreign private issuer status if, for example, more than 50% of our ordinary
shares are directly or indirectly held by residents of the United States on June 30, 2021 and we fail to meet additional requirements
necessary to maintain our foreign private issuer status. If we lose our foreign private issuer status on this date, we will be required to file
with the SEC periodic reports and registration statements on U.S. domestic issuer forms beginning on January 1, 2022, which are more
detailed and extensive than the forms available to a foreign private issuer. We will also have to mandatorily comply with U.S. federal
proxy requirements, and our officers, directors and principal shareholders will become subject to the short-swing profit disclosure and
recovery provisions of Section 16 of the Exchange Act. In addition, we will lose our ability to rely upon exemptions from certain
corporate governance requirements under the Nasdaq listing rules. As a U.S.-listed public company, should we lose our foreign private
issuer status, we will incur significant additional legal, accounting and other expenses that we would not incur as a foreign private issuer.
We do not currently intend to pay dividends on our securities, and, consequently, your ability to achieve a return on your investment
will depend on appreciation in the price of the ADSs.
We have never declared or paid any dividends on our ordinary shares. We currently intend to invest our future earnings, if any, to
fund our growth. Therefore, you are not likely to receive any dividends on your ADSs at least in the near term, and the success of an
investment in ADSs will depend upon any future appreciation in its value. Consequently, investors may need to sell all or part of their
holdings of ADSs after price appreciation, which may never occur, to realize any future gains on their investment. There is no guarantee
that the ADSs will appreciate in value or even maintain the price at which our shareholders have purchased the ADSs.
The trading prices for our ADSs may be volatile which could result in substantial losses to you.
The market price of our ADSs has been volatile. From March 17, 2016 to March 1, 2021, the closing sale price of our ADSs ranged
from a high of $41.14 to a low of $11.26 per ADS.
The market price for our ADSs is likely to be highly volatile and subject to wide fluctuations in response to factors, including the
following:
•
•
•
announcements of competitive developments;
regulatory developments affecting us, our customers or our competitors;
announcements regarding litigation or administrative proceedings involving us;
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•
•
•
•
•
actual or anticipated fluctuations in our period-to-period operating results;
changes in financial estimates by securities research analysts;
additions or departures of our executive officers;
release or expiry of lock-up or other transfer restrictions on our outstanding ordinary shares or ADSs; and
sales or perceived sales of additional ordinary shares or ADSs.
In addition, the securities markets have from time to time experienced significant price and volume fluctuations that are not related
to the operating performance of particular companies. For example, in 2020, the exchanges in China experienced a sharp decline as a
result of a slowdown in the Chinese economy and trade tensions with the United States. Prolonged global capital markets volatility may
affect overall investor sentiment towards our ADSs, which would also negatively affect the trading prices for our ADSs.
The dual listing of our ordinary shares and the ADSs may adversely affect the liquidity and value of the ADSs.
Our ordinary shares are listed on the AIM market of the London Stock Exchange. The dual listing of our ordinary shares and the
ADSs may dilute the liquidity of these securities in one or both markets and may adversely affect the development of an active trading
market for the ADSs in the United States. The price of the ADSs could also be adversely affected by trading in our ordinary shares on
the AIM market. Furthermore, our ordinary shares trade on the AIM market of the London Stock Exchange in the form of depository
interests, each of which is an electronic book-entry interest representing one of our ordinary shares. However, the ADSs are backed by
physical ordinary share certificates, and the depositary for our ADS program is unable to accept depository interests into its custody in
order to issue ADSs. As a result, if an ADS holder wishes to cancel its ADSs and instead hold depository interests for trading on the
AIM market or vice versa, the issuance and cancellation process may be longer than if the depositary could accept such depository
interests.
Although our ordinary shares continue to be listed on the AIM market following our initial public offering in the United States
completed in March 2016, we may decide at some point in the future to propose to our ordinary shareholders to delist our ordinary
shares from the AIM market, and our ordinary shareholders may approve such delisting. We cannot predict the effect such delisting of
our ordinary shares on the AIM market would have on the market price of the ADSs on the Nasdaq Global Select Market.
Fluctuations in the exchange rate between the U.S. dollar and the pound sterling may increase the risk of holding the ADSs.
Our share price is quoted on the AIM market of the London Stock Exchange in pence sterling, while the ADSs will trade on Nasdaq
in U.S. dollars. Fluctuations in the exchange rate between the U.S. dollar and the pound sterling may result in temporary differences
between the value of the ADSs and the value of our ordinary shares, which may result in heavy trading by investors seeking to exploit
such differences. In addition, as a result of fluctuations in the exchange rate between the U.S. dollar and the pound sterling, the U.S.
dollar equivalent of the proceeds that a holder of the ADSs would receive upon the sale in the United Kingdom of any shares withdrawn
from the depositary and the dollar equivalent of any cash dividends paid in pound sterling on our shares represented by the ADSs could
also decline.
Securities traded on the AIM market of the London Stock Exchange may carry a higher risk than shares traded on other exchanges
and may impact the value of your investment.
Our ordinary shares are currently traded on the AIM market of the London Stock Exchange. Investment in equities traded on AIM
is perceived by some to carry a higher risk than an investment in equities quoted on exchanges with more stringent listing requirements,
such as the New York Stock Exchange or the Nasdaq. This is because the AIM market imposes less stringent ongoing reporting
requirements than those other exchanges. You should be aware that the value of our ordinary shares may be influenced by many factors,
some of which may be specific to us and some of which may affect AIM-listed companies generally, including the depth and liquidity
of the market, our performance, a large or small volume of trading in our ordinary shares, legislative changes and general economic,
political or regulatory conditions, and that the prices may be volatile and subject to extensive fluctuations. Therefore, the market price
of our ordinary shares underlying the ADSs may not reflect the underlying value of our company.
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The depositary for our ADSs gives us a discretionary proxy to vote our ordinary shares underlying your ADSs if you do not vote at
shareholders’ meetings, except in limited circumstances, which could adversely affect your interests.
Under the deposit agreement for the ADSs, the depositary gives us a discretionary proxy to vote our ordinary shares underlying
your ADSs at shareholders’ meetings if you do not vote, unless:
• we do not wish a discretionary proxy to be given;
• we are aware or should reasonably be aware that there is substantial opposition as to a matter to be voted on at the meeting; or
•
a matter to be voted on at the meeting would materially and adversely affect the rights of shareholders.
The effect of this discretionary proxy is that you cannot prevent our ordinary shares underlying your ADSs from being voted, absent
the situations described above, and it may make it more difficult for shareholders to influence the management of our company. Holders
of our ordinary shares are not subject to this discretionary proxy.
Holders of ADSs have fewer rights than shareholders and must act through the depositary to exercise their rights.
Holders of our ADSs do not have the same rights as our shareholders and may only exercise the voting rights with respect to the
underlying ordinary shares in accordance with the provisions of the deposit agreement. Under our amended and restated Memorandum
and Articles of Association, an annual general meeting and any extraordinary general meeting at which the passing of a special resolution
is to be considered may be called with not less than 21 clear days’ notice, and all other extraordinary general meetings may be called
with not less than 14 clear days’ notice. When a general meeting is convened, you may not receive sufficient notice of a shareholders’
meeting to permit you to withdraw the ordinary shares underlying your ADSs to allow you to vote with respect to any specific matter.
If we ask for your instructions, we will give the depositary notice of any such meeting and details concerning the matters to be voted
upon at least 30 days in advance of the meeting date and the depositary will send a notice to you about the upcoming vote and will
arrange to deliver our voting materials to you. The depositary and its agents, however, may not be able to send voting instructions to
you or carry out your voting instructions in a timely manner. We will make all reasonable efforts to cause the depositary to extend voting
rights to you in a timely manner, but we cannot assure you that you will receive the voting materials in time to ensure that you can
instruct the depositary to vote the ordinary shares underlying your ADSs. Furthermore, the depositary will not be liable for any failure
to carry out any instructions to vote, for the manner in which any vote is cast or for the effect of any such vote. As a result, you may not
be able to exercise your right to vote and you may lack recourse if your ADSs are not voted as you request. In addition, in your capacity
as an ADS holder, you will not be able to call a shareholders’ meeting.
You may not receive distributions on our ADSs or any value for them if such distribution is illegal or if any required government
approval cannot be obtained in order to make such distribution available to you.
Although we do not have any present plan to pay any dividends, the depositary of our ADSs has agreed to pay to you the cash
dividends or other distributions it or the custodian receives on ordinary shares or other deposited securities underlying our ADSs, after
deducting its fees and expenses and any applicable taxes and governmental charges. You will receive these distributions in proportion
to the number of ordinary shares your ADSs represent. However, the depositary is not responsible if it decides that it is unlawful or
impractical to make a distribution available to any holders of ADSs. For example, it would be unlawful to make a distribution to a holder
of ADSs if it consists of securities whose offering would require registration under the Securities Act but is not so properly registered
or distributed under an applicable exemption from registration. The depositary may also determine that it is not reasonably practicable
to distribute certain property. In these cases, the depositary may determine not to distribute such property. We have no obligation to
register under the U.S. securities laws any offering of ADSs, ordinary shares, rights or other securities received through such
distributions. We also have no obligation to take any other action to permit the distribution of ADSs, ordinary shares, rights or anything
else to holders of ADSs. This means that you may not receive distributions we make on our ordinary shares or any value for them if it
is illegal or impractical for us to make them available to you. These restrictions may cause a material decline in the value of our ADSs.
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Your right to participate in any future rights offerings may be limited, which may cause dilution to your holdings.
We may from time to time distribute rights to our shareholders, including rights to acquire our securities. However, we cannot make
rights available to you in the United States unless we register the rights and the securities to which the rights relate under the Securities
Act or an exemption from the registration requirements is available. Also, under the deposit agreement, the depositary bank will not
make rights available to you unless either both the rights and any related securities are registered under the Securities Act, or the
distribution of them to ADS holders is exempted from registration under the Securities Act. We are under no obligation to file a
registration statement with respect to any such rights or securities or to endeavor to cause such a registration statement to be declared
effective. Moreover, we may not be able to establish an exemption from registration under the Securities Act. If the depositary does not
distribute the rights, it may, under the deposit agreement, either sell them, if possible, or allow them to lapse. Accordingly, you may be
unable to participate in our rights offerings and may experience dilution in your holdings.
If we are classified as a passive foreign investment company, U.S. investors could be subject to adverse U.S. federal income tax
consequences.
The rules governing passive foreign investment companies, or PFICs, can have adverse effects for U.S. investors for U.S. federal
income tax purposes. The tests for determining PFIC status for a taxable year depend upon the relative values of certain categories of
assets and the relative amounts of certain kinds of income. As discussed in “Taxation—Material U.S. Federal Income Tax
Considerations,” we do not believe that we are currently a PFIC. Notwithstanding the foregoing, the determination of whether we are a
PFIC depends on particular facts and circumstances (such as the valuation of our assets, including goodwill and other intangible assets)
and may also be affected by the application of the PFIC rules, which are subject to differing interpretations. The fair market value of
our assets is expected to depend, in part, upon (1) the market price of our ordinary shares and ADSs and (2) the composition of our
income and assets, which will be affected by how, and how quickly, we spend any cash that is raised in any financing transaction. In
light of the foregoing, no assurance can be provided that we are not currently a PFIC or that we will not become a PFIC in any future
taxable year. Furthermore, if we are treated as a PFIC, then one or more of our subsidiaries may also be treated as PFICs.
If we are or become a PFIC, and, if so, if one or more of our subsidiaries are treated as PFICs, U.S. holders of our ordinary shares
and ADSs would be subject to adverse U.S. federal income tax consequences, such as ineligibility for any preferential tax rates on capital
gains or on actual or deemed dividends, interest charges on certain taxes treated as deferred, and additional reporting requirements under
U.S. federal income tax laws and regulations. Whether U.S. holders of our ordinary shares or ADSs make (or are eligible to make) a
timely qualified electing fund, or QEF, election or a mark-to-market election may affect the U.S. federal income tax consequences to
U.S. holders with respect to the acquisition, ownership and disposition of our ordinary shares and ADSs and any distributions such U.S.
holders may receive. We do not, however, expect to provide the information regarding our income that would be necessary in order for
a U.S. holder to make a QEF election if we are classified as a PFIC. Investors should consult their own tax advisors regarding all aspects
of the application of the PFIC rules to our ordinary shares and ADSs.
You may have difficulty enforcing judgments obtained against us.
We are a company incorporated under the laws of the Cayman Islands, and substantially all of our assets are located outside the
United States. Substantially all of our current operations are conducted in the PRC. In addition, most of our directors and officers are
nationals and residents of countries other than the United States. A substantial portion of the assets of these persons are located outside
the United States. As a result, it may be difficult for you to effect service of process within the United States upon these persons. It may
also be difficult for you to enforce in U.S. courts judgments obtained in U.S. courts based on the civil liability provisions of the U.S.
federal securities laws against us and our officers and directors, all of whom are not residents in the United States and whose assets are
located outside the United States. In addition, there is uncertainty as to whether the courts of the Cayman Islands or the PRC would
recognize or enforce judgments of U.S. courts against us or such persons predicated upon the civil liability provisions of the securities
laws of the United States or any state.
You may be subject to limitations on transfers of your ADSs.
Your ADSs are transferable on the books of the depositary. However, the depositary may close its transfer books at any time or
from time to time when it deems expedient in connection with the performance of its duties. In addition, the depositary may refuse to
deliver, transfer or register transfers of ADSs generally when our books or the books of the depositary are closed, or at any time if we
or the depositary deems it advisable to do so because of any requirement of law or of any government or governmental body, or under
any provision of the deposit agreement, or for any other reason.
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It may be difficult for overseas regulators to conduct investigations or collect evidence within China.
Shareholder claims or regulatory investigation that are common in the United States generally are difficult to pursue as a matter of
law or practicality in China. For example, in China, there are significant legal and other obstacles to providing information needed for
regulatory investigations or litigation initiated outside China. Although the authorities in China may establish a regulatory cooperation
mechanism with the securities regulatory authorities of another country or region to implement cross-border supervision and
administration, such cooperation with the securities regulatory authorities in the Unities States may not be efficient in the absence of
mutual and practical cooperation mechanisms. Furthermore, according to Article 177 of the PRC Securities Law, or Article 177, which
became effective in March 2020, no overseas securities regulator is allowed to directly conduct investigations or evidence collection
activities within the territory of the PRC. While detailed interpretations of or implementation rules under Article 177 have yet to be
promulgated, the inability for an overseas securities regulator to directly conduct investigations or evidence collection activities within
China may further increase difficulties you may face in protecting your interests.
We are a Cayman Islands company. As judicial precedent regarding the rights of shareholders is more limited under Cayman Islands
law than under U.S. law or English law, shareholders may have different shareholder rights than they would have under U.S. law
or English law and may face difficulties in protecting your interests.
We are an exempted company with limited liability incorporated in the Cayman Islands. Our corporate affairs are governed by our
Articles of Association (as may be further amended from time to time), the Companies Act (as amended) of the Cayman Islands and the
common law of the Cayman Islands. The rights of shareholders to take action against the directors, actions by minority shareholders
and the fiduciary responsibilities of our directors are to a large extent governed by the common law of the Cayman Islands. This common
law is derived in part from comparatively limited judicial precedent in the Cayman Islands as well as from English common law, which
has persuasive, but not binding, authority on a court in the Cayman Islands. The rights of our shareholders and the fiduciary
responsibilities of our directors under Cayman Islands law are not as clearly established as they would be under statutes or judicial
precedent in England and some jurisdictions in the United States. In particular, the Cayman Islands has a less developed body of
securities law than the United States or the United Kingdom. In addition, some states in the United States, such as Delaware, have more
fully developed and judicially interpreted bodies of corporate law than the Cayman Islands.
In addition, as a Cayman Islands exempted company, our shareholders have no general rights under Cayman Islands law to inspect
corporate records and accounts or to obtain copies of lists of shareholders of these companies with the exception that the shareholders
may request a copy of the Articles of Association. Our directors have discretion under our Articles of Association to determine whether
or not, and under what conditions, our corporate records may be inspected by our shareholders, but are not obliged to make them
available to our shareholders. This may make it more difficult for you to obtain the information needed to establish any facts necessary
for a shareholder motion or to solicit proxies from other shareholders in connection with a proxy contest. As a Cayman Islands company,
we may not have standing to initiate a derivative action in U.S. federal courts or English courts. As a result, you may be limited in your
ability to protect your interests if you are harmed in a manner that would otherwise enable you to sue in U.S. federal courts or English
courts. In addition, shareholders of Cayman Islands companies may not have standing to initiate a shareholder derivative action in U.S.
federal courts or English courts.
Some of our directors and executive officers reside outside of the United States and a substantial portion of their assets are located
outside of the United States. As a result, it may be difficult or impossible for you to bring an action against us or against these individuals
in the United States in the event that you believe that your rights have been infringed under the securities laws of the United States or
otherwise. In addition, some of our operating subsidiaries are incorporated in China. To the extent our directors and executive officers
reside in China or their assets are located in China, it may not be possible for investors to effect service of process upon us or our
management inside China. Even if you are successful in bringing an action, the laws of the Cayman Islands and China may render you
unable to enforce a judgment against our assets or the assets of our directors and officers. There is no statutory recognition in the Cayman
Islands of judgments obtained in the United States or China, although the courts of the Cayman Islands will generally recognize and
enforce a non-penal judgment of a foreign court of competent jurisdiction without retrial on the merits.
As a result of all of the above, public shareholders may have more difficulty in protecting their interests in the face of actions taken
by management, members of the board of directors or controlling shareholders than they would as public shareholders of an English
company or a U.S. company.
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ITEM 4. INFORMATION ON THE COMPANY
A. History and Development of the Company.
Hutchison China MediTech Limited was incorporated in the Cayman Islands on December 18, 2000 as an exempted company with
limited liability under the Companies Act, Cap 22 (Act 3 of 1961, as consolidated and revised) of the Cayman Islands. Our company
was founded by a wholly owned subsidiary of CK Hutchison, a multinational conglomerate with operations in over 50 countries. CK
Hutchison is the ultimate parent company of our largest shareholder Hutchison Healthcare Holdings Limited.
We launched our novel drug research and development operations in 2002 with the establishment of our subsidiary Hutchison
MediPharma, which is focused on discovering, developing and marketing drugs for the treatment of cancer and immunological diseases.
Ten of our drug candidates have entered clinical trials around the world and two have so far been approved for sale. Since 2001, we
have also developed drug marketing and distribution platforms in China, which primarily focus on prescription drug and consumer
health products through several joint ventures and subsidiary companies and are included in our Other Ventures. We listed our ordinary
shares on the AIM market of the London Stock Exchange in 2006 and ADSs on the Nasdaq Global Select Market in 2016.
In January and February of 2020, we sold 4,733,663 ADSs in a follow-on offering, raising gross proceeds of approximately $118.3
million. In July 2020, we sold 20,000,000 ordinary shares via a private placement to General Atlantic. We also granted a warrant to
General Atlantic to purchase up to an additional equivalent of 16,666,670 ordinary shares, at an exercise price of US$6.00 per ordinary
share, and a term of 18 months. In November 2020, we sold 16,666,670 ordinary shares via a private placement to Canada Pension Plan
Investment Board.
On March 4, 2021 we announced the consolidation of the two corporate identities that we have used since our inception. Hutchison
China MediTech, or Chi-Med, has been used as our group identity, while Hutchison MediPharma has been the identity of our novel
drug research and development operations under which our oncology products have been developed and are now being marketed. The
brand Hutchmed will immediately replace Chi-Med as our abbreviated name, and we will, subject to shareholder approval, formally
change our group company name at our Annual General Meeting scheduled to be held in April 2021.
Our principal executive offices are located at 48th Floor, Cheung Kong Center, 2 Queen’s Road Central, Hong Kong. Our telephone
number at that address is +852 2121 8200. The address of our registered office in the Cayman Islands is P.O. Box 309, Ugland House,
Grand Cayman, KY1-1104, Cayman Islands.
See Item 5.B. “Liquidity and Capital Resources” for details on our capital expenditures for the years ended December 31, 2018,
2019 and 2020.
We are subject to the informational requirements of the Exchange Act and are required to file reports and other information with
the SEC. The SEC maintains a website at www.sec.gov that contains reports, proxy and information statements, and other information
regarding registrants that make electronic filings with the SEC using its EDGAR system. We also make available on our website’s
investor relations page, free of charge, our annual report and the text of our reports on Form 6-K, including any amendments to these
reports, as well as certain other SEC filings, as soon as reasonably practicable after they are electronically filed with or furnished to the
SEC. The address for our investor relations page is www.chi-med.com/shareholder-information. The information contained on our
website is not incorporated by reference in this annual report.
B. Business Overview.
Overview
We are a global commercial-stage biopharmaceutical company focused on the discovery, development and commercialization of
targeted therapies and immunotherapies for the treatment of patients with cancer and immunological diseases. Our company started in
China in 2000 and has since developed fully integrated capabilities and expanded oncology and immunology drug development
operations globally. Our operational achievements and capabilities to date include:
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Broad pipeline of targeted therapies and immunotherapies built with a risk-balanced approach for the global market. Our drug
candidates cover both novel and validated targets, including MET, Syk, CSF1R, IDH, VEGFR, PI3Kδ and fibroblast growth factor
receptor, or FGFR, and extracellular signal-regulated kinase, or ERK. Our research focuses on developing drugs with high selectivity
and superior safety profiles, a key benefit of which is that our drug candidates have the potential to be effectively paired with other
oncology and immunology therapies at their maximum dosages with fewer side effects.
Commercially launching products while continuing to discover new assets. In China, we have brought two of our internally
developed drugs, fruquintinib (Elunate in China) and surufatinib (Sulanda in China), to patients, and we have filed for marketing
authorization for a third, savolitinib. All three drugs are in late-stage development outside of China, with the most advanced being
surufatinib for which we are filing a rolling NDA in the United States. In addition, we have seven additional drug candidates in earlier
stage clinical development and several advanced preclinical drug candidates.
Comprehensive global in-house discovery and development capabilities. We have a comprehensive drug discovery and
development operation covering chemistry, biology, pharmacology, toxicology, chemistry and manufacturing controls for clinical and
commercial supply, clinical and regulatory and other functions. It is led by a team of approximately 600 scientists and staff, who created
one of the broadest global clinical pipelines among our peer oncology and immunology focused biotechnology companies. Currently,
we are conducting and planning clinical studies in 40 different cohorts of oncology patients globally, including at least four registration-
intent studies.
Fast expanding and productive international organization. Our U.S. and European clinical teams of approximately 60 staff have
significantly broadened our international clinical development operations, particularly in the United States, Europe, Japan and Australia.
This team has established a productive track record since it was established in 2018, including the initiation of a rolling U.S. NDA filing
for surufatinib, a large randomized controlled study for fruquintinib and U.S. and European Phase I trials for our drug candidates HMPL-
523, HMPL-689 and HMPL-306. The FDA granted surufatinib fast track designations for non-pancreatic and pancreatic neuroendocrine
tumors as well as an orphan drug designation for pancreatic neuroendocrine tumors. Fruquintinib has also received FDA fast track
designation, for late stage colorectal cancer.
Long-standing drug marketing and distribution experience to support the realization of in-house oncology innovations. We have
built large-scale and profitable drug marketing and distribution platforms through the joint ventures and subsidiaries in Other Ventures,
which primarily manufacture, market and distribute prescription drugs and consumer health products in China. Our 20-year track record
and deep institutional knowledge of the drug marketing and distribution process are being leveraged to bring our in-house oncology
innovations to patients. We have built, as of March 1, 2021, and continue to expand, a 420-person in-house oncology drug sales team
to support the commercialization of Elunate, Sulanda and our other innovative drugs, if approved, throughout China. Our oncology
drug sales team has the capability to cover over 2,300 oncology hospitals and over 20,000 oncology physicians in China, a network that
we estimate represents over 90% of oncology drug sales in China. We are also in the process of expanding the geographic reach of our
commercial capabilities to the United States with the recruitment of a senior leadership team based in New Jersey to support the potential
launch of surufatinib.
Our Strategy
Our vision is to be a global leader in the discovery, development and commercialization of targeted therapies and immunotherapies
for the treatment of patients with cancer and immunological diseases. Key elements of our strategy are to:
Continue designing and creating molecules to develop into medicines with specific and differentiated characteristics for the
benefit of patients
We believe our world-class drug discovery engine is our key competitive advantage. We aim to retain and grow our team of skilled
scientists and provide them a stable and well-funded platform, with a clear strategic focus and long-term purpose to deliver global first-
in-class and best-in-class medicines to patients.
We strive to create differentiated novel oncology and immunology treatments with global potential. These include furthering both
small molecule and monoclonal antibody therapies which address aberrant genetic drivers, inactivated T-cell response and insufficient
T-cell response. Our drug discovery team has utilized our expertise in advanced medicinal chemistry to develop next-generation tyrosine
kinase inhibitors that have both high selectivity and superior pharmacokinetic properties. We believe these characteristics are crucial to
maximizing effectiveness, such as in inhibiting targeted genetic drivers of cancer cell proliferation and angiogenesis. Equally
importantly, we will continue to design chemical and biologic drug candidates with profiles that allow them to be used in innovative
combinations with other selective inhibitors, chemotherapy agents and immunotherapies. Such combination therapies enable treatment
of cancer via multiple pathways and modalities simultaneously, which has the potential to significantly improve treatment outcomes.
58
We plan to continue to build out our global pipeline of self-discovered drug candidates by advancing a rich pipeline of early-stage
drug candidates, which include biologics addressing novel targets designed for use in combination with our small molecules as well as
potentially a broad range of third-party therapies.
Realize the global potential of our oncology drug candidates
Our first wave of innovation, surufatinib (unpartnered), fruquintinib (partnered in China with Eli Lilly) and savolitinib (partnered
globally with AstraZeneca), are either commercialized, under review for marketing authorization, in the process of being filed for
marketing authorization or in registrational studies in multiple jurisdictions. In tandem with our ongoing progression of such drugs, we
will continue to invest in the future with our deep pipeline of unpartnered next wave of oncology assets for which we own all rights
globally and have significant flexibility in driving their development. Over the next 12 months, we plan to initiate late stage global
development of HMPL-689 (PI3Kδ) and HMPL-523 (Syk) and progressing early development of HMPL-453 (selective FGFR 1/2/3
inhibitor) and HMPL-306 (IDH 1/2 inhibitor). We plan to continue to add to our pipeline as novel drug candidates progress through
IND-enabling studies.
We intend to accelerate our global drug development by leveraging our advanced clinical trial data from China. We may also
selectively conduct clinical trials concurrently in China and other jurisdictions so that the programs progress in parallel globally. To
broaden and scale our international operations and support the increasing clinical activities in the United States and Europe, we also
plan to continue significantly expanding our clinical teams in those geographies.
Build and scale our marketing and commercialization capabilities globally
We plan to leverage our long-standing drug marketing and distribution know-how and infrastructure to support our innovative
oncology product launches. We have a 20-year track record of marketing and selling products in China. We aim to grow our in-house
oncology drug sales team in China of 420 persons as of March 1, 2020 to approximately 900 persons by the end of 2023.
Outside of China, we intend to commercialize our products, if approved, in the United States where we have already begun to build
our own sales team and are preparing to be ready to launch surufatinib, if approved, at the end of 2021 or early 2022. In Europe, Japan
and other major markets we intend to form collaborations with leading biopharmaceutical companies and/or contract sales organizations.
We are also focused on building out our commercial infrastructure to support our existing products and potential launches.
We will also continue to scale our manufacturing capacity to support the sales of our approved drugs, including our new plant in
Shanghai, which we recently started constructing. This new plant represents a five-fold expansion of our existing production capacity,
and we will look to maintain appropriate capacity in the future in line with the development of our pipeline of drug candidates and
approved drugs.
Capitalize on regulatory reforms currently underway in China aimed at addressing existing major unmet medical needs
and improving the health of its people
We believe the Chinese oncology market, which comprises approximately a quarter of the global oncology patient population,
represents a substantial and fast-growing market opportunity. The oncology drug market in China is growing rapidly as a result of
important government reforms that are underway, including the expansion of the NRDL to improve access to innovative drugs. We
intend to capitalize on this market opportunity by leveraging and expanding our large and well-established drug discovery and
commercial sales operations in China.
Historically, cumbersome pharmaceutical registration regulations led to limited availability of advanced therapies in China and high
prices for those that were available. This led to surgery and chemotherapy being the standard of care for most patients in China. During
the past decade, the PRC government has endeavored to foster an innovative biopharmaceutical ecosystem, and in the last few years,
the pace of reforms has accelerated with a clear focus on providing Chinese patients access to world-class oncology therapies through
expanded insurance reimbursement and reduced time for clinical trials and drug approvals.
Having invested in drug innovation in China for over 20 years, beginning at a time when almost no other domestic companies were
involved in innovative oncology research, we believe we are well positioned to capture this market opportunity. Supported by China’s
improving regulatory environment, we intend to rapidly advance our drug candidates to meet the country’s significant unmet medical
needs in oncology.
59
Working with partners to complement our internal research and development activities and continue to adapt existing
collaborations as necessary
We plan to explore opportunities to access complementary drug candidates and/or interests in other biopharmaceutical companies
to supplement our in-house research and development capabilities and to enhance our current drug candidate pipeline. In addition, we
expect to progress some of our drug candidates by pursuing business development opportunities with other biopharmaceutical companies
both in China and globally.
For instance, in 2020 we began collaborating with BeiGene Ltd., or BeiGene, to evaluate combining surufatinib and fruquintinib
with its anti-PD-1 antibody tislelizumab for the treatment of various solid tumor cancers in the U.S., Europe, China and Australia. In
2021, we partnered with Inmagene Biopharmaceuticals, or Inmagene, to develop four of our self-discovered preclinical drug candidates
for the potential treatment of various immunological diseases.
We will also continue to work with our partners, AstraZeneca and Eli Lilly, to optimize the potential of our drug candidates
savolitinib (globally with AstraZeneca) and fruquintinib (in China with Eli Lilly). For example, in May 2020, we received acceptance
for review of the savolitinib NDA in China for the treatment of non-small cell lung cancer harboring mesenchymal epithelial transition
factor, or MET, Exon 14 skipping alteration. If approved, this would be the first marketing authorization for savolitinib anywhere in
the world. In July 2020, we amended our collaboration with Eli Lilly to assume responsibility for all on-the-ground medical detailing,
promotion and local and regional marketing activities in China for Elunate, thereby expanding its potential economic value to our
company.
Oncology Commercial Operations
We are able to rapidly establish and grow our dedicated Sulanda and Elunate oncology commercial organization, building on our
long-standing drug marketing and distribution platforms. Currently, our oncology commercial team in China comprises over 420 staff,
compared to approximately 90 at the end of 2019. At the same time, we are expanding our U.S. based international commercial
capabilities.
We have received regulatory approvals and commercially launched two of our self-discovered drug candidates in China and are
working to obtain approval for commercial sales of a third drug candidate in China, as described below:
Surufatinib – Sulanda in China
We received approval from the NMPA for Sulanda, the brand name in China of surufatinib, as a treatment for patients with advanced
non-pancreatic neuroendocrine tumors, or NET, in December 2020 and commercially launched it in mid-January 2021, within three
weeks of approval. By the end of January 2021, Sulanda prescriptions had been written in 30 provinces in China. Further activities are
underway. Most notably, we are working to reduce cost as a barrier for patients to access Sulanda. We have implemented a broad-scale,
need-based patient access program which could materially reduce patient out-of-pocket costs, while applying for Sulanda to be included
in the 2022 NRDL.
In China, there were an estimated 67,600 newly diagnosed NET patients in 2018, of which an estimated 60% were diagnosed with
advanced NETs. Considering the current incidence to prevalence ratio, there may be more than 300,000 patients living with the disease
in China.
Fruquintinib – Elunate in China
At the end of 2018, our collaboration partner Eli Lilly commenced commercial sales of Elunate, the brand name in China of
fruquintinib, targeting the more than 55,000 metastatic colorectal cancer third-line patients in China each year. In January 2020, Elunate
was included on China’s NRDL and is therefore now available in public hospitals throughout China at a reduced price, paving the way
to significantly broaden access for advanced colorectal cancer patients and rapidly build penetration in China over the coming years. In
October 2020, we took over the development and execution of all on-the-ground medical detailing, promotion and local and regional
marketing activities in China through an amendment to our collaboration terms with Eli Lilly.
Driven in part by the inclusion of Elunate in the 2020 NRDL and our assumption of responsibility for detailing, promotion and
marketing in China in October 2020, total in-market sales of Elunate by Eli Lilly, as provided to us by Eli Lilly, increased by 91.5% to
$33.7 million for the year ended December 31, 2020 compared to $17.6 million for the year ended December 31, 2019. We recognize
revenue for royalties and manufacturing costs and, since October 1, 2020, additional service payments in association with our expanded
role in the commercialization of Elunate paid to us by Eli Lilly.
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Savolitinib – to be marketed by AstraZeneca, if approved, in China
We have submitted a NDA to the NMPA for the treatment of patients with MET Exon 14 skipping alteration NSCLC. The NDA
was accepted in May 2020, priority review status was granted in July 2020 and review is underway. If the NDA is approved, we will
be the marketing authorization holder, and AstraZeneca is expected to launch savolitinib in China through the same oncology
commercial organization that markets Tagrisso, Imfinzi, Iressa and Lynparza, among others.
Global Clinical Drug Development
Our fast expanding international organization, led mainly from the United States, is developing six oncology drug candidates. In
2020, the organization initiated the rolling submission of surufatinib, our first U.S. NDA filing, as well as a global Phase III study for
fruquintinib. Further, the organization is progressing three oncology drug candidates (HMPL-689, HMPL-523, HMPL-306) toward
proof-of-concept or registration enabling studies later this year. Savolitinib, via a global collaboration with AstraZeneca, is in a
registration-enabling Phase II study with additional programs to start in 2021.
The following table summarizes the status of our global clinical drug portfolio’s development as of the date of the filing of this
annual report:
Our Global Clinical Development Pipeline
Program
Treatment
Indication
Target patient
Savolitinib + Tagrisso
NSCLC
2L/3L EGFRm; Tagrisso ref.; MET+
Savolitinib + Imfinzi (PD-L1)
Papillary RCC
MET+
Study
name
SAVANNAH
Sites
Global
Global
Savolitinib
MET
Savolitinib + Imfinzi (PD-L1)
Papillary RCC
All
CALYPSO
UK/Spain
Savolitinib + Imfinzi (PD-L1)
Clear cell RCC
VEGFR TKI refractory
CALYPSO
UK/Spain
Savolitinib
Savolitinib
Surufatinib
Surufatinib
Surufatinib
Surufatinib
Gastric cancer
MET+
Colorectal cancer
MET+
NET
NET
Refractory
Refractory
Biliary tract cancer
Soft tissue sarcoma
VIKTORY
S Korea
US
US
EU
US
US
Suru. + tislelizumab (PD-1)
Solid tumors
US/EU
**
Colorectal cancer
Refractory
FRESCO-2 US/EU/JP
Dose finding /
safety run-in
Proof-of-concept
Registration
*
**
***
***
***
***
NDA Initiated
MAA Planned
Surufatinib
VEGFR 1/2/3;
FGFR1; CSF-1R
Fruquintinib
VEGFR 1/2/3
Fruquintinib
Fruquintinib
Breast cancer
Fruq. + tislelizumab (PD-1)
TN breast cancer
Fruq. + tislelizumab (PD-1)
Solid tumors
HMPL-689
PI3K
HMPL-689
HMPL-689
HMPL-523 HMPL-523
HMPL-523
Syk
HMPL-306
IDH 1/2
HMPL-306
HMPL-306
Healthy volunteers
Indolent NHL
Indolent NHL
Indolent NHL
Solid tumors
Hem. malignancies
US
US
TBD
**
**
Australia
US/EU
Australia
US/EU
US/EU
US/EU
**
**
* Phase II registration-intent study subject to regulatory discussion; ** In planning; and *** Investigator-initiated trials (IIT).
Notes: MET = mesenchymal epithelial transition receptor; VEGFR = vascular endothelial growth factor receptor; TKI = tyrosine
kinase inhibitor; EGFRm = epidermal growth factor receptor mutation; NET = neuroendocrine tumors; FGFR1 = fibroblast
growth factor receptor 1; CSF-1R = colony stimulating factor-1 receptor; Syk = spleen tyrosine kinase; PI3Kδ =
Phosphatidylinositol-3-Kinase delta; NSCLC = non-small cell lung cancer; RCC = renal cell carcinoma; NHL = Non-
Hodgkin’s Lymphoma; TN = triple negative; IDH 1/2 = isocitrate dehydrogenase 1/2.
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Surufatinib—unique angio-immuno kinase inhibitor with NDA being submitted in the United States
Surufatinib, which has been approved in China for the treatment of non-pancreatic neuroendocrine tumors, is a novel, oral angio-
immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR and FGFR, which both inhibit
angiogenesis, and colony stimulating factor-1 receptor, or CSF-1R, which regulates tumor-associated macrophages, promoting the
body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with
other immunotherapies.
In the United States, the FDA granted orphan drug designation to surufatinib for the treatment of pancreatic neuroendocrine tumors
in November 2019 and granted Fast Track Designations for the treatment of both pancreatic neuroendocrine tumors and non-pancreatic
neuroendocrine tumors in April 2020. In May 2020, we reached an agreement with the FDA that the completed SANET-ep (non-
pancreatic NET) and SANET-p (pancreatic NET) studies, along with existing data from surufatinib in U.S. non-pancreatic and pancreatic
NET patients, could form the basis to support a NDA submission. Pharmacokinetic and safety data from U.S. Phase Ib neuroendocrine
tumor cohorts demonstrated similar profiles of surufatinib between Chinese and U.S. patients.
In December 2020, we initiated a rolling NDA submission for surufatinib for the treatment of pancreatic and non-pancreatic
neuroendocrine tumors. We plan to complete the NDA submission in the first half of 2021, which would be our first NDA in the United
States. Filing acceptance of the NDA is subject to FDA review of the complete application. The data package will also be used to file
a Marketing Authorization Application, or MAA, to the European Medicines Agency, or EMA, based on scientific advice from the
EMA Committee for Medicinal Products for Human Use, or CHMP.
We have various additional clinical trials of surufatinib ongoing as a single agent in patients with biliary tract cancer and soft-tissue
sarcoma, as well as in combination with checkpoint inhibitors. We also intend to conduct a combination study of surufatinib with
tislelizumab, an anti-PD-1 antibody being developed by BeiGene, in the United States and Europe. In addition, we believe surufatinib
has potential in a number of other tumor types such as breast cancer with FGFR 1 activation.
Surufatinib is the first oncology candidate that we have launched in China and expanded development globally without the support
of a development partner. We own all rights to surufatinib globally.
Fruquintinib—potential best-in-class selective VEGFR 1, 2 and 3 inhibitor in Phase III development
Fruquintinib, which has been approved in China for the treatment of advanced metastatic colorectal cancer, is a highly selective
and potent oral inhibitor of vascular endothelial growth factor receptors, known as VEGFR 1, 2 and 3. We believe that fruquintinib has
the potential to become the global best-in-class selective small molecule VEGFR 1, 2 and 3 inhibitor for many types of solid tumors,
and we are currently studying fruquintinib in colorectal cancer, gastric cancer, lung cancer and other solid tumor types. Fruquintinib
was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target
coverage. The tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical
assessment, suggests that it may be highly suitable for combinations with other anti-cancer therapies.
Building on the data collected from our successful Phase III trial in China, known as the FRESCO study, which supported
fruquintinib’s approval in China, we initiated FRESCO-2, a large randomized controlled study of fruquintinib in the United States,
Europe and Japan. The first patient was dosed in September 2020, and the study is enrolling over 680 patients in approximately 150
sites in 14 countries. The FDA granted fast track designation for the development of fruquintinib for the treatment of patients with
metastatic colorectal cancer in June 2020. The FDA, EMA and Japanese Pharmaceuticals and Medical Devices Agency, or PMDA,
have all acknowledged the totality of the fruquintinib clinical data, including the FRESCO-2 study, if positive, the prior positive Phase
III FRESCO study demonstrating improvement in overall survival, or OS, that led to fruquintinib approval for metastatic CRC in China
in 2018 and additional completed and ongoing supporting studies in metastatic CRC, could support a future NDA for the treatment of
patients with third-line and above metastatic colorectal cancer. Preliminary data of U.S. Phase I/Ib colorectal cancer cohorts
demonstrated encouraging efficacy in patients refractory or intolerant to Stivarga and Lonsurf.
We are conducting global combination studies of fruquintinib with BeiGene’s anti-PD-1 antibody tislelizumab for the treatment of
various solid tumor cancers in the United States, Europe and China, including enrolling a Phase Ib/II study in advanced, refractory triple
negative breast cancer.
Fruquintinib is being commercialized and developed in partnership with Eli Lilly in China, where we are responsible for
development, manufacturing, on-the-ground medical detailing, promotion and local and regional marketing activities. We own all rights
to fruquintinib outside of China.
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Savolitinib—selective MET inhibitor in late-stage clinical development as a monotherapy and in combination therapies in global
partnership with AstraZeneca
Savolitinib is a potent and selective inhibitor of the MET receptor tyrosine kinase, an enzyme which has been shown to function
abnormally in many types of solid tumors. We designed savolitinib through chemical structure modification to specifically address
kidney toxicity, the primary issue that halted development of several other selective MET inhibitors. In clinical trials to date in over
1,100 patients globally, savolitinib has shown promising signs of clinical efficacy in patients with multiple types of MET gene alterations
in lung cancer, kidney cancer and gastric cancer with an acceptable safety profile.
We are currently testing savolitinib in global partnership with AstraZeneca, both as a monotherapy and in combination with
immunotherapy, targeted therapy and chemotherapy drugs. Most notably, we are currently progressing the Savannah study on
savolitinib in combination with Tagrisso for treating epidermal growth factor receptor mutation positive, or EGFRm+, non-small cell
lung cancer patients who have progressed following first or second-line Tagrisso therapy due to MET amplification. The study has fully
enrolled one of the three dose cohorts and is expected to complete enrollment in mid-2021, with planning for the global Phase III study
now underway.
Proof-of-concept studies of savolitinib in kidney cancer (as a monotherapy as well as in combination with a PD-L1 inhibitor) and
gastric cancer (as a monotherapy as well as in combinations with chemotherapy) have demonstrated positive results, with subsequent
clinical development in planning. For example, we are initiating a global Phase III pivotal trial for savolitinib in combination with
Imfinzi, AstraZeneca’s anti-PD-L1 antibody durvalumab, in MET positive patients with papillary renal cell carcinoma, a form of kidney
cancer. Savolitinib opportunities are also continuing to be explored in multiple other MET-driven tumor settings via investigator-
initiated studies including colorectal cancer.
HMPL-689—potential best-in-class selective PI3Kδ inhibitor
HMPL-689 is a novel, highly selective and potent small molecule inhibitor targeting the isoform PI3Kδ. In preclinical
pharmacokinetic studies, HMPL-689’s pharmacokinetic properties have been found to be favorable with good oral absorption, moderate
tissue distribution and low clearance. HMPL-689 is also expected to have low risk of drug accumulation and drug-drug interaction and
is highly potent, particularly at the whole blood level.
We have early-stage clinical trials of HMPL-689 ongoing and preliminary evidence suggests that HMPL-689 may perform in the
clinic as designed. Based on extensive Phase I/Ib proof-of-concept clinical data in China and Australia on HMPL-689, we have opened
17 U.S. and European sites for a Phase I/Ib study with patient enrollment underway, focusing on advanced relapsed or refractory
lymphoma. In the second half of 2021, we plan to complete FDA regulatory discussions, followed by the initiation of registration intent
studies.
We own all rights to HMPL-689 globally.
HMPL-523—potential first-in-class selective Syk inhibitor for oncology
HMPL-523 is a novel, highly selective, oral inhibitor targeting the spleen tyrosine kinase, or Syk, for the treatment of hematological
cancers and certain chronic immune diseases. Syk is a major component in B-cell receptor signaling and is an established therapeutic
target in multiple subtypes of B-cell lymphomas. Because B-cell malignancies are heterogeneous and patients commonly experience
relapse despite current therapies, there is a need for new therapies.
We have various clinical trials of HMPL-523 ongoing. We have 11 U.S. and European sites for a Phase I/Ib study with patient
enrollment underway, focusing on advanced relapsed or refractory lymphoma and are close to establishing our Phase II dose.
We own all rights to HMPL-523 globally.
HMPL-306—highly selective IDH 1 and 2 inhibitor with potential in hematological malignancies, gliomas and solid tumors
HMPL-306 is a novel small molecule dual-inhibitor of isocitrate dehydrogenase 1 and 2, or IDH 1 and 2, enzymes. IDH1 and IDH2
mutations have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among acute
myeloid leukemia patients. U.S. IND applications for solid tumors and hematologic malignancies were cleared in October 2020. We
expect to initiate Phase I development in the U.S. during the first half of 2021.
HMPL-295—an investigative and highly selective small molecule inhibitor of ERK in the MAPK pathway with the potential to
address intrinsic or acquired resistance from upstream mechanisms such as RAS-RAF-MEK
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HMPL-295, a novel ERK inhibitor, is our 10th in-house discovered small molecule oncology drug candidate. ERK is a downstream
component of the RAS-RAF-MEK-ERK signaling cascade (MAPK pathway). This is our first of multiple candidates in discovery
targeting the MAPK pathway.
China Clinical Drug Development
We are the marketing authorization holder of two internally developed innovative oncology medicines (Elunate and Sulanda) and
may have a third (savolitinib) if the NDA currently under review is approved. Elunate and Sulanda are being commercialized by our
dedicated oncology sales force and supported by our long-standing drug marketing and distribution platforms. Savolitinib, if approved,
would be marketed by our global partner AstraZeneca, alongside Tagrisso for the treatment of a type of lung cancer (EGFRm+) estimated
to represent approximately half of lung cancer patients in Asia. As these internally developed medicines are being approved and
launched, we continue to devote significant resources to the discovery of potential new medicines. We have seven additional drug
candidates in earlier stage clinical development and several advanced preclinical drug candidates.
The following table summarizes the status of our China clinical programs as of the date of the filing of this annual report.
Our China Clinical Development Pipeline
Study
name
Dose finding /
safety run-in
Proof-of-concept
Registration
NDA Submitted
NDA Submitted
Marketed
Marketed
*
*
*
*
Program
Treatment
Indication
Target patient
Savolitinib
Savolitinib
MET
Savolitinib + Tagrisso
Savolitinib + Tagrisso
NSCLC
NSCLC
NSCLC
MET Exon 14 skipping
2L EGFR TKI ref. NSCLC; MET+
Naïve MET+ & EGFRm NSCLC
Surufatinib
VEGFR 1/2/3;
FGFR1; CSF-1R
Savolitinib
Surufatinib
Surufatinib
Surufatinib
Gastric cancer
2L; MET+
Pancreatic NET
Non-Pancreatic NET
All
All
SANET-p
SANET-ep
Biliary tract cancer
2L; chemotherapy refractory
Surufatinib + Tuoyi (PD-1)
NEN, ESCC, BTC
Surufatinib + Tuoyi (PD-1)
SCLC, GC, Sarcoma
Surufatinib + Tuoyi (PD-1)
TC, EMC, NSCLC
Surufatinib + Tyvyt (PD-1)
Solid tumors
Fruquintinib
Colorectal cancer
≥3L; chemotherapy refractory
FRESCO
Fruquintinib + Taxol
Gastric cancer
2L
FRUTIGA
Fruquintinib
VEGFR 1/2/3
Fruquintinib + Tyvyt (PD-1)
CRC, EMC, RCC, HCC
Fruquintinib + Tyvyt (PD-1)
GI tumors
Fruq. + geptanolimab (PD-1)
Fruq. + geptanolimab (PD-1)
CRC
NSCLC
HMPL-689
HMPL-689
HMPL-523
HMPL-523
HMPL-453
FL, MZL, MCL, DLBCL
CLL/SLL, HL
B-cell malignancies
ITP
IHCC
All
All
HMPL-306
Hem. Malignancies
HMPL-295
Solid tumors
Epitinib
Glioblastoma
EGFR gene amplified
HMPL-689
PI3Kδ
HMPL-523
Syk
HMPL-453
FGFR 1/2/3
HMPL-306
IDH 1/2
HMPL-295
(ERK, MAPK pathway)
Epitinib
EGFR
* In planning.
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Notes: MET = mesenchymal epithelial transition receptor; VEGFR = vascular endothelial growth factor receptor; TKI = tyrosine
kinase inhibitor; EGFRm = epidermal growth factor receptor mutation; FGFR1 = fibroblast growth factor receptor 1; CSF-1R
= colony stimulating factor-1 receptor; NET = neuroendocrine tumors; NEN = neuroendocrine neoplasms; ESCC = esophageal
cancer; BTC = biliary tract cancer; SCLC = small cell lung cancer; GC = gastric cancer; TC = thyroid cancer; EMC =
endometrial cancer; CRC = colorectal cancer; HCC = hepatocellular carcinoma; GI = gastrointestinal; Syk = spleen tyrosine
kinase; PI3Kδ = Phosphatidylinositol-3-Kinase delta; NSCLC = non-small cell lung cancer; RCC = renal cell carcinoma; NHL
= Non-Hodgkin’s Lymphoma; FL = follicular lymphoma; MZL = marginal zone lymphoma; MCL = mantle cell lymphoma;
DLBCL = diffuse large B cell lymphoma; CLL/SLL = chronic lymphocytic leukemia/small lymphocytic lymphoma; HL =
Hodgkin’s lymphoma; ITP = immune thrombocytopenic purpura; IHCC = Intrahepatic cholangiocarcinoma; IDH 1/2 =
isocitrate dehydrogenase 1/2; ERK = extracellular-signal-regulated kinase; MAPK = mitogen activated protein kinase.
Fruquintinib—commercially launched as Elunate in China in colorectal cancer in November 2018
Fruquintinib was first commercially launched in China, marketed by our partner Eli Lilly, in November 2018 for the treatment of
advanced colorectal cancer. In January 2020, fruquintininb was included in the NRDL thereby broadening access by advanced colorectal
cancer patients in China. Since launch, Eli Lilly deployed a dedicated team of about 140 oncology commercial personnel to market
fruquintinib in China. Since October 1, 2020, we took over development and execution of all on-the-ground medical detailing,
promotion and local and regional marketing activities for fruquintinib in China, using our 420-person in-house oncology drug sales team
supported by our long-standing drug marketing and distribution platforms. Subject to meeting pre-agreed sales targets, Eli Lilly will
pay us an estimated total of 70% to 80% of Elunate sales in the form of royalties, manufacturing costs and service payments.
In addition to its commercial launch in colorectal cancer in China, we have made progress with fruquintinib in various other cancer
indications, including the FRUTIGA study in China, a pivotal Phase III study in approximately 700 patients to evaluate the efficacy and
safety of fruquintinib in combination with Taxol, a chemotherapy medication, compared with Taxol monotherapy for second-line
treatment of advanced gastric cancer in patients who had failed first-line chemotherapy. We expect to complete enrollment of the study
around the end of 2021.
We believe that fruquintinib is a best-in-class VEGFR 1, 2 and 3 inhibitor and could be considered for development in China in
many solid tumor indications in which VEGFR inhibitors have been approved globally. To this end, since 2018, we assumed all
planning, execution and decision-making responsibilities for life cycle indication development of fruquintinib in China.
We are conducting Phase Ib/II dose expansion studies in China of fruquintinib with Tyvyt, a PD-1 monoclonal antibody being
developed by Innovent Biologics (Suzhou) Co., Inc., or Innovent, in different tumor types, including hepatocellular carcinoma (HCC),
endometrial cancer, RCC and CRC. Moreover, Genor is conducting Phase Ib studies of fruquintinib plus geptanolimab, a PD-1
monoclonal antibody, in second-line CRC and NSCLC. Furthermore, we intend to develop fruquintinib in combination with BeiGene’s
tislelizumab for the treatment of various solid tumor cancers in China.
Surufatinib—commercially launched as Sulanda in China in non-pancreatic neuroendocrine tumors in January 2021; potential
first-in-class inhibitor for all advanced neuroendocrine tumors
Surufatinib was approved by the NMPA in December 2020 for the treatment of non-pancreatic neuroendocrine tumors and is now
being marketed in China under the brand name Sulanda. The NMPA approval of surufatinib was based on results from the SANET-ep
study, a Phase III trial in patients with advanced non-pancreatic neuroendocrine tumors conducted in China. The positive results of this
trial were highlighted in an oral presentation at the 2019 ESMO Congress and published in The Lancet Oncology in September 2020.
Our 420-person in-house oncology drug sales team is now supporting the marketing and commercialization of surufatinib throughout
China for this indication.
We have submitted a second NDA in China for surufatinib in advanced pancreatic neuroendocrine tumors supported by our SANET-
p study, a Phase III trial in patients with advanced pancreatic neuroendocrine tumors conducted in China. The NDA was accepted in
September 2020 and review is underway. If approved, we believe surufatinib would be the only approved targeted therapy able to
address and treat all subtypes of neuroendocrine tumors.
We are commencing combination studies of surufatinib with Tuoyi, a PD-1 monoclonal antibody being developed by Shanghai
Junshi Biosciences Co. Ltd., or Junshi, in China, where we are currently enrolling Phase II studies in nine solid tumor indications,
including NENs, biliary tract cancer, gastric cancer, thyroid cancer, small cell lung cancer, soft tissue sarcoma, endometrial cancer,
esophageal cancer and non-small cell lung cancer.
65
Phase Ib studies in China in combination with BeiGene’s anti-PD-1 antibody, tislelizumab, are in the planning stage. In addition,
we have expanded our collaboration with Innovent and, in July 2020, started a Phase I study in China to evaluate the safety and efficacy
of Tyvyt in combination with surufatinib.
Savolitinib—NDA filed for potential first-in-class selective MET inhibitor in China
In May 2020, an NDA for savolitinib for the treatment of non-small cell lung cancer with MET Exon 14 skipping alterations was
accepted for review by the NMPA, supported by a Phase II registration study, and the NMPA subsequently granted it priority review
status. This is the first NDA filing for savolitinib globally and first for a selective MET inhibitor in China. Data from this study were
most recently presented at the American Society of Clinical Oncology 2020 Virtual Scientific Program.
We intend to initiate several studies in China in 2021, including a potential registrational Phase II study in metastatic gastric cancer
in mid-2021, and two further pivotal Phase III studies in combination with Tagrisso in non-small cell lung cancer patients in the second
half of 2021.
HMPL-689—highly selective PI3Kδ inhibitor with potential in hematological cancer
Our Phase I dose escalation study on HMPL-689 in China has been completed, and a recommended Phase II dose was selected.
HMPL-689 was well tolerated, exhibiting dose-proportional pharmacokinetics, a manageable toxicity profile, and single-agent clinical
activity in relapsed/refractory B-cell lymphoma patients. Our Phase Ib expansion study in China is ongoing in multiple sub-categories
of indolent non-Hodgkin’s lymphoma. Based on the highly promising preliminary results, we are now planning registration studies in
follicular lymphoma and marginal zone lymphoma in China, which are anticipated to start in mid-2021.
HMPL-523—highly selective Syk inhibitor with potential in hematological cancer and immunological diseases
Data from an extensive Phase I/Ib dose escalation and expansion study (covering more than 200 patients) on HMPL-523 has
encouraged us to initiate exploratory studies in China on multiple indolent non-Hodgkin’s lymphoma sub-categories, including chronic
lymphoma, Waldenstrom’s
follicular
lymphocytic
macroglobulinemia and mantle cell lymphoma.
lymphoma, marginal zone
leukemia/small
lymphocytic
lymphoma,
Furthermore, in August 2019 we commenced a Phase I study of HMPL-523 in China for the treatment of immune thrombocytopenia,
an autoimmune disorder characterized by low platelet count and an increased bleeding risk. Dose escalation is near complete with
planning and preparation for a Phase III trial in China now underway.
HMPL-453—highly selective FGFR 1/2/3 inhibitor with potential in solid tumors
HMPL-453 is a highly selective and potent FGFR 1/2/3 inhibitor. Aberrant FGFR signaling is associated with tumor growth,
promotion of angiogenesis, as well as resistance to anti-tumor therapies. A Phase II study is ongoing in patients with advanced
intrahepatic cholangiocarcinoma, or IHCC, with FGFR2 fusion that had failed at least one line of systemic therapy, and other solid
tumor indications are being investigated. IHCC is a cancer that develops within the bile ducts, the second most common primary hepatic
malignancy after hepatocellular carcinoma. Approximately 10-15% of IHCC patients have tumors that harbor FGFR2 fusion.
HMPL-306—highly selective IDH 1 and 2 inhibitor with potential in hematological malignancies, gliomas and solid tumors
A Phase I trial in China was initiated in July 2020, in patients of relapsed or refractory hematological malignancies with an IDH1
and/or IDH2 mutation. Multiple sites have been initiated and we aim to establish the Phase II dose in 2021.
Epitinib—clinical-stage EGFR inhibitors
We have completed Phase I/Ib studies of epitinib, an epidermal growth factor receptor, or EGFR, inhibitor with demonstrated ability
to penetrate the blood-brain barrier. We are evaluating further development strategies for epitinib.
Discovery Research & Preclinical Development
We strive to create differentiated novel oncology and immunology treatments with global potential. These include furthering both
small molecule and monoclonal antibody therapies which address aberrant genetic drivers; cancer cell metabolism; modulate tumor
immune microenvironment; and target immune cell checkpoints. We design drug candidates with profiles that enable them to be used
in innovative combinations with other therapies, such as chemotherapy, immunotherapy and other targeted therapy in order to attack
disease simultaneously through multiple modalities and pathways. We believe that this approach can significantly improve treatment
outcomes for patients.
66
In addition to the ten clinical-stage assets, we have three more novel oncology drug candidates in late-preclinical stage, including
HMPL-653 (targeting solid tumors), HMPL-A83 (targeting solid tumors and hematological malignancies) and HMPL-760 (targeting
hematological malignancies). We retain all worldwide rights to these assets and are targeting dual U.S. and China IND submissions
during 2021.
Manufacturing
Our manufacturing site in Suzhou is a GMP-certified production facility, providing supplies of our drug candidates for clinical trials
and Elunate and Sulanda for commercial sale. We plan to continue to invest resources in the Suzhou facility, expanding the production
team in phases. We are also commencing construction of a large-scale manufacturing plant for innovative drugs in Shanghai. The
Shanghai factory will be our largest manufacturing facility, with production capacity estimated to be five times that of our manufacturing
plant in Suzhou. The first phase will be primarily for small molecule production, while the second phase is expected to include expansion
into large molecule production.
Other Ventures
320
In addition to our Oncology/Immunology operations, our Other Ventures include large-scale drug marketing and distribution
platforms covering approximately 315 cities and towns in China with approximately 4,800 mainly manufacturing and commercial
personnel as of December 31, 2020. Built over the past 20 years, it primarily focuses on prescription drug and consumer health products
mainly through: (i) Shanghai Hutchison Pharmaceuticals, a non-consolidated joint venture with a commercial team of about 2,200 staff
managing the medical detailing and marketing of a range of own-brand prescription drug products, (ii) Hutchison Sinopharm, a
consolidated joint venture focused on marketing third-party prescription drug products and our science-based infant nutrition products,
as well as providing commercial services for our own marketed drugs, and (iii) Hutchison Baiyunshan, a non-consolidated joint venture
focused on the manufacture, marketing and distribution of primarily own-brand OTC drugs.
Net income attributable to our company from our Other Ventures totaled $41.4 million, $41.5 million and $72.8 million for the
years ended December 31, 2018, 2019 and 2020, respectively, and are passed to our group through dividend payments primarily from
our non-consolidated joint ventures mentioned above. In 2020, dividends of $86.7 million were paid from these joint ventures to our
group, with aggregate dividends received since inception of over $300 million.
The following is a summary of the clinical pipeline for our drug candidates, many of which are being investigated against multiple
Our Clinical Pipeline
indications.
1. Savolitinib MET Inhibitor
Savolitinib is a potent and selective inhibitor of MET, an enzyme which has been shown to function abnormally in many types of
solid tumors. We designed savolitinib to address human metabolite-related renal toxicity, the primary issue that halted development of
several other selective MET inhibitors. In clinical studies to date, savolitinib has shown promising signs of clinical efficacy in patients
with MET gene alterations in NSCLC, papillary renal cell carcinoma, CRC, gastric cancer and prostate cancer with an acceptable safety
profile. In global partnership with AstraZeneca, savolitinib has been studied in over 1,000 patients to date, both as a monotherapy and
in combinations. For more information regarding our partnership with AstraZeneca, see “—Overview of Our Collaborations—
AstraZeneca.”
Mechanism of Action
MET is a signaling pathway that has specific roles in normal mammalian growth and development. However, the MET pathway
has also been shown to function abnormally in a range of different cancers, primarily through MET gene amplification, overexpressed
and gene mutations. The aberrant activation of MET has been demonstrated to be highly correlated in many cancer indications, including
kidney, lung, gastric, colorectal, esophageal and brain cancer. It plays a major role in cancer pathogenesis (i.e., the development of the
cancer), including tumor growth, survival, invasion, metastasis, the suppression of cell death as well as tumor angiogenesis.
MET also plays a role in drug resistance in many tumor types. For instance, MET gene amplification has been found in NSCLC
and CRC following anti-EGFR treatment, leading to drug resistance. Furthermore, MET dysregulation is considered to play a role in
the immunosuppression and pathogenesis of kidney cancer.
67
Savolitinib Research Background
First generation selective MET inhibitors previously discovered by multinational pharmaceutical companies had positive pre-
clinical data that supported their high MET selectivity and pharmacokinetic and toxicity profiles, but did not progress very far due to
kidney toxicity. The issue appeared to be that certain metabolites of earlier compounds had dramatically reduced solubility and appeared
to crystalize in the kidney, resulting in obstructive toxicity. With this understanding, we designed our compound, savolitinib (also known
as AZD6094 and HMPL-504, formerly known as volitinib), differently while preserving high MET inhibition properties across multiple
types of MET aberrations. Savolitinib has not shown any renal toxicity to date and does not appear to carry the same metabolite problems
as the earlier selective MET compounds.
Savolitinib Pre-clinical Evidence
In pre-clinical trials, savolitinib demonstrated strong in vitro activity against MET, affecting its downstream signaling targets and
thus blocking the related cellular functions effectively, including proliferation, migration, invasion, scattering and the secretion of
vascular endothelial growth factor, or VEGF, that plays a pivotal role in tumor angiogenesis.
One of our key areas of focus in our pre-clinical trials is to achieve superior selectivity on a number of kinases. A commonly used
quantitative measure of selectivity is through comparing enzyme IC50, which represents the concentration of a drug that is required for
50% inhibition of the target kinase in vitro and the plasma concentration required for obtaining 50% of a maximum effect in vivo. High
selectivity is achieved with a very low IC50 for the target cells, and a very high IC50 for the healthy cells (approximately 100 times higher
than for the target cells). IC50 is measured in nM (nano-mole, a microscopic unit of measurement for the number of small molecules
required to deliver the desired inhibitory effect).
In the MET enzymatic assay, savolitinib showed potent activity with IC50 of 5 nM. In a kinase selectivity screening with 274 kinases,
savolitinib had potent activity against the MET Y1268T mutant (comparable to the wild-type), weaker activity against other MET
mutants and almost no activity against all other kinases. Savolitinib was found to be approximately 1,000 times more potent to MET
than the next non-MET kinase. Similarly, in cell-based assays measuring activity against MET phosphorylation, savolitinib
demonstrated potent activity in both ligand-independent (gene amplified) and ligand-dependent (overexpressed) cells with IC50 at low
nanomolar levels. In target related tumor cell function assays, savolitinib showed high potency with IC50 of less than 10 nM. Furthermore,
savolitinib demonstrated cytotoxicity only on tumor cells that were MET gene amplified or MET overexpressed. In other cells, inhibition
measurements demonstrated that IC50 amounts were over 30,000 nM, which is thousands of times higher than the IC50 on MET tumor
cells.
The data above suggest that (i) savolitinib has potent activity against tumor cell lines with MET gene amplification in the absence
of hepatocyte growth factor, or HGF, indicating that there is HGF-independent MET activation in these cells; (ii) savolitinib has potent
activity in tumor cell lines with MET overexpressed, but only in the presence of HGF, indicating HGF-dependent MET activation; and
(iii) savolitinib has no activity in tumor cell lines with low MET overexpressed/gene amplification, suggesting that savolitinib has strong
kinase selectivity.
Savolitinib Clinical Development
As discussed below, we have tested, and are currently testing, savolitinib in partnership with AstraZeneca in multiple indications,
both as a monotherapy and in combination with other targeted therapies.
68
Non-small Cell Lung Cancer
We have two ongoing studies, which subject to positive clinical outcome, are designed to support NDA submission in NSCLC.
The table below shows a summary of the clinical trials that we have recently completed and underway for savolitinib in NSCLC patients.
Treatment
Savolitinib
Savolitinib + Tagrisso
Savolitinib + Tagrisso
Savolitinib + Tagrisso
Current and Recent Clinical Trials of Savolitinib in NSCLC
Name, Line, Patient Focus
MET Exon 14 skipping alteration
Savannah: 2L/3L
EGFRm+; Tagrisso
refractory; MET+
2L/3L EGFRm+;
Tagrisso refractory;
MET+
2L EGFR TKI refractory
NSCLC; MET+
Sites
China
Global
Phase
Status/Plan
NCT #
II
Registration
II
Registration-intent
NDA accepted NCT02897479
(May 2020)
Ongoing
NCT03778229
Global
III
In planning
N/A
China
III
In planning
N/A
Savolitinib + Tagrisso
Naïve patients with EGFRm & MET+ China
III
In planning
N/A
Notes: Global = more than two countries; 2L = second line; 3L = third line; and refractory = resistant to prior treatment.
Savolitinib Monotherapy
It is estimated that 2-3% of newly diagnosed NSCLC patients have a specific genetic mutation, known as MET Exon 14 skipping
alterations which leads to poor prognosis. This equates to approximately 10,000 new patients per year in China. Current chemotherapies
and immunotherapies provide limited efficacy in MET Exon 14 deletion NSCLC patients.
Phase II study of savolitinib monotherapy in NSCLC patients with MET Exon 14 alteration (Status: NDA accepted; NCT02897479)
We have completed enrollment of a 70-patient Phase II registration-intent study in China of savolitinib as a monotherapy for MET
Exon 14 deletion NSCLC patients who have progressed following prior systemic therapy, or unable to receive chemotherapy.
At the American Society of Clinical Oncology, or ASCO, Annual Meeting in June 2020, we presented interim data on 70 treated
patients, of which 61 patients were efficacy evaluable at the data cut-off date of March 31, 2020. The overall data were encouraging,
with efficacy in line with other selective MET inhibitors, despite the inclusion of patients with a more aggressive subtype (36% with
pulmonary sarcomatoid carcincoma) and with tolerable safety. Efficacy measurements included the objective response rate, or ORR,
(the percentage of patients in the study who show either partial response (tumor measurement reduction of greater than 30%) or complete
response), disease control rate, median progression-free survival and median OS.
At data cut-off, in the 61 evaluable patients, ORR was 49.2% and disease control rate was 93.4%. Median duration of response
was 9.6 months (95% confidence interval: 5.5–not reached) with maturity of 40%. Median progression-free survival was 6.9 months
(95% confidence interval: 4.2–19.3) with maturity of 50%. Median OS was 14.0 months (95% confidence interval: 9.7–not
reached) with maturity of 46%. A 95% confidence interval means that there is a 95% chance that the results will be within the stated
range. CTC grade 3 or above treatment emergent adverse events, or TEAEs, with greater than 5% incidence related to savolitinib
treatment were peripheral edema (7%), increased aspartate aminotransferase (13%) and increased alanine aminotransferase (10%).
Clinical data demonstrated an acceptable safety profile with an adverse events-related discontinuations rate of 14.3%.
Results from this study formed the basis for an NDA filing which was accepted by the NMPA in May 2020. Priority review status
was granted in July 2020 and, subject to approval, launch is expected as early as mid-2021.
69
Phase II Study of Savolitinib Monotherapy Showing Effect in MET Exon 14 Alteration NSCLC Patients
Par(cid:28)al response
Stable disease
Progressive disease
Notes: N = number of patients; ORR = objective response rate; DCR = disease control rate; and CI = confidence interval
Source: Lu S, Fang J et al. Phase II study of savolitinib in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other types
of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14+). Journal of Clinical Oncology
2020 38:15_suppl, 9519-9519.
Savolitinib and Tagrisso Combination
In 2015, AstraZeneca received FDA approval for Tagrisso, its drug for the treatment of T790M+ EGFRm+, tyrosine kinase
inhibitor-resistant NSCLC. A drug with this type of activity is known as a third-generation EGFR inhibitor. In 2018, Tagrisso’s label
was expanded to include previously untreated patients with EGFRm+ NSCLC. Tagrisso has been established as a new standard of care
in the treatment of EGFRm+ NSCLC and has now been approved in over 80 countries. Understanding the mechanism of acquired
resistance following Tagrisso treatment is a key clinical question to inform the next treatment choice. A portion of EGFRm+ tyrosine
kinase inhibitor-resistant patients and a portion of T790M+ EGFRm+ tyrosine kinase inhibitor-resistant patients progress because of
MET gene amplification.
At the European Society of Medical Oncology Congress in 2018, AstraZeneca presented the first results on the acquired resistance
spectrum detected in patient plasma samples after progression in the first-line (FLAURA) and second-line T790M (AURA3) Phase III
studies. MET amplification was among the most frequent mechanisms of acquired resistance to Tagrisso, with 15% of patients in the
FLAURA study and 19% of patients in the AURA3 study exhibiting MET amplification after treatment with Tagrisso. Ongoing research
with tissue (biopsy) samples will further elucidate the incidence of MET and other mechanisms in the development of resistance to
EGFR inhibitors.
70
Data presented in June 2017 at the ASCO by Harvard Medical School and Massachusetts General Hospital Cancer Center showed
that about 30% (7/23 patients) of Tagrisso-resistant third-line NSCLC patients harbor MET gene amplification based on analysis of
tissue samples. This third-line patient population is generally heavily pre-treated and highly complex from a molecular analysis
standpoint, with the study showing that more than half of the MET gene amplification patients also harbored additional genetic
alterations, including EGFR gene amplification and K-Ras mutations.
As discussed in more detail below, we and AstraZeneca are studying savolitinib in combination with Tagrisso as a treatment choice
for patients who have developed a resistance to tyrosine kinase inhibitors (primarily Tagrisso). The acceptance and uptake of Tagrisso
indicates that the market potential for savolitinib in Tagrisso-resistant, NSCLC could be material.
TATTON study: Phase Ib/II expansion studies of savolitinib in combination with Tagrisso in NSCLC EGFRm+ inhibitor refractory
patients (Status: complete; NCT02143466)
The TATTON study is a global exploratory Phase I/Ib study in NSCLC aiming to recruit patients with MET gene amplification
who had progressed after prior treatment with EGFR inhibitors to support a decision on global Phase II/III registration strategy. This
followed the completion of TATTON Part A, a Phase I study that established that a savolitinib and Tagrisso combination could be safe
and well tolerated and also demonstrated preliminary signs of efficacy. In 11 evaluable patients who were MET positive, the ORR was
55% with a disease control rate of 100%.
As of data cut-off on March 4, 2020, a total of over 220 patients had received the savolitinib plus the Tagrisso combination treatment
across six TATTON treatment arms, Parts A, B1, B2, B3, C and D. Final analysis for the B and D parts of the study were most recently
presented at the 2020 World Conference on Lung Cancer Worldwide Virtual Event held in January 2021, and interim data (data cut-off
on March 29, 2019) were previously published in The Lancet Oncology in February 2020. As summarized below, the combination
demonstrated an encouraging anti-tumor activity and an acceptable risk-benefit profile, regardless of dose.
First and second-generation EGFRm+ inhibitor refractory patients with acquired resistance driven by MET amplification
TATTON Part B2 tested patients who were T790M negative with no prior third-generation EGFR tyrosine kinase inhibitor
treatment. Of the 51 patients who received treatment (48 efficacy evaluable), 33 patients had confirmed responses (65% of treated
patients; 69% of evaluable patients) with 45 patients experiencing disease control (88% of treated patients; 94% of evaluable patients).
The median progression-free survival was 9.1 months (95% confidence interval: 5.5-12.8 months). Pooled CTC grade 3 or above
TEAEs in Part B of the study with greater than 5% incidence independent of causality were decreased neutrophil count (7%), increased
aspartate aminotransferase (6%), increased alanine aminotransferase (5%), and pneumonia (5%).
TATTON Part B3 tested patients who were T790M positive with no prior third-generation EGFR tyrosine kinase inhibitor
treatment. Of the 18 patients who received treatment, 12 patients had confirmed responses (67%) with 18 patients experiencing disease
control (100%). The median progression-free survival was 11.1 months (95% confidence interval: 4.1 months – 22.1 months).
In late 2017, the TATTON Part D study was initiated to study Tagrisso combined with a lower savolitinib dose (300 mg once daily)
in the context of maximizing long-term tolerability of the combination for patients who could be in poor condition and/or on the
combination for long periods of time. Of the 42 patients who received treatment (40 efficacy evaluable), 26 patients had confirmed
responses (62% of all patients; 65% of evaluable patients) with 39 patients experiencing disease control (93% of all patients; 98% of
evaluable patients). The median progression-free survival was 9.0 months (95% confidence interval: 5.6-12.7 months). CTC grade 3
or above TEAEs in Part D of the study with greater than 5% incidence independent of causality were pneumonia (10%), drug
hypersensitivity (7%), pulmonary embolism (5%), diarrhea (5%), myalgia (5%) and generalized edema (5%). Overall the combination
regimen of savolitinib 300 mg and Tagrisso was tolerable. In Part D of the study, there was lower incidence of grade ≥ 3 AEs and SAEs
as compared to Part B. The TATTON Part D study demonstrated that a lower dose did not impair clinical efficacy, while maintaining
a better tolerability profile. The results led to the selection of the 300 mg savolitinib plus 80 mg Tagrisso combination dose for the
Savannah study, and two additional cohorts of savolitinib 300 mg twice daily dose (BID) and 600 mg once daily dose (QD) plus 80 mg
Tagrisso combination doses are recruiting, as discussed below.
71
Tagrisso or another experimental third-generation EGFRm tyrosine kinase inhibitor refractory patients with acquired resistance driven
by MET amplification
The TATTON Part B1 study enrolled NSCLC patients that had progressed after treatment with a third-generation EGFR inhibitor
as a result of MET gene amplification acquired resistance. These patients were recruited prior to the April 2018 FDA approval of
Tagrisso as a first-line treatment and the January 2019 update to the National Comprehensive Cancer Network guidelines that state that
Tagrisso is the preferred first-line treatment for patients with EGFR mutation regardless of pre-treatment T790M mutation status.
Savolitinib in combination with Tagrisso from the TATTON Part B1 study showed promising data. Of the 69 patients that had
progressed on Tagrisso monotherapy and harbored MET amplification (60 patients were efficacy evaluable), there were 23 patients with
confirmed responses (33% of all patients; 38% of evaluable patients) with 52 patients experiencing disease control (75% of all patients;
87% of evaluable patients). The median progression-free survival was 5.5 months (95% confidence interval: 4.1-7.7 months).
72
Savolitinib plus Tagrisso combination showing effect in EGFR refractory patients who are either Tagrisso refractory (Part B1) or
Tagrisso naïve (Parts B2, B3, D)
TATTON Part B
Osimertinib 80mg
+Savolitinib
600mg1
TATTON Part D
Osimertinib 80mg
+Savolitinib 300mg
Part B1(n=69)
Prior third-
generation EGFR-
TKI
Part B2 (n=51)
No prior third-
generation EGFR-
TKI (T790M
negative)
Part B3 (n=18)
No prior third-
generation
EGFR-TKI (T790M
positive)
Part D (n=42)
No prior third-
generation EGFR-
TKI
(T790M negative)
33% [22, 46]
0
33%
65% [50, 78]
0
65%
67% [41, 87]
0
67%
62% [46, 76]
0
62%
42%
12%
13%
24%
6%
6%
33%
0
0
31%
2%
5%
ORR, % [95%CI]
Complete response, %
Partial response, %
Non-response, %
Stable disease (≥ 6 weeks)
Progressive disease
Not evaluable
Disease control rate, % [95% CI]
75% [64, 85]
88% [76, 96]
100% [81, 100]
93% [81, 99]
Median DoR, months [95% CI]
9.5 [4.2, 14.7]
10.7 [6.1, 14.8]
11.0 [2.8, NR]
9.7 [4.5, 14.3]
Median PFS, months [95% CI]
5.5 [4.1, 7.7]
9.1 [5.5, 12.8]
11.1 [4.1, 22.1]
9.0 [5.6, 12.7]
Notes: [1] Most patients were enrolled to Part B1, B2, B3 on 600 mg savolitinib, prior to weight-based dosing implementation, but
following a protocol amendment in response to a safety signal of hypersensitivity, the final 21 patients enrolled in Part B were
dosed with savolitinib by body weight as follows: patients who weighed ≤55 kg (n=8) received 300 mg daily and those weighing
>55 kg (n=13) received 600 mg daily; Best response data are for patients who had an opportunity to have two follow-up scans;
CI = confidence interval; n = number of patients; NR = not reached; ORR = objective response rate; DoR = duration of response;
PFS = progression free survival; and EGFR-TKI = epidermal growth factor receptor tyrosine kinase.
Source: Han JY, Sequist LV, Ahn MJ, et al. Osimertinib + savolitinib in patients with EGFRm MET-amplified/overexpressed NSCLC:
Phase Ib TATTON Parts B and D final analysis. Poster presented at: 2021 World Conference on Lung Cancer Singapore;
January 28-21, 2021; Virtual. https://bit.ly/3cl7QRE
Savannah study; Phase II study of savolitinib in combination with Tagrisso in NSCLC Tagrisso-refractory EGFRm+ patients (Status:
enrolling; NCT03778229)
Based on the encouraging results of the multiple TATTON studies, we and AstraZeneca have initiated a global Phase II study of
savolitinib in combination with Tagrisso in EGFRm+ NSCLC patients with MET gene amplification who have progressed following
first or second-line Tagrisso therapy. The Savannah study is a single-arm study in North and South America, Europe and Asia. Subject
to positive clinical outcomes and regulatory interactions, the Savannah study is designed to support potential NDA submission for
savolitinib.
The Savannah study has now fully enrolled the savolitinib 300mg QD and Tagrisso cohort, and is currently enrolling two additional
cohorts of savolitinib 300mg BID and 600mg QD. The Savannah study will also determine optimal design of the planned global Phase
III study regarding optimal biomarker strategy and dosage regimen. Enrollment is expected to complete in mid-2021 and planning for
the global Phase III study is now underway.
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The Savannah Study Design: Addressing Tagrisso Resistance Through Combination Therapies
2L+ LOCALLY ADVANCED / METASTATIC
EGFRM+ NSCLC PATIENTS
(cid:31) Progression on 1L or 2L TAGRISSO;
(cid:31) No prior chemo or immunotherapy;
(cid:31) MET amplification / over-expression
(central FISH/IHC or pre-existing local
NGS);
(cid:31) No prior MET inhibitor therapy;
(cid:31) Stable/asymptomatic CNS mets.
permitted;
(cid:31) ECOG performance status 0-1.
Enrolled
Savolitinib 300mg QD
+ TAGRISSO® 80mg QD
Enrolling
Savolitinib 300mg BID
+ TAGRISSO® 80mg QD
Enrolling
Savolitinib 600mg QD
+ TAGRISSO® 80mg QD
PRIMARY ENDPOINT
(cid:31) 300mg QD ORR
SECONDARY ENDPOINTS
(cid:31) 300mg QD
(cid:30) ORR by MET FISH+ / IHC+;
PFS; DoR; OS
(cid:30) Safety
(cid:31) 300mg BID & 600mg QD
(cid:30) Efficacy (ORR; PFS; DoR;
OS)
(cid:30) Safety / tolerability
Notes: 1L = first line; 2L = second line; 2L+ = second line and above; EGFRM+ = epidermal growth factor receptor mutation positive;
ECOG = Eastern Cooperative Oncology Group; BID = twice daily; QD = once daily; FISH (+) = fluorescence in situ
hybridization ( positive ); IHC (+) = immunohistochemistry ( positive ); ORR = objective response rate; PFS = progression
free survival; DoR = duration of response; OS = overall survival; and MET = mesenchymal epithelial transition receptor.
Source: Company.
In-Planning – China Phase III study of combination with Targrisso in 2L EGFR TKI refractory, MET amplified NSCLC patients
We intend to initiate a Phase III study in China targeting EGFR TKI refractory second-line NSCLC patient in the second half of
2021.
In-Planning – China Phase III study of combination with Targrisso in EGFR mutant and MET positive NSCLC patients
We intend to initiate a Phase III study in China targeting treatment naïve patients who are both EGFR mutation and MET positive
in the second half of 2021.
Kidney Cancer
The table below shows a summary of the clinical trials that we have recently completed or underway for savolitinib in kidney cancer
patients.
Treatment
Savolitinib + Imfinzi
Savolitinib + Imfinzi
Savolitinib + Imfinzi
Current and Recent Clinical Trials of Savolitinib in Kidney Cancer
Name, Line, Patient Focus
MET-driven, unresectable
and locally advanced or
metastatic PRCC
CALYPSO: PRCC
CALYPSO: Clear cell
RCC; VEGFR TKI
refractory
Sites
Phase Status/Plan
NCT #
Global
III
In planning
N/A
U.K./Spain
U.K./Spain
II
II
Interim data
ASCO GU 2020
Ongoing
NCT02819596
NCT02819596
Notes: PRCC = papillary renal cell carcinoma; RCC = renal cell carcinoma; ASCO GU 2020 = the American Society of Clinical
Oncology’s 2020 Genitourinary Cancers Symposium; VEGFR TKI refractory = resistant to prior VEGFR tyrosine kinase
inhibitor treatment; Global = more than two countries; PFS = progression free survival; and MET = mesenchymal epithelial
transition receptor.
74
Papillary renal cell carcinoma is the most common of the non-clear cell renal cell carcinomas representing about 14% of kidney
cancer, with approximately half estimated to harbor MET-driven disease. No targeted therapies have been approved specifically for
papillary renal cell carcinoma, although some efficacy was observed for cabozantinib in an investigator sponsored study, PAPMET,
which reported ORR of 23% and median progression-free survival of 9 months in 44 patients not selected for MET status and who
mostly (95%) did not receive prior systemic therapy (Pal SK, et al. Lancet. 2021). Modest efficacy in non-clear cell renal cell carcinoma
has been reported in sub-group analyses of broader renal cell carcinoma studies of VEGFR (e.g., Sutent) and mammalian target of
rapamycin (e.g., Afinitor) tyrosine kinase inhibitors, with ORR of <10% and median progression-free survival in first-line setting of
four to six months and second-line setting of only one to three months (ESPN study, Tannir N. M. et al.).
During an Australian Phase I study, our investigators noted positive outcomes among papillary renal cell carcinoma patients with a
strong correlation to MET gene amplification status. Out of a total of eight papillary renal cell carcinoma patients in our Australia Phase
I study who were treated with various doses of savolitinib, three achieved confirmed partial responses. A further three of these eight
papillary renal cell carcinoma patients achieved stable disease, which means patients without partial response but with a tumor
measurement increase of less than 20%. This aggregate ORR of 38% was very encouraging for papillary renal cell carcinoma, which
has no effective approved treatments. These responses were also durable as demonstrated by a patient who has been on the therapy for
over 30 months and had tumor measurement reduction of greater than 85%. Importantly, the level of tumor response among these
papillary renal cell carcinoma patients correlated closely with the level of MET gene amplification. The patients with consistent MET
gene amplification across the whole tumor responded most to savolitinib, and with those patients with the highest level of MET gene
amplification responding most to the treatment.
Recent data have emerged to show that papillary renal cell carcinoma responds to immunotherapy such as inhibitors of an immune
checkpoint known as PD-1 used by cancer cells to avoid being attacked by the immune system. Preliminary data from the KEYNOTE-
427 study (Cohort B) as presented by Merck & Co at the ASCO’s 2019 Genitourinary Cancers Symposium showed objective response
in treatment naïve papillary renal cell carcinoma patients treated with the PD-1 inhibitor Keytruda was 25%. In the broader kidney
cancer setting, combinations of PD-1 or PD-L1 drugs with targeted therapies that demonstrated single agent effect have demonstrated
additive benefits.
Savolitinib and Immunotherapy Combinations
Immunotherapy combinations are rapidly changing the treatment landscape in kidney cancer. Immune checkpoints such as PD-L1
are sometimes used by cancer cells to avoid being attacked by the immune system. As such, drugs that target these checkpoints are being
developed or marketed as cancer treatments. Imfinzi is an anti-PD-L1 antibody owned by AstraZeneca. Anti-PD-L1 antibodies have
been associated with clinical benefits in metastatic renal cell carcinoma, and MET dysregulation has been considered to play an
important role in papillary renal cell carcinoma pathogenesis (including in our savolitinib Phase I and Phase II monotherapy studies)
and is a mechanism of resistance against kinase inhibitors in clear cell renal cell carcinoma. Moreover, it is believed that the MET
signaling pathway has a complex interplay with the immune system, including correlation with PD-L1 expression, immune suppression
through angiogenesis and many other facets of the immune system. Our CALYPSO study discussed below aims to explore and
potentially confirm this interplay.
CALYPSO study; Phase II study of savolitinib in combination with Imfinzi in both papillary renal cell carcinoma and clear cell renal
cell carcinoma patients (status: dose expansion ongoing; NCT02819596)
The CALYPSO study is an investigator-initiated open-label Phase II study of savolitinib in combination with Imfinzi. The study is
evaluating the safety and efficacy of the savolitinib and Imfinzi combination in both papillary renal cell carcinoma and clear cell renal
cell carcinoma patients at sites in the U.K. and Spain.
Interim results of the papillary renal cell carcinoma cohort of the CALYPSO study were presented at the 2020 ASCO’s
Genitourinary Cancers Symposium and showed encouraging efficacy across all patients, both MET+ and MET-. The interim CALYPSO
data reported an ORR of 27% (11/41), while median progression-free survival was 4.9 months (95% confidence interval: 2.5-12.0
months). Median OS was 12.3 months (95% confidence interval: 5.8-21.3 months). For the study’s 27 previously untreated patients, the
ORR was 33% (9/27). Tolerability was consistent with established single agent safety profiles. There were 13 treatment related CTC
grade 3 or above TETAs that occurred in more than three patients, with edema (10%), nausea (5%) and transaminitis (5%) being most
frequent. We and AstraZeneca continue to explore development of the savolitinib-Imfinzi combination in papillary renal cell carcinoma
patients.
75
In-Planning – Phase III in combination with Imfinzi PD-L1 inhibitor in MET-driven, unresectable and locally advanced or metastatic
PRCC
Based on the encouraging results of the SAVOIR and CALYPSO studies, we intend to initiate a global Phase III, open-label,
randomized, controlled study of savolitinib plus Imfinzi versus sunitinib monotherapy versus Imfinzi monotherapy in patients with
MET-driven, unresectable and locally advanced or metastatic PRCC. The study is expected to begin enrollment by mid-2021.
Savolitinib Monotherapy
Phase II study of savolitinib monotherapy in papillary renal cell carcinoma (Status: completed; NCT02127710)
In early 2017, we presented the results of our global Phase II study in papillary renal cell carcinoma at the ASCO’s Genitourinary
Cancers Symposium and subsequently published these results in the Journal of Clinical Oncology. Of 109 patients treated with
savolitinib, papillary renal cell carcinoma was MET driven in 44 patients (40%), MET independent in 46 patients (42%) and MET status
unknown in 19 patients (17%). The ORR based on confirmed partial responses in all patients was 7% (8/109). MET-driven papillary
renal cell carcinoma was strongly associated with encouragingly durable response to savolitinib with an ORR in the MET-driven group
of 18% (8/44) as compared to 0% (0/46) in the MET independent group (p=0.002). Of the eight patients exhibiting a partial response,
six were still responding to treatment at data cutoff, with a duration of response of 2.4 to 16.4 months. Two patients who achieved a
partial response subsequently experienced progressive disease after 1.8 and 2.8 months. P-value is a measure of the probability of
obtaining the observed sample results, with a lower value indicating a higher degree of statistical confidence in these studies. Median
progression-free survival for patients with MET-driven and MET-independent papillary renal cell carcinoma patients was 6.2 months
(95% confidence interval: 4.1-7.0) and 1.4 months (95% confidence interval: 1.4-2.7), respectively (hazard ratio=0.33; 95% confidence
interval: 0.20-0.52; p<0.0001). Hazard ratio is the probability of an event (such as disease progression or death) occurring in the
treatment arm divided by the probability of the event occurring in the control arm of a study, with a ratio of less than one indicating a
lower probability of an event occurring for patients in the treatment arm. Savolitinib had a disease control rate of 73% in the MET-
driven group and 28% in the MET independent group. Savolitinib was well tolerated, with no reported CTC grade 3 or above TEAEs
with greater than 5% incidence. Total aggregate savolitinib CTC grade 3 or above TEAEs occurred in just 19% of patients.
Phase II Study of Savolitinib Monotherapy in Papillary Renal Cell Carcinoma in the United States, Canada and Europe. This Study
Clearly Demonstrated MET-Driven Patients had Better Progression-free Survival Compared to MET Independent Patients.
100
)
%
(
l
a
v
i
v
r
u
s
e
e
r
f
-
n
o
i
s
s
e
r
g
o
r
p
f
o
y
t
i
l
i
b
a
b
o
r
P
80
60
40
20
0
0
Stratified HR [95% CI]: 0.33 [0.20-0.52] P<0.0001
MET driven (n=44)
median PFS, months: 6.2 (4.1, 7.0)
MET independent (n=46)
median PFS, months: 1.4 (1.4, 2.7)
MET unknown
2
4
6
8
10
Months
12
14
16
18
Notes: n = number of patients; CI = confidence interval; and HR = hazard ratio. Disease progression occurred in 33 (75%), 44 (96%),
and 14 patients (74%) with MET-driven, MET-independent, and MET-unknown papillary renal cell carcinoma, respectively.
76
Source: Choueiri TK, Plimack E, Arkenau HT, et al. Biomarker-Based Phase II Trial of Savolitinib in Patients With Advanced Papillary
Renal Cell Cancer. J Clin Oncol. 2017;35(26):2993-3001. doi:10.1200/JCO.2017.72.2967.
SAVOIR study; Phase III study of savolitinib monotherapy in papillary renal cell carcinoma (Status: enrollment suspended;
NCT03091192)
We initiated the SAVOIR study in June 2017. The SAVOIR study was designed to be a global Phase III, open-label, randomized,
controlled trial evaluating the efficacy and safety of savolitinib (600 mg once daily) compared with Sutent in patients with MET-driven,
unresectable, locally advanced or metastatic papillary renal cell carcinoma. MET status was confirmed by the novel targeted next-
generation sequencing assay developed for savolitinib. Patients were randomized in a 1:1 ratio to receive either treatment with
savolitinib, or treatment with Sutent. The primary endpoint for efficacy in the SAVOIR study was median progression-free survival,
with secondary endpoints of OS, ORR, duration of response, best percentage change in tumor size, disease control rate, and safety and
tolerability.
To further understand the role of MET-driven disease in papillary renal cell carcinoma, we conducted a global molecular
epidemiology study, which screened, using our companion diagnostic, archived tissue samples from papillary renal cell carcinoma
patients to identify MET-driven disease. Historical medical records from these patients were then used to determine if MET-driven
disease is predictive of worse outcome, in terms of progression-free survival and OS, in papillary renal cell carcinoma patients.
Confounding results from this external study led to the early termination of SAVOIR in December 2018, with 60 patients randomized
at the time.
77
Results from the 60 randomized patients (33 savolitinib, 27 Sutent) were promising and data was presented at ASCO and published
simultaneously in JAMA Oncology in May 2020. In terms of OS, savolitinib patients had not reached median OS at data cut-off,
compared to 13.2 months for Sutent patients (HR 0.51; 95% CI: 0.21–1.17; p=0.110). Median PFS was 7.0 months for savolitinib
patients, compared to 5.6 for Sutent patients (HR 0.71; 95% CI 0.37–1.36; p=0.313). Responses were observed in 27% and 7% of
savolitinib and Sutent patients, respectively. This difference did not reach statistical significance due to the small sample size. In terms
of safety, Grade ≥3 AEs were reported in 42% of savolitinib patients versus 81% of Sutent patients, with AEs leading to dose
modification in 30% and 74% of savolitinib and Sutent patients, respectively. CTC grade 3 or above adverse events with greater than
5% incidence related to savolitinib treatment were increased aspartate aminotransferase (15%) and increased alanine aminotransferase
(12%). Those related to Sutent were anemia (15%), hypertension (15%), thrombocytopenia (7%), increased aspartate aminotransferase
(7%), and increased alanine aminotransferase (7%).
SAVOIR 60-Patient Study of Savolitinib Monotherapy in MET-Driven Papillary Renal Cell Carcinoma Patients. This Study
Demonstrated a Strong Signal of Response and Potential Survival Benefit Compared to Sutent Monotherapy
Objective response rate, % [95% CI]
Progression-free survival, months [95% CI]
Savolitinib (N=33)
27.3% [13.3, 45.5]
7.0 [2.8, NC]
Sutent (sunitinib, N=27)
7.4% [0.9, 24.3]
5.6 [4.1, 6.9]
Hazard Ratio: 0.71 [0.37, 1.36]
Disease control rate @ 6 months, % [95% CI]
Disease control rate @ 12 months, % [95% CI]
48.4% [30.8, 66.5]
30.3% [15.6, 48.7]
37.0% [19.4, 57.6]
22.2% [8.6, 42.3]
78
Notes: At data cut-off, all nine savolitinib responders remained in response, while one of two sunitinib responders remained in
response. * One out of two sunitinib responders remained in response. n = number of patients; CI = confidence interval; DCR
= disease control rate; NC = not calculated; OS = overall survival; PFS = progression-free survival; and HR = hazard ratio.
Source: Choueiri TK, et al. Efficacy of Savolitinib vs Sunitinib in Patients With MET-Driven Papillary Renal Cell Carcinoma: The
2020.
3 Randomized Clinical Trial.
JAMA Oncol. Published
online May
29,
SAVOIR Phase
doi:10.1001/jamaoncol.2020.2218.
Based on these data, we and AstraZeneca are actively evaluating the opportunity to restart clinical trials of savolitinib in
combination with Imfinzi versus Sutent monotherapy and versus Imfinzi monotherapy in patients with MET-driven, unresectable and
locally advanced or metastatic papillary renal cell carcinoma. The study is expected to begin enrollment in mid-2021.
Gastric Cancer
The table below shows a summary of our clinical trial for savolitinib in gastric cancer patients.
Clinical Trial of Savolitinib in Gastric Cancer
Treatment
Savolitinib monotherapy
Name, Line, Patient Focus
Gastric cancer (MET
amplification) and Viktory
Sites
Phase
Status/Plan
China & South Korea Ib/II
Completed
NCT #
NCT01985555/
NCT02449551
Phase II gastric cancer studies have been completed in China and in South Korea. A total of over 1,000 gastric cancer patients have
been screened in these studies and those patients with confirmed MET-driven disease were treated with savolitinib.
Phase Ib/II study of savolitinib monotherapy in MET amplified gastric cancer in China (Status: completed; NCT01985555)
Preliminary results of the China study were presented at the 2017 Chinese Society of Clinical Oncology for the efficacy evaluable
MET gene amplified patients. Based on confirmed and unconfirmed partial responses, the ORR was 43% (3/7) and disease control rate
was 86% (6/7), with ORR of 14% (3/22) and disease control rate of 41% (9/22) among the overall efficacy evaluable aberrant MET set
of patients with MET amplification (n=7) and MET overexpression (n=15). As of data cut-off, the longest duration of treatment was in
excess of two years. Savolitinib monotherapy was determined to be safe and well tolerated in patients with advanced gastric cancer.
CTC grade 3 or above TEAEs with greater than 5% incidence included abnormal hepatic function in 13% (4/31), gastrointestinal
bleeding or decreased appetite in 10% (3/31 each), and diarrhea or gastrointestinal perforation in 6% (2/31 each). This China study
concluded that savolitinib monotherapy demonstrated promising anti-tumor efficacy in gastric cancer patients with MET gene
amplification, and that the potential benefit to these patients warranted further exploration, with enrollment continuing.
Viktory Phase II study of savolitinib in MET amplified gastric cancer in South Korea (Status: completed; NCT02449551)
The Viktory study is a biomarker-based, Phase II umbrella trial in gastric cancer conducted by the Samsung Medical Center in
South Korea. Patients were allocated to one of 12 biomarker-driven arms, based on a master screening protocol with tissue-based
molecular analyses. Patients that tested positive for MET amplification or overexpression were treated with either savolitinib
monotherapy or a combination of savolitinib and Taxotere. A total of 715 gastric cancer patients were successfully sequenced and MET
amplification was observed in 3.5% of these patients (25/715). Of the 10 associated clinical trials under the Viktory umbrella, the highest
ORR was observed in the MET amplification arm in patients treated with savolitinib monotherapy, which reported an ORR of 50%
(10/20, 95% confidence interval: 28.0-71.9) and met pre-specified 6-week progression-free survival rates. While the savolitinib and
Taxotere combination was well tolerated, the Viktory study investigators decided to stop enrollment in the two combination cohorts in
order to direct patients to the savolitinib monotherapy arm of the Viktory study as discussed above.
The Viktory study investigators have concluded that encouraging clinical efficacy of savolitinib in MET-amplified gastric cancer
warrants further study.
In-Planning - China Phase II study with potential for registration intent in 2L+ gastric cancer with MET amplification
In mid-2021, we intend to initiate a Phase II registration-intent study in MET-amplified gastric cancer in China. This is a two-
stage, single-arm study which targets advanced gastric cancer patients who have failed at least one line of treatment. The primary
79
endpoint is ORR. Subject to the results of the first-stage of this study we will discuss with the CDE of NMPA the appropriate approach
and necessary criteria for registration.
Savolitinib Exploratory Development
The table below shows a summary of the clinical study that is underway for savolitinib in other solid tumors.
Clinical Trial of Savolitinib in CRC
Treatment
Savolitinib monotherapy
Name, Line, Patient Focus
Sites Phase Status/Plan
MET-driven mCRC
U.S.
II
Enrolling
NCT #
NCT03592641
Phase II study of savolitinib monotherapy in mCRC (Status: enrolling; NCT03592641)
This study is sponsored by the National Cancer Institute and targets to screen up to 150 patients in order to enroll approximately 15
patients with MET amplified mCRC. The primary objective of the study is ORR. Secondary objectives include additional measures of
clinical efficacy, safety and tolerability.
Partnership with AstraZeneca
In December 2011, we entered into a global licensing, co-development, and commercialization agreement for savolitinib with
AstraZeneca. As noted above, given the complexity of many of the signal transduction pathways and resistance mechanisms in oncology,
the industry is increasingly studying combinations of targeted therapies (tyrosine kinase inhibitors, monoclonal antibodies and
immunotherapies) and chemotherapy as potentially the best approach to treating this complex and constantly mutating disease. Based
on savolitinib showing early clinical benefit as a highly selective MET inhibitor in a number of cancers, in August 2016 and December
2020 we and AstraZeneca amended our global licensing, co-development, and commercialization agreement for savolitinib. We believe
that AstraZeneca’s portfolio of proprietary targeted therapies is well suited to be used in combinations with savolitinib, and we are
studying combinations with Tagrisso (EGFRm+, T790M+) and Imfinzi (PD-L1). These combinations of multiple global first-in-class
compounds are difficult to replicate, and we believe represent a significant opportunity for us and AstraZeneca.
For more information regarding our partnership with AstraZeneca, see “—Overview of Our Collaborations—AstraZeneca.”
2. Surufatinib VEGFR 1, 2 and 3, FGFR1 and CSF-1R Inhibitor
Surufatinib is an oral small molecule angio-immuno kinase inhibitor targeting VEGFR and FGFR, which both inhibit angiogenesis,
and CSF-1R, which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique
angio-immuno kinase profile could help improve the anti-tumor activity of PD-1 antibodies.
Surufatinib is the first oncology candidate that we have taken through proof-of-concept in China and expanded globally ourselves.
Surufatinib is in proof-of-concept clinical trials in the United States, successfully completed two late-stage clinical trials, is in further
late-stage clinical trials in China and is expected to start late-stage trials in the United States and Europe as a monotherapy. Furthermore,
it is being investigated in combination with PD-1 inhibitors.
Surufatinib was approved by the NMPA in December 2020 for the treatment of non-pancreatic neuroendocrine tumors and is now
being marketed in China under the brand name Sulanda.
Mechanism of Action
Both VEGFR and FGFR signaling pathways can mediate tumor angiogenesis. CSF-1R plays an important role in the functions of
macrophages. Recently, the roles in increasing tumor immune evasion of VEGFR, FGFR in regulation of T cells, tumor-associated
macrophages and myeloid-derived suppressor cells have been demonstrated. Therefore, blockade of tumor angiogenesis and tumor
immune evasion by simultaneously targeting VEGFR 1, 2 and 3, FGFR1 and CSF-1R kinases may represent a promising approach for
oncology therapy.
80
Surufatinib Pre-clinical Evidence
Surufatinib inhibited VEGFR 1, 2, and 3, FGFR1 and CSF-1R kinases with IC50 in a range of 1 nM to 24 nM. It also strongly
blocked VEGF-induced VEGFR2 phosphorylation in HEK293 cells and CSF-1R phosphorylation in RAW264.7 cells with an IC50 of
2 nM and 79 nM, respectively. Surufatinib also reduced VEGF- or FGF-stimulated human umbilical vein endothelial cell proliferation
with an IC50 < 50 nM. In animal studies, a single oral dose of surufatinib inhibited VEGF-stimulated VEGFR2 phosphorylation in lung
tissues of nude mice in an exposure-dependent manner. Furthermore, elevation of FGF23 levels in plasma 24 hours post dosing
suggested suppression of FGFR signaling.
Surufatinib demonstrated potent tumor growth inhibition in multiple human xenograft models and decreased cluster of
differentiation 31 expression remarkably, suggesting strong inhibition on angiogenesis through VEGFR and FGFR signaling. In a
syngeneic murine colon cancer model, surufatinib demonstrated moderate tumor growth inhibition after single-agent treatment. Flow
cytometry and immunohistochemistry analysis revealed an increase of certain T cells and a significant reduction in certain tumor-
associated macrophages, including CSF-1R mutation positive tumor-associated macrophages in tumor tissue, indicating surufatinib has
a strong effect on CSF-1R. Interestingly, a combination of surufatinib with a PD-L1 antibody resulted in enhanced anti-tumor effect.
These results suggested that surufatinib has a strong effect in modulating angiogenesis and cancer immunity.
Surufatinib Clinical Trials
We currently have various clinical trials of surufatinib ongoing or expected to begin in the near term in patients with neuroendocrine
tumors and biliary tract cancer, or BTC, and in combination with checkpoint inhibitors.
Neuroendocrine Tumors
Neuroendocrine tumors begin in the specialized cells of the body’s neuroendocrine system. Cells have traits of both hormone-
producing endocrine cells and nerve cells. Neuroendocrine tumors are found throughout the body’s organ system and have complex
and fragmented epidemiology with about 40-60% of neuroendocrine tumors originating in the gastrointestinal tract and pancreas, 20-
30% in the lung or bronchus, and a further 20-30% in other organs or unknown origins.
In China, there were about 67,600 newly diagnosed NET patients in 2018 and, while no China prevalence data exists, we believe
that there could be over 300,000 patients living with the disease.
Neuroendocrine tumors can be functional, releasing hormones and peptides that cause symptoms like diarrhea and flushing, or non-
functional with no symptoms. Early-stage neuroendocrine tumors, which are often functional, can be treated with somatostatin analogue
subcutaneous injections, which are approved and reimbursed in China and alleviate symptoms and slow neuroendocrine tumor growth,
but have limited tumor reduction efficacy.
Advanced neuroendocrine tumors grow more quickly. In China, Sutent is approved in pancreatic NET while Afinitor, an m-TOR
inhibitor, is approved in non-functional neuroendocrine tumors in the pancreas, lung and gastrointestinal tract. These approvals,
however, cover only about half of advanced neuroendocrine tumor patients.
81
The table below shows a summary of the clinical trials that we have completed or are in planning for surufatinib in neuroendocrine
cancer patients. Our Phase Ib study in planning for the United States and Europe will also include expansion cohorts to explore
surufatinib in patients with BTC and sarcoma.
Clinical Trials of Surufatinib in Neuroendocrine Tumors
Treatment
Surufatinib monotherapy
Surufatinib monotherapy
Name, Line, Patient Focus
SANET-ep: Non-pancreatic NET
SANET-p: Pancreatic NET
Sites
China
China
Phase
III
III
Surufatinib monotherapy
NETs
Surufatinib monotherapy
NETs
U.S.
Europe
Ib
Ib
Status/Plan
Approved and launched
Met primary endpoint;
NDA accepted (Sept
2020)
NDA rolling submission
initiated; est. complete
H1 2021
Expect to file MAA in
mid-2021
NCT #
NCT02588170
NCT02589821
NCT02549937
N/A
Notes: NET = neuroendocrine tumor; BTC = biliary tract cancer; and MAA = marketing authorization applications.
SANET-ep study; Phase III study of surufatinib monotherapy in non-pancreatic neuroendocrine tumors (Status: completed and
product launched in China in January 2021; NCT02588170)
In 2015, we initiated the SANET-ep study, which is a Phase III study in China in patients with grade 1 and 2 advanced non-
pancreatic neuroendocrine tumors. In this study, patients were randomized at a 2:1 ratio to receive either an oral dose of 300 mg of
surufatinib or a placebo once daily on a 28-day treatment cycle. The primary endpoint was progression-free survival, with secondary
endpoints including ORR, disease control rate, time to response, duration of response, OS, safety and tolerability.
A 198-patient interim analysis was conducted on SANET-ep in mid-2019, leading the independent data monitoring committee, or
IDMC, to determine that it had met the pre-defined primary endpoint of progression-free survival and should be stopped early. The
positive results of this trial were highlighted in an oral presentation at the 2019 European Society for Medical Oncology Congress, and
subsequently published in The Lancet Oncology in September 2020. Median progression-free survival per investigator assessment was
9.2 months for patients treated with surufatinib, as compared to 3.8 months for patients in the placebo group (HR 0.334; 95% CI: 0.223,
0.499; p<0.0001). Efficacy was also supported by a blinded independent image review committee assessment. Surufatinib was well-
tolerated in this study and the safety profile is consistent with observations in prior clinical studies. CTC grade 3 or above TEAEs in
this study with greater than 5% incidence were hypertension (36%), proteinuria (19%) and anemia (5%).
82
SANET-ep Clearly Succeeded in Meeting Primary Endpoint of Progression-Free Survival
)
%
(
l
a
v
i
v
r
u
s
e
e
r
f
-
n
o
i
s
s
e
r
g
o
r
P
100
90
80
70
60
50
40
30
20
10
0
0
Surufatinib
Placebo
HR 0.334 (95% CI 0.223–0.499); p<0·0001
2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
Number at risk
(number censored)
Time (months)
Surufatinib
Placebo
129 (0)
69 (0)
100 (16)
43 (11)
83 (24)
25 (15)
63 (31)
16 (16)
46 (36)
10 (16)
37 (36)
6 (17)
25 (42)
6 (17)
13 (47)
4 (17)
13 (47)
4 (17)
8 (49)
1 (18)
7 (49)
0 (18)
7 (49)
··
4 (50)
··
3 (50)
··
2 (51)
··
2 (51)
··
0 (52)
··
Notes: P-value is obtained from the stratified one-sided log-rank test; Hazard ratio is obtained from stratified Cox model; CI =
confidence interval; and HR = hazard ratio.
Source: Xu J, Shen L, Zhou Z, et al. Surufatinib in advanced extrapancreatic neuroendocrine tumours (SANET-ep): a randomised,
double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(11):1500-1512. doi:10.1016/S1470-2045(20)30496-
4.
In late 2020, surufatinib was granted approval for drug registration by the NMPA for the treatment of non-pancreatic NET, followed
by launch in mid-January 2021 within three weeks of approval. We believe the benefit of surufatinib as a monotherapy to patients with
non-pancreatic neuroendocrine tumors in China could be significant as compared to the minimal treatment alternatives currently
available to them.
83
SANET-p study; Phase III study of surufatinib monotherapy in pancreatic neuroendocrine tumors (Status: met primary endpoint early;
NDA accepted in September 2020; NCT02589821)
In 2016, we initiated the SANET-p study, which is a Phase III study in China in patients with low- or intermediate-grade, advanced
pancreatic neuroendocrine tumors. In this study, patients are randomized at a 2:1 ratio to receive either an oral dose of 300 mg of
surufatinib or a placebo once daily on a 28-day treatment cycle. The primary endpoint is progression-free survival, with secondary
endpoints including ORR, disease control rate, time to response, duration of response, OS, safety and tolerability.
In early 2020, an interim analysis was conducted on SANET-p, leading the IDMC to recommend that the study stop early as the
pre-defined primary endpoint of progression-free survival had already been met. Median PFS was 10.9 months for patients treated with
surufatinib, as compared to 3.7 months for patients in the placebo group (HR 0.491; 95% CI: 0.319-0.755; p=0.0011). ORRs were 19.2%
for the efficacy evaluable patients in the surufatinib group versus 1.9% for the placebo group, with a DCR of 80.8% versus 66.0%,
respectively. Most patients in the trial had Grade 2 disease with heavy tumor burden, including liver metastasis and multiple organ
involvement. Efficacy was also supported by blinded independent image review committee assessment, with a median PFS of 13.9
months for surufatinib as compared to 4.6 months for placebo (HR 0.339; 95% CI 0.209-0.549; p<0.0001). The safety profile of
surufatinib was manageable and consistent with observations in prior studies. Treatment was well tolerated for most patients, with
discontinuation rates as a result of TEAEs of 10.6% in the surufatinib group as compared to 6.8% in the placebo group. CTC grade 3
or above TEAEs in this study with greater than 5% incidence were hypertension (38%), proteinuria (10%) and hypertriglyceridemia
(7%).
SANET-p Clearly Succeeded in Meeting Primary Endpoint of Progression-Free Survival
Surufatinib
Placebo
HR for progression or death 0.49 (95% CI 0.32–0.76); p=0·0011
Notes: P-value is obtained from the stratified one-sided log-rank test; Hazard ratio is obtained from stratified Cox model; CI =
confidence interval; and HR = hazard ratio.
Source: Xu J, Shen L, Bai C, et al. Surufatinib in advanced pancreatic neuroendocrine tumours (SANET-p): a randomised, double-
blind, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21(11):1489-1499. doi:10.1016/S1470-2045(20)30493-9.
Following the success of SANET-p, a second NDA was filed and accepted by the NMPA in September 2020. We believe the
benefits of surufatinib as a monotherapy to the approximately 23,400 new patients with pancreatic neuroendocrine tumors in China in
2018 could be significant as compared to the treatment alternatives currently available to them.
The positive SANET-ep and SANET-p Phase III studies now position surufatinib to potentially be approved in the full spectrum of
advanced-NET disease in China. We believe that no other approved targeted therapy can address and treat all subtypes of NETs.
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Phase Ib study of surufatinib monotherapy in heavily pretreated progressive neuroendocrine tumors (Status: ongoing; NCT02549937)
We are conducting a multi-center, open-label, Phase Ib clinical study to evaluate the safety, tolerability and pharmacokinetics of
surufatinib in U.S. patients, which established the U.S. recommended Phase II dose, or RP2D, to be 300 mg, the same as that in China.
At ASCO 2020, preliminary data presented from the two NET cohorts in the ongoing U.S. Phase Ib trial for surufatinib demonstrated
efficacy comparable to China data in heavily pretreated patients, including Afinitor and Sutent, with pancreatic or non-pancreatic NETs.
The safety profile was also consistent with the larger pool of surufatinib safety data. As of April 21, 2020, 16 patients with pancreatic
NET were treated for a median of 7.1 months (range 2.0-17.5) and 16 patients with non-pancreatic NET were treated for a median of
4.9 months (range of 1.0-10.2). All 32 patients have pretreated progressive NETs (median prior lines of treatment: 3; range 1-8).
Confirmed response was observed in 18.8% of pancreatic NET patients; all remaining patients had stable disease (including 1
unconfirmed response), for a DCR of 100%. In the non-pancreatic NET cohort all patients had stable disease (including 1 unconfirmed
response).
The FDA granted surufatinib orphan drug designation for the treatment of pancreatic neuroendocrine tumors in November 2019
and Fast Track Designations for our pancreatic and non-pancreatic NET development programs in April 2020. In December 2020, we
initiated the filing of a NDA to the U.S. FDA – the first portion of a rolling submission for surufatinib for the treatment of pancreatic
and non-pancreatic NET. We plan to complete the NDA submission in the first half of 2021, which would be our first NDA in the U.S.
Filing acceptance of the NDA is subject to FDA review of the complete application. We also plan to file a MAA to the EMA in mid-
2021, based on scientific advice from the EMA’s Committee for Medicinal Products for Human Use (CHMP).
US Phase Ib: Encouraging Preliminary Efficacy in Afinitor and Sutent Refractory/Intolerant Neuroendocrine Tumor Patients
surufatinib
everolimus
sunitinib
Other Tx
8
12
10
24
3
3
2
X
15
3
11
2
3
2
5
7
8
36
18
7
8
8
24
X
X
12
4
8
15
10
12
4
7
11
9
18
6
6
3
2
2
1
3
2
6
6
X
X
X
6
14
2
3
1
36
12
24
32
12
3
22
5
12
36
6
18
6
-48
-36
-24
-12
0
24
22
12
12
6
24
PR
Confirmed PR (n=3)
uPR
Unconfirmed PR (n=1)
Treatment ongoing (n=5)
X
X
X
Rx stop – AE (n=1)
Rx stop – PD (n=7)
Rx stop – Other (n=3)
PR
uPR
X
4
12
X
4
13
12
12
PR
X
PR
12
3
24
48
8
X
8
X
36
48
60
72
84
Months since treatment of
everolimus (AFINITOR®) or sunitinib (SUTENT®)
85
Notes: Data cut-off as of April 21, 2020. PR = partial response; AE = adverse event; PD = progressive disease; Rx = treatment; Tx =
treatment; and n = number of patients.
Source: Dasari, et al. Efficacy and safety of surufatinib in United States (US) patients (pts) with neuroendocrine tumors (NETs). Journal
of Clinical Oncology 2020 38:15_suppl, 4610-4610.
Biliary Tract Cancer
BTC (also known as cholangiocarcinoma) is a heterogeneous group of rare malignancies arising from the biliary tract epithelia.
Gemzar, a type of chemotherapy, is the currently approved first-line therapy for BTC patients, with median survival of less than 12
months for patients with unresectable or metastatic disease at diagnosis. As a result, this is a major unmet medical need for patients
who have progressed on chemotherapy. There is currently no standard of care for these patients. Surufatinib may offer a new targeted
treatment option in this tumor type. The table below shows a summary of the clinical studies that we have underway for surufatinib in
BTC patients.
Clinical Trial of Surufatinib in BTC
Treatment
Surufatinib monotherapy
Surufatinib monotherapy
Surufatinib monotherapy
Name, Line, Patient Focus
Sites Phase
Status/Plan
NCT #
Chemotherapy refractory BTC China
Chemotherapy refractory BTC China
BTC and soft tissue sarcoma
U.S.
Ib/II
IIb/III Ongoing
Ongoing
Ib
Enrollment complete NCT02966821
NCT03873532
NCT02549937
Note: Chemotherapy refractory = resistant to prior chemotherapy treatment; BTC = biliary tract cancer.
Phase Ib/II surufatinib monotherapy in chemotherapy refractory BTC – China (Status: enrollment complete; NCT02966821)
In early 2017, we began a Phase Ib/II proof-of-concept study in patients with BTC. Preliminary efficacy led us to begin the Phase
II/III study discussed below.
Phase IIb/III study of surufatinib monotherapy in second line BTC – China (Status: ongoing; NCT03873532)
In March 2019, based on preliminary Phase Ib/IIa data, we initiated a registration-intent Phase IIb/III study comparing surufatinib
with capecitabine in patients with unresectable or metastatic BTC whose disease progressed on first-line chemotherapy. The primary
endpoint is OS. Enrollment for the BTC monotherapy Phase II portion (80 patients) was completed in 2020, and we expect to conduct
an interim analysis for futility in 2021 when OS data are mature. The interim analysis will inform the Phase III study decision.
Surufatinib Combinations with Checkpoint Inhibitors
Surufatinib’s ability to inhibit angiogenesis, block the accumulation of tumor associated macrophages and promote infiltration of
effector T cells into tumors, could help improve the anti-tumor activity of PD-1 antibodies.
The table below shows a summary of the clinical trials that we have underway or in planning for surufatinib in combination with
checkpoint inhibitors.
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Clinical Trials of Surufatinib with Checkpoint Inhibitors
Treatment
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tuoyi (PD-1)
Surufatinib and Tyvyt (PD-1)
Surufatinib and tislelizumab (PD-1)
Name, Line, Patient Focus
Sites
Phase
Status/Plan
Solid tumors (eight indications) China
China
Neuroendocrine neoplasms
China
BTC
Gastric cancer
China
China
Small cell lung cancer
China
Soft tissue sarcoma
China
Endometrial cancer
China
Esophageal cancer
China
NSCLC
China
Solid tumors
U.S. / Europe Ib/II
Solid tumors
II
II
II
II
II
II
II
II
II
I
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
In planning
NCT #
NCT03879057
NCT04169672
NCT04169672
NCT04169672
NCT04169672
NCT04169672
NCT04169672
NCT04169672
NCT04169672
NCT04427774
NCT04579757
In late 2018, we entered into a global collaboration with Junshi to evaluate the combination of surufatinib with Tuoyi. We have
completed a Phase I dose-finding study and presented the data at the AACR Conference in April 2020. The data showed that surufatinib
plus Tuoyi were well tolerated with no unexpected safety signals observed. At the recommend Phase 2 dose, a DCR of 100% and ORR
of 63.6% were reported for 11 efficacy evaluable patients, with 2 unconfirmed partial responses. Surufatinib plus Tuoyi showed
encouraging antitumor activity in patients with advanced solid tumors. A Phase II China study is enrolling patients in nine solid tumor
indications, including NENs, BTC, gastric cancer, thyroid cancer, small cell lung cancer, soft tissue sarcoma, endometrial cancer,
esophageal cancer and NSCLC.
Phase I dose finding study: Encouraging Anti-Tumor Efficacy for Surufatinib Combined with the anti-PD-1 Antibody Tuoyi in G3
NET/NEC patients
87
Notes: RP2D = Recommended Phase 2 Dose. NET/NEN: neuroendocrine tumor/neoplasm; NEC: neuroendocrine carcinoma; CRC:
colorectal carcinoma; GC: gastric adenocarcinoma; EC: esophageal squamous cell carcinoma; GEJ: gastroesophageal junction;
MAC G2: mediastinal atypical carcinoid; PNET G2: Pancreas NET G2; MSCC: metastatic squamous cell carcinoma with
unknown primary; NSCLC: non-small cell lung cancer; LAC: Lung atypical carcinoid; *: Left supraclavicular lymph node
neuroendocrine tumor; #: Merkel cell carcinoma.
Source: Cao Y, et al. “A phase I trial of surufatinib plus toripalimab in patients with advanced solid tumors.” Presented at American
Association for Cancer Research (AACR) Virtual Annual Meeting I on April 27, 2020.
In late 2019, we expanded our global collaboration agreement with Innovent to evaluate the safety and efficacy of Tyvyt in
combination with surufatinib, and in July 2020, started a Phase I study in China to evaluate the safety and efficacy of the combination.
In addition, in May 2020, we entered into a global clinical collaboration agreement to evaluate the safety, tolerability and efficacy
of combining surufatinib with BeiGene’s anti-PD-1 antibody, tislelizumab, for the treatment of various solid tumor cancers in the U.S.,
Europe, China and Australia. In the first half of 2021, we plan to start an open-label, Phase Ib/II study of surufatinib in combination
with tislelizumab in the U.S. and Europe, evaluating the safety, tolerability, pharmacokinetics and efficacy in patients with advanced
solid tumors, including CRC, NET, small cell lung cancer, gastric cancer and soft tissue sarcoma.
Surufatinib Exploratory Development
We are conducting multiple Phase Ib expansion cohorts in the United States to explore the use of surufatinib in BTC and soft tissue
sarcoma. In China, we intend to initiate multiple exploratory studies, both as a single agent, and in combinations, to evaluate the efficacy
of surufatinib. We are also supporting dozens of investigator-initiated studies in various tumor settings.
3. Fruquintinib VEGFR 1, 2 and 3 Inhibitor
Fruquintinib (also known as HMPL-013) is a VEGFR inhibitor that we believe is highly differentiated due to its superior kinase
selectivity compared to other small molecule VEGFR inhibitors, which can be prone to excessive off-target toxicities. Fruquintinib’s
selectivity on VEGFR 1, 2 and 3 results in fewer off-target toxicities, thereby allowing for better target coverage, as well as possible use
in combination with other agents such as chemotherapies, targeted therapies and immunotherapies.
We believe these are meaningful points of differentiation compared to other approved small molecule VEGFR inhibitors such as
Sutent, Nexavar and Stivarga, and can potentially significantly expand the use and market potential of fruquintinib. Consequently, we
believe that fruquintinib has the potential to become the global best-in-class selective small molecule VEGFR inhibitor for many types
of solid tumors.
We received full approval for launch of fruquintinib (under the brand name Elunate) in CRC in September 2018. In partnership
with Eli Lilly, we launched fruquintinib in China in late November 2018. Elunate is indicated for the treatment of patients with mCRC
that have been previously treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-
VEGF therapy and/or anti-EGFR therapy (Ras wild type). We manufacture all commercial supplies of Elunate in our factory in Suzhou
and expanded our role in the commercialization of Elunate on October 1, 2020. For more information regarding the Elunate product
launch, see “—Overview of Elunate Commercial Launch.”
Mechanism of Action
During the development of cancer, tumors at an advanced stage can secrete large amounts of VEGF, a protein ligand, to stimulate
formation of excessive vasculature (angiogenesis) around the tumor in order to provide greater blood flow, oxygen, and nutrients to fuel
the rapid growth of the tumor. Since essentially all solid tumors require angiogenesis to progress beyond a few millimeters in diameter,
antiangiogenesis drugs have demonstrated benefits in a wide variety of tumor types. VEGF and other ligands can bind to three VEGF
receptors, VEGFR 1, 2 and 3, each of which has been shown to play a role in angiogenesis. Therefore, inhibition of the VEGF/VEGFR
signaling pathway can act to stop the growth of the vasculature around the tumor and thereby starve the tumor of the nutrients and
oxygen it needs to grow rapidly.
88
This therapeutic strategy has been well validated with several first-generation VEGF inhibitors having been approved globally since
2005 and 2006. These include both small molecule multi-kinase inhibitor drugs such as Nexavar and Sutent as well as monoclonal
antibodies such as Avastin. The success of these drugs validated VEGFR inhibition as a new class of therapy for the treatment of cancer.
Fruquintinib Pre-clinical Evidence
Pre-clinical trials have demonstrated that fruquintinib is a highly selective VEGFR 1, 2 and 3 inhibitor with high potency and low
cell toxicity at the enzymatic and cellular levels. In a kinase selectivity screening, fruquintinib was found to be approximately 250 times
more selective to VEGFR 3 than to the next non-VEGFR kinase.
As a result of off-target side effects, existing VEGFR inhibitors are often unable to be dosed high enough to completely inhibit
VEGFR, the intended target. In addition, the complex off-target toxicities resulting from inhibition of multiple signaling pathways are
often difficult to be managed in clinical practice. Combining such drugs with chemotherapy can lead to severe toxicities that can cause
more harm than benefit to patients. To date, the first generation VEGFR tyrosine kinase inhibitors have been rarely used in combination
with other therapies, thereby limiting their potential. Because of the potency and selectivity of fruquintinib, we believe that it has the
potential to be safely combined with other oncology drugs, which could significantly expand its clinical potential.
Fruquintinib Clinical Trials
Colorectal Cancer
The table below shows a summary of the clinical trials we have recently completed, are underway or are in planning for fruquintinib
in CRC patients. We have two additional trials in progress for fruquintinib in CRC in combination with a checkpoint inhibitor as
discussed in more detail below under “— Fruquintinib Combinations with Checkpoint Inhibitors.”
Treatment
Fruquintinib monotherapy
Fruquintinib monotherapy
Fruquintinib monotherapy
Current Clinical Trials of Fruquintinib in CRC
Name, Line, Patient Focus
Sites
FRESCO: >3L CRC;
chemotherapy refractory
China
Phase Status/Plan
III Approved
and
launched
NCT #
NCT02314819
FRESCO-2: mCRC
CRC, TN & HR+/Her2 and breast US
cancer
US/Europe/Japan
III Ongoing
Ib Ongoing
NCT04322539
NCT03251378
Notes: CRC = colorectal cancer; >3L= third line or above; refractory = resistant to prior treatment ; TN = triple-negative; HR+ =
hormone receptor-positive; and Her2 = human epidermal growth factor receptor 2.
FRESCO study; Phase III study of fruquintinib monotherapy in third-line CRC (Status: completed and product launched in November
2018; NCT02314819)
In 2014, we initiated the FRESCO study, which is a randomized, double-blind, placebo-controlled, multi-center, Phase III pivotal
trial in China in patients with locally advanced or mCRC who have failed at least two prior systemic antineoplastic therapies, including
fluoropyrimidine, Eloxatin and Camptosar. No drugs had been approved in third-line CRC in China with best supportive care being the
general standard of care. This study followed a Phase II proof-of-concept trial in third-line CRC that met its primary endpoint of
progression-free survival in 2014.
Enrollment was completed in May 2016, and 519 patients were screened. The intent-to-treat population of 416 patients was
randomized at a 2:1 ratio to receive either: 5 mg of fruquintinib orally once daily, on a three-weeks-on/one-week-off cycle, plus best
supportive care (278 patients) or placebo plus best supportive care (138 patients). Randomization was stratified for prior anti-VEGF
therapy and K-RAS gene status. The trial concluded in January 2017.
In June 2017, we presented the results of the FRESCO study in an oral presentation during the ASCO Annual Meeting. Results
showed that FRESCO met all primary and secondary endpoints including significant improvements in OS and progression-free survival
with a manageable safety profile and lower off-target toxicities compared to other targeted therapies.
89
The primary endpoint of median OS was 9.30 months (95% confidence interval: 8.18-10.45 months) in the fruquintinib group
versus 6.57 months (95% confidence interval: 5.88-8.11 months) in the placebo group, with a hazard ratio of 0.65 (95% confidence
interval: 0.51-0.83; two-sided p<0.001).
Phase III Study in China of Fruquintinib Monotherapy in Third-line Colorectal Cancer.
FRESCO Clearly Succeeded in Meeting the Primary Efficacy Endpoint of Overall Survival
Notes: N = number of patients; BSC = best supportive care; 95% CI = 95% confidence interval; and HR = hazard ratio.
Source: Li J, Qin S, Xu RH, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated Metastatic
Colorectal Cancer: The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486 2496.
doi:10.1001/jama.2018.7855.
90
The secondary endpoint of median progression-free survival was 3.71 months (95% confidence interval: 3.65-4.63 months) in the
fruquintinib group versus 1.84 months (95% confidence interval: 1.81-1.84 months) in the placebo group, with a hazard ratio of 0.26
(95% confidence interval: 0.21-0.34; two-sided p<0.001). Significant benefits were also seen in other secondary endpoints. The disease
control rate in the fruquintinib group was 62% versus 12% for placebo (p<0.001), while the ORR based on confirmed responses was
5% versus 0% for placebo (p=0.012).
FRESCO Clearly Succeeded in Meeting
Endpoint of Progression-free Survival
Note: BSC = best supportive care.
Source: Li J, Qin S, Xu RH, et al. Effect of Fruquintinib vs Placebo on Overall Survival in Patients With Previously Treated mCRC:
The FRESCO Randomized Clinical Trial. JAMA. 2018;319(24):2486 -2496. doi:10.1001/jama.2018.7855.
While it is difficult to directly evaluate and compare clinical results across separate trials, data from the FRESCO study compare
favorably to the data from the CONCUR study, a Phase III study of Stivarga monotherapy in CRC conducted in Asia, and the CORRECT
study, a global Phase III study of Stivarga in CRC. In particular, in the Chinese patient subgroup of the CONCUR study, Stivarga had
a disease control rate of 46% versus 7% in the placebo group. Median progression-free survival was 2.0 months in the Stivarga group
versus 1.7 months in the placebo group, and median OS was 8.4 months in the Stivarga group versus 6.2 months in the placebo group.
In the CORRECT study, Stivarga had a disease control rate of 41% versus 15% in the placebo group. Median progression-free survival
was 1.9 months in the Stivarga group versus 1.7 months for the placebo group, and median OS was 6.4 months in the Stivarga group
versus 5.0 in the placebo group.
91
In terms of safety, results showed that fruquintinib had a manageable safety profile with lower off-target toxicities compared to
other VEGFR tyrosine kinase inhibitors. Of particular interest was that the CTC grade 3 or above hepatotoxicity was similar for the
fruquintinib group as compared to the placebo group, which is in contrast to Stivarga which was markedly higher and often difficult to
manage in the Chinese patient population in the CONCUR study. Adverse events led to dose interruptions in 69% of patients in the
Chinese patient subgroup of the CONCUR study, compared to 35% in the FRESCO study. The most frequently reported fruquintinib-
related CTC grade 3 or above TEAEs included hypertension (21%), hand-foot skin reaction (11%), proteinuria (3%) and diarrhea (3%),
all possibly associated with VEGFR inhibition. No other CTC grade 3 or above TEAEs exceeded 2% in the fruquintinib population,
including hepatic function adverse events such as elevations in bilirubin (1%), alanine aminotransferase (<1%) or aspartate
aminotransferase (<1%).
In terms of tolerability, dose interruptions or reductions occurred in only 35% and 24% of patients in the fruquintinib arm,
respectively, and only 15% of patients discontinued treatment of fruquintinib due to adverse events versus 6% for placebo. The FRESCO
study was published in the Journal of the American Medical Association in June 2018.
Subgroup analysis
In June 2018, a further subgroup analysis of data from the FRESCO Phase III study was presented during the ASCO Annual
Meeting. This analysis explored possible effects of prior target therapy on the efficacy and safety of fruquintinib by analyzing the
subgroups of patients with prior target therapy and those without prior target therapy.
Results showed that the benefits of fruquintinib were generally consistent across all subgroups. Among a total of 278 fruquintinib-
treated patients, 111 had received prior target therapy while 55 of the 138 placebo-treated patients had received prior target therapy. In
the prior target therapy subgroup, fruquintinib significantly prolonged overall survival and progression-free survival. Median OS was
7.69 months for patients treated with fruquintinib versus 5.98 months for placebo (hazard ratio = 0.63; p = 0.012). Median progression-
free survival was 3.65 months for patients treated with fruquintinib versus 1.84 months for placebo (hazard ratio = 0.24; p < 0.001).
Overall Survival Subgroup Analysis by Prior Treatment.
OS Subgroup Analysis by Prior Treatment.
Fruquintinib Demonstrated Consistent Results Across Sub-Groups
Fruquintinib Demonstrated Consistent Results Across Sub-Groups
Notes: CI = confidence interval; and p-value = probability value.
Source: Xu RH, Li J, Bai YX, et al. Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized,
double-blind, phase 3 trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with mCRC.
Journal of Clinical Oncology. 2018;36:15_suppl, 3537-3537. doi:10.1200/JCO.2018.36.15_suppl.3537.
Among these 278 patients, the results showed that a subgroup of 84 patients who had received prior anti-VEGF treatment also
benefited from fruquintinib. In this subgroup, the median OS was 7.20 months for fruquintinib versus 5.91 months for placebo (hazard
ratio = 0.68; p=0.066) and the median progression-free survival was 3.48 months for fruquintinib versus 1.84 months for placebo (hazard
ratio = 0.24; p < 0.001).
In the subgroup of 250 patients without prior target therapy, the median OS was 10.35 months for 167 patients treated with
fruquintinib versus 6.93 months for 83 patients treated with placebo (hazard ratio = 0.63; p = 0.003), and the median progression-free
survival for patients treated with fruquintinib was 3.81 months versus 1.84 months for placebo (hazard ratio = 0.28; p < 0.001).
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Progression-free Survival by Prior Therapy.
Fruquintinib Demonstrated Consistent Results Across Sub-Groups
Notes: CI = confidence interval; and p-value = probability value.
Source: Xu RH, Li J, Bai YX, et al. Subgroup analysis by prior anti-VEGF or anti-EGFR target therapy in FRESCO, a randomized,
double-blind, phase 3 trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with mCRC.
Journal of Clinical Oncology. 2018;36:15_suppl, 3537-3537. doi:10.1200/JCO.2018.36.15_suppl.3537.
Additional data showed that there were no observed cumulative CTC grade 3 or above TEAEs in the subgroup of patients with
prior target therapy. The CTC grade 3 or above TEAEs rates of fruquintinib were similar in the subgroups with prior target therapy
(61.3%) and without prior target therapy (61.1%). This subgroup analysis is consistent with the previously reported results from the
FRESCO study’s intent-to-treat population.
The results of this analysis showed that fruquintinib had clinically meaningful benefits in third-line mCRC patients regardless of
prior target therapy without observed cumulative toxicity.
Quality-adjusted survival analysis
At the 2018 ASCO Annual Meeting, an analysis was presented that aimed to compare the quality-adjusted survival between the
two arms of the FRESCO study using quality-adjusted time without symptoms or toxicity, or Q-TWiST, methodology and to investigate
the Q-TWiST benefit of fruquintinib treatment among subgroups. Q-TWiST is a tool to evaluate relative clinical benefit-risk from a
patient’s perspective and has been widely used in oncology treatment assessment. The survival time for each patient was divided into
three portions: time with CTC grade 3 or above toxicity before progression, time without symptoms or CTC grade 3 or above toxicity,
and time from progression or relapse until death or end of follow-up.
Patients treated with fruquintinib had longer Q-TWiST periods compared to patients treated with placebo. Q-TWiST benefits were
observed regardless of prior lines of chemotherapy and prior anti-VEGF or anti-EGFR targeted therapy. The relative improvement of
Q-TWiST with fruquintinib represents a clinically important quality-of-life benefit for mCRC patients.
Supported by data from the successful FRESCO study, we submitted an NDA for fruquintinib in June 2017. Fruquintinib was
subsequently awarded priority review status by the NMPA in view of its clinical value in September 2017, and in September 2018, the
NMPA approved fruquintinib for the treatment of patients with advanced CRC and was launched in November 2018. For more
information regarding the Elunate product launch, see “—Overview of Elunate Commercial Launch.”
Phase Ib study of fruquintinib monotherapy in metastatic colorectal and breast cancers - U.S. (Status: enrolling; NCT03251378)
We are conducting a multi-center, open-label, Phase Ib clinical study to evaluate the safety, tolerability and pharmacokinetics of
fruquintinib in U.S. patients, which established the U.S. RP2D to be 5 mg, the same as that in China. This dose is being further evaluated
in patients with mCRC and breast cancers.
Encouraging preliminary results of the U.S. Phase I/Ib study were presented at ESMO Congress 2020. As of the data cut-off in
August 2020, fruquintinib was generally well-tolerated with preliminary evidence of anti-tumor activity in patients with heavily
penetrated refractory mCRC. Among 34 total patients, 16 received prior Lonsurf treatment, 8 received Stivarga treatment and 10 received
both Lonsurf and Stivarga treatments. The median duration of fruquintinib treatment was 19.1 weeks, higher than 12.0 weeks of Lonsurf
93
and 9.2 weeks of Stivarga. DCR in 31 evaluable patients was 80.6%. The safety profile was consistent with that seen in the FRESCO
study.
US Phase Ib: Encouraging Preliminary Efficacy in STIVARGA and LONSURF Refractory/Intolerant Metastatic Colorectal
Cancer Patients
Notes: Data cut-off as of August 20, 2020. d/c = treatment discontinued; PI = primary inefficacy; N = number of patients; and Tx =
treatment.
94
Source: Dasari, et al. Phase 1/1b Trial of Fruquintinib in Patients with Advanced Solid Tumors: Preliminary Results of the Dose
Expansion Cohort in Refractory mCRC. ESMO 2020 Abstract #2217.
Phase III study of fruquintinib monotherapy in mCRC – Global (Status: enrolling; NCT04322539)
We initiated a global Phase III registration study, known as the FRESCO-2 study, in refractory metastatic CRC which is expected
to enroll over 680 patients from approximately 150 sites in 14 countries. The first patient was dosed in September 2020 in the U.S. and
enrollment is targeted to complete in late 2021.
The U.S. FDA, EMA and Japanese Pharmaceuticals and Medical Devices Agency (PMDA) have all acknowledged the totality of
the fruquintinib clinical data, including the FRESCO-2 study (if positive), the prior positive Phase III FRESCO study demonstrating
improvement in OS that led to fruquintinib approval for metastatic CRC in China in 2018, and additional completed and ongoing
supporting studies in metastatic CRC, could potentially support an NDA for the treatment of patients with metastatic CRC in the third-
line setting.
Gastric Cancer
Advanced gastric cancer is a major medical need, particularly in Asian populations, with limited treatment options for patients who
have failed first-line standard chemotherapy with 5-fluorouracil and platinum doublets. There were approximately 442,300 new cases
of gastric cancer in China in 2018. The table below shows a summary of the clinical study we have underway for fruquintinib in gastric
cancer patients.
Clinical Trials of Fruquintinib in Gastric Cancer
Treatment
Fruquintinib and Taxol
Note: 2L = second line.
Name, Line, Patient Focus Sites Phase
FRUTIGA: 2L gastric
cancer
China
III
Status/Plan
Ongoing; Completed
second interim
analysis
NCT #
NCT03223376
FRUTIGA study; Phase III study of fruquintinib in combination with Taxol in gastric cancer (second-line) (Status: first interim analysis
reported; NCT03223376)
In October 2017, we initiated the FRUTIGA study, a pivotal Phase III clinical trial of fruquintinib in combination with Taxol for
the treatment in advanced gastric or gastroesophageal junction adenocarcinoma patients in China. This randomized, double-blind,
placebo-controlled, multi-center trial is being conducted in patients with advanced gastric cancer who have progressed after first-line
standard chemotherapy. All subjects will receive fruquintinib or placebo combined with paclitaxel. Patients will be randomized at a 1:1
ratio and stratified according to factors such as stomach versus gastroesophageal junction tumors and ECOG performance status, a scale
established by the Eastern Cooperative Oncology Group which determines ability of patient to tolerate therapies in serious illness,
specifically for chemotherapy.
The primary efficacy endpoint is OS. Secondary efficacy endpoints include progression-free survival, ORR, disease control rate,
duration of response and quality-of-life score (EORTC QLQ-C30, version 3.0). Biomarkers related to the antitumor activity of
fruquintinib will also be explored.
In June 2020, the IDMC of the FRUTIGA study completed a second planned interim data review and, based on the preset criteria,
the IDMC and Joint Steering Committees recommended that the trial continue with a sample size increase to ~700 patients. We expect
to complete enrollment of FRUTIGA around the end of 2021.
Fruquintinib Combinations with Checkpoint Inhibitors
The table below shows a summary of the clinical trials we have ongoing and in planning for fruquintinib in combination with
checkpoint inhibitors.
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Clinical Trials of Fruquintinib with Checkpoint Inhibitors
Treatment
Fruquintinib and Tyvyt (PD-1)
Fruquintinib and Tyvyt (PD-1)
Fruquintinib and Tyvyt (PD-1)
Fruquintinib and Tyvyt (PD-1)
Fruquintinib and Tyvyt (PD-1)
Fruquintinib and tislelizumab (PD-1)
Fruquintinib and tislelizumab (PD-1)
Fruquintinib and genolimzumab (PD-1)
Fruquintinib and genolimzumab (PD-1)
Name, Line, Patient Focus
Sites Phase
CRC
Hepatocellular carcinoma
Endometrial cancer
Renal cell carcinoma
Gastrointestinal tumor
Triple negative breast cancer
Solid tumors
CRC
NSCLC
China
China
China
China
China
U.S.
TBD
China
China
I/II
Ib/II
Ib/II
Ib/II
Ib/II
Ib/II
Ib/II
Ib
Ib
Status/Plan
Ongoing
Ongoing
Ongoing
Ongoing
Ongoing
In planning
In planning
Ongoing
Ongoing
NCT #
NCT04179084
NCT03903705
NCT03903705
NCT03903705
NCT03903705
NCT04577963
NCT04716634
NCT03977090
NCT03976856
Note: CRC = colorectal cancer; NSCLC = non-small cell lung cancer; and TBD = to be determined.
In November 2018, we entered into two collaboration agreements to evaluate the safety, tolerability and efficacy of fruquintinib in
combination with checkpoint inhibitors. These include a global collaboration with Innovent to evaluate the combination of fruquintinib
with Innovent’s Tyvyt, a PD-1 monoclonal antibody approved in China, and a collaboration in China with Genor to evaluate the
fruquintinib combination with genolimzumab, a PD-1 monoclonal antibody being developed by Genor. We are now approaching
completion of the Phase I dose-finding study in China of fruquintinib in combination with Tyvyt, with the Phase I dose-expansion study
already underway in five solid tumor indications. Phase Ib studies of fruquintinib in combination with genolimzumab in second-line
CRC and NSCLC are also underway.
In addition, in May 2020, we entered into a global clinical collaboration agreement to evaluate the safety, tolerability and efficacy
of combining fruquintinib with BeiGene’s anti-PD-1 antibody, tislelizumab, for the treatment of various solid tumor cancers in the
United States, Europe, China and Australia. In the first half of 2021, we plan to initiate a Phase Ib/II study for fruquintinib in combination
with tislelizumab in patients with advanced refractory triple negative breast cancer, to be followed by a further study in additional solid
tumor types.
Fruquintinib Exploratory Development
We are conducting multiple Phase Ib expansion cohorts in the United States to explore fruquintinib in CRC and breast cancer. In
China, we are currently supporting dozens of investigator-initiated studies in various solid tumor settings.
Overview of Elunate Commercial Launch
Fruquintinib capsules, sold under the brand name Elunate, were approved for marketing in China by the NMPA in September 2018
and commercially launched in late November 2018. Elunate is for the treatment of patients with mCRC that have been previously
treated with fluoropyrimidine, oxaliplatin and irinotecan, including those who have previously received anti-VEGF therapy and/or anti-
EGFR therapy (RAS wild type).
Starting on January 1, 2020, Elunate was included on China’s NRDL at a 63% discount to its initial retail price, paving the way to
significantly broaden access for advanced CRC patients and rapidly build penetration in China over the coming years.
The revenues we generate from Elunate are comprised of royalty revenue, revenue from the sales of Elunate primarily to Eli Lilly
which we manufacture and sell at cost and, starting in 2020, revenue from promotion and marketing services. In 2019, we generated
$10.8 million in total revenue from Elunate, of which $2.7 million was royalty revenue and $8.1 million was revenue from sales to Eli
Lilly. In 2020, we generated $20.0 million in total revenue from Elunate, of which $4.9 million was royalty revenue, $11.3 million was
revenue from sales of goods primarily to Eli Lilly and $3.8 million was revenue from promotion and marketing services to Eli Lilly.
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Partnership with Eli Lilly
In October 2013, we entered into a license and collaboration agreement with Eli Lilly in order to accelerate and broaden our
fruquintinib development program in China. As a result, we were able to quickly expand the clinical development of fruquintinib in
three indications with major unmet medical needs in China: CRC, NSCLC and gastric cancer, as discussed above. In December 2018,
we amended our license and collaboration agreement with Eli Lilly. This amendment gives us, among other things, all planning,
execution and decision making responsibilities for life cycle indication development of fruquintinib in China. Support from Eli Lilly
has also helped us to establish our own manufacturing (formulation) facility in Suzhou, China, which now produces clinical and
commercial supplies of fruquintinib. In July 2020, we reached an agreement with Eli Lilly to take over development and execution of
all on-the-ground medical detailing, promotion and local and regional marketing activities for Elunate in China starting on October 1,
2020. Under the terms of the new agreement, we will share gross profits linked to sales target performance. Subject to meeting pre-
agreed sales targets, Eli Lilly will pay us an estimated total of 70% to 80% of Elunate sales in the form of royalties, manufacturing costs
and service payments.
For more information regarding our partnership with Eli Lilly, see “—Overview of Our Collaborations—Eli Lilly.”
4. HMPL-689 PI3Kδ Inhibitor
HMPL-689 is a novel, highly selective and potent small molecule inhibitor targeting the isoform PI3Kδ, a key component in the B-
cell receptor signaling pathway. We have designed HMPL-689 with superior PI3Kδ isoform selectivity, in particular to not inhibit PI3K-
ℽ (gamma), offering advantages over Zydelig to minimize the risk of serious infection caused by immune suppression. HMPL-689’s
strong potency, particularly at the whole blood level, also allows for reduced daily doses to minimize compound related toxicity, such
as the high level of gastrointestinal and liver toxicity observed with several first-generation PI3Kδ inhibitors. HMPL-689’s
pharmacokinetic properties have been found to be favorable with good oral absorption, moderate tissue distribution and low clearance
in pre-clinical pharmacokinetic studies. We also expect that HMPL-689 will have low risk of drug accumulation and drug-to-drug
interaction.
Mechanism of Action
Targeting the B-cell signaling pathway is emerging as a potential means to treat both hematological cancer and immunological
diseases. Inhibiting different kinases found along the B-cell signaling pathway has proven to have clinical efficacy in hematological
cancers, with breakthrough therapies having been recently approved by the FDA.
The high efficacy and successful approvals of Bruton’s tyrosine kinase, or BTK, inhibitors and PI3Kδ inhibitors are evidence that
modulation of the B-cell signaling pathway is critical for the effective treatment of B-cell malignancies.
Class I phosphatidylinositide-3-kinases, or PI3Ks, are lipid kinases that, through a series of intermediate processes, control the
activation of several important signaling proteins including the serine/threonine kinase AKT.
There are multiple sub-families of PI3K kinases, and PI3Kδ is a lipid kinase that, through a series of intermediate processes, controls
the activation of several important signaling proteins, including the serine/threonine protein kinase B, or AKT. In most cells, AKT is a
key PI3Kδ affector that regulates cell proliferation, carbohydrate metabolism, cell motility and apoptosis and other cellular processes.
Upon an antigen binding to B-cell receptors, PI3Kδ can be activated through the Lyn and Syk signaling cascade.
Aberrant B-cell function has been observed in multiple immunological diseases and B-cell mediated malignancies. Therefore,
PI3Kδ is considered to be a promising target for drugs that aim to prevent or treat hematologic cancer, autoimmunity and transplant
organ rejection and other related inflammation diseases.
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HMPL-689 Pre-clinical Evidence
Compared to other PI3Kδ inhibitors, HMPL-689 shows higher potency and selectivity.
Enzyme Selectivity (IC50, in nM) of HMPL-689 Versus Competing PI3Kδ Inhibitors; This Shows HMPL-689 is Approximately Five-
fold More Potent than Zydelig on Whole Blood Level and, unlike Copiktra, does not Inhibit PI3K-γ.
Enzyme IC50 (nM)
PI3Kδ
PI3Kγ (fold vs. PI3Kδ)
PI3Kα (fold vs. PI3Kδ)
PI3Kδ human whole blood CD63+
PI3Kβ (fold vs. PI3Kδ)
Source: Company.
HMPL-689 Clinical Development
HMPL‑689
0.8 (n = 3)
114 (142x)
>1,000 (>1,250x)
3
87 (109x)
Zydelig
2
104 (52x)
866 (433x)
14
293 (147x)
Copiktra
1
2 (2x)
143 (143x)
15
8 (8x)
Aliqopa
0.7
6.4 (9x)
0.5 (1x)
n/a
3.7 (5x)
The table below shows a summary of the clinical studies for HMPL-689.
Treatment
HMPL-689 monotherapy
HMPL-689 monotherapy
HMPL-689 monotherapy
HMPL-689 monotherapy
Clinical Trials of HMPL-689
Name, Line, Patient Focus
Sites
Phase
Indolent non-Hodgkin’s lymphoma China
Indolent non-Hodgkin’s lymphoma China
Indolent non-Hodgkin’s lymphoma U.S. / Europe I/Ib
Indolent non-Hodgkin’s lymphoma U.S. / Europe II registration-intent In planning N/A
Ib
II registration-intent In planning N/A
Ongoing
NCT03786926
Status/Plan
Ongoing
NCT #
NCT03128164
Phase Ib study of HMPL-689 in patients with Indolent non-Hodgkin’s lymphoma (Status: enrolling; NCT03128164)
Our Phase I/Ib study of HMPL-689 in China has successfully established a Phase II dose and has now expanded into multiple sub-
categories of indolent non-Hodgkin’s lymphoma.
In December 2020, we presented preliminary results from a Phase I dose escalation study of HMPL-689 in Chinese patients with
relapsed/refractory lymphoma at the American Society of Hematology (ASH) Annual Meeting. A total of 56 patients were enrolled
resulting in an ORR of 51.9% (27/52) and complete response rate of 11.5% (6/52) in efficacy evaluable patients. The median time to
response and duration of response were 1.8 months (1.8-1.9) and 9.2 months (3.9-NR), respectively. One patient with follicular
lymphoma who achieved complete response (per post hoc independent radiologic review) was on treatment for over 19 months. In the
nine efficacy evaluable patients treated with the RP2D of 30mg QD orally, efficacy was encouraging with an ORR of 100% (4/4) in
follicular lymphoma, 100% in marginal zone lymphoma (2/2) and 67% (2/3) in diffuse large B-cell lymphoma.
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Phase 1 dose escalation Study : Promising HMPL-689 single-agent clinical activity in relapsed/refractory B-cell lymphoma
patients
CLL/SLL DLBCL
FL
HL
MCL
MZL
Intent-to-treat population (n=56)
e
n
i
l
e
s
a
b
m
o
r
f
e
g
n
a
h
c
t
s
e
B
+80%
+60%
+40%
+20%
0%
-20%
-40%
-60%
-80%
-100%
5mg QD
10mg QD
20mg QD
30mg QD
2.5mg QD
5mg QD
7.5mg QD
10mg QD
40mg QD
Best Response
Complete Response, %
Partial Response, %
% ,esaesiD elbatS
Progressive Disease, %
Overall Response Rate
Clinical Benefit Rate
Time on Treatment
Time to Response
Duration of Response
11 (4-22)
37
43
11
48% (35-62)
82% (70-91)
5.6 months (0.7–23.2)
1.8 months (1.8–1.9)
9.2 months (3.9–NA)
Progression Free Survival
10.1 months (5.5–15.7)
1-year PFS rate
40% (27–57)
PR
Notes: CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma; DLBCL = diffuse large B-cell lymphoma; FL =
follicular lymphoma; HL = Hodgkin’s lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma; BID =
twice daily; QD = once daily; PR = partial response; n = number of patients; PFS = progression free survival; and NA = not
available.
Source: Cao JN, et al. “Results from a Phase 1 Dose Escalation Study of HMPL-689, a Selective Oral Phosphoinositide 3-Kinase-Delta
Inhibitor, in Chinese Patients with relapsed/refractory (R/R) Lymphoma” Presented at the 62nd American Society of
Hematology (ASH) Annual Meeting and Exposition on December 5, 2020. Abstract #1135.
HMPL-689 was well tolerated at the RP2D exhibiting dose-proportional pharmacokinetics and a manageable toxicity profile.
Grade 3 or more non-hematologic TEAEs occurring in more than two patients were pneumonia, rash, hypertension, and increased lipase.
Grade 3 or more hematologic TEAEs occurring more than two patients were neutropenia, and no Grade 5 TEAEs were reported.
The Phase Ib dose expansion study in China is ongoing in multiple sub-categories of indolent non-Hodgkin’s lymphoma. Based
on the encouraging preliminary results, we are now planning registration studies in select indolent non-Hodgkin’s lymphoma in China,
which are anticipated to start in mid-2021.
Phase I/Ib study of HMPL-689 in patients with Indolent non-Hodgkin’s lymphoma (Status: enrolling; NCT03786926)
In September 2019, we initiated an international Phase I/Ib study of HMPL-689 in patients with relapsed or refractory lymphoma.
The international clinical study, with 17 sites in the United States and Europe, is a multi-center, open-label, two-stage study, including
dose escalation and expansion, investigating the effects of HMPL-689 administered orally to patients with relapsed or refractory
lymphoma. The primary outcome measures are safety and tolerability. Secondary outcomes include pharmacokinetic measurements and
preliminary efficacy such as ORR. Dose escalation is near complete and we expect to be able to engage with regulatory authorities in
mid-2021 to discuss potential registration pathways with a target to initiate registration studies later in 2021.
5. HMPL-523 Syk Inhibitor
The result of our over six-year program of discovery and pre-clinical work against Syk is HMPL-523, a highly selective Syk
inhibitor with a unique pharmacokinetic profile which provides for higher drug exposure in the tissue than on a whole blood level. We
designed HMPL-523 intentionally to have high tissue distribution because it is in the tissue that the B-cell activation associated with
rheumatoid arthritis and lupus occurs most often. Furthermore, and somewhat counter intuitively, in hematological cancer the vast
majority of cancer cells nest in tissue, with a small proportion of cancer cells releasing and circulating in the blood where they cannot
survive for long. We assessed that an effective small molecule Syk inhibitor would need to have superior tissue distribution.
However, many pharmaceutical and biotechnology companies had experienced difficulties in developing a safe and efficacious
Syk-targeted drug. For example, the development of the Syk inhibitor Tavalisse for rheumatoid arthritis was one such failed program,
although clear efficacy was observed in Phase II and Phase III trials. The main problem was off-target toxicities associated with poor
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kinase selectivity, such as hypertension and severe diarrhea. Therefore, we believe that kinase selectivity is critical to a successful Syk
inhibitor. In addition, Tavalisse was designed as a prodrug in order to improve solubility and oral absorption. A prodrug is medication
administered in a pharmacologically inactive form which is converted to an active form once absorbed into circulation. The rate of the
metabolism required to release the active form can vary from patient to patient, resulting in large variation in active drug exposures that
can impact efficacy. In addition to convenient oral dosing, we believe HMPL-523 offers important advantages over intravenous
monoclonal antibody immune modulators in rheumatoid arthritis in that small molecule compounds generally clear the system faster,
thereby reducing the risk of infections from sustained suppression of the immune system.
Mechanism of Action
Syk is a key kinase upstream to PI3Kδ and BTK within the B-cell signaling pathway and therefore thought to be an important target
for modulating B-cell signaling.
Syk, a target for autoimmune diseases
The central role of Syk in signaling processes is not only in cells of immune responses but also in cell types known to be involved
in the expression of tissue pathology in autoimmune, inflammatory and allergic diseases. Therefore, interfering with Syk could represent
a possible therapeutic approach for treating these disorders. Indeed, several studies have highlighted Syk as a key player in the
pathogenesis of a multitude of diseases, including rheumatoid arthritis, systemic lupus erythematosus and multiple sclerosis.
Syk, a target for oncology
In hematological cancer, we believe Syk is a high potential target. In hematopoietic cells, Syk is recruited to the intracellular
membrane by activated membrane receptors like B-cell receptors or another receptor called Fc and then binds to the intracellular domain
of the receptors. Syk is activated after being phosphorylated by certain kinases and then further induces downstream intracellular signals
including B-cell linker, PI3Kδ, BTK and Phospholipase C-y2 to regulate B-cell proliferation, growth, differentiation, homing, survival,
maturation, and immune responses. Syk not only involves the regulation of lymphatic cells but also signal transduction of non-lymphatic
cells such as mast cells, macrophages, and basophils, resulting in different immunological functions such as degranulation to release
immune active substances, leading to immunological reaction and disease. Therefore, regulating B-cell signal pathways through Syk is
expected to be effective for treating lymphoma.
Syk is upstream of both BTK and PI3Kδ, and we believe it could deliver the same outcome as inhibitors of BTK and PI3Kδ,
assuming no unintentional toxicities are derived from Syk inhibition. Entospletinib, a Syk inhibitor developed by Gilead (now under
the ownership of Kronos Bio), reported promising Phase II study results in late 2015 with a nodal response rate of 65% observed in
chronic lymphocytic leukemia and small lymphocytic lymphoma. Nodal response is defined as a greater than 50% decrease from
baseline in the sum of lymph node diameters. Gilead has also reported that entospletinib demonstrated a nodal response rate of 44% in
an exploratory clinical study in chronic lymphocytic leukemia patients previously treated with Imbruvica and Zydelig, thereby indicating
that Syk inhibition has the potential to overcome resistance to Imbruvica and Zydelig.
HMPL-523 Research Background
The threshold of safety for a Syk inhibitor in chronic disease is extremely high, with no room for material toxicity. The failure of
Tavalisse in a global Phase III registration study in rheumatoid arthritis provided important insights for us in the area of toxicity. While
Tavalisse clearly showed patient benefit in rheumatoid arthritis, a critical proof-of-concept for Syk modulation, it also caused high levels
of hypertension which is widely believed to be due to the high levels of off-target kinase insert domain receptor inhibition. In addition,
Tavalisse has also been shown to strongly inhibit the Ret kinase, and in pre-clinical trials it was demonstrated that inhibition of the Ret
kinase was associated with developmental and reproductive toxicities.
The requirement for Syk kinase activity in inflammatory responses was first evaluated with Tavalisse, which was co-developed by
AstraZeneca/Rigel Pharmaceuticals, Inc. In 2013, AstraZeneca announced results from pivotal Phase III clinical trials that Tavalisse
statistically significantly improved ACR20 (a 20% improvement from baseline based on the study criteria) response rates of patients
inadequately responding to conventional disease-modifying anti-rheumatic drugs and a single anti-TNFα (a key pro-inflammatory
cytokine involved in rheumatoid arthritis pathogenesis) antagonist at 24 weeks, but failed to demonstrate statistical significance in
comparison to placebo at 24 weeks. As a result, AstraZeneca decided not to proceed.
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Tavalisse was also in trials for B-cell lymphoma and T-cell lymphoma. It demonstrated some clinical efficacy in diffused large B-
cell lymphoma patients with an ORR of 22%. Entospletinib has features of high potency and good selectivity toward kinases. However,
while the Phase II study discussed above showed that it had significant efficacy in patients with chronic lymphocytic leukemia and small
lymphocytic lymphoma, its poor solubility and permeability into intestinal epithelial cells resulted in unsatisfactory oral absorption and
a great variation of individual drug exposure. In addition, entospletinib shows some inhibition of the CYP3A4, CYP2D6, and CYP1A2
enzymes involved in the metabolism of certain drugs, and therefore their inhibition could increase the risk of drug-to-drug interaction
when used in combined therapy.
HMPL-523 Pre-clinical Evidence
The safety profile of HMPL-523 was evaluated in multiple in vitro and in vivo pre-clinical trials under good laboratory practice
guidelines and found to be well tolerated following single dose oral administration. Toxic findings were seen in repeat dose animal
safety evaluations in rats and dogs at higher doses and found to be reversible. These findings can be readily monitored in the clinical
trials and fully recoverable upon drug withdrawal. The starting dose in humans was suggested to be 5 mg. This dose level is
approximately 5% of the human equivalent dose extrapolated from the pre-clinical “no observed adverse event levels,” which is below
the 10% threshold recommended by FDA guidelines.
HMPL-523 Clinical Trials
As discussed below, we currently have various clinical trials of HMPL-523 ongoing in Australia, the United States, Europe and
China as a monotherapy. The table below shows a summary of the clinical trials that we have underway for HMPL-523.
Current Clinical Trials of HMPL-523
Treatment
HMPL‑523 monotherapy
HMPL‑523 monotherapy
HMPL‑523 monotherapy
HMPL‑523 monotherapy
Name, Line, Patient Focus
Sites
China
Immune thrombocytopenia purpura
Australia
Indolent non-Hodgkin’s lymphoma
Indolent non-Hodgkin’s lymphoma
US/EU
Multiple sub-types of B-cell malignancies China
Phase
Status/Plan
NCT #
NCT03951623
Active, not recruiting NCT02503033
NCT03779113
Enrollment completed NCT02857998
I/Ib Ongoing
Ib
I/Ib Ongoing
I/Ib
Phase I/Ib study of HMPL-523 in patients with immune thrombocytopenia (Status: ongoing)
In mid-2019, we initiated a Phase I study of HMPL-523 in patients with immune thrombocytopenia purpura. Immune
thrombocytopenia purpura is an autoimmune disorder characterized by low platelet count and an increased bleeding risk. Despite
availability of several treatments with differing mechanisms of action, a significant proportion of patients develop resistance to treatment
and are prone to relapse. In addition, there is a significant population of patients who have limited sensitivity to currently available
agents and are in need of a new approach to treatment.
The study is a randomized, double-blinded, placebo-controlled Phase Ib clinical trial investigating the safety, tolerability,
pharmacokinetics and preliminary efficacy of HMPL-523 in adult patients with immune thrombocytopenia purpura. The primary
endpoint is the number of patients with any adverse event. The secondary endpoints are maximum plasma concentration, area under
the concentration-time curve in a selected time interval, and rate of clinical remission at week eighty. The trial is comprised of a dose
escalation stage and a dose expansion stage. Approximately 50 to 60 patients are expected to be enrolled. Dose escalation is near
complete with planning and preparation for a Phase III trial in China now underway.
Phase Ib studies of HMPL-523 in indolent non-Hodgkin’s lymphoma and multiple subtypes of B-cell malignancies (Status: enrolling;
NCT02503033/NCT02857998)
In early 2016, we initiated a Phase I dose escalation study of HMPL-523 in Australia and have completed seven dose cohorts. A
Phase I study in China began in early 2017 and has now completed five dose cohorts. In both Australia and China, we have established
both efficacious once daily and twice daily dose regimens. Our Phase I/Ib dose escalation and expansion studies in Australia and China
have now enrolled over 200 patients in a broad range of hematological cancers and have identified indications of interest for future
development.
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Phase I/Ib study of HMPL-523 in indolent non-Hodgkin’s lymphoma (Status: enrolling; NCT03779113)
Based on extensive proof-of-concept clinical data in China and Australia, we have now initiated a Phase I/Ib study in the United
States and Europe. Patient enrollment is underway in 11 sites, multiple dose cohorts have been completed already and we are close to
establishing our Phase II dose.
6. HMPL-453 FGFR Inhibitor
Mechanism of Action
FGFR belongs to a subfamily of receptor tyrosine kinases. Four different FGFRs (FGFR1-4) and at least 18 ligand FGFs constitute
the FGF/FGFR signaling system. Activation of the FGFR pathway through the phosphorylation of various downstream molecules
ultimately leads to increased cell proliferation, migration and survival. FGF/FGFR signaling regulates a wide range of basic biological
processes, including tissue development, angiogenesis, and tissue regeneration. Given the inherent complexity and critical roles in
physiological processes, dysfunction in the FGF/FGFR signaling leads to a number of developmental disorders and is consistently found
to be a driving force in cancer. Deregulation of the FGFR can take many forms, including receptor amplification, activating mutations,
gene fusions, and receptor isoform switching, and the molecular alterations are found at relatively low frequencies in most tumors. The
incidence of FGFR aberrance in various cancer types is listed in the table below.
Common FGFR Alterations in Certain Tumor Types
Gene amplification
Gene translocation
Gene mutation
FGFR1
FGFR2
FGFR3
Lung squamous (7-15%)
H&N squamous (10-17%)
Esophageal squamous (9%)
Breast (10-15%)
Gastric (5-10%)
Breast (5-10%)
Bladder (3%)
Salivary adenoid cystic (n/a)
Breast (1%)
Lung squamous (n/a)
Glioblastoma (n/a)
Myeloproliferative
syndrome (n/a) Breast (n/a)
Intra-hepatic biliary tract
cancer (14%) Breast (n/a)
Bladder (3-6%)
Lung squamous (3%)
Glioblastoma (3-7%)
Myeloma (15-20%)
Gastric (4%) Pilocytic
astrocytoma (5-8%)
Endometrial (12-14%)
Lung squamous (5%)
Bladder (60-80% NMIBC;
15-20% MIBC) Cervical (5%)
Notes: H&N = head and neck; NMIBC = non-muscle invasive bladder cancer; MIBC = muscle invasive bladder cancer; and n/a =
data not available.
Source: M. Touat et al., “Targeting FGFR Signaling in Cancer,” Clinical Cancer Research (2015); 21(12); 2684-94
HMPL-453 Research Background
We noted a growing body of evidence has demonstrated the oncogenic potential of FGFR aberrations in driving tumor growth,
promoting angiogenesis, and conferring resistance mechanisms to oncology therapies. Targeting the FGF/FGFR signaling pathway has
therefore attracted attention from biopharmaceutical companies and has become an important exploratory target for new anti-tumor
target therapies.
Currently, FGFR monoclonal antibodies, FGF ligand traps and small molecule FGFR tyrosine kinase inhibitors are being evaluated
in clinical trials and by regulatory authorities for marketing authorization. These recently approved and late stage molecules provided
substantial proof-of-concept with regard to anti-tumor efficacy and pharmacodynamic markers of effective FGFR pathway inhibition.
In April 2019, Johnson & Johnson received FDA approval for Balversa in the United States for the treatment of bladder cancer in
patients who have susceptible FGFR3 or FGFR2 genetic alterations and experienced disease progression during or after at least one line
of chemotherapy. Further studies are either in progress or planning. In April 2020, Incyte received marketing authorization in the
United States and in February 2021, the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP)
recommended conditional approval for pemigatinib for the treatment of cholangiocarcinoma, with further studies in progress for
additional solid tumor indications. Late stage studies are underway for futibatinib (Taiho, a subsidiary of Otuska), derazantinib (Basilea),
and BGJ-398 (QED Therapeutics).
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The main FGFR on-target toxicities observed to date in these compounds are all mild and manageable, including
hyperphosphatemia, nail and mucosal disorder, and reversible retinal pigmented epithelial detachment. However, there are still many
challenges in the development of FGFR-directed therapies. Uncertainties include the screening and stratifying of patients who are most
likely to benefit from FGFR targeted therapy. Intra-tumor heterogeneity observed in FGFR amplified cancer may compromise the anti-
tumor activity. In addition, the low frequency of specific FGFR molecular aberrance in each cancer type may hinder clinical trial
enrollment.
HMPL-453 Pre-clinical Evidence
HMPL-453 is a potential best-in-class, highly selective and potent, small molecule that targets FGFR 1/2/3 with an IC50 in the low
nanomolar range. Its good selectivity was revealed in the screening against 292 kinases. HMPL-453 exhibited strong anti-tumor activity
that correlated with target inhibition in tumor models with abnormal FGFR activation.
HMPL-453 has good pharmacokinetic properties characterized by rapid absorption following oral dosing, good bioavailability,
moderate tissue distribution and moderate clearance in all pre-clinical animal species. HMPL-453 was found to have little inhibitory
effect on major cytochrome P450 enzymes, indicating low likelihood of drug-to-drug interaction issues.
HMPL-453 Clinical Development
The table below shows a summary of the clinical trials that we have recently completed and underway for HMPL-453.
Clinical Trials of HMPL-453
Treatment
HMPL-453 monotherapy
HMPL-453 monotherapy
Name, Line, Patient Focus
Solid tumors
Cholangiocarcinoma (IHCC)
Sites
China
China
Phase
Status/Plan
NCT #
I
II
Enrollment completed NCT03160833
NCT04353375
Ongoing
Phase I HMPL-453 monotherapy in solid tumors–China (Status: enrollment complete; NCT03160833)
In June 2017, we initiated a Phase I clinical trial of HMPL-453 in China. This Phase I study is a multi-center, single-arm, open-
label, two-stage study to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of HMPL-453 monotherapy in patients
with solid tumors harboring FGFR genetic alterations. The dose-escalation stage is currently enrolling patients to further evaluate safety,
tolerability and pharmacokinetics as well as preliminary anti-tumor efficacy at the RP2D. This stage will enroll primarily cancer patients
harboring FGFR dysregulated tumors, including those with advanced bladder cancer, advanced cholangiocarcinoma and other solid
tumors. For this second stage, the primary endpoint is ORR, with secondary endpoints including duration of response, disease control
rate, progression-free survival, OS and safety.
Phase II HMPL-453 monotherapy in advanced intrahepatic cholangiocarcinoma–China (Status: ongoing; NCT04353375)
In September 2020, we initiated a Phase II, single-arm, multi-center, open-label study, evaluating the efficacy, safety and
pharmacokinetics of HMPL-453 in patients with advanced intrahepatic cholangiocarcinoma with FGFR2 fusion that had failed at least
one line of systemic therapy. IHCC is a cancer that develops within the bile ducts, the second most common primary hepatic malignancy
after hepatocellular carcinoma. Approximately 10-15% of IHCC patients have tumors that harbor FGFR2 fusion.
7. HMPL-306
HMPL-306 is a novel small molecule dual-inhibitor of IDH1 and 2 enzymes. IDH1 and IDH2 mutations have been implicated as
drivers of certain hematological malignancies, gliomas and solid tumors, particularly among acute myeloid leukemia patients. The table
below shows a summary of the clinical trials that we have recently underway or in planning for HMPL-306.
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Treatment
HMPL-306 monotherapy
HMPL-306 monotherapy
Clinical Trials of HMPL-306
Name, Line, Patient Focus
Sites
Hematological malignancies China
Solid tumors &
hematological malignancies
U.S.
Phase Status/Plan
NCT #
NCT04272957
Ongoing
In planning NCT04762602 /
I
I
NCT04764474
Phase I HMPL-306 monotherapy–China (Status: ongoing; NCT04272957)
In July 2020, we initiated our Phase I development in China. This is a multi-center study to evaluate the safety, pharmacokinetics,
pharmacodynamics and efficacy of HMPL-306 in patients of relapsed or refractory hematological malignancies with an IDH1 and/or
IDH2 mutation. Multiple sites have been initiated and we anticipate to be able to establish the Phase II dose during 2021.
Phase I HMPL-306 monotherapy–U.S. (Status: ongoing; NCT04762602 / NCT04764474)
In the U.S., IND applications for solid tumors and hematologic malignancies were cleared in October 2020. We expect to initiate
Phase I development in the U.S. during the first half of 2021.
8. HMPL-295
HMPL-295, a novel ERK inhibitor, is our 10th in-house discovered small molecule oncology drug candidate. ERK is a downstream
component of the RAS-RAF-MEK-ERK signaling cascade (MAPK pathway). This is our first of multiple candidates in discovery
addressing the MAPK pathway.
RAS and RAF mutations are present in almost 50% of human cancers, predict worse clinical prognosis in a wide variety of tumor
types, mediate resistance to targeted therapies, and decrease the response to the approved standards of care, namely, targeted therapy
and immunotherapy. On the MAPK pathway, KRAS inhibitors are under clinical evaluation, and acquired resistance develops for
RAF/MEK targeted therapies. ERK inhibition has the potential to overcome or avoid the intrinsic or acquired resistance from upstream
mechanisms.
We currently retain all rights to HMPL-295 worldwide. Planning for the Phase I study in China is now underway and set to start in
mid-2021.
9. Epitinib EGFR Inhibitor
Epitinib (also known as HMPL-813) is a potent and highly selective oral EGFR inhibitor designed to optimize brain penetration.
A significant portion of patients with NSCLC go on to develop brain metastasis. Patients with brain metastasis suffer from poor
prognosis and low quality of life with limited treatment options. EGFR inhibitors have revolutionized the treatment of NSCLC with
EGFR activating mutations. However, approved EGFR inhibitors such as Iressa and Tarceva cannot penetrate the blood-brain barrier
effectively, leaving the majority of patients with brain metastasis without an effective targeted therapy.
Our strategy has been to create targeted therapies in the EGFR area that would go beyond the already approved EGFRm+ NSCLC
patient population to address certain areas of unmet medical needs that represent significant market opportunities, including: (i) brain
metastasis and/or primary brain tumors with EGFRm+, which we seek to address with epitinib; and (ii) tumors with EGFR gene
amplification or EGFR overexpressed.
Epitinib Pre-clinical Evidence
Pre-clinical trials and orthotopic brain tumor models have shown that epitinib demonstrated brain penetration and efficacy superior
to that of current globally marketed EGFRm+ inhibitors such as Iressa and Tarceva. In orthotopic brain tumor models, epitinib
demonstrated good brain penetration, efficacy and pharmacokinetic properties as well as a favorable safety profile.
Epitinib Clinical Development
The table below shows a summary of the clinical trial that is underway for epitinib.
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Clinical Trials of Epitinib
Treatment
Epitinib monotherapy
Name, Line, Patient Focus
Sites
Glioblastoma
China
Phase
Ib/II
Status/Plan
Enrolling
NCT #
NCT03231501
Phase Ib/II epitinib monotherapy in glioblastoma (Status: enrolling; NCT03231501)
Glioblastoma is the most aggressive of the gliomas, which are tumors that arise from glial cells or their precursors within the central
nervous system. Glioblastoma is classified as grade IV under the World Health Organization grading of central nervous system tumors,
and is the most common brain and central nervous system malignancy, accounting for about half of such tumors according to the Cancer
Genome Atlas Research Network. The standard of care for treatment is surgery, followed by radiotherapy and chemotherapy. Median
survival is approximately 15 months, and the five-year OS rate is 6%. There are currently no target therapies approved for glioblastoma.
Epitinib is a highly differentiated EGFR inhibitor designed for optimal blood-brain barrier penetration. EGFR gene amplification
has been identified in about half of glioblastoma patients, according to The Cancer Genome Atlas Research Network, and hence is a
potential therapeutic target in glioblastoma.
In March 2018, we initiated a Phase Ib/II proof-of-concept study of epitinib in glioblastoma patients with EGFR gene amplification
in China. This Phase Ib/II study will be a multi-center, single-arm, open-label study to evaluate the efficacy and safety of epitinib as a
monotherapy in patients with EGFR gene amplified, histologically confirmed glioblastoma.
We have also developed a novel small molecule EGFR inhibitor, theliatinib, for which we have completed a Phase I/Ib study and
are evaluating further development strategies.
Overview of Our Collaborations
Collaborations and joint ventures with corporate partners have provided us with significant funding and access to our partners’
scientific, development, regulatory and commercial capabilities. Our current oncology collaborations focus on savolitinib (collaboration
with AstraZeneca) and fruquintinib (collaboration with Eli Lilly). Our collaboration partners fund a significant portion of our research
and development costs for drug candidates developed in collaboration with them. In addition, we receive upfront payments upon our
entry into these collaboration arrangements and upon the achievement of certain development milestones for the relevant drug candidate.
We have received upfront payments, equity contributions and milestone payments totaling approximately $158.5 million mainly from
our collaborations with AstraZeneca and Eli Lilly as of December 31, 2020. In return, our collaboration partners are entitled to a
significant proportion of any future revenue from our drug candidates developed in collaboration with them, as well as a degree of
influence over the clinical development process for such drug candidates.
AstraZeneca
In December 2011, we entered into an agreement with AstraZeneca under which we granted to AstraZeneca co-exclusive,
worldwide rights to develop, and exclusive worldwide rights to manufacture and commercialize savolitinib for all diagnostic,
prophylactic and therapeutic uses. In August 2016 and December 2020, we and AstraZeneca amended the terms of the agreement. We
refer to this agreement, including the amendments thereto, as the AstraZeneca Agreement.
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AstraZeneca paid $20.0 million upon execution of the AstraZeneca Agreement and agreed to pay royalties and additional amounts
upon the achievement of development and sales milestones. Under the original terms of the AstraZeneca Agreement, we and
AstraZeneca agreed to share the development costs for savolitinib in China, with AstraZeneca being responsible for the development
costs for savolitinib in the rest of the world. With respect to global pivotal Phase III development in patients with MET-driven papillary
renal cell carcinoma, we subsequently agreed to contribute up to $50 million and to share any additional costs equally with AstraZeneca.
As of December 31, 2020, we had received $24.9 million in milestone payments in addition to approximately $44.4 million in
reimbursements for certain development costs. We may potentially receive future clinical development and first sales milestones
payments for clinical development and initial sales of savolitinib, plus significant further milestone payments based on sales.
AstraZeneca also reimburses us for certain development costs. Subject to approval of savolitinib in papillary renal cell carcinoma, under
the amended AstraZeneca Agreement, AstraZeneca is obligated to pay us increased tiered royalties from 14% to 18% annually on all
sales made of any product outside of China, which represents a five percentage point increase over the original terms, subject to
adjustment based on the amount of any contribution by AstraZeneca to the Phase III development in patients with such indication. After
total aggregate additional royalties have reached five times our contribution to the Phase III development in patients with such indication,
this royalty will step down over a two-year period, to an ongoing royalty rate of 10.5% to 14.5%. AstraZeneca is also obligated to pay
us a fixed royalty of 30% on all sales made of any product in China.
Development and collaboration under this agreement are overseen by a joint steering committee that is comprised of three of our
senior representatives as well as three senior representatives from AstraZeneca. AstraZeneca is responsible for the development of
savolitinib and all regulatory matters related to this agreement in all countries and territories other than China, and we are responsible
for the development of savolitinib and all regulatory matters related to this agreement in China.
Subject to earlier termination, the AstraZeneca Agreement will continue in full force and effect on a country-by-country basis as
long as any collaboration product is being developed or commercialized. The AstraZeneca Agreement is terminable by either party upon
a breach that is uncured, upon the occurrence of bankruptcy or insolvency of either party, or by mutual agreement of the parties. The
AstraZeneca Agreement may also be terminated by AstraZeneca for convenience with 180 days’ prior written notice. Termination for
cause by us or AstraZeneca or for convenience by AstraZeneca will have the effect of, among other things, terminating the applicable
licenses granted by us. Termination for convenience by AstraZeneca will have the effect of obligating AstraZeneca to grant to us all of
its rights to regulatory approvals and other rights necessary to commercialize savolitinib. Termination by AstraZeneca for convenience
will not have the effect of terminating any license granted by AstraZeneca to us.
Eli Lilly
In October 2013, we entered into an agreement with Eli Lilly whereby we granted Eli Lilly an exclusive license to develop,
manufacture and commercialize fruquintinib for all uses in China and Hong Kong. In December 2018, following the commercial launch
of fruquintinib in China, we and Eli Lilly amended the terms of the agreement and further amended the terms of the agreement in July
2020. We refer to this agreement, including the amendments thereto, as the Eli Lilly Agreement.
Eli Lilly paid a $6.5 million upfront fee following the 2013 execution of the Eli Lilly Agreement, and agreed to pay royalties and
additional amounts upon the achievement of development and regulatory approval milestones. As of December 31, 2020, Eli Lilly had
paid us $37.2 million in milestone payments in addition to approximately $53.2 million in reimbursements for certain development
costs.
We could potentially receive future milestone payments for the achievement of development and regulatory approval milestones in
China. Additionally, Eli Lilly is obligated to pay us tiered royalties from 15% to 20% annually on sales made of fruquintinib in China
and Hong Kong, the rate to be determined based upon the dollar amount of sales made for all products in that year. Under the terms of
our 2018 amendment, upon the first commercial launch of fruquintinib in China in a new life cycle indication, these tiered royalties
increased to 15% to 29%. Under the terms of our 2020 amendment, we and Eli Lilly share gross profits linked to sales target performance.
Subject to meeting pre-agreed sales targets, Eli Lilly will pay us an estimated total of 70% to 80% of Elunate sales in the form of
royalties, manufacturing costs and service payments.
Development, collaboration and manufacture of products under this agreement are overseen by a joint steering committee comprised
of equal numbers of representatives from each party. Under the terms of our 2018 amendment, we assumed responsibility for all
development activities and costs for fruquintinib in China in new life cycle indications, and we have the liberty to collaborate with third-
parties to explore combination therapies of fruquintinib with various immunotherapy agents. Under the terms of our 2020 amendment,
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we took over development and execution of all on-the-ground medical detailing, promotion and local and regional marketing activities
for Elunate in China.
Once development is complete, Eli Lilly is obligated to use commercially reasonable efforts to commercialize products and bears
all the costs and expenses incurred in such commercialization efforts until the achievement of a non-fruquintinib related Eli Lilly
commercial action.
We are responsible in consultation with Eli Lilly for the supply of, and have the right to supply, all clinical and commercial supplies
for fruquintinib pursuant to an agreed strategy for manufacturing. For the term of the Eli Lilly Agreement, such supplies will be provided
by us at a transfer price that accounts for our cost of goods sold.
The Eli Lilly Agreement is terminable by either party for breach that is uncured. The Eli Lilly Agreement is also terminable by Eli
Lilly for convenience with 120 days’ prior written notice or if there is a major unexpected safety issue with respect to a product.
Termination by either us or Eli Lilly for any reason will have the effect of, among other things, terminating the applicable licenses
granted by us, and will obligate Eli Lilly to transfer to us all regulatory materials necessary for us to continue development efforts for
fruquintinib.
BeiGene
In May 2020, we entered into a clinical collaboration agreement with BeiGene to evaluate the safety, tolerability and efficacy of
combining surufatinib and fruquintinib with BeiGene’s anti-PD-1 antibody tislelizumab, for the treatment of various solid tumor cancers,
in the U.S., Europe, China and Australia. Under the terms of the agreement, we and BeiGene each plan to explore development of the
combination of surufatinib with tislelizumab or fruquintinib with tislelizumab in different indications and regions. We have agreed to
provide mutual drug supply and other support.
Inmagene
In January 2021, we and Inmagene entered into a strategic partnership to further develop four novel preclinical drug candidates
discovered by us for the potential treatment of multiple immunological diseases. Funded by Inmagene, the companies will work together
to move the drug candidates towards IND submission. If successful, Inmagene will then move the drug candidates through global clinical
development.
Under the terms of the agreement, we have granted Inmagene exclusive options to four drug candidates solely for the treatment of
immunological diseases. If Inmagene exercises the option, it will have the right to further develop, manufacture and commercialize that
specific drug candidate worldwide, while we retain first right to co-commercialization in mainland China. For each of the drug
candidates, Chi-Med will be entitled to development milestones of up to $95 million and up to $135 million in commercial milestones,
as well as up to double-digit royalties upon commercialization.
Other Collaborations
In October and November 2018, we entered into multiple collaborations to evaluate combinations of fruquintinib and surufatinib.
These include a global collaboration with Innovent to evaluate the combination of fruquintinib with Tyvyt, a collaboration in China with
Genor to evaluate the fruquintinib combination with genolimzumab (a PD-1 monoclonal antibody being developed by Genor) and a
global collaboration with Junshi to evaluate the combination of surufatinib with Tuoyi. In September 2019, we expanded our global
collaboration agreement with Innovent to evaluate the safety and efficacy of Tyvyt in combination with surufatinib.
Other Ventures is our large-scale, high-performance drug marketing and distribution platform covering about 320 cities and towns
in China with approximately 4,800 manufacturing and commercial personnel as of December 31, 2020. Built over the past 20 years, it
has been focused on the sale of prescription drug products and consumer health products conducted through the following entities:
Other Ventures
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Shanghai Hutchison Pharmaceuticals
Shanghai Hutchison Pharmaceuticals, our non-consolidated joint venture, primarily engages in the manufacture and sale of
prescription drug products originally contributed by our joint venture partner, as well as third-party prescription drugs with a focus on
cardiovascular medicine. Shanghai Hutchison Pharmaceuticals’ proprietary products are sold under the “Shang Yao” brand, literally
meaning “Shanghai pharmaceuticals,” a trademark that has been used for over 40 years in the pharmaceutical retail market, primarily in
Eastern China. In early 2019, Shanghai Hutchison Pharmaceuticals was awarded the 2018 State Scientific and Technological Progress
Award – Second Prize, which was presented by President Xi Jinping, Premier Li Keqiang and other state leaders of the PRC at the
National Science and Technology Awards Ceremony. This award was one of only two such awards given that year to studies in the
botanical drug industry.
As of December 31, 2020, Shanghai Hutchison Pharmaceuticals had a commercial team of about 2,200 medical sales representatives
allowing for the promotion and scientific detailing of our products not just in hospitals in provincial capitals and medium-sized cities,
but also in the majority of county-level hospitals in China. Shanghai Hutchison Pharmaceuticals holds 74 drug product manufacturing
licenses, of which 17 are included in the national list of drugs in China that have been determined to have met basic healthcare
requirements of proper dosage form, rational price, supply guarantee and fair accessibility to the public and forms the basis for healthcare
facility drug allocation and use, or National Essential Medicines List, and three are in active production. The factory is operated by over
530 manufacturing staff.
Its key product is She Xiang Bao Xin pills, a vasodilator for the long-term treatment of coronary artery and heart disease and for
rapid control and prevention of acute angina pectoris, a form of chest pain. There are over one million deaths due to coronary artery
disease per year in China. SXBX pill is the third largest botanical prescription drug in this indication in China, with market share in
2020 of 18.3% (2019: 17.9%) nationally and 47.5% (2019: 51.0%) in Shanghai. She Xiang Bao Xin pills’ sales represented 90.5% of
all Shanghai Hutchison Pharmaceuticals sales in 2020.
She Xiang Bao Xin pills were first approved in 1983 and subsequently enjoyed 22 proprietary commercial protections under the
prevailing regulatory system in China. In 2005, Shanghai Hutchison Pharmaceuticals was able to attain “Confidential State Secret
Technology” status protection, as certified by China’s Ministry of Science and Technology and State Secrecy Bureau, which extended
proprietary protection in China until late 2016. The Science and Technology Commission of Shanghai Municipality has subsequently
extended such protection. Shanghai Hutchison Pharmaceuticals holds an invention patent in China covering its formulation, which
extends proprietary protection through 2029. SXBX pill is one of less than two dozen proprietary prescription drugs represented on
China’s National Essential Medicines List, which means that all Chinese state-owned health care institutions are required to carry it.
SXBX pill is fully reimbursed in all of China.
Shanghai Hutchison Pharmaceuticals manufactures its products at its 78,000 square meter production facility located in Feng Pu
district outside the center of Shanghai.
Hutchison Sinopharm
Hutchison Sinopharm is our consolidated joint venture with Sinopharm. Based in Shanghai, Hutchison Sinopharm focuses on
providing logistics services to, and distributing and marketing prescription drugs in China. As of December 31, 2020, Hutchison
Sinopharm had a dedicated team of over 120 commercial staff focused on two key areas of operation—a commercial team that markets
approximately 1,000 third-party prescription drug and other products directly to over 500 public and private hospitals in the Shanghai
region and through a network of over 40 distributors to cover all other provinces in China, and a second commercial team that markets
our Zhi Ling Tong infant nutrition brand through a network of over 29,000 promoters in over 7,500 outlets in China.
Since early 2015, Hutchison Sinopharm had been the exclusive marketing agent for Seroquel tablets in China. In June 2018,
AstraZeneca sold and licensed its rights to Seroquel to Luye Pharma Group, Ltd., including its rights in China. The terms of our
agreement with AstraZeneca were assigned to Luye Pharma Hong Kong Ltd., or Luye HK. In May 2019, we received a notice from
Luye HK purporting to terminate our agreement. We believe that Luye HK has no basis for termination and have commenced legal
proceedings to seek for damages.
In 2019, we began building an in-house oncology commercial sales and marketing team at Hutchison Sinopharm to support the
launch of certain of our innovative oncology drugs. By December 31, 2020, this team had grown to over 360 commercial sales and
marketing staff.
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Hutchison Baiyunshan
Hutchison Baiyunshan, our non-consolidated joint venture, focuses primarily on the manufacture, marketing and distribution of
over-the-counter pharmaceutical products. Hutchison Baiyunshan’s “Bai Yun Shan” brand is a market-leading household-name,
established over 40 years ago and is known by the majority of Chinese consumers. As of December 31, 2020, Hutchison Baiyunshan
held 185 registered drug licenses in China. In addition, 30 of Hutchison Baiyunshan’s products, of which six are in active production,
are represented on China’s National Essential Medicines List. In addition to about 1,000 manufacturing staff in Guangdong and Anhui
provinces, Hutchison Baiyunshan has a commercial team of about 900 sales staff that covers the national retail pharmacy channel in
China.
Hutchison Baiyunshan’s key products are two generic over-the-counter therapies:
• Banlangen granules—for the treatment of viral flu, fever, and respiratory tract infections which represented approximately
35.9% of the sales of Hutchison Baiyunshan in 2020; and
• Fu Fang Dan Shen tablets—generic over-the-counter drugs for the treatment of chest congestion and angina pectoris to promote
blood circulation and relieve pain, which represented approximately 16.5% of the sales of Hutchison Baiyunshan in 2020.
Hutchison Baiyunshan’s products are mainly manufactured in-house at facilities in Guangzhou, Guangdong province and Bozhou,
Anhui province. Third-party contract manufacturers are also used. Hutchison Baiyunshan also operates cultivation sites through its
subsidiaries for growing and sourcing the herbs used in its over-the-counter products in Guangdong, Yunnan and Heilongjiang provinces
in China. In addition, Hutchison Baiyunshan generates revenue by supplying raw materials produced by its cultivation operations to its
collaboration partner, Guangzhou Pharmaceuticals.
Hutchison Baiyunshan sells its products directly to regional distributors across China who on-sell to local distributors, hospitals and
clinics, pharmacies and other retailers, and employs its own sales representatives at a local level to market its products and promote
over-the-counter sales to retailers.
In June 2020, Hutchison Baiyunshan entered into a land compensation agreement with the Guangzhou government for the return
of its land use rights for an approximately 30,000 square meter unused plot of land in Guangzhou for cash compensation of up to
approximately $100 million. As of December 31, 2020, Hutchison Baiyunshan had surrendered the land use rights certificate for
deregistration, had satisfied all major obligations under the land compensation agreement and received approximately $40 million in
compensation. Hutchison Baiyunshan is expected to receive approximately $60 million in 2021, of which approximately $17 million is
subject to the Guangzhou government’s confirmation of the completion of the remaining administrative procedures before June 2021.
The land return had no impact on manufacturing operations, which continue to be conducted at larger sites in Guangzhou and Bozhou.
Hutchison Hain Organic
Hutchison Hain Organic is a consolidated joint venture with Hain Celestial, a Nasdaq-listed, natural and organic food and personal
care products company. Hutchison Hain Organic distributes a broad range of over 500 imported organic and natural products. Pursuant
to its joint venture agreement, Hutchison Hain Organic has rights to manufacture, market and distribute Hain Celestial’s products within
nine Asian territories. We believe the key strategic product for Hutchison Hain Organic is Earth’s Best organic baby products, a leading
brand in the United States. Hutchison Hain Organic’s other products are distributed to hypermarkets, specialty stores and other retail
outlets in Hong Kong, China and across seven other territories in Asia mainly through third-party local distributors, including retail
chains owned by affiliates of CK Hutchison.
Hutchison Healthcare
Hutchison Healthcare is our wholly owned subsidiary and is primarily engaged in the manufacture and sale of health supplements.
Hutchison Healthcare’s major product is Zhi Ling Tong DHA capsules, a health supplement made from algae DHA oil for the promotion
of brain and retinal development in babies and young children, which is distributed by Hutchison Sinopharm.
The majority of Hutchison Healthcare’s products are contract manufactured at a dedicated and certified manufacturing facility
operated by a third party.
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Hutchison Consumer Products
Hutchison Consumer Products is our wholly owned subsidiary that is primarily engaged in the distribution of third-party consumer
products in Asia.
Oncology/Immunology Competition
Competition
The biotechnology and pharmaceutical industries are highly competitive. While we believe that our highly selective drug
candidates, experienced development team and chemistry-focused scientific approach provide us with competitive advantages, we face
potential competition from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology
companies. Any drug candidates that we successfully develop and commercialize will compete with existing drugs and/or new drugs
that may become available in the future.
We compete in the segments of the pharmaceutical, biotechnology and other related markets that address inhibition of key biological
pathways in cancer and immunological diseases. There are other companies working to develop kinase inhibitors and monoclonal
antibodies as targeted therapies for cancer and immunological diseases. These companies include divisions of large pharmaceutical
companies and biotechnology companies of various sizes.
Many of our competitors, either alone or with their strategic partners, have substantially greater financial, technical and human
resources than we do and significantly greater experience in the discovery and development of drug candidates, obtaining regulatory
approvals of products and the commercialization of those products. Accordingly, our competitors may be more successful than we may
be in obtaining approval for drugs and achieving widespread market acceptance. Our competitors’ drugs may be more effective, or
more effectively marketed and sold, than any drug we may commercialize and may render our drug candidates obsolete or non-
competitive before we can recover the expenses of developing and commercializing any of our drug candidates. We anticipate that we
will face intense and increasing competition as new drugs enter the market and advanced technologies become available.
Below is a summary of existing therapies and therapies currently under development that may become available in the future which
may compete with each of our clinical-stage drug candidates.
Savolitinib
While there are currently no approved selective MET inhibitors on the market in China, two selective MET inhibitors are on the
market in the US and Japan: Tepmetko (tepotinib) and Tabrect (capmatinib) are approved for MET exon 14 skipping NSCLC with
additional programs underway focused on lung cancer. Other selective MET inhibitors in development include telisotuzumab /
telisotuzumab vedotin (in Phase I/II for advanced solid tumors, including NSCLC), TPX-0022 (in early-stage clinical development for
advanced solid tumors), AMG 337 (in Phase II for advanced or metastatic clear cell sarcoma harboring the EWSR1-ATF1 gene fusion),
and glumetinib (in Phase I/II in China for advanced solid tumors, including MET-altered NSCLC). Sym-015 is a bi-specific antibody
that binds to non-overlapping epitopes on the extracellular domain of the Met receptor tyrosine kinase (in Phase IIa development).
Approved compounds that inhibit MET as well as other kinases include Xalkori (crizotinib) (ALK, ROS1 and MET inhibitor
marketed for NSCLC) and Cabometyx (cabozantinib) (VEGFR/MET/Ret inhibitor approved for renal cell carcinoma and liver cancer
as well as in development for genitourinary cancers). Amivantamab (JNJ-61186372) (EGFR/MET bi-specific antibody) is under
regulatory review for NSCLC harboring EGFR exon 20 insertion mutation and in late-stage development for EGFRm+ NSCLC.
MP0250 (VEGF-A/HGF inhibitor) is in development for multiple myeloma. Merestinib (MST1R, FLT3, AXL, MERTK, TEK, ROS1,
DDR1/2, MKNK1/2 and MET inhibitor) is in development for advanced solid tumors, including NSCLC.
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Surufatinib
Sutent (VEGFR inhibitor) and Afinitor (mTOR inhibitor) have been approved for the treatment of pancreatic neuroendocrine
tumors. Somatuline Depot (Lanreotide) is a growth hormone release inhibitor that has been approved for the treatment of
gastroenteropancreatic neuroendocrine tumors. Sandostatin (octreotide) is a growth hormone and insulin-like growth factor-1 inhibitor
that has also been approved for neuroendocrine tumors. Lutathera (Lu-dotatate), a somatostatin receptor targeting radiotherapy, has
been approved by the FDA for the treatment of somatostatin receptor positive gastroenteropancreatic neuroendocrine tumors.
Furthermore, small molecules, monoclonal antibodies and radiotherapies are being developed for the treatment of neuroendocrine
tumors. Compounds undergoing development for neuroendocrine tumors include Inlyta (axitinib, tyrosine kinase inhibitor), and
Vargatef (nintedanib, a tyrosine kinase inhibitor). Cometriq (an additional brand name for cabozantinib) has been marketed for thyroid
cancer and is being studied for neuroendocrine tumors. In addition, Avastin is an anti-VEGF monoclonal antibody being studied for
neuroendocrine tumors.
Fruquintinib
Approved VEGF inhibitors on the market for the treatment of CRC include Avastin (anti-VEGF monoclonal antibody), Cyramza
(anti-VEGFR2 monoclonal antibody), Stivarga (VEGFR/TIE2 inhibitor) and Zaltrap (ziv-aflibercept) (VEGF inhibitor). Cyramza is
additionally approved for the treatment of NSCLC, gastric cancer, and a certain type of liver cancer. Avastin is approved for NSCLC
and nintedanib is approved for the treatment of lung disease associated with fibrosis (under the name Ofev) as well asadeno-NSCLC in
Europe (under the name Vargatef). Other VEGFR inhibitors being developed for the treatment of NSCLC include Cabometyx, Lenvima
(lenvatinib), lucitanib and Caprelsa. VEGFR inhibitors being developed for the treatment of gastric cancer include dovitinib, telatinib
and Stivarga. In China, Aitan (apatinib) has been approved for the treatment of third-line gastric cancer and Focus-V (anlotinib) has
been approved for the treatment of third-line NSCLC.
HMPL-523 and HMPL-689
There has been extensive research on oral small-molecule Syk inhibitors due to the major unmet medical need in inflammation and
oncology. However, many Syk inhibitors have failed in the development stage due to their off-target toxicity as a result of lower kinase
selectivity and possibly poor pharmacokinetic properties. The only small molecule drug candidate targeting Syk specifically has been
approved to date is Tavalisse for the treatment of chronic immune thrombocytopenia. Lanraplenib (GS-9876) is a Syk inhibitor that has
been studied for autoimmune diseases, but not currently in active development. Syk inhibitors currently in clinical studies for
hematological cancers include entospletinib (AML harboring NPM1c or FLT3 mutations ), and cerdulatinib (lymphoma).
All three of the first generation PI3K inhibitors have boxed warnings in their prescribing information pertaining to safety and
adverse events. Zydelig is a PI3Kδ inhibitor that has been approved for the treatment of relapsed follicular lymphoma, small lymphocytic
lymphoma as a monotherapy and for the treatment of chronic lymphatic leukemia in combination with Rituxan. Copiktra (duvelisib,
PI3K-δ/γ dual inhibitor) has been approved for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma and
follicular lymphoma as a monotherapy. In February 2021, Ukoniq (umbralisib) was approved for the treatment of relapsed or refractory
marginal zone lymphoma and follicular lymphoma. Aliqopa (copanlisib, pan-PI3K inhibitor) also has been approved for relapsed
follicular lymphoma as a monotherapy. In addition, several drug candidates that inhibit PI3Kδ are in clinical development for
hematological cancers, including parsaclisib, zandelisib (ME-401), ACP 319 and YY-20394.
In addition, Janus tyrosine kinase, or JAK, inhibitors such as Xeljanz (tofacitinib JAK-3 inhibitor, marketed for rheumatoid arthritis
and in development for ulcerative colitis, Crohn’s disease and myelofibrosis), Jakafi (ruxolitinib, JAK-1/2 inhibitor, marketed for
myelofibrosis and in development for acute myelogenous leukemia), Olumiant (baricitinib, JAK-1/2 inhibitor marketed for rheumatoid
arthritis), filgotinib (JAK-1 inhibitor in development for rheumatoid arthritis, ulcerative colitis and Crohn’s disease) and upadacitinib
(JAK-1 inhibitor in development for rheumatoid arthritis, Crohn’s disease, ulcerative colitis, atopic dermatitis, psoriatic arthritis and
axial SpA).
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HMPL-453
To date, Balversa and Pemazyre are the only approved therapies that specifically target the FGFR signaling pathway. Late stage
studies are underway for futibatinib, derazantinib, and infigratinib (BGJ-398). Several small molecule FGFR tyrosine kinase inhibitors
are in clinical trials for solid tumors, including AZD4547, rogaratinib, fisogatinib (BLU-554), famitinib, Debio 1347, E7090, ICP-192,
ICP-105, ASP5878, FGF401, RLY-4008 and HH185. Additionally, a FGFR specific monoclonal antibody, bemarituzumab, is in
development.
HMPL-306
Tilbsovo (ivosidenib) is an approved therapy that specifically inhibits IDH1 while Idhifa (enasidenib) is an approved therapy that
specifically inhibits IDH2. To date, there are no approved therapies that inhibit both IDH1 and IDH2, which could be advantageous in
deferring resistance to therapy. A pan-IDH inhibitor, vorasidenib, is currently in late stage development for glioma. IDH1 inhibitors in
development include olutasidenib (FT-2102), BAY1436032, DS-1001b and LY3410738.
Epitinib
Although no EGFR tyrosine kinase inhibitors have been specifically approved for NSCLC with brain metastasis or primary brain
tumor, Tagrisso has been found to have an effect on brain metastasis in advanced lung cancer. Additional approved treatments of
NSCLC with EGFR activating mutations have shown some activities in these settings, including Gilotrif (EGFR/HER2 inhibitor), Iressa
and Tarceva. Further, AZD3759 is currently being studied in China for the treatment of advanced NSCLC that has metastasized to the
central nervous system.
Other Ventures Competition
Our Other Ventures operations which focus on prescription drugs compete in the pharmaceutical industry in China, which is highly
competitive and is characterized by a number of established, large pharmaceutical companies, as well as some smaller emerging
pharmaceutical companies. This business faces competition from other pharmaceutical companies in China engaged in the development,
production, marketing or sales of prescription drugs, in particular cardiovascular drugs.
The barrier to entry for the PRC pharmaceutical industry primarily relates to regulatory requirements in connection with the
production of pharmaceutical products and new product launches. The identities of the key competitors with respect to our prescription
drugs business vary by product, and, in certain cases, different competitors that have greater financial resources than us may elect to
focus these resources on developing, importing or in-licensing and marketing products in the PRC that are substitutes for our products
and may have broader sales and marketing infrastructure with which to do so.
We believe that we compete primarily on the basis of brand recognition, pricing, sales network, promotion activities, product
efficacy, safety and reliability. We believe our continued success will depend on our business’s capability to: maintain profitability of
its core product, She Xiang Bao Xin pills, obtain and maintain regulatory approvals, develop drug candidates with market potential,
maintain an efficient operational model, apply technologies to production lines, attract and retain talented personnel, maintain high
quality standards, and effectively market and promote the products sold by our prescription drugs business. Key competitors for She
Xiang Bao Xin pills include Tasly Holding (Compound Danshen Dropping Pill) and Shijiazhuang Yiling Pharmaceutical (Tong Xin
Luo Capsule).
Our Other Ventures operations which focus on consumer health products competes in a highly fragmented market in Asia,
particularly in our primary market in China. We believe that this business competes primarily on the basis of brand recognition, pricing,
sales network, promotion activities, product safety and reliability. We believe our continued success will depend on our business’s
capability to: maintain profitability of its core products, Fu Fang Dan Shen tablets and Banlangen granules, differentiate its products
vis-a-vis those of competitors, successfully market and distribute in-licensed products such as Earth’s Best infant formula, maintain an
efficient operational model, attract and retain talented personnel, maintain high quality standards, and effectively market and promote
the products sold by our business. In China, Fu Fang Dan Shen tablets and Banlangen granules are generic over-the-counter drugs
marketed by several manufacturers. Key competitors include Shanghai LeiYunShang Pharmaceutical, Yunnan Baiyao and Beijing
Tongrentang in the Fu Fang Dan Shen market, and include Beijing Tongrentang and Guangzhou Xiangxue Pharmaceutical for the
Banlangen market.
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Patents and Other Intellectual Property
Our commercial success depends in part on our ability to obtain and maintain proprietary or intellectual property protection for our
Oncology/Immunology drugs and drug candidates, our Other Ventures’ products and other know-how. Our policy is to seek to protect
our proprietary and intellectual property position by, among other methods, filing patent applications in various jurisdictions related to
our proprietary technology, inventions and improvements that are important to the development and implementation of our business.
We also rely on trade secrets, know-how and continuing technological innovation to develop and maintain our proprietary and
intellectual property position.
Patents
We and our joint ventures file patent applications directed to our Oncology/Immunology drugs and drug candidates and our Other
Ventures’ products in an effort to establish intellectual property positions with regard to new small molecule compounds and/or extracts
of natural herbs, their compositions as well as their medical uses in the treatment of diseases. In relation to our Oncology/Immunology
operations, we also file patent applications directed to crystalline forms, formulations, processes, key intermediates, and secondary uses
as clinical trials for our drug candidates evolve. We file such patent applications in major market jurisdictions, including the United
States, Europe, Japan and China as well as Argentina, Australia, Brazil, Canada, Chile, India, Indonesia, Israel, Mexico, Malaysia, New
Zealand, Peru, the Philippines, Singapore, South Korea, Ukraine and South Africa.
Our Oncology/Immunology Patents
As of December 31, 2020, we had 235 issued patents, including 19 Chinese patents, 22 U.S. patents and 13 European patents, 155
patent applications pending in the above major market jurisdictions, and six pending PCT patent applications relating to the drugs and
drug candidates of our Oncology/Immunology operations. The intellectual property portfolios for our most advanced drug candidates
are summarized below. With respect to most of the pending patent applications covering our drug candidates, prosecution has yet to
commence. Prosecution is a lengthy process, during which the scope of the claims initially submitted for examination by the relevant
patent office is often significantly narrowed by the time when they issue, if they issue at all. We expect this to be the case for our pending
patent applications referred to below.
Savolitinib—The intellectual property portfolio for savolitinib contains two patent families.
The first patent family for savolitinib is directed to novel small molecule compounds as well as methods of treating cancers with
such compounds. As of December 31, 2020, we owned 48 patents in this family, including patents in China, the United States, Europe
and Japan, and we had 15 patent applications pending in various other jurisdictions. Our European patent is also registered in Hong
Kong. Our issued patents will expire in 2030.
The second patent family is directed to the method for the preparation of savolitinib. With respect to this family, we have PCT,
Argentina and Taiwan applications pending, each of which, if issued, would have an expiration date in 2039. This patent family is co-
owned by us and AstraZeneca.
Our collaboration partner AstraZeneca is responsible for maintaining and enforcing the intellectual property portfolio for savolitinib.
Surufatinib—The intellectual property portfolio for surufatinib contains five patent families.
The first patent family for surufatinib is directed to novel small molecule compounds as well as methods of treating tumor
angiogenesis-related disorders with such compounds. As of December 31, 2020, in this patent family we owned one Chinese patent
expiring in 2027 and 12 patents in various other jurisdictions, including the United States expiring in 2031, and Europe and Japan, each
expiring in 2028. As of December 31, 2020, we also had one patent application pending in Brazil.
The second patent family is directed to the crystalline forms of surufatinib as well as methods of treating tumor angiogenesis-related
disorders with such forms. As of December 31, 2020, in this patent family we owned two patents in China expiring in 2029 and 2030,
respectively, and we owned 15 patents in other countries, including the United States which will expire in 2031 and Europe which will
expire in 2030. As of December 31, 2020, we also had one patent application pending in Brazil.
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The third patent family is directed to the formulation of a micronized active pharmaceutical ingredient used in surufatinib as well
as methods of treating tumor angiogenesis-related disorders with such formulation. As of December 31, 2020, in this patent family we
owned three patents in Europe, Russia and Indonesia expiring in 2036. We also had 15 patent applications pending in various
jurisdictions, including China, the United States and Japan, each of which, if issued, would have an expiration date in 2036.
The fourth patent family is directed to clinical indications of surufatinib. With respect to this patent family, we have four patent
applications pending in China, the United States, Hong Kong and Japan, which, if issued, will each have expiration dates in 2036.
The fifth patent family is subject to confidential review by the patent authorities. With respect to this family, we had one patent
application pending in China, which, if issued, would have an expiration date in 2040.
Fruquintinib—The intellectual property portfolio for fruquintinib contains five patent families.
The first patent family for fruquintinib is directed to novel small molecule compounds as well as methods of treating tumor
angiogenesis-related disorders with such compounds. As of December 31, 2020, we owned three United States patents, one Chinese
patent and one Taiwanese patent in this family, each of which will expire in 2028. We also owned patents in Europe and 14 other
jurisdictions expiring in 2029 and had one patent application pending in Brazil.
The second patent family is directed to crystalline forms of fruquintinib as well as methods of treating tumor angiogenesis-related
disorders with such forms. As of December 31, 2020, we owned 13 patents in this family in various jurisdictions, including the United
States, China, Europe and Japan, each of which will expire in 2035, and we had 13 patent applications pending in various jurisdictions,
including Brazil, Peru and Chile.
The third patent family is directed to the method of preparing one of the critical intermediates used in the manufacturing process of
fruquintinib. With respect to this patent family, we have one patent in China, which has an expiration date in 2034.
The fourth patent family is directed to the pharmaceutical composition of fruquintinib. With respect to this family, we have one
patent application pending in China, which, if issued, would have an expiration date in 2038. We also have PCT, Argentina and Taiwan
applications pending for this family, which, if issued, would have an expiration date in 2039.
The fifth patent family is subject to confidential review by the patent authorities. With respect to this family, we had one patent
application pending in China, which, if issued, would have an expiration date in 2040. This patent family is co-owned by us and Genor
Biopharma Co. Ltd.
HMPL-523 Syk Inhibitor—The intellectual property portfolio for HMPL-523 contains two patent families.
The first patent family is directed to novel small molecule compounds as well as methods of treating cancers, inflammatory diseases,
allergic diseases, cell-proliferative diseases, and immunological diseases with such compounds. As of December 31, 2020, we owned
22 patents in this family in various jurisdictions, including the United States, China and South Korea, each of which will expire in 2032.
As of December 31, 2020, we also had three patent applications in this family pending in other jurisdictions.
The second patent family is directed to the salts of HMPL-523. As of December 31, 2020, in this patent family we had 22 patent
applications pending in various jurisdictions, including China, the United States, Europe and Taiwan, each of which, if issued, would
have an expiration date in 2038.
HMPL-689—The intellectual property portfolio for HMPL-689 contains two patent families.
The first patent family is directed to novel small molecule compounds as well as uses of such compounds. As of December 31,
2020, we owned 21 patents in this family in various jurisdictions, including China, the United States, Europe, Australia and Japan, each
of which will expire in 2035. As of December 31, 2020, we also had six patent applications pending in this family in other various
jurisdictions.
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The second patent family is directed to crystalline forms of HMPL-689. With respect to this family, we had one patent application
pending in China as of December 31, 2020, which, if issued, would have an expiration date in 2038. We also had 22 patent applications
in this family pending in various jurisdictions, including China, the United States, Europe and Taiwan, each of which, if issued, would
have an expiration date in 2039.
Epitinib—The intellectual property portfolio for epitinib contains two patent families.
The first patent family is directed to novel small molecule compounds as well as methods of treating cancers with such compounds.
As of December 31, 2020, we owned two patents in China and Taiwan expiring in 2028, one patent in the United States expiring in
2031 and 14 patents in other jurisdictions, including Europe, each expiring in 2029.
The second patent family is directed to the salts and solvates of epitinib and crystalline forms thereof, as well as methods of treating
cancers with such forms. As of December 2020, we had one patent application pending in China in this family, which, if issued, would
have an expiration date in 2038.
Theliatinib—The intellectual property portfolio for theliatinib contains three patent families.
The first patent family is directed to novel small molecule compounds as well as methods of treating cancers with such compounds.
As of December 31, 2020, we owned 18 patents in this family in various jurisdictions, including China and Japan, each of which will
expire in 2031. As of December 31, 2020, we also had one patent application in this family pending in Brazil. Our Chinese patent was
also registered in Hong Kong and Macau.
The second patent family is directed to the crystalline forms of theliatinib as well as methods of treating cancers with such forms.
As of December 31, 2020, we had one patent application pending in China in this family, which, if issued, will have an expiration date
in 2037.
The third patent family is directed to the salts and solvates of theliatinib and crystalline forms thereof. With respect to this family,
we have one Chinese application pending, which, if issued, would have an expiration date in 2038.
HMPL-453—The intellectual property portfolio for HMPL-453 contains two patent families.
The first patent family is directed to novel small molecule compounds as well as methods of treating cancers with the compounds.
As of December 31, 2020, we owned 21 patents in this family in various jurisdictions, including China, Europe, Japan and the United
States, each of which will expire in 2034. As of December 31, 2020, we had four patent applications pending in other various
jurisdictions.
The second patent family is subject to confidential review by the patent authorities. With respect to this family, we have PCT,
Argentina and Taiwan applications pending, each of which, if issued, would have an expiration date in 2040.
HMPL-306—The intellectual property portfolio for HMPL-306 contains one patent family.
The patent family is directed to novel small molecule compounds as well as methods of treating cancers with the compounds. As
of December 31, 2020, in this patent family we had 24 patent applications pending in various jurisdictions, including China, the United
States, Europe and Taiwan, each of which, if issued, would have an expiration date in 2038.
Other Ventures Patents
As of December 31, 2020, our joint venture Shanghai Hutchison Pharmaceuticals had 58 issued patents and 22 pending patent
applications in China, including patents for its key prescription products described below.
She Xiang Bao Xin Pills. As of December 31, 2020, Shanghai Hutchison Pharmaceuticals held an invention patent in China directed
to the formulation of the She Xiang Bao Xin pill. Under PRC law, invention patents are granted for new technical innovations with
respect to products or processes. Invention patents in China have a maximum term of 20 years. This patent will expire in 2029. The
“Confidential State Secret Technology” status protection on the She Xiang Bao Xin pill technology held by Shanghai Hutchison
Pharmaceuticals, as certified by China’s Ministry of Science and Technology and State Secrecy Bureau, is currently active.
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Danning Tablets. As of December 31, 2020, Shanghai Hutchison Pharmaceuticals also held an invention patent in China directed
to the formulation of the Danning tablet. This patent will expire in 2027.
Many of the products sold by our joint venture Hutchison Baiyunshan, including its Banlangen granules and Fu Fang Dan Shen
tablets, are generic, over-the-counter products for which Hutchison Baiyunshan does not hold patents. As of December 31, 2020,
Hutchison Baiyunshan had 80 issued patents and 26 pending patents in China, two PCT patents and one in Australia.
Patent Term
The term of a patent depends upon the laws of the country in which it is issued. In most jurisdictions, a patent term is 20 years from
the earliest filing date of a non-provisional patent application. In the United States, a patent’s term may be lengthened by patent term
adjustment, which compensates a patentee for administrative delays by the USPTO in examining and granting a patent, or may be
shortened if a patent is terminally disclaimed over an earlier filed patent. The term of a patent that covers a drug or biological product
may also be eligible for patent term extension when FDA approval is granted, provided statutory and regulatory requirements are met.
In the future, if and when our drug candidates receive approval by the FDA or other regulatory authorities, we expect to apply for patent
term extensions on issued patents covering those drugs, depending upon the length of the clinical trials for each drug and other factors.
There can be no assurance that any of our pending patent applications will be issued or that we will benefit from any patent term
extension.
As with other pharmaceutical companies, our or our joint ventures’ ability to maintain and solidify our proprietary and intellectual
property position for our drugs and drug candidates or our or their products and technologies will depend on our or our joint ventures’
success in obtaining effective patent claims and enforcing those claims if granted. However, our or our joint ventures’ pending patent
applications and any patent applications that we or they may in the future file or license from third parties may not result in the issuance
of patents. We also cannot predict the breadth of claims that may be allowed or enforced in our or our joint ventures’ patents. Any
issued patents that we may receive in the future may be challenged, invalidated or circumvented. For example, we cannot be certain of
the priority of filing covered by pending third-party patent applications. If third parties prepare and file patent applications in the United
States, China or other markets that also claim technology or therapeutics to which we or our joint ventures have rights, we or our joint
ventures may have to participate in interference proceedings, which could result in substantial costs to us, even if the eventual outcome
is favorable to us, which is highly unpredictable. In addition, because of the extensive time required for clinical development and
regulatory review of a drug candidate we may develop, it is possible that, before any of our drug candidates can be commercialized, any
related patent may expire or remain in force for only a short period following commercialization, thereby limiting protection such patent
would afford the respective product and any competitive advantage such patent may provide.
Trade Secrets
In addition to patents, we and our joint ventures rely upon unpatented trade secrets and know-how and continuing technological
innovation to develop and maintain our or their competitive position. We and our joint ventures seek to protect our proprietary
information, in part, by executing confidentiality agreements with our collaborators and scientific advisors, and non-competition,
non-solicitation, confidentiality, and invention assignment agreements with our employees and consultants. We and our joint ventures
have also executed agreements requiring assignment of inventions with selected scientific advisors and collaborators. The confidentiality
agreements we and our joint ventures enter into are designed to protect our or our joint ventures’ proprietary information and the
agreements or clauses requiring assignment of inventions to us or our joint ventures, as applicable, are designed to grant us or our joint
ventures, as applicable, ownership of technologies that are developed through our or their relationship with the respective counterpart.
We cannot guarantee, however, that these agreements will afford us or our joint ventures adequate protection of our or their intellectual
property and proprietary information rights.
Trademarks and Domain Names
We conduct our business using trademarks with various forms of the “Hutchison,” “Chi-Med”, “Hutchison China
MediTech”, “Hutchmed”, “Elunate” and “Sulanda” brands, the logo used by Hutchison MediPharma, as well as domain names
incorporating some or all of these trademarks. In April 2006, we entered into a brand license agreement (as amended and restated on
June 13, 2019) with Hutchison Whampoa Enterprises Limited, an indirect wholly owned subsidiary of CK Hutchison, pursuant to
which we have been granted a non-exclusive, non-transferrable, royalty-free right to use the “Hutchison”, “Hutchison China
MediTech”, “Chi-Med”, “Hutchmed” trademarks, domain names and other intellectual property rights owned by the CK Hutchison
group in connection with the operation of our business worldwide. See Item 7.B. “Related Party Transactions—Relationship with
CK Hutchison—Intellectual
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property licensed by the CK Hutchison group” for more details. The Elunate trademark is licensed to us in China by our collaboration
partner Eli Lilly. The trademarks for the Hutchison MediPharma logo and “Sulanda” are owned by us.
In addition, our joint ventures seek trademark protection in China for their products. As of December 31, 2020, our joint ventures
Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan owned a total of 316 trademarks in the aggregate related to products
sold by them. For example, the name “Shang Yao” is a registered trademark of Shanghai Hutchison Pharmaceuticals in China for certain
uses including pharmaceutical preparations. In addition, our joint venture Hutchison Baiyunshan has been granted a royal-free license
to use the registered trademark “Bai Yun Shan” for a term equal to its operational period of the joint venture by Guangzhou Baiyunshan.
Raw Materials and Supplies
Raw materials and supplies are ordered based on our or our joint ventures’ respective sales plans and reasonable order forecasts and
are generally available from our or our joint ventures’ own cultivation operations and various third-party suppliers in quantities adequate
to meet our needs. We typically order raw materials on short-term contract or purchase order basis and do not enter into long-term
dedicated capacity or minimum supply arrangements.
For our Oncology/Immunology operations, the active pharmaceutical ingredient used in our drug candidates are supplied to us from
third-party vendors. Our ability to successfully develop our drug candidates, and to ultimately supply our commercial drugs in quantities
sufficient to meet the market demand, depends in part on our ability to obtain the active pharmaceutical ingredients for these drugs in
accordance with regulatory requirements and in sufficient quantities for commercialization and clinical testing.
We generally aim to identify and qualify one or more manufacturers to provide such active pharmaceutical ingredients prior to
submission of an NDA to the FDA and/or NMPA. We contract with a single supplier to manufacture and supply us with the active
pharmaceutical ingredient for fruquintinib for commercial purposes and are in the process of engaging a second supplier. We have
already validated the second supplier’s cGMP production processes and submitted an application for its approval to the NMPA. We also
contract with a single supplier to manufacture and supply us with the active pharmaceutical ingredient for surufatinib for commercial
purposes. We manage the risk of price fluctuations and supply disruptions of active pharmaceutical ingredients by purchasing them in
bulk quantities as these ingredients have a relatively long shelf life. Other than the foregoing, we do not currently have arrangements in
place for a contingent or second-source supply of the active pharmaceutical ingredients for fruquintinib or surufatinib in the event any
of our current suppliers of such active pharmaceutical ingredients cease their operations for any reason, which may lead to an interruption
in our production. However, to date, while we have experienced price fluctuations associated with our raw materials, we have not
experienced any material disruptions in the supply of the active pharmaceutical ingredients or the other raw materials we and our joint
venture partners use. See Item 3.D. “Risk Factors—Certain of our joint venture parties principal products involve the cultivation or
sourcing of key raw materials including botanical products, and any quality control or supply failure or price fluctuations could adversely
affect our ability to manufacture our products and/or could materially and adversely affect our operating results.”
Quality Control and Assurance
We have our own independent quality control system and devote significant attention to quality control for the designing,
manufacturing and testing of our products. We have established a strict quality control system in accordance with the NMPA regulations.
Our laboratories fully comply with the Chinese manufacturing guidelines and are staffed with highly educated and skilled technicians
to ensure quality of all batches of product release. We monitor in real time our operations throughout the entire production process, from
inspection of raw and auxiliary materials, manufacture, delivery of finished products, clinical testing at hospitals, to ethical sales tactics.
Our quality assurance team is also responsible for ensuring that we are in compliance with all applicable regulations, standards and
internal policies. Our senior management team is actively involved in setting quality policies and managing internal and external quality
performance of our company and our joint ventures, Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan.
Hutchison MediPharma (Suzhou) Limited holds a pharmaceutical manufacturing permit issued by its local regulatory authority
expiring on September 13, 2025. It also holds a good manufacturing practice, or GMP, certificate issued by its local regulatory authority
expiring on September 16, 2023.
Certificates and Permits
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Hutchison Sinopharm holds a pharmaceutical trading license issued by its local regulatory authority expiring on July 30, 2024.
Hutchison Sinopharm also holds a good supply practice, or GSP, certificate issued by its local regulatory authority which expires on
July 30, 2024.
Shanghai Hutchison Pharmaceuticals holds a pharmaceutical manufacturing permit from its local regulatory authorities expiring on
December 31, 2025. Shanghai Hutchison Pharmaceuticals also holds three GMP certificates issued by its local regulatory authority. The
three GMP certificates will expire on August 14, 2021, November 16, 2021 and December 3, 2022, respectively.
Shanghai Shangyao Hutchison Whampoa GSP Company Limited, a subsidiary of Shanghai Hutchison Pharmaceuticals, holds a
pharmaceutical trading license from its local regulatory authority expiring on November 17, 2024. It also holds a GSP certificate issued
by its local regulatory authority expiring on April 21, 2020.
Hutchison Baiyunshan holds a pharmaceutical manufacturing permit issued by its local regulatory authority expiring on November
26, 2025. Hutchison Baiyunshan holds a GMP certificate issued by its local regulatory authority expiring on December 11, 2023.
Hutchison Whampoa Guangzhou Baiyunshan Pharmaceuticals Limited, a subsidiary of Hutchison Baiyunshan, holds a GSP
certificate issued by its local regulatory authority expiring on October 14, 2024. It also holds a pharmaceutical trading license issued by
its local regulatory authority expiring on November 5, 2024.
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine (Bozhou) Company Limited, a subsidiary of Hutchison
Baiyunshan, holds a GMP certificate issued by its local regulatory authority expiring on January 18, 2022. It also holds a pharmaceutical
manufacturing license issued by its local regulatory authority expiring on December 31, 2025.
Hutchison Whampoa Baiyunshan Lai Da Pharmaceutical (Shan Tou) Company Limited, a subsidiary of Hutchison Baiyunshan,
holds a GMP certificate issued by its local regulatory authority expiring on February 28, 2021. It also holds a pharmaceutical
manufacturing license issued by its local regulatory authority expiring on October 25, 2025.
Regulation
This section sets forth a summary of the most significant rules and regulations affecting our business activities in China and the
United States.
Government Regulation of Pharmaceutical Product Development and Approval
PRC Regulation of Pharmaceutical Product Development and Approval
Since China’s entry to the World Trade Organization in 2001, the PRC government has made significant efforts to standardize
regulations, develop its pharmaceutical regulatory system and strengthen intellectual property protection.
Regulatory Authorities
In the PRC, the NMPA is the authority that monitors and supervises the administration of pharmaceutical products and medical
appliances and equipment as well as cosmetics. The NMPA’s predecessor, the State Drug Administration, or the SDA, was established
on August 19, 1998 as an organization under the State Council to assume the responsibilities previously handled by the Ministry of
Health of the PRC, or the MOH, the State Pharmaceutical Administration Bureau of the PRC and the State Administration of Traditional
Chinese Medicine of the PRC. The SDA was replaced by the State Food and Drug Administration, or the SFDA, in March 2003 and
was later reorganized into the China Food and Drug Administration, or the CFDA, in March 2013. On March 17, 2018, the First Session
of the Thirteenth National People’s Congress approved the State Council Institutional Reform Proposal, according to which the duties
of the CFDA were consolidated into the State Administration for Market Regulation, or the SAMR, and the NMPA was established
under the management and supervision of the SAMR.
The primary responsibilities of the NMPA include:
• monitoring and supervising the administration of pharmaceutical products, medical appliances and equipment as well as
cosmetics in the PRC;
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•
•
•
formulating administrative rules and policies concerning the supervision and administration of cosmetics and the
pharmaceutical industry; evaluating, registering and approving of new drugs, generic drugs, imported drugs and traditional
Chinese medicine;
undertaking the standard, registration, quality and post marketing risk management of pharmaceutical products, medical
appliances and equipment as well as cosmetics; and
examining, evaluating and supervising the safety of pharmaceutical products, medical appliances and equipment as well as
cosmetics.
The MOH is an authority at the ministerial level under the State Council and is primarily responsible for national public health.
Following the establishment of the SFDA in 2003, the MOH was put in charge of the overall administration of the national health in the
PRC excluding the pharmaceutical industry. In March 2008, the State Council placed the SFDA under the management and supervision
of the MOH. The MOH performs a variety of tasks in relation to the health industry such as establishing social medical institutes and
producing professional codes of ethics for public medical personnel. The MOH is also responsible for overseas affairs, such as dealings
with overseas companies and governments. In 2013, the MOH and the National Population and Family Planning Commission were
integrated into the National Health and Family Planning Commission of the PRC, or the NHFPC. On March 17, 2018, the First Session
of the Thirteenth National People’s Congress approved the State Council Institutional Reform Proposal, according to which the
responsibilities of NHFPC and certain other governmental authorities are consolidated into the National Health Commission, or the
NHC, and the NHFPC shall no longer be reserved. The responsibilities of the NHC include organizing the formulation of national drug
policies, the national essential medicine system and the National Essential Medicines List and drafting the administrative rules for the
procurement, distribution and use of national essential medicines.
Healthcare System Reform
The PRC government has promulgated several healthcare reform policies and regulations to reform the healthcare system. On
March 17, 2009, the Central Committee of the PRC Communist Party and the State Council jointly issued the Guidelines on
Strengthening the Reform of Healthcare System. On March 18, 2009, the State Council issued the Implementation Plan for the Recent
Priorities of the Healthcare System Reform (2009-2011). On July 22, 2009, the General Office of the State Council issued the Five Main
Tasks of Healthcare System Reform in 2009.
Highlights of these healthcare reform policies and regulations include the following:
•
•
•
The overall objective of the reform is to establish a basic healthcare system to cover both urban and rural residents and provide
the Chinese people with safe, effective, convenient and affordable healthcare services. The PRC government aims to extend
basic medical insurance coverage to at least 90% of the country’s population by 2011 and increase the amount of subsidies on
basic medical insurance for urban residents and rural cooperative medical insurance to RMB120 ($18.32) per person per year
by 2010. By 2020, a basic healthcare system covering both urban and rural residents should be established.
The reforms aim to promote orderly market competition and improve the efficiency and quality of the healthcare system to
meet the various medical needs of the Chinese population. From 2009, basic public healthcare services such as preventive
healthcare, maternal and child healthcare and health education will be provided to urban and rural residents. In the meantime,
the reforms also encourage innovations by pharmaceutical companies to eliminate low-quality and duplicative products.
The five key tasks of the reform from 2009 to 2011 are as follows: (1) to accelerate the formation of a basic medical insurance
system, (2) to establish a national essential drug system, (3) to establish a basic healthcare service system, (4) to promote equal
access to basic public healthcare services, and (5) to promote the reform of public hospitals.
Drug Administration Laws and Regulations
The PRC Drug Administration Law as promulgated by the Standing Committee of the National People’s Congress in 1984 and the
Implementing Measures of the PRC Drug Administration Law as promulgated by the MOH in 1989 have laid down the legal framework
for the establishment of pharmaceutical manufacturing enterprises, pharmaceutical trading enterprises and for the administration of
pharmaceutical products including the development and manufacturing of new drugs and medicinal preparations by medical institutions.
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The PRC Drug Administration Law also regulates the packaging, trademarks and the advertisements of pharmaceutical products in the
PRC.
Certain revisions to the PRC Drug Administration Law took effect on December 1, 2001. They were formulated to strengthen the
supervision and administration of pharmaceutical products, and to ensure the quality of pharmaceutical products and the safety of
pharmaceutical products for human use. The revised PRC Drug Administration Law applies to entities and individuals engaged in the
development, production, trade, application, supervision and administration of pharmaceutical products. It regulates and prescribes a
framework for the administration of pharmaceutical manufacturers, pharmaceutical trading companies, and medicinal preparations of
medical institutions and the development, research, manufacturing, distribution, packaging, pricing and advertisements of
pharmaceutical products.
The PRC Drug Administration Law was later amended on December 28, 2013 and April 24, 2015 by the Standing Committee of
the National People’s Congress. It provides the basic legal framework for the administration of the production and sale of pharmaceutical
products in China and covers the manufacturing, distributing, packaging, pricing and advertising of pharmaceutical products.
On August 26, 2019, the Standing Committee of the National People’s Congress promulgated the amended PRC Drug
Administration Law, which took effect on December 1, 2019. The amendment brought a series of changes to the drug supervision and
administration system, including but not limited to the clarification of the marketing authorization holder system, pursuant to which the
marketing authorization holder shall assume responsibilities for non-clinical studies, clinical trials, manufacturing and marketing, post-
marketing studies, monitoring, reporting and handling of adverse reactions of the drug. The amendment also stipulated that the PRC
supports the innovation of drugs with clinical value and specific or special effects on human diseases, encourages the development of
drugs with new therapeutic mechanisms and promotes the technological advancement of such drugs.
According to the PRC Drug Administration Law, no pharmaceutical products may be produced without a pharmaceutical production
license. A manufacturer of pharmaceutical products must obtain a pharmaceutical production license from one of NMPA’s provincial
level branches in order to commence production of pharmaceuticals. Prior to granting such license, the relevant government authority
will inspect the manufacturer’s production facilities, and decide whether the sanitary conditions, quality assurance system, management
structure and equipment within the facilities have met the required standards.
The PRC Drug Administration Implementation Regulations promulgated by the State Council took effect on September 15, 2002
and were later amended on February 6, 2016 and March 2, 2019 to provide detailed implementation regulations for the revised PRC
Drug Administration Law.
Examination and Approval of New Medicines
On January 22, 2020, the NMPA promulgated the Administrative Measures on the Registration of Pharmaceutical Products, or the
Registration Measures, which became effective on July 1, 2020. According to the Registration Measures, an applicant who has obtained
a drug registration certificate shall be a drug marketing authorization holder. The approval process for medicines seeking marketing
authorization mainly consists of the following steps:
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upon the completion of pharmaceutical, pharmacological and toxicological research and related activities, an application for
clinical trial will be submitted to the Center for Drug Evaluation of the NMPA, or the Center for Drug Evaluation, for review.
The Center for Drug Evaluation will organize pharmacists, medical personnel and other professionals to review the application
for clinical trial. A decision on approval or non-approval of the application for clinical trial of drugs will be made within 60
working days from acceptance of the application, and the applicant shall be notified of the examination and approval result
through the website of the Center for Drug Evaluation. If the applicant is not notified within the stipulated period, the
application shall be deemed approved. The applicant who is approved to conduct clinical trial shall act as the sponsor for the
clinical trial;
if the application for clinical trial is approved, the sponsor shall, prior to conducting subsequent phases of the clinical trial,
formulate a corresponding program for the clinical trial, carry out the clinical trial after the review and approval by the Ethics
Committee, and submit the corresponding program for clinical trial and supporting materials on the website of the Center for
Drug Evaluation. The applicant may proceed with the relevant clinical research (which is generally conducted in three phases
for a new medicine under the Registration Measures) at institutions with appropriate qualification:
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Phase I refers to the preliminary clinical trial for clinical pharmacology and body safety. It is conducted to observe
the human body tolerance for new medicine and pharmacokinetics, so as to provide a basis for determining the
prescription plan.
Phase Ib or II refers to the stage of preliminary evaluation of clinical effectiveness. The purpose is to preliminarily
evaluate the clinical effectiveness and safety of the medicine used on patients with targeted indication, as well as to
provide a basis for determining the Phase III clinical trial research plan and the volume under the prescription plan.
Phase III is a clinical trial stage to verify the clinical effectiveness. The purpose is to test and determine the clinical
effectiveness and safety of the medicine used on patients with targeted indication, to evaluate the benefits and risks
thereof and, eventually, to provide sufficient basis for review of the medicine registration application.
Phase IV refers to the stage of surveillance and research after the new medicines is launched. The purpose is to observe
the clinical effectiveness and adverse effects of the medicine over a much larger patient population and longer time
period than in Phase I to III clinical trials, and evaluate the benefits and risks when it is administered to general or
special patient population in larger prescription volume;
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the sponsor shall submit a safety update report during the research and development period on the website of the NMPA on a
regular basis. The safety update report during the research and development period shall be submitted once a year, and within
two months of every full year after the clinical drug trial is approved. The NMPA may require the sponsor to adjust the reporting
period if deemed necessary;
after (i) completing relevant pharmaceutical, pharmacological and toxicological research, clinical drug trials, and other research
supporting the marketing registration of a medicine, (ii) determining medicine quality standards, (iii) completing the
verification of commercial scale manufacturing process, and (iv) making preparations for drug registration inspections, the
applicant shall file the application for drug marketing authorization with the Center for Drug Evaluation;
the Center for Drug Evaluation will organize pharmaceutical, medical and other professionals to review accepted drug
marketing authorization applications in accordance with relevant requirements;
upon acceptance of an application for drug registration, the Center for Drug Evaluation will conduct a preliminary examination
within 40 working days from acceptance of the application; if there is a need to conduct an examination of manufacturing
premises for drug registration, the Center for Drug Evaluation will notify the Centre for Food and Drug Inspection of the NMPA
to organize an examination, provide the relevant materials required, and simultaneously notify the applicant as well as the
provincial drug administrative authorities where the applicant or the manufacturing enterprise is located. The Centre for Food
and Drug Inspection of the NMPA shall in principle complete the examination 40 working days before expiry of the review
period, and give feedback to the Center for Drug Evaluation on the status and findings of the examinations;
if the application is approved through the comprehensive review process, the drug shall be approved for marketing and a drug
registration certificate shall be issued. The drug registration certificate will state the approval number for the drug, the holder
of the certificate and information of the manufacturing enterprise. A drug registration certificate for non-prescription drugs will
also state the non-prescription drug category.
Any applicant who is not satisfied with the Center for Drug Evaluation’s decision to deny an application during the application of
the drug registration period can appeal within 15 working days after it is notified by the Center for Drug Evaluation of such decision.
Upon termination for examination and approval of the application for drug registration, if the applicant is dissatisfied with the
administrative licensing decision, the applicant may apply for administrative review or file an administrative lawsuit.
In accordance with the Provisions on the Administration of Special Examination and Approval of Registration of New Drugs
promulgated by the NMPA, issued and effective on January 7, 2009, an NDA that meets certain requirements as specified below will
be handled with priority in the review and approval process, so-called “green-channel” approval. In addition, the applicant is entitled
to provide additional materials during the review period besides those requested by the NMPA, and will have access to enhanced
communication channels with the NMPA.
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Applicants for the registration of the following new drugs are entitled to request priority treatment in review and approval: (i) active
ingredients and their preparations extracted from plants, animals and minerals, and newly discovered medical materials and their
preparations that have not been sold in the China market, (ii) chemical drugs and their preparations and biological products that have
not been approved for sale at its origin country or abroad, (iii) new drugs with obvious clinical treatment advantages for such diseases
as AIDS, therioma, and rare diseases, and (iv) new drugs for diseases that have not been treated effectively. Under category (i) or
(ii) above, the applicant for drug registration may apply for special examination and approval when applying for the clinical trial of new
drugs; under category (iii) or (iv) above, the applicant may only apply for special examination and approval when applying for
manufacturing.
In addition, on July 7, 2020, the NMPA released the Priority Review and Approval Procedures for Drug Marketing Authorizations
(for Trial Implementation), which further clarified that a fast track process for drug registration will be available to the following drugs
with distinctive clinical value: (i) (a) drugs in urgent clinical demand and in shortage and (b) innovative drugs and modified new drugs
for prevention and treatment of serious infectious diseases, rare diseases and other diseases; (ii) new varieties, dosage forms and
specifications of children’s drugs that conform to children’s physiological characteristics; (iii) (a) vaccines that are in urgent need for
disease prevention and control and (b) innovative vaccines; (iv) drugs that have been included in the procedures for breakthrough therapy
designation; (v) drugs that are subject to conditional approval; and (vi) other drugs which the NMPA deems applicable.
It also specified that fast track status would be given to clinical trial applications for drugs with patent expiry within three years and
manufacturing authorization applications for drugs with patent expiry within one year. Concurrent applications for new drug
clinical trials which are already approved in the United States or E.U. are also eligible for fast track NMPA approval.
Drug Technology Transfer Regulations
On August 19, 2009, the NMPA promulgated the Administrative Regulations for Technology Transfer Registration of Drugs to
standardize the registration process of drug technology transfer, which includes application for, and evaluation, examination, approval
and monitoring of, drug technology transfer. Drug technology transfer refers to the transfer of drug production technology by the owner
to a drug manufacturer and the application for drug registration by the transferee according to the provisions in the new regulations.
Drug technology transfer includes new drug technology transfer and drug production technology transfer.
Conditions for the application for new drug technology transfer
Applications for new drug technology transfer may be submitted prior to the expiration date of the monitoring period of the new
drugs with respect to:
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drugs with new drug certificates only; or
drugs with new drug certificates and drug approval numbers.
For drugs with new drug certificates only and not yet in the monitoring period, or drug substances with new drug certificates,
applications for new drug technology transfer should be submitted prior to the respective expiration date of the monitoring periods for
each drug registration category set forth in the new regulations and after the issue date of the new drug certificates.
Conditions for the application of drug production technology transfer
Applications for drug production technology transfer may be submitted if:
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the transferor holds new drug certificates or both new drug certificates and drug approval numbers, and the monitoring period
has expired or there is no monitoring period;
• with respect to drugs without new drug certificates, both the transferor and the transferee are legally qualified drug
manufacturing enterprises, one of which holds over 50% of the equity interests in the other, or both of which are majority-owned
subsidiaries of the same drug manufacturing enterprise;
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• with respect to imported drugs with imported drug licenses, the original applicants for the imported drug registration may
transfer these drugs to local drug manufacturing enterprises.
Application for, and examination and approval of, drug technology transfer
Applications for drug technology transfer should be submitted to the provincial drug administration. If the transferor and the
transferee are located in different provinces, the provincial drug administration where the transferor is located should provide
examination opinions. The provincial drug administration where the transferee is located is responsible for examining application
materials for technology transfer and organizing inspections on the production facilities of the transferee. Medical examination institutes
are responsible for testing three batches of drug samples.
The Center for Drug Evaluation should further review the application materials, provide technical evaluation opinions and form a
comprehensive evaluation opinion based on the site inspection reports and the testing results of the samples. The NMPA should
determine whether to approve the application according to the comprehensive evaluation opinion of the Center for Drug Evaluation. An
approval letter of supplementary application and a drug approval number will be issued to qualified applications. An approval letter of
clinical trials will be issued when necessary. For rejected applications, a notification letter of the examination opinions will be issued
with the reasons for rejection.
Permits and Licenses for Manufacturing and Registration of Drugs
Production Licenses
To manufacture pharmaceutical products in the PRC, a pharmaceutical manufacturing enterprise must first obtain a Pharmaceutical
Manufacturing Permit issued by the relevant pharmaceutical administrative authorities at the provincial level where the enterprise is
located. Among other things, such a permit must set forth the permit number, the name, legal representative and registered address of
the enterprise, the site and scope of production, issuing institution, date of issuance and effective period.
Each Pharmaceutical Manufacturing Permit issued to a pharmaceutical manufacturing enterprise is effective for a period of five
years. The enterprise is required to apply for renewal of such permit within six months prior to its expiry and will be subject to
reassessment by the issuing authorities in accordance with then prevailing legal and regulatory requirements for the purposes of such
renewal.
Business Licenses
In addition to a Pharmaceutical Manufacturing permit, the manufacturing enterprise must also obtain a business license from the
administrative bureau of industry and commerce at the local level. The name, legal representative and registered address of the enterprise
specified in the business license must be identical to that set forth in the Pharmaceutical Manufacturing Permit.
Registration of Pharmaceutical Products
All pharmaceutical products that are produced in the PRC must bear a registered number issued by the NMPA, with the exception
of Chinese herbs and Chinese herbal medicines in soluble form. The medicine manufacturing enterprises must obtain the medicine
registration number before manufacturing any medicine.
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GMP Certificates
The Guidelines on Good Manufacturing Practices, as amended in 1998 and 2010, or the Guidelines, took effect on August 1, 1999
and set the basic standards for the manufacture of pharmaceuticals. These Guidelines cover issues such as the production facilities, the
qualification of the personnel at the management level, production plant and facilities, documentation, material packaging and labeling,
inspection, production management, sales and return of products and customers’ complaints. On October 23, 2003, the NMPA issued
the Notice on the Overall Implementation and Supervision of Accreditation of Good Manufacturing Practice Certificates for
Pharmaceuticals, which required all pharmaceutical manufacturers to apply for the GMP certificates by June 30, 2004. Those enterprises
that failed to obtain the GMP certificates by December 31, 2004 would have their Pharmaceutical Manufacturing Permit revoked by the
drug administrative authorities at the provincial level. On October 24, 2007, the NMPA issued Evaluation Standard on Good
Manufacturing Practices which became effective on January 1, 2008. On December 1, 2019, the latest amendment of Drug
Administration Law abolished GMP certificates.
Marketing Authorization Holder System
In May 2016, the State Council announced the piloting of the “marketing authorization holder” system in ten provinces in China,
where the market authorization/drug license holders are no longer required to be the actual manufacturers. The “marketing authorization
holder” system will allow for more flexibilities in contract manufacturing arrangements.
Under the authorization of the Standing Committee of the National People’s Congress, the State Council issued the Pilot Plan for
the Drug Marketing Authorization Holder Mechanism on May 26, 2016, providing a detailed pilot plan for the marketing authorization
holder system in ten provinces in China. Under the marketing authorization holder system, domestic drug research and development
institutions and individuals in the pilot regions are eligible to be holders of drug registrations without having to become drug
manufacturers. The marketing authorization holders may engage contract manufacturers for manufacturing, provided that the contract
manufacturers are licensed and are also located within the pilot regions. Drugs that qualify for the marketing authorization holder system
include: (1) new drugs (including biological products for curative uses of Class I, Class VII and biosimilars under the Administration of
Drug Registration) approved after the implementation of the marketing authorization holder system; (2) generic drugs approved as
Category 3 or 4 drugs under the Reform Plan for Registration Category of Chemical Medicine issued by the NMPA on March 4, 2016;
(3) previously approved generics that have passed equivalence assessments against their original drugs; and (4) previously approved
drugs whose licenses were held by drug manufacturers originally located within the pilot regions but have moved out of the pilot regions
due to corporate mergers or other reasons.
On August 15, 2017, the NMPA issued the Circular on the Matters Relating to Promotion of the Pilot Program for the Drug
Marketing Authorization Holder System, clarifying that the marketing authorization holder shall be responsible for managing the whole
manufacturing and marketing chain and the whole life cycle of drugs and shall assume full legal liabilities for the non-clinical drug
study, clinical trials, manufacturing, marketing and distribution and adverse drug reaction monitoring. The marketing authorization
holder is permitted to entrust several drug manufacturers under the drug quality management system established by the marketing
authorization holder. The marketing authorization holder shall submit a report of drug manufacturing, marketing, prescription,
techniques, pharmacovigilance, quality control measures and certain other matters to the NMPA within 20 working days after the end
of each year.
On December 1, 2019, the latest amendment of Drug Administration Law came into effect, marking the success of the pilot work,
and the marketing authorization holder system has become a national system. Pursuant to the latest amendment, the legal representative
and the key person-in-charge of a drug marketing authorization holder shall be fully responsible for the quality of drugs.
Administrative Protection for New Drugs
The Administrative Measures Governing the Production Quality of Pharmaceutical Products, or the Administrative Measures for
Production, provides detailed guidelines on practices governing the production of pharmaceutical products. A manufacturer’s factory
must meet certain criteria in the Administrative Measures for Production, which include: institution and staff qualifications, production
premises and facilities, equipment, hygiene conditions, production management, quality controls, product operation, maintenance of
sales records and manner of handling customer complaints and adverse reaction reports.
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Distribution of Pharmaceutical Products
According to the PRC Drug Administration Law and its implementing regulations and the Measures for the Supervision and
Administration of Circulation of Pharmaceuticals, a manufacturer of pharmaceutical products in the PRC can only engage in the trading
of the pharmaceutical products that the manufacturer has produced itself. In addition, such manufacturer can only sell its products to:
• wholesalers and distributors holding Pharmaceutical Distribution Permits;
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other holders of Pharmaceutical Manufacturing Permits; or
• medical practitioners holding Medical Practice Permits.
A pharmaceutical manufacturer in the PRC is prohibited from selling its products to end-users, or individuals or entities other than
holders of Pharmaceutical Distribution Permits, the Pharmaceutical Manufacturing Permits or the Medical Practice Permits.
The granting of a Pharmaceutical Distribution Permit to wholesalers shall be subject to approval of the provincial level drug
regulatory authorities, while the granting of a retailer permit shall be subject to the approval of the drug regulatory authorities above the
county level. Unless otherwise expressly approved, no pharmaceutical wholesaler may engage in the retail of pharmaceutical products,
and neither may pharmaceutical retailers engage in wholesale.
A pharmaceutical distributor shall satisfy the following requirements:
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personnel with pharmaceutical expertise as qualified according to law;
business site, facilities, warehousing and sanitary environment compatible to the distributed pharmaceutical products;
quality management system and personnel compatible to the distributed pharmaceutical products; and
rules and regulations to ensure the quality of the distributed pharmaceutical products.
Operations of pharmaceutical distributors shall be conducted in accordance with the Pharmaceutical Operation Quality Management
Rules.
Pharmaceutical distributors must keep true and complete records of any pharmaceutical products purchased, distributed or sold with
the generic name of such products, specification, approval code, term, manufacturer, purchasing or selling party, price and date of
purchase or sale. A pharmaceutical distributor must keep such record at least until one year after the expiry date of such products and in
any case, such record must be kept for no less than three years. Penalties may be imposed for any violation of record-keeping.
Pharmaceutical distributors can only distribute pharmaceutical products obtained from those with a Pharmaceutical Manufacturing
Permit and a Pharmaceutical Distribution Permit.
On December 26, 2016, the Medical Reform Office of the State Council, the National Health and Family Planning Commission,
the NMPA and other five government authorities promulgated the “Two-Invoice System” Opinions, which became effective on the
same date. On April 25, 2017, the General Office of the State Council further promulgated the Notice on Issuing the Key Working Tasks
for Deepening the Reform of Medicine and Health System in 2017. According to these rules, a two-invoice system is encouraged to be
gradually adopted for drug procurement. The two-invoice system generally requires a drug manufacturer to issue only one invoice to its
distributor followed by the distributor issuing a second invoice directly to the end customer hospital. Only one distributor is permitted
to distribute drug products between the manufacturer and the hospital. The system also encourages manufacturers to sell drug products
directly to hospitals. Public medical institutions are required to adopt the two-invoice system, and its full implementation nationwide is
targeted for 2018. Pharmaceutical manufacturers and distributors who fail to implement the two-invoice system may be disqualified
from attending future bidding events or providing distribution for hospitals and blacklisted for drug procurement practices. These rules
aim to consolidate drug distribution and reduce drug prices. The impact on our company is that Shanghai Hutchison Pharmaceuticals
was required to restructure its distribution and logistics network and Hutchison Sinopharm began to shift its prior Seroquel distribution
model to a fee-for-service model. For more details, please refer to Item 4.B. “Business Overview–Other Ventures.”
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Foreign Investment and “State Secret” Technology
The interpretation of certain PRC laws and regulations governing foreign investment and “state secret” technology is uncertain.
Depending on the industry sectors, foreign investments are classified as “encouraged”, “restricted” or “prohibited” under the Guidance
Catalogue of Industries for Foreign Investment, or the Catalogue, published by the MOFCOM and the NDRC. Under the Catalogue,
“manufacturing of modern Chinese medicines with confidential proprietary formula” has been deemed prohibited for any foreign
investment. The technology and know-how of the She Xiang Bao Xin pill is classified as “state secret” technology by China’s Ministry
of Science and Technology, or the MOST, and the National Administration for the Protection of State Secrets, or NAPSS.
There are currently no PRC laws or regulations or official interpretations, and therefore there can be no assurance, as to whether
the use of “state secret” technology constitutes the “manufacturing of Chinese medicines with confidential proprietary formula” under
the Catalogue. However, under the Rules on Confidentiality of Science and Technology promulgated by the State Science and
Technology Commission (the predecessor of the MOST and the NAPSS) on January 6, 1995, cooperation with foreign parties or
establishing joint ventures with foreign parties in respect of state secret technology is expressly allowed, provided that such cooperation
has been duly approved by the relevant science and technology authorities. The establishment of Shanghai Hutchison Pharmaceuticals
as a sino-foreign joint venture, including the re-registration of licenses for She Xiang Bao Xin pills in its name, was approved by the
local counterpart of the MOFCOM and the Shanghai Drug Administration in 2001. Subsequently, the “Confidential State Secret
Technology” status protection for She Xiang Bao Xin pills was also granted in 2005 to Shanghai Hutchison Pharmaceuticals as a
sino-foreign joint venture by the MOST and NAPSS. Consequently, we believe Shanghai Hutchison Pharmaceuticals is in compliance
with all applicable PRC laws and regulations governing foreign investment and “state secret” technology. Moreover, we believe that
our other joint ventures and wholly-foreign owned enterprises in the PRC are also in compliance with all applicable PRC laws and
regulations governing foreign investment.
U.S. Regulation of Pharmaceutical Product Development and Approval
In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and the Public Health
Service Act, or PHSA, and their implementing regulations. The process of obtaining approvals and the subsequent compliance with
appropriate federal, state and local rules and regulations requires the expenditure of substantial time and financial resources. Failure to
comply with the applicable regulatory requirements at any time during the product development process, approval process or after
approval may subject an applicant and/or sponsor to a variety of administrative or judicial sanctions, including refusal by FDA to approve
pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of warning letters and other types of enforcement
correspondence, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of
government contracts, restitution, disgorgement of profits, or civil or criminal investigations and penalties brought by FDA and the U.S.
Department of Justice, or DOJ, or other governmental entities. Drugs are also subject to other federal, state and local statutes and
regulations.
Our drug candidates must be approved by the FDA through the NDA process before they may be legally marketed in the United
States. The process required by the FDA before a drug may be marketed in the United States generally involves the following:
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completion of extensive pre-clinical studies, sometimes referred to as pre-clinical laboratory tests, pre-clinical animal studies
and formulation studies all performed in compliance with applicable regulations, including the FDA’s good laboratory practice
regulations;
submission to the FDA of an IND application which must become effective before human clinical trials may begin and must
be updated annually;
IRB approval before each clinical trial may be initiated;
performance of adequate and well-controlled human clinical trials in accordance with study protocols, the applicable GCPs and
other clinical trial-related regulations, to establish the safety and efficacy of the proposed drug product for its proposed
indication;
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preparation and submission to the FDA of an NDA;
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a determination by the FDA within 60 days of its receipt of an NDA whether the NDA is acceptable for filing; if the FDA
determines that the NDA is not sufficiently complete to permit substantive review, it may request additional information and
decline to accept the application for filing until the information is provided;
in-depth review of the NDA by FDA, which may include review by a scientific advisory committee;
satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the active
pharmaceutical ingredient and finished drug product are produced to assess compliance with the FDA’s cGMP;
potential FDA audit of the pre-clinical and/or clinical trial sites that generated the data in support of the NDA;
payment of user fees and FDA review and approval of the NDA prior to any commercial marketing or sale of the drug in the
United States; and
compliance with any post-approval requirements, such as REMS and post-approval studies required by FDA.
Pre-clinical Studies
The data required to support an NDA is generated in two distinct development stages: pre-clinical and clinical. For new chemical
entities, or NCEs, the pre-clinical development stage generally involves synthesizing the active component, developing the formulation
and determining the manufacturing process, evaluating purity and stability, as well as carrying out non-human toxicology, pharmacology
and drug metabolism studies in the laboratory, which support subsequent clinical testing. The conduct of the pre-clinical tests must
comply with federal regulations, including good laboratory practices. The sponsor must submit the results of the pre-clinical tests,
together with manufacturing information, analytical data, any available clinical data or literature and a proposed clinical protocol, to the
FDA as part of the IND. An IND is a request for authorization from the FDA to administer an investigational drug product to humans.
The central focus of an IND submission is on the general investigational plan and the protocol(s) for human trials. The IND automatically
becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed clinical trials
and places the IND on clinical hold within that 30-day time period. In such a case, the IND sponsor must resolve with the FDA any
outstanding concerns or questions before the clinical trial can begin. Some long-term pre-clinical testing, such as animal tests of
reproductive adverse events and carcinogenicity, may continue after the IND is submitted. The FDA may also impose clinical holds on
a drug candidate at any time before or during clinical trials due to safety concerns or non-compliance. Accordingly, submission of an
IND does not guarantee the FDA will allow clinical trials to begin, or that, once begun, issues will not arise that could cause the trial to
be suspended or terminated.
Clinical Studies
The clinical stage of development involves the administration of the drug product to human subjects or patients under the
supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control, in accordance with
GCPs, which include the requirement that, in general, all research subjects provide their informed consent in writing for their
participation in any clinical trial. Clinical trials are conducted under written study protocols detailing, among other things, the objectives
of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety
and assess efficacy. Each protocol, and any subsequent amendments to the protocol, must be submitted to the FDA as part of the IND.
Further, each clinical trial must be reviewed and approved by each institution at which the clinical trial will be conducted. An IRB is
charged with protecting the welfare and rights of trial participants and considers such items as whether the risks to individuals
participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also reviews and approves
the informed consent form that must be provided to each clinical trial subject or his or her legal representative and must monitor the
clinical trial until completed. There are also requirements governing the reporting of ongoing clinical trials and completed clinical trial
results to public registries. For example, information about certain clinical trials must be submitted within specific timeframes to the
National Institutes of Health for public dissemination on their ClinicalTrials.gov website.
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Clinical trials are generally conducted in three sequential phases that may overlap or be combined, known as Phase I, Phase II and
Phase III clinical trials.
• Phase I: In a standard Phase I clinical trial, the drug is initially introduced into a small number of subjects who are initially
exposed to a range of doses of the drug candidate. The primary purpose of these clinical trials is to assess the metabolism,
pharmacologic action, appropriate dosing, side effect tolerability and safety of the drug.
• Phase Ib: Although Phase I clinical trials are not intended to treat disease or illness, a Phase Ib trial is conducted in
patient populations who have been diagnosed with the disease for which the study drug is intended. The patient
population typically demonstrates a biomarker, surrogate, or other clinical outcome that can be assessed to show
“proof-of-concept.” In a Phase Ib study, proof-of-concept typically confirms a hypothesis that the current prediction
of a biomarker, surrogate or other outcome benefit is compatible with the mechanism of action of the study drug.
• Phase I/II: A Phase I and Phase II trial for the same treatment is combined into a single study protocol. The drug is
administered first to determine a maximum tolerable dose, and then additional patients are treated in the Phase II
portion of the study to further assess safety and/or efficacy.
• Phase II: The drug is administered to a limited patient population to determine dose tolerance and optimal dosage required to
produce the desired benefits. At the same time, safety and further pharmacokinetic and pharmacodynamic information is
collected, as well as identification of possible adverse effects and safety risks and preliminary evaluation of efficacy.
• Phase III: The drug is administered to an expanded number of patients, generally at multiple sites that are geographically
dispersed, in well-controlled clinical trials to generate enough data to demonstrate the efficacy of the drug for its intended use,
its safety profile, and to establish the overall benefit/risk profile of the drug and provide an adequate basis for drug approval
and labeling of the drug product. Phase III clinical trials may include comparisons with placebo and/or other comparator
treatments. The duration of treatment is often extended to mimic the actual use of a drug during marketing. Generally, two
adequate and well-controlled Phase III clinical trials are required by the FDA for approval of an NDA. A pivotal study is a
clinical study that adequately meets regulatory agency requirements for the evaluation of a drug candidate’s efficacy and safety
such that it can be used to justify the approval of the drug. Generally, pivotal studies are also Phase III studies but may be
Phase II studies if the trial design provides a well-controlled and reliable assessment of clinical benefit, particularly in situations
where there is an unmet medical need. Post-approval trials, sometimes referred to as Phase 4 clinical trials, are conducted after
initial regulatory approval, and they are used to collect additional information from the treatment of patients in the intended
therapeutic indication or to meet other regulatory requirements. In certain instances, FDA may mandate the performance of
Phase 4 clinical trials.
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA, and more frequently if
serious adverse events occur. Written IND safety reports must be submitted to the FDA and the investigators for serious and unexpected
adverse events or any finding from tests in laboratory animals that suggests a significant risk to human subjects. The FDA, the IRB, or
the clinical trial sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research
subjects or patients are being exposed to an unacceptable health risk. The FDA will typically inspect one or more clinical sites to assure
compliance with GCPs and the integrity of the clinical data submitted. Similarly, an IRB can suspend or terminate approval of a clinical
trial at its institution, or an institution it represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements
or if the drug has been associated with unexpected serious harm to patients. Additionally, some clinical trials are overseen by an
independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board or committee.
This group provides authorization for whether or not a trial may move forward at designated check points based on access to certain
data from the trial. Concurrent with clinical trials, companies usually complete additional animal studies and must also develop
additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the
drug in commercial quantities in accordance with cGMP requirements. The manufacturing process must be capable of consistently
producing quality batches of the drug candidate and, among other things, cGMPs impose extensive procedural, substantive and
recordkeeping requirements to ensure and preserve the long-term stability and quality of the final drug product. Additionally, appropriate
packaging must be selected and tested and stability studies must be conducted to demonstrate that the drug candidate does not undergo
unacceptable deterioration over its shelf life.
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NDA Submission and FDA Review Process
Following trial completion, trial results and data are analyzed to assess safety and efficacy. The results of pre-clinical studies and
clinical trials are then submitted to the FDA as part of an NDA, along with proposed labeling for the drug, information about the
manufacturing process and facilities that will be used to ensure drug quality, results of analytical testing conducted on the chemistry of
the drug, and other relevant information. The NDA is a request for approval to market the drug and must contain adequate evidence of
safety and efficacy, which is demonstrated by extensive pre-clinical and clinical testing. The application includes both negative or
ambiguous results of pre-clinical and clinical trials as well as positive findings. Data may come from company-sponsored clinical trials
intended to test the safety and efficacy of a use of a drug, or from a number of alternative sources, including studies initiated by
investigators. To support regulatory approval, the data submitted must be sufficient in quality and quantity to establish the safety and
efficacy of the investigational drug product to the satisfaction of the FDA. Under federal law, the submission of most NDAs is subject
to the payment of an application user fees; a waiver of such fees may be obtained under certain limited circumstances. FDA approval of
an NDA must be obtained before a drug may be offered for sale in the United States.
In addition, under the Pediatric Research Equity Act of 2003, or PREA, an NDA or supplement to an NDA must contain data to
assess the safety and efficacy of the drug for the claimed indications in all relevant pediatric subpopulations and to support dosing and
administration for each pediatric subpopulation for which the drug is safe and effective. The FDA may grant deferrals for submission
of data or full or partial waivers.
Under the Prescription Drug User Fee Act, or PDUFA, as amended, each NDA must be accompanied by an application user fee.
The FDA adjusts the PDUFA user fees on an annual basis. According to the FDA’s fee schedule, effective through September 30, 2021,
the user fee for an application requiring clinical data, such as an NDA, is $2,875,842. PDUFA also imposes a program fee for
prescription human drugs $336,432. Fee waivers or reductions are available in certain circumstances, including a waiver of the
application fee for the first application filed by a small business. Additionally, no user fees are assessed on NDAs for products designated
as orphan drugs, unless the product also includes a non-orphan indication. The FDA reviews all NDAs submitted before it accepts them
for filing and may request additional information rather than accepting an NDA for filing. The FDA conducts a preliminary review of
an NDA within 60 days of receipt and informs the sponsor by the 74th day after FDA’s receipt of the submission to determine whether
the application is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins an in-
depth review of the NDA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has 10 months from the filing
date in which to complete its initial review of a standard NDA and respond to the applicant, and six months from the filing date for a
“priority review” NDA. The FDA does not always meet its PDUFA goal dates for standard and priority review NDAs, and the review
process is often significantly extended by FDA requests for additional information or clarification.
After the NDA submission is accepted for filing, the FDA reviews the NDA to determine, among other things, whether the proposed
drug is safe and effective for its intended use, and whether the drug is being manufactured in accordance with cGMP to assure and
preserve the drug’s identity, strength, quality and purity. The FDA may refer applications for drugs or drug candidates that present
difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review,
evaluation and a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound
by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. The FDA
may re-analyze the clinical trial data, which can result in extensive discussions between the FDA and us during the review process.
Before approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new drug to
determine whether they comply with cGMPs. The FDA will not approve the drug unless it determines that the manufacturing processes
and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the drug within required
specifications. In addition, before approving an NDA, the FDA may also audit data from clinical trials to ensure compliance with GCP
requirements. After the FDA evaluates the application, manufacturing process and manufacturing facilities where the drug product
and/or its active pharmaceutical ingredient will be produced, it may issue an approval letter or a Complete Response Letter. An approval
letter authorizes commercial marketing of the drug with specific prescribing information for specific indications. A Complete Response
Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete Response
Letter usually describes all of the specific deficiencies in the NDA identified by the FDA. The Complete Response Letter may require
additional clinical data and/or an additional pivotal clinical trial(s), and/or other significant, expensive and time-consuming requirements
related to clinical trials, pre-clinical studies or manufacturing. If a Complete Response Letter is issued, the applicant may either resubmit
the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information is
submitted, the FDA may ultimately decide that the NDA does not satisfy the criteria for approval. Data obtained from clinical trials are
not always conclusive and the FDA may interpret data differently than we interpret the same data.
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If a drug receives regulatory approval, the approval may be limited to specific diseases and dosages or the indications for use may
otherwise be limited. Further, the FDA may require that certain contraindications, warnings or precautions be included in the drug
labeling or may condition the approval of the NDA on other changes to the proposed labeling, development of adequate controls and
specifications, or a commitment to conduct post-market testing or clinical trials and surveillance to monitor the effects of approved
drugs. For example, the FDA may require Phase 4 testing which involves clinical trials designed to further assess a drug’s safety and
effectiveness and may require testing and surveillance programs to monitor the safety of approved drugs that have been commercialized.
The FDA may also place other conditions on approvals including the requirement for a REMS to ensure that the benefits of a drug or
biological product outweigh its risks. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS.
The FDA will not approve the NDA without an approved REMS, if required. A REMS could include medication guides, physician
communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk
minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription
or dispensing of drugs. Drug approvals may be withdrawn for non-compliance with regulatory standards or if problems occur following
initial marketing.
Section 505(b)(2) NDAs
NDAs for most new drug products are based on two full clinical studies which must contain substantial evidence of the safety and
efficacy of the proposed new product. These applications are submitted under Section 505(b)(1) of the FDCA. The FDA is, however,
authorized to approve an alternative type of NDA under Section 505(b)(2) of the FDCA, which authorizes FDA to approve an NDA
based on safety and effectiveness data that were not developed by the applicant. Section 505(b)(2) allows the applicant to rely, in part,
on the FDA’s previous findings of safety and efficacy for a similar product, or published literature. Specifically, Section 505(b)(2)
applies to NDAs for a drug for which the investigations relied upon to show that the drug is safe and effective for the intended use “were
not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for
whom the investigations were conducted.”
Section 505(b)(2) authorizes NDAs filed under Section 505(b)(2) may provide an alternate and potentially more expeditious
pathway to FDA approval for new or improved formulations or new uses of previously approved products. If the 505(b)(2) applicant
can establish that reliance on the FDA’s previous approval is scientifically appropriate, the applicant may eliminate the need to conduct
certain pre-clinical or clinical studies of the new product. The FDA may also require companies to perform additional studies or
measurements to support the change from the approved product. The FDA may then approve the new drug candidate for all or some of
the label indications for which the referenced product has been approved, as well as for any new indication sought by the
Section 505(b)(2) applicant.
Abbreviated New Drug Applications for Generic Drugs
In 1984, with passage of the Drug Price Competition and Patent Term Restoration Act of 1984, commonly referred to as the
Hatch-Waxman Act, Congress authorized the FDA to approve generic drugs that are the same as drugs previously approved by the FDA
under the NDA provisions of the statute. To obtain approval of a generic drug, an applicant must submit an abbreviated new drug
application, or ANDA, to the agency. In support of such applications, a generic manufacturer may rely on the pre-clinical and clinical
testing previously conducted for a drug product previously approved under an NDA, known as the reference listed drug, or RLD.
Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect
to the active ingredients, the route of administration, the dosage form, and the strength of the drug. At the same time, the FDA must also
determine that the generic drug is “bioequivalent” to the innovator drug. Under the statute, a generic drug is bioequivalent to a RLD if
“the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed
drug.” The Generic Drug User Fee Act (GDUFA), as reauthorized, sets forth performance goals for FDA to review standard ANDA’s
within 10 months of their submission, and priority ANDA’s within 8 months of their submission if they satisfy certain requirements.
Upon approval of an ANDA, the FDA indicates that the generic product is “therapeutically equivalent” to the RLD and it assigns a
therapeutic equivalence rating to the approved generic drug in its publication “Approved Drug Products with Therapeutic Equivalence
Evaluations,” also referred to as the “Orange Book.” Physicians and pharmacists consider an “AB” therapeutic equivalence rating to
mean that a generic drug is fully substitutable for the RLD. In addition, by operation of certain state laws and numerous health insurance
programs, FDA’s designation of an “AB” rating often results in substitution of the generic drug without the knowledge or consent of
either the prescribing physician or patient.
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Special FDA Expedited Review and Approval Programs
The FDA has various programs, including Fast Track Designation, accelerated approval, priority review and Breakthrough Therapy
Designation, that are intended to expedite or simplify the process for the development and FDA review of drugs that are intended for
the treatment of serious or life threatening diseases or conditions and demonstrate the potential to address unmet medical needs. The
purpose of these programs is to provide important new drugs to patients earlier than under standard FDA review procedures. While these
pathways can reduce the time it takes for the FDA to review an NDA, they do not guarantee that a product will receive FDA approval.
In addition, the Right to Try Act of 2018 established a new regulatory pathway to increase access to unapproved, investigational
treatments for patients diagnosed with life-threatening diseases or conditions who have exhausted approved treatment options and who
are unable to participate in a clinical trial.
Fast Track Designation
To be eligible for a Fast Track Designation, the FDA must determine, based on the request of a sponsor, that a drug is intended to
treat a serious or life threatening disease or condition for which there is no effective treatment and demonstrates the potential to address
an unmet medical need for the disease or condition. Under the fast track program, the sponsor of a drug candidate may request FDA to
designate the product for a specific indication as a fast track product concurrent with or after the filing of the IND for the drug candidate.
The FDA must make a fast track designation determination within 60 days after receipt of the sponsor’s request.
In addition to other benefits, such as the ability to use surrogate endpoints and have greater interactions with FDA, FDA may initiate
review of sections of a fast track product’s NDA before the application is complete. This rolling review is available if the applicant
provides, and FDA approves, a schedule for the submission of the remaining information and the applicant pays applicable user fees.
However, FDA’s time period goal for reviewing a fast track application does not begin until the last section of the NDA is submitted.
A fast track drug also may be eligible for accelerated approval and priority review. In addition, the fast track designation may be
withdrawn by FDA if FDA believes that the designation is no longer supported by data emerging in the clinical trial process.
Priority Review
The FDA may give a priority review designation to drugs that offer major advances in treatment, or provide a treatment where no
adequate therapy exists. A priority review means that the goal for the FDA to review an application is six months, rather than the standard
review of 10 months under current PDUFA guidelines. These 6- and 10-month review periods are measured from the “filing” date rather
than the receipt date for NDAs for new molecular entities, which typically adds approximately two months to the timeline for review
and decision from the date of submission. Most products that are eligible for Fast Track Designation are also likely to be considered
appropriate to receive a priority review.
Breakthrough Therapy Designation
Under the provisions of the new Food and Drug Administration Safety and Innovation Act, or FDASIA, enacted by Congress in
2012, a sponsor can request designation of a drug candidate as a “breakthrough therapy,” typically by the end of the drug’s Phase II
trials. A breakthrough therapy is defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a
serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial
improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early
in clinical development. Drugs designated as breakthrough therapies are also eligible for accelerated approval. For breakthrough
therapies, the FDA may take certain actions, such as intensive and early guidance on the drug development program, that are intended
to expedite the development and review of an application for approval.
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Accelerated Approval
FDASIA also codified and expanded on FDA’s accelerated approval regulations, under which FDA may approve a drug for a
serious or life-threatening illness that provides meaningful therapeutic benefit over existing treatments based on a surrogate endpoint
that is reasonably likely to predict clinical benefit, or on an intermediate clinical endpoint that can be measured earlier than irreversible
morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit. A
surrogate endpoint is a marker that does not itself measure clinical benefit but is believed to predict clinical benefit. This determination
takes into account the severity, rarity or prevalence of the disease or condition and the availability or lack of alternative treatments. As
a condition of approval, the FDA may require a sponsor of a drug receiving accelerated approval to perform Phase 4 or post-marketing
studies to verify and describe the predicted effect on irreversible morbidity or mortality or other clinical endpoint, and the drug may be
subject to accelerated withdrawal procedures. All promotional materials for drug candidates approved under accelerated regulations are
subject to prior review by the FDA.
Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the
conditions for qualification or decide that the time period for FDA review or approval will not be shortened. Furthermore, Fast Track
Designation, priority review, accelerated approval and Breakthrough Therapy Designation, do not change the standards for approval
and may not ultimately expedite the development or approval process.
Pediatric Trials
Under PREA, an NDA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the drug
product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric
subpopulation for which the product is safe and effective. With the enactment of FDASIA, a sponsor who is planning to submit a
marketing application for a drug that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new
route of administration must also submit an initial Pediatric Study Plan, or PSP, within sixty days of an end-of-Phase II meeting or as
may be agreed between the sponsor and FDA. The initial PSP must include an outline of the pediatric study or studies that the sponsor
plans to conduct, including study objectives and design, age groups, relevant endpoints and statistical approach, or a justification for not
including such detailed information, and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement
to provide data from pediatric studies along with supporting information. FDA and the sponsor must reach agreement on the PSP. A
sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to the pediatric plan need to be considered based
on data collected from pre-clinical studies, early phase clinical trials, and/or other clinical development programs. The law requires the
FDA to send a non-compliance letters to sponsors who do not submit their pediatric assessments as required.
Under the Best Pharmaceuticals for Children Act, or BPCA, certain therapeutic candidates may obtain an additional six months of
exclusivity if the sponsor submits information requested by the FDA, relating to the use of the active moiety of the product candidate in
children. Although the FDA may issue a written request for studies on either approved or unapproved indications, it may only do so
where it determines that information relating to that use of a product candidate in a pediatric population, or part of the pediatric
population, may produce health benefits in that population.
FDASIA permanently reauthorized PREA and BPCA, modifying some of the requirements under these laws, and established
priority review vouchers for rare pediatric diseases. Pursuant to the Consolidated Appropriations Act of 2021, the FDA's authority to
award rare pediatric disease vouchers has been extended until September 30, 2024, and until September 30, 2026 for products that
receive Rare Pediatric Disease designation by September 30, 2024.
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Orphan Drug Designation and Exclusivity
Under the Orphan Drug Act, FDA may designate a drug product as an “orphan drug” if it is intended to treat a rare disease or
condition (generally meaning that it affects fewer than 200,000 individuals in the United States, or more in cases in which there is no
reasonable expectation that the cost of developing and making a drug product available in the United States for treatment of the disease
or condition will be recovered from sales of the product). A company must request orphan product designation before submitting an
NDA. If the request is granted, FDA will disclose the identity of the therapeutic agent and its potential use. Orphan product designation
does not convey any advantage in or shorten the duration of the regulatory review and approval process, but the product will be entitled
to orphan product exclusivity, meaning that FDA may not approve any other applications for the same product for the same indication
for seven years, except in certain limited circumstances. Competitors may receive approval of different products for the indication for
which the orphan product has exclusivity and may obtain approval for the same product but for a different indication. If a drug or drug
product designated as an orphan product ultimately receives regulatory approval for an indication broader than what was designated in
its orphan product application, it may not be entitled to exclusivity. The 21st Century Cures Act, which became law in December 2016,
expanded the types of studies that qualify for orphan drug grants. Orphan drug designation also may qualify an applicant for federal and
possibly state tax credits relating to research and development costs.
Post-Marketing Requirements
Following approval of a new drug, a pharmaceutical company and the approved drug are subject to continuing regulation by the
FDA, including, among other things, monitoring and recordkeeping activities, reporting to the applicable regulatory authorities of
adverse experiences with the drug, providing the regulatory authorities with updated safety and efficacy information, drug sampling and
distribution requirements, and complying with applicable promotion and advertising requirements.
Prescription drug advertising is subject to federal, state and foreign regulations. In the United States, the FDA regulates prescription
drug promotion, including standards for direct-to-consumer advertising, restrictions on promoting drugs for uses or in patient populations
that are not described in the drug’s approved labeling (known as “off-label use”), limitations on industry-sponsored scientific and
educational activities, and requirements for promotional activities involving the internet. Although physicians may legally prescribe
drugs for off-label uses, manufacturers may not market or promote such off-label uses. Prescription drug promotional materials must be
submitted to the FDA in conjunction with their first use. Modifications or enhancements to the drug or its labeling or changes of the site
of manufacture are often subject to the approval of the FDA and other regulators, which may or may not be received or may result in a
lengthy review process. Any distribution of prescription drugs and pharmaceutical samples also must comply with the U.S. Prescription
Drug Marketing Act a part of the FDCA.
In the United States, once a drug is approved, its manufacture is subject to comprehensive and continuing regulation by the FDA.
The FDA regulations require that drugs be manufactured in specific approved facilities and in accordance with cGMP. Applicants may
also rely on third parties for the production of clinical and commercial quantities of drugs, and these third parties must operate in
accordance with cGMP regulations. cGMP regulations require among other things, quality control and quality assurance as well as the
corresponding maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP. Drug
manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their
establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain
state agencies for compliance with cGMP and other laws. Accordingly, manufacturers must continue to expend time, money, and effort
in the area of production and quality control to maintain cGMP compliance. These regulations also impose certain organizational,
procedural and documentation requirements with respect to manufacturing and quality assurance activities. NDA holders using
third-party contract manufacturers, laboratories or packagers are responsible for the selection and monitoring of qualified firms, and, in
certain circumstances, qualified suppliers to these firms. These firms and, where applicable, their suppliers are subject to inspections by
the FDA at any time, and the discovery of violative conditions, including failure to conform to cGMP, could result in enforcement
actions that interrupt the operation of any such facilities or the ability to distribute drugs manufactured, processed or tested by them.
Discovery of problems with a drug after approval may result in restrictions on a drug, manufacturer, or holder of an approved NDA,
including, among other things, recall or withdrawal of the drug from the market, and may require substantial resources to correct.
The FDA also may require post-approval testing, sometimes referred to as Phase 4 testing, risk minimization action plans and
post-marketing surveillance to monitor the effects of an approved drug or place conditions on an approval that could restrict the
distribution or use of the drug. Discovery of previously unknown problems with a drug or the failure to comply with applicable FDA
requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, warning letters from
the FDA, mandated corrective advertising or communications with doctors, and civil or criminal penalties, among others. Newly
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discovered or developed safety or effectiveness data may require changes to a drug’s approved labeling, including the addition of new
warnings and contraindications, and also may require the implementation of other risk management measures. Also, new government
requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay
or prevent regulatory approval of our drugs under development.
Other U.S. Regulatory Matters
Manufacturing, sales, promotion and other activities following drug approval are also subject to regulation by numerous regulatory
authorities in addition to the FDA, including, in the United States, the Centers for Medicare & Medicaid Services, other divisions of the
Department of Health and Human Services, the Drug Enforcement Administration for controlled substances, the Consumer Product
Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection
Agency and state and local governments. In the United States, sales, marketing and scientific/educational programs must also comply
with state and federal fraud and abuse laws. Pricing and rebate programs must comply with the Medicaid rebate requirements of the
U.S. Omnibus Budget Reconciliation Act of 1990 and more recent requirements in the Affordable Care Act. If drugs are made available
to authorized users of the Federal Supply Schedule of the General Services Administration, additional laws and requirements apply. The
handling of any controlled substances must comply with the U.S. Controlled Substances Act and Controlled Substances Import and
Export Act. Drugs must meet applicable child-resistant packaging requirements under the U.S. Poison Prevention Packaging Act.
Manufacturing, sales, promotion and other activities are also potentially subject to federal and state consumer protection and unfair
competition laws.
The distribution of pharmaceutical drugs is subject to additional requirements and regulations, including extensive record-keeping,
licensing, storage and security requirements intended to prevent the unauthorized sale of pharmaceutical drugs.
The failure to comply with regulatory requirements subjects firms to possible legal or regulatory action. Depending on the
circumstances, failure to meet applicable regulatory requirements can result in criminal prosecution, fines or other penalties, injunctions,
recall or seizure of drugs, total or partial suspension of production, denial or withdrawal of product approvals, or refusal to allow a firm
to enter into supply contracts, including government contracts. In addition, even if a firm complies with FDA and other requirements,
new information regarding the safety or efficacy of a product could lead the FDA to modify or withdraw product approval. Prohibitions
or restrictions on sales or withdrawal of future products marketed by us could materially affect our business in an adverse way.
Changes in regulations, statutes or the interpretation of existing regulations could impact our business in the future by requiring, for
example: (i) changes to our manufacturing arrangements; (ii) additions or modifications to product labeling; (iii) the recall or
discontinuation of our products; or (iv) additional record-keeping requirements. If any such changes were to be imposed, they could
adversely affect the operation of our business.
Patent Term Restoration and Marketing Exclusivity
Depending upon the timing, duration and specifics of the FDA approval of our drug candidates, some of our U.S. patents may be
eligible for limited patent term extension under the Hatch-Waxman Act. The Hatch-Waxman Act permits a patent restoration term of
up to five years as compensation for patent term lost during product development and the FDA regulatory review process. However,
patent term restoration cannot extend the remaining term of a patent beyond a total of 14 years from the product’s approval date. The
patent term restoration period is generally one-half the time between the effective date of an IND and the submission date of an NDA
plus the time between the submission date of an NDA and the approval of that application. Only one patent applicable to an approved
drug is eligible for the extension and the application for the extension must be submitted prior to the expiration of the patent. The
USPTO, in consultation with the FDA, reviews and approves the application for any patent term extension or restoration. In 2018, the
FDA advanced policies aimed at promoting drug competition and patient access to generic drugs, such as issuing guidance about making
complex generic drugs and the circumstances in which approval of a generic product application may be delayed.
Marketing exclusivity provisions under the FDCA can also delay the submission or the approval of certain marketing applications.
The FDCA provides a five-year period of non-patent marketing exclusivity within the United States to the first applicant to obtain
approval of an NDA for a NCE. A drug is a NCE if the FDA has not previously approved any other new drug containing the same active
moiety, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not
accept for review an ANDA, or a 505(b)(2) NDA submitted by another company for another drug based on the same active moiety,
regardless of whether the drug is intended for the same indication as the original innovator drug or for another indication, where the
applicant does not own or have a legal right of reference to all the data required for approval. However, an application may be submitted
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after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the
innovator NDA holder. Specifically, the applicant must certify with respect to each relevant patent that: the required patent information
has not been filed; the listed patent has expired; the listed patent has not expired, but will expire on a particular date and approval is
sought after patent expiration, or the listed patent is invalid, unenforceable or will not be infringed by the new product. A certification
that the new product will not infringe the already approved product’s listed patents or that such patents are invalid or unenforceable is
called a Paragraph IV certification. If the applicant does not challenge the listed patents or indicate that it is not seeking approval of a
patented method of use, the ANDA application will not be approved until all the listed patents claiming the referenced product have
expired. If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the
Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent
holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent
infringement lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving the
ANDA until the earlier of 30 months after the receipt of the Paragraph IV notice, expiration of the patent, or a decision in the
infringement case that is favorable to the ANDA applicant. To the extent that the Section 505(b)(2) applicant relies on prior FDA
findings of safety and efficacy, the applicant is required to certify to the FDA concerning any patents listed for the previously approved
product in the Orange Book to the same extent that an ANDA applicant would.
The FDCA also provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA if new clinical
investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be
essential to the approval of the application, for example new indications, dosages or strengths of an existing drug. This three-year
exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does
not prohibit the FDA from approving ANDAs for drugs containing the active agent for the original indication or condition of use.
Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full
NDA would be required to conduct or obtain a right of reference to all of the pre-clinical studies and adequate and well-controlled
clinical trials necessary to demonstrate safety and effectiveness. Orphan drug exclusivity, as described above, may offer a seven-year
period of marketing exclusivity, except in certain circumstances. Pediatric exclusivity is another type of regulatory market exclusivity
in the United States. Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month
exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion
of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.
Rest of the World Regulation of Pharmaceutical Product Development and Approval
For other countries outside of China and the United States, such as countries in Europe, Latin America or other parts of Asia, the
requirements governing the conduct of clinical trials, drug licensing, pricing and reimbursement vary from country to country. In all
cases the clinical trials must be conducted in accordance with GCP requirements and the applicable regulatory requirements and ethical
principles.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things, fines, suspension
or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.
PRC Coverage and Reimbursement
Coverage and Reimbursement
Historically, most of Chinese healthcare costs have been borne by patients out-of-pocket, which has limited the growth of more
expensive pharmaceutical products. However, in recent years the number of people covered by government and private insurance has
increased. According to the PRC National Bureau of Statistics, as of December 31, 2019, approximately 1.4 billion employees and
residents in China were enrolled in the national medical insurance program, representing an increase of 9.8 million from December 31,
2018. The PRC government has announced a plan to give every person in China access to basic healthcare by year 2020.
Reimbursement under the National Medical Insurance Program
The National Medical Insurance Program was adopted pursuant to the Decision of the State Council on the Establishment of the
Urban Employee Basic Medical Insurance Program issued by the State Council on December 14, 1998, under which all employers in
urban cities are required to enroll their employees in the basic medical insurance program and the insurance premium is jointly
contributed by the employers and employees. The State Council promulgated Guiding Opinions of the State Council about the Pilot
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Urban Resident Basic Medical Insurance on July 10, 2007, under which urban residents of the pilot district, rather than urban employees,
may voluntarily join Urban Resident Basic Medical Insurance. The State Council expects the Pilot Urban Resident Basic Medical
Insurance to cover the whole nation by 2010.
Participants of the National Medical Insurance Program and their employers, if any, are required to contribute to the payment of
insurance premiums on a monthly basis. Program participants are eligible for full or partial reimbursement of the cost of medicines
included in the NRDL. The Notice Regarding the Tentative Measures for the Administration of the Scope of Medical Insurance Coverage
for Pharmaceutical Products for Urban Employees, jointly issued by several authorities including the Ministry of Labor and Social
Security and the MOF, among others, on May 12, 1999, provides that a pharmaceutical product listed in the NRDL must be clinically
needed, safe, effective, reasonably priced, easy to use, available in sufficient quantity, and must meet the following requirements:
•
•
•
it is set forth in the Pharmacopoeia of the PRC;
it meets the standards promulgated by the NMPA; and
if imported, it is approved by the NMPA for import.
Factors that affect the inclusion of a pharmaceutical product in the NRDL include whether the product is consumed in large volumes
and commonly prescribed for clinical use in the PRC and whether it is considered to be important in meeting the basic healthcare needs
of the general public.
The PRC Ministry of Labor and Social Security, together with other government authorities, has the power to determine the
medicines included in the NRDL, which is divided into two parts, Part A and Part B. Provincial governments are required to include all
Part A medicines listed on the NRDL in their provincial NRDL, but have the discretion to adjust upwards or downwards by no more
than 15% from the number of Part B medicines listed in the NRDL. As a result, the contents of Part B of the provincial NRDL may
differ from region to region in the PRC.
Patients purchasing medicines included in Part A of the NRDL are entitled to reimbursement of the entire amount of the purchase
price. Patients purchasing medicines included in Part B of the NRDL are required to pay a certain percentage of the purchase price and
obtain reimbursement for the remainder of the purchase price. The percentage of reimbursement for Part B medicines differs from region
to region in the PRC.
The total amount of reimbursement for the cost of medicines, in addition to other medical expenses, for an individual participant
under the National Medical Insurance Program in a calendar year is capped at the amounts in such participant’s individual account under
such program. The amount in a participant’s account varies, depending on the amount of contributions from the participant and his or
her employer.
National Essential Medicines List
On August 18, 2009, MOH and eight other ministries and commissions in the PRC issued the Provisional Measures on the
Administration of the National Essential Medicines List, which was later amended in 2015, and the Guidelines on the Implementation
of the Establishment of the National Essential Medicines System, which aim to promote essential medicines sold to consumers at fair
prices in the PRC and ensure that the general public in the PRC has equal access to the drugs contained in the National Essential
Medicines List. MOH promulgated the National Essential Medicines List (Catalog for the Basic Healthcare Institutions) on August 18,
2009, and promulgated the revised National Essential Medicines List on March 13, 2013 and September 30, 2018. According to these
regulations, basic healthcare institutions funded by government, which primarily include county-level hospitals, county-level Chinese
medicine hospitals, rural clinics and community clinics, shall store up and use drugs listed in the National Essential Medicines List. The
drugs listed in National Essential Medicines List shall be purchased by centralized tender process and shall be subject to the price control
by the NDRC. Remedial drugs in the National Essential Medicines List are all listed in the NRDL and the entire amount of the purchase
price of such drugs is entitled to reimbursement.
Price Controls
According to the Pharmaceutical Administration Law and the Regulations of Implementation of the Law of the People’s Republic
of China on the Administration of Pharmaceuticals, pharmaceutical products are subject to fixed or directive pricing system or to be
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adjusted by the market. Those pharmaceutical products included in the NRDL and the National Essential Medicines List and those drugs
the production or trading of which are deemed to constitute monopolies, are subject to price controls by the PRC government in the
form of fixed retail prices or maximum retail prices. Manufacturers and distributors cannot set the actual retail price for any given price
controlled product above the maximum retail price or deviate from the fixed retail price set by the government. The retail prices of
pharmaceutical products that are subject to price controls are administered by the NDRC and provincial and regional price control
authorities. From time to time, the NDRC publishes and updates a list of pharmaceutical products that are subject to price controls.
According to the Notice Regarding Measures on Government Pricing of Pharmaceutical Products issued by NDRC effective on
December 25, 2000, maximum retail prices for pharmaceutical products shall be determined based on a variety of factors, including
production costs, the profit margins that the relevant government authorities deem reasonable, the product’s type, and quality, as well
as the prices of substitute pharmaceutical products.
Further, pursuant to the Notice Regarding Further Improvement of the Order of Market Price of Pharmaceutical Products and
Medical Services jointly promulgated by the NDRC, the State Council Legislative Affairs Office and the State Council Office for
Rectifying, the MOH, the NMPA, the MOFCOM, the MOF and Ministry of Labor and Social Security on May 19, 2006, the PRC
government exercises price control over pharmaceutical products included in the NRDL and made an overall adjustment of their prices
by reducing the retail price of certain overpriced pharmaceutical products and increasing the retail price of certain underpriced
pharmaceutical products in demand for clinical use but that have not been produced in large quantities by manufacturers due to their
low retail price level. In particular, the retail price charged by hospitals at the county level or above may not exceed 115% of the
procurement cost of the relevant pharmaceutical products or 125% for Chinese herbal pieces.
On February 9, 2015, the General Office of the State Council issued the Guiding Opinion on Enhancing Consolidated Procurement
of Pharmaceutical Products by Public Hospitals, or the Opinion. The Opinion encourages public hospitals to consolidate their demands
and to play a more active role in the procurement of pharmaceutical products. Hospitals are encouraged to directly settle the prices of
pharmaceutical products with manufacturers. Consolidated procurement of pharmaceutical products should facilitate hospital reform,
reduce patient costs, prevent corrupt conducts, promote fair competition and induce the healthy growth of the pharmaceutical industry.
According to the Opinion, provincial tendering processes will continue to be used for the pricing of essential drugs and generic drugs
with significant demands, and transparent multi-party price negotiation will be used for some patented drugs and exclusive drugs.
On April 26, 2014, the NDRC issued the Notice on Issues concerning Improving the Price Control of Low Price Drugs, or the Low
Price Drugs Notice, together with the Low Price Drug List, or LPDL. According to the Low Price Drugs Notice, for drugs with relatively
low average daily costs within the current government-guided pricing scope (low price drugs), the maximum retail prices set by the
government were cancelled. Within the standards of average daily costs, the specific purchase and sale prices are fixed by the producers
and operators based on the drug production costs, market supply and demand and market competition. The standards of average daily
costs of low price drugs are determined by the NDRC in consideration of the drug production costs, market supply and demand and
other factors and based on the current maximum retail prices set by the government (or the national average bid-winning retail prices
where the government does not set the maximum retail prices) and the average daily dose calculated according to the package insert.
Under the Low Price Drugs Notice, the current standards for the daily cost of low price chemical pharmaceuticals and of low price
traditional Chinese medicine pharmaceuticals are less than RMB3.0 ($0.46) per day and RMB5.0 ($0.76) per day respectively.
On May 4, 2015, the NDRC, the National Health and Family Planning Commission, the NMPA, MOFCOM and three other
departments issued Opinions on Promoting Drug Pricing Reform. Under these opinions, beginning on June 1, 2015, the restrictions on
the prices of the drugs that were subject to government pricing were cancelled except for narcotic drugs and Class I psychotropic drugs
which are still subject to maximum factory prices and maximum retail prices set by the NDRC. The medical insurance regulatory
authority now has the power to prescribe the standards, procedures, basis and methods of the payment for drugs paid by medical
insurance funds. The prices of patented drugs are set through transparent and public negotiation among multiple parties. The prices for
blood products not listed in the NRDL, immunity and prevention drugs that are purchased by the Chinese government in a centralized
manner, and AIDS antiviral drugs and contraceptives provided by the Chinese government for free, are set through a tendering process.
Except as otherwise mentioned above, the prices for other drugs may be determined by the manufacturers and the operators on their
own on the basis of production or operation costs and market supply and demand.
Centralized Procurement and Tenders
The Guiding Opinions concerning the Urban Medical and Health System Reform, promulgated on February 21, 2000, aim to provide
medical services with reasonable price and quality to the public through the establishment of an urban medical and health system. One
of the measures used to realize this aim is the regulation of the purchasing process of pharmaceutical products by medical institutions.
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Accordingly, the MOH and other relevant government authorities have promulgated a series of regulations and releases in order to
implement the tender requirements.
According to the Notice on Issuing Certain Regulations on the Trial Implementation of Centralized Tender Procurement of Drugs
by Medical Institutions promulgated on July 7, 2000 and the Notice on Further Improvement on the Implementation of Centralized
Tender Procurement of Drugs by Medical Institutions promulgated on August 8, 2001, medical institutions established by county or
higher level government are required to implement centralized tender procurement of drugs.
The MOH promulgated the Working Regulations of Medical Institutions for Procurement of Drugs by Centralized Tender and Price
Negotiations (for Trial Implementation), or the Centralized Procurement Regulations, on March 13, 2002, and promulgated Sample
Document for Medical Institutions for Procurement of Drugs by Centralized Tender and Price Negotiations (for Trial Implementation),
or the Centralized Tender Sample Document in November 2001, as amended in 2010, to implement the tender process requirements and
ensure the requirements are followed uniformly throughout the country. The Centralized Tender Regulations and the Centralized Tender
Sample Document provide rules for the tender process and negotiations of the prices of drugs, operational procedures, a code of conduct
and standards or measures of evaluating bids and negotiating prices. On January 17, 2009, the MOH, the NMPA and other four national
departments jointly promulgated the Opinions on Further Regulating Centralized Procurement of Drugs by Medical Institutions.
According to the notice, public medical institutions owned by the government at the county level or higher or owned by state-owned
enterprises (including state-controlled enterprises) shall purchase pharmaceutical products through centralized procurement. Each
provincial government shall formulate its catalogue of drugs subject to centralized procurement. Specifically, the procurement could be
achieved through public tendering, online bidding, centralized price negotiations and online competition platform. Except for drugs in
the National Essential Medicines List (the procurement of which shall comply with the relevant rules on National Essential Medicines
List), certain pharmaceutical products which are under the national government’s special control and traditional Chinese medicines, in
principle, all drugs used by public medical institutions shall be covered by the catalogue of drugs subject to centralized procurement.
On July 7, 2010, the MOH and six other ministries and commissions jointly promulgated the Working Regulations of Medical
Institutions for Centralized Procurement of Drugs to further regulate the centralized procurement of drugs and clarify the code of conduct
of the parties in centralized drug procurement.
The centralized tender process takes the form of public tender operated and organized by provincial or municipal government
agencies. The centralized tender process is in principle conducted once every year in all provinces and cities in China. Drug
manufacturing enterprises, in principle, shall bid directly for the centralized tender process. Certain related parties, however, may be
engaged to act as bidding agencies for the centralized tender process. Such intermediaries are not permitted to engage in the distribution
of drugs and must have no conflict of interest with the organizing government agencies. The bids are assessed by a committee composed
of pharmaceutical experts who will be randomly selected from a database of experts approved by the relevant government authorities.
The committee members assess the bids based on a number of factors, including but not limited to, bid price, product quality, clinical
effectiveness, qualifications and reputation of the manufacturer, and after-sale services. Only pharmaceuticals that have won in the
centralized tender process may be purchased by public medical institutions funded by government in the relevant region.
4+7 Quality Consistency Evaluation
On November 15, 2018, China’s Joint Procurement Office published its Paper on Centralized Drug Procurement in “4+7 Cities,”
known as the 4+7 Quality Consistency Evaluation process, or 4+7 QCE. The 4+7 QCE initiative is aimed at driving consolidation in
the fragmented generic drug market in China. The 4+7 QCE initiative began as a pilot program in 11 cities: Beijing, Tianjin, Shanghai,
Chongqing, Shenyang, Dalian, Xiamen, Guangzhou, Shenzhen, Chengdu and Xi’an. Under this pilot program, the public medical
institutions in these 11 cities bulk- buy certain generic drugs together, forcing companies to bid for contracts and driving down prices.
The 4+7 QCE initiative has expanded nationwide and now covers more varieties of drugs. On September 1, 2019, the Joint Procurement
Office published its Paper on Centralized Drug Procurement in Alliance Areas (GY-YD2019-1), such areas covering 25 provinces and
regions across China. On December 29, 2019, the Joint Procurement Office published its Paper on Nationwide Centralized Drug
Procurement (GY-YD2019-2), promoting procurement nationwide, and on January 13, 2020, the National Healthcare Security
Administration, the NHC, the NMPA, the Ministry of Industrial and Information Technology and the Logistics Support Department of
the Central Military Commission promulgated the Notice on the Commencement of the Second Batch of State Organized Centralized
Drug Procurement and Use, which states that the second batch of national organization of centralized procurement and use of drugs
would not be carried out in selected areas but nationwide.
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U.S. Coverage and Reimbursement
Successful sales of our products or drug candidates in the U.S. market, if approved, will depend, in part, on the extent to which our
drugs will be covered by third-party payors, such as government health programs, commercial insurance and managed healthcare
organizations. Patients who are provided with prescriptions as part of their medical treatment generally rely on such third-party payors
to reimburse all or part of the costs associated with their prescriptions and therefore adequate coverage and reimbursement from such
third-party payors are critical to new product success. These third-party payors are increasingly reducing reimbursements for medical
drugs and services. Additionally, the containment of healthcare costs has become a priority of federal and state governments, and the
prices of drugs have been a focus in this effort. The U.S. government, state legislatures and foreign governments have shown significant
interest in implementing cost-containment programs, including price controls, restrictions on reimbursement and requirements for
substitution of generic drugs. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in
jurisdictions with existing controls and measures, could further limit our net revenue and results. Decreases in third-party reimbursement
for our drug candidates, if approved, or a decision by a third-party payor to not cover our drug candidates could reduce physician usage
of such drugs and have a material adverse effect on our sales, results of operations and financial condition.
The Medicare Prescription Drug, Improvement, and Modernization Act of 2003, or the MMA, established the Medicare Part D
program to provide a voluntary prescription drug benefit to Medicare beneficiaries. Under Part D, Medicare beneficiaries may enroll in
prescription drug plans offered by private entities that provide coverage of outpatient prescription drugs. Unlike Medicare Part A and
B, Part D coverage is not standardized. Part D prescription drug plan sponsors are not required to pay for all covered Part D drugs, and
each drug plan can develop its own drug formulary that identifies which drugs it will cover and at what tier or level. However, Part D
prescription drug formularies must include drugs within each therapeutic category and class of covered Part D drugs, though not
necessarily all the drugs in each category or class. Any formulary used by a Part D prescription drug plan must be developed and
reviewed by a pharmacy and therapeutic committee. Medicare payment for some of the costs of prescription drugs may increase demand
for drugs for which we receive regulatory approval. However, any negotiated prices for our drugs covered by a Part D prescription drug
plan will likely be lower than the prices we might otherwise obtain. Moreover, while the MMA applies only to drug benefits for Medicare
beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting their own payment rates. Any
reduction in payment that results from the MMA may result in a similar reduction in payments from non-governmental payors.
The American Recovery and Reinvestment Act of 2009 provides funding for the federal government to compare the effectiveness
of different treatments for the same illness. The plan for the research was published in 2012 by the U.S. Department of Health and
Human Services, the Agency for Healthcare Research and Quality and the National Institutes for Health, and periodic reports on the
status of the research and related expenditures are made to Congress. Although the results of the comparative effectiveness studies are
not intended to mandate coverage policies for public or private payors, if third-party payors do not consider a drug to be cost-effective
compared to other available therapies, they may not cover such drugs as a benefit under their plans or, if they do, the level of payment
may not be sufficient.
The Affordable Care Act, enacted in March 2010, has had a significant impact on the health care industry. The Affordable Care Act
expanded coverage for the uninsured while at the same time containing overall healthcare costs. With regard to pharmaceutical products,
the Affordable Care Act, among other things, addressed a new methodology by which rebates owed by manufacturers under the Medicaid
Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected, increased the minimum Medicaid
rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in
Medicaid managed care organizations, established annual fees and taxes on manufacturers of certain branded prescription drugs, and
created a new Medicare Part D coverage gap discount program, in which, beginning in 2019, manufacturers must agree to offer 70%
point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a
condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D. The Bipartisan Budget Act of 2018 made certain
changes to Medicare Part D coverage, including changing the date when the Medicare Part D coverage gap is eliminated from 2020 to
2019, sunsetting the exclusion of biosimilars from the Medicare Part D coverage gap discount program in 2019 and reallocating
responsibility for discounted pricing under the Medicare Part D coverage gap discount program from third-party payors to
pharmaceutical companies. In December 2017, Congress also repealed the “individual mandate,” which was an Affordable Care Act
requirement that individuals obtain healthcare insurance coverage or face a penalty. This repeal could affect the total number of patients
who have coverage from third-party payors that reimburse for use of our products.
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On December 14, 2018, a United States District Court judge in Texas ruled that the Affordable Care Act is unconstitutional in its
entirety because of Congress’s repeal of the individual mandate. On December 18, 2019, the United States Court of Appeals for the
Fifth Circuit affirmed the portion of the district court’s ruling declaring the individual mandate unconstitutional and remanded for the
district court to conduct analysis in the first instance on which provisions of the statute are severable from it and thus remain intact. The
U.S. Supreme Court agreed to hear the case and a decision is expected by the Spring of 2021.
In addition, other legislative and regulatory changes have been proposed and adopted in the United States since the Affordable Care
Act was enacted that affect reimbursement for prescription drugs. On August 2, 2011, the Budget Control Act of 2011 among other
things, created measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked with
recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals,
thereby triggering the legislation’s automatic reduction to several government programs. This includes aggregate reductions to Medicare
payments to providers of up to 2% per fiscal year, started in April 2013. Section 4408 of the CARES Act temporarily suspended
Medicare sequestration during the period of May 1, 2020 through December 31, 2020, while extending the Medicare sequestration
sunset date through 2030. On January 2, 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which
among other things, also reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment
centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
Recent regulations adopted by the Centers for Medicare & Medicaid Services grant Medicare Part B plans authority to apply new
cost control measures to steer patients toward lower-priced drug products prior to covering non-preferred, more expensive products.
This could potentially have the result of reducing coverage of our products under Medicare Part B.
In addition, other proposed legislative and regulatory changes could affect reimbursement for prescription drugs. In January 2017,
the Medicare Prescription Drug Price Negotiation Act was proposed in Congress, which would require the government to negotiate
Medicare prescription drug prices with pharmaceutical companies. In October 2017, a similar bill, the Medicare Drug Price Negotiation
Act of 2017 was proposed in Congress. In November 2017, the Centers for Medicare & Medicaid Services announced a Final Rule that
would adjust the applicable payment rate as necessary for certain separately payable drugs and biologicals acquired under the 340B
Program from average sales price plus 6% to average sales price minus 22.5%. Congress and the U.S. administration continue to
evaluate other proposals that could affect third-party reimbursement for our drug candidates, if approved.
In October 2020, the U.S. Department of Health and Human Services and the FDA issued a final rule and guidance concerning two
new pathways for importing lower-cost drugs into the United States. The final rule allows certain prescription drugs to be imported
from Canada, and the guidance describes procedures for drug manufacturers to facilitate the importation of FDA-approved drugs and
biologics manufactured abroad and originally intended for sale in a foreign country into the United States.
In November 2020, the Department of Health and Human Services, under the outgoing Trump administration, issued two rules
aimed at lowering the cost of prescription drugs. The first rule would cap the price Medicare can pay for a drug to the lowest price paid
in an economically comparable country within the Organization for Economic Cooperation and Development. The rule was immediately
challenged in at least four federal courts. On December 23, 2020, the U.S. District Court in Maryland issued a temporary restraining
order preventing the rule from going into effect because the agency failed to conduct the required notice-and-comment rulemaking
proceedings before promulgating the final rule. Shortly thereafter, the U.S. District Court for the Northern District of California issued
a nation-wide preliminary injunction, largely adopting the Maryland courts’ reasoning. Under the Biden administration, the Department
of Health and Human Services has indicated that the Most Favored Nation model will not be implemented without further rulemaking
proceeding. It is unclear whether or how the Biden administration will move forward with the rule. The rule will not take effect until
at least April 23, 2021, as litigation has been stayed pending a CMS decision whether to rescind the rule or adopt it in final form. The
second rule eliminates the safe harbor shielding Medicare Part D rebates to pharmacy benefit managers from the Anti-Kickback Statute.
In response to litigation brought by a trade association on behalf of pharmacy benefit managers, the Biden administration has agreed to
delay the rule’s effective date until January 1, 2023. It is unclear whether or how the Biden administration will move forward with these
rules. Such regulatory changes could have the effect of lowering the level of coverage or reimbursement for our products.
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Rest of the World Coverage and Reimbursement
In some foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements
governing drug pricing vary widely from country to country. For example, the E.U. provides options for its member states to restrict
the range of medicinal drugs for which their national health insurance systems provide reimbursement and to control the prices of
medicinal drugs for human use. A member state may approve a specific price for the medicinal drug or it may instead adopt a system
of direct or indirect controls on the profitability of our company placing the medicinal drug on the market. Historically, drugs launched
in the E.U. do not follow price structures of the United States and generally tend to be significantly lower.
Other Healthcare Laws
Other PRC Healthcare Laws
Advertising of Pharmaceutical Products
Pursuant to the Provisions for Drug Advertisement Examination, which were promulgated on March 13, 2007, effective on May 1,
2007 and subsequently amended on December 21, 2018, an enterprise seeking to advertise its drugs must apply for an advertising
approval code. The validity term of an advertisement approval number for pharmaceutical drugs is one year. The content of an approved
advertisement may not be altered without prior approval. Where any alteration to the advertisement is needed, a new advertisement
approval number shall be obtained.
Packaging of Pharmaceutical Products
According to the Measures for The Administration of Pharmaceutical Packaging, effective on September 1, 1988, pharmaceutical
packaging must comply with the provisions of the national standard and professional standard. If there are no standards, the enterprise
can formulate its own standard after obtaining the approval of the provincial level drug administration or bureau of standards. The
enterprise shall reapply for the relevant authorities if it needs to change the packaging standard. Drugs without packing must not be sold
in PRC (except for drugs needed by the army).
Labor Protection
Under the Labor Law of the PRC, effective on January 1, 1995 and subsequently amended on August 27, 2009 and December 29,
2018, the Labor Contract Law of the PRC, effective on January 1, 2008 and subsequently amended on December 28, 2012, and the
Implementing Regulations of the Labor Contract Law of the PRC, effective on September 18, 2008, employers must establish a
comprehensive management system to protect the rights of their employees, including a system governing occupational health and safety
to provide employees with occupational training to prevent occupational injury, and employers are required to truthfully inform
prospective employees of the job description, working conditions, location, occupational hazards and status of safe production as well
as remuneration and other conditions as requested by the Labor Contract Law of the PRC.
Pursuant to the Law of Manufacturing Safety of the People’s Republic of China effective on November 1, 2002 and subsequently
amended on December 1, 2014, manufacturers must establish a comprehensive management system to ensure manufacturing safety in
accordance with applicable laws and regulations. Manufacturers not meeting relevant legal requirements are not permitted to commence
their manufacturing activities.
Pursuant to the Administrative Measures Governing the Production Quality of Pharmaceutical Products effective on March 1, 2011,
manufacturers of pharmaceutical products are required to establish production safety and labor protection measures in connection with
the operation of their manufacturing equipment and manufacturing process.
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Pursuant to applicable PRC laws, rules and regulations, including the Social Insurance Law which became effective on July 1, 2011
and subsequently amended on December 29, 2018, the Interim Regulations on the Collection and Payment of Social Security Funds
which became effective on January 22, 1999 and subsequently amended on March 24, 2019, the Interim Measures concerning the
Maternity Insurance which became effective on January 1, 1995 and the Regulations on Work-related Injury Insurance which became
effective on January 1, 2004 and were subsequently amended on December 20, 2010, employers are required to contribute, on behalf of
their employees, to a number of social security funds, including funds for basic pension insurance, unemployment insurance, basic
medical insurance, work-related injury insurance, and maternity insurance. If an employer fails to make social insurance contributions
timely and in full, the social insurance collecting authority will order the employer to make up outstanding contributions within the
prescribed time period and impose a late payment fee at the rate of 0.05% per day from the date on which the contribution becomes due.
If such employer fails to make social insurance registration, the social insurance collecting authority will order the employer to correct
within the prescribed time period. The relevant administrative department may impose a fine equivalent to three times the overdue
amount and management personnel who are directly responsible can be fined RMB500 ($76.34) to RMB3,000 ($458.02) if the employer
fails to correct within the prescribed time period.
Commercial Bribery
Medical production and operation enterprises involved in criminal, investigation or administrative procedure for commercial bribery
will be listed in the Adverse Records of Commercial Briberies by provincial health and family planning administrative department.
Pursuant to the Provisions on the Establishment of Adverse Records of Commercial Briberies in the Medicine Purchase and Sales
Industry enforced on March 1, 2014 by the National Health and Family Planning Commission, if medical production and operation
enterprises are listed into the Adverse Records of Commercial Briberies for the first time, their production shall not be purchased by
public medical institutions, and medical and health institutions receiving financial subsidies in local province in two years from public
of the record, and public medical institutions, and medical and health institutions receiving financial subsidies in other provinces shall
lower their rating in bidding or purchasing process. If medical production and operation enterprises are listed into the Adverse Records
of Commercial Briberies twice or more times in five years, their production may not be purchased by public medical institutions, and
medical and health institutions receiving financial subsidies nationwide in two years from public of the record.
As advised by our PRC legal advisor, from a PRC law perspective, a pharmaceutical company will not be penalized by the relevant
PRC government authorities merely by virtue of having contractual relationships with distributors or third-party promoters who are
engaged in bribery activities, so long as such pharmaceutical company and its employees are not utilizing the distributors or third-party
promoters for the implementation of, or acting in conjunction with them in, the prohibited bribery activities. In addition, a pharmaceutical
company is under no legal obligation to monitor the operating activities of its distributors and third-party promoters, and will not be
subject to penalties or sanctions by relevant PRC government authorities as a result of failure to monitor their operating activities.
Product Liability
In addition to the strict new drug approval process, certain PRC laws have been promulgated to protect the rights of consumers and
to strengthen the control of medical products in the PRC. Under current PRC law, manufacturers and vendors of defective products in
the PRC may incur liability for loss and injury caused by such products. Pursuant to the Civil Code of the PRC, or the PRC Civil Code,
promulgated on May 28, 2020 and effective on January 1, 2021, a defective product which causes property damage or physical injury
to any person may subject the manufacturer or vendor of such product to civil liability for such damage or injury.
On February 22, 1993 the Product Quality Law of the PRC, or the Product Quality Law, was promulgated aiming to define
responsibilities for product quality, to protect the legitimate rights and interests of the end-users and consumers and to strengthen the
supervision and control of the quality of products. The Product Quality Law was amended by the Ninth National People’s Congress on
July 8, 2000 and was later amended by the Eleventh National People’s Congress on August 27, 2009 and the Thirteenth National
People’s Congress on December 29, 2018. Pursuant to the amended Product Quality Law, manufacturers who produce defective
products may be subject to civil or criminal liability and have their business licenses revoked.
The Law of the PRC on the Protection of the Rights and Interests of Consumers was promulgated on October 13, 1993 and was
amended on October 25, 2013 to protect consumers’ rights when they purchase or use goods and accept services. All business operators
must comply with this law when they manufacture or sell goods and/or provide services to customers. Under the amendment on
October 25, 2013, all business operators shall pay high attention to protect the customers’ privacy which they obtain during the business
operation. In addition, in extreme situations, pharmaceutical product manufacturers and operators may be subject to criminal liabilities
under applicable laws of the PRC if their goods or services lead to the death or injuries of customers or other third parties.
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Pursuant to the PRC Civil Code, if damages to other persons are caused by defective products that are resulted from the fault of a
third party such as the parties providing transportation or warehousing, the producers and the sellers of the products have the right to
recover their respective losses from such third parties. If defective products are identified after they have been put into circulation, the
producers or the sellers shall take remedial measures such as issuance of warning and recall of products in a timely manner. The
producers or the sellers shall be liable under tort if they cause damages due to their failure to take remedial measures in a timely manner
or have not made efforts to take remedial measures, thus causing damages. If the products are produced and sold with known defects,
causing deaths or severe damage to the health of others, the infringed party shall have the right to claim respective punitive damages in
addition to compensatory damages.
Other PRC National- and Provincial-Level Laws and Regulations
We are subject to changing regulations under many other laws and regulations administered by governmental authorities at the
national, provincial and municipal levels, some of which are or may become applicable to our business. Our hospital customers are also
subject to a wide variety of laws and regulations that could affect the nature and scope of their relationships with us.
For example, regulations control the confidentiality of patients’ medical information and the circumstances under which patient
medical information may be released for inclusion in our databases, or released by us to third parties. These laws and regulations
governing both the disclosure and the use of confidential patient medical information may become more restrictive in the future.
We also comply with numerous additional state and local laws relating to matters such as safe working conditions, manufacturing
practices, environmental protection and fire hazard control. We believe that we are currently in compliance with these laws and
regulations; however, we may be required to incur significant costs to comply with these laws and regulations in the future. Unanticipated
changes in existing regulatory requirements or adoption of new requirements could therefore have a material adverse effect on our
business, results of operations and financial condition.
Other U.S. Healthcare Laws
We may also be subject to healthcare regulation and enforcement by the U.S. federal government and the states where we may
market our drug candidates, if approved. These laws include, without limitation, state and federal anti-kickback, fraud and abuse, false
claims, privacy and security and physician sunshine laws and regulations.
Anti-Kickback Statute
The federal Anti-Kickback Statute prohibits, among other things, any person from knowingly and willfully offering, soliciting,
receiving or providing remuneration, directly or indirectly, to induce either the referral of an individual, for an item or service, or the
purchase or order of a good or service, for which payment may be made under federal healthcare programs such as the Medicare and
Medicaid programs. The majority of states also have anti-kickback laws, which establish similar prohibitions and in some cases may
apply to items or services reimbursed by any third-party payor, including commercial insurers. The Anti-Kickback Statute is subject to
evolving interpretations. In the past, the government has enforced the Anti-Kickback Statute to reach large settlements with healthcare,
pharmaceutical, and biotechnology companies based on a range of financial arrangements with physicians and other healthcare industry
entities. A person or entity does not need to have actual knowledge of the Anti-Kickback Statute or specific intent to violate it in order
to have committed a violation. Violations of the Anti-Kickback Statute can result in criminal, civil, or administrative liability. In
addition, the government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback
Statute constitutes a false or fraudulent claim for purposes of the federal False Claims Act.
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False Claims
Additionally, the civil False Claims Act prohibits knowingly presenting or causing the presentation of a false, fictitious or fraudulent
claim for payment to the U.S. government. Actions under the False Claims Act may be brought by the U.S. Attorney General or as a qui
tam action by a private individual in the name of the government. Analogous state law equivalents may apply and may be broader in
scope than the federal requirements. Violations of the False Claims Act can result in very significant monetary penalties and treble
damages. The federal government is using the False Claims Act, and the accompanying threat of significant liability, in its investigation
and prosecution of pharmaceutical and biotechnology companies throughout the United States, for example, in connection with
violations of the Anti-Kickback Statute, the promotion of products for unapproved uses and other sales and marketing practices. The
government has obtained multi-million and multi-billion dollar settlements under the False Claims Act in addition to individual criminal
convictions and corporate resolutions under applicable criminal statutes. Given the significant size of actual and potential settlements,
it is expected that the government will continue to devote substantial resources to investigating healthcare providers’ and manufacturers’
compliance with applicable fraud and abuse laws.
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, also created new federal criminal statutes that
prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit
program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program,
willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up
a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for
healthcare benefits, items or services. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual
knowledge of the statute or specific intent to violate it in order to have committed a violation.
Payments to Physicians
There has also been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare
providers. The Affordable Care Act, among other things, imposes new reporting requirements on drug manufacturers for payments made
by them to physicians and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate
family members. Failure to submit required information may result in civil monetary penalties of up to an aggregate of $150,000 per
year (or up to an aggregate of $1 million per year for “knowing failures”), for all payments, transfers of value or ownership or investment
interests that are not timely, accurately and completely reported in an annual submission. Drug manufacturers were required to begin
collecting data on August 1, 2013 and submit reports to the government by March 31, 2014 and June 30, 2014, and the 90th day of each
subsequent calendar year. Certain states also mandate implementation of compliance programs, impose restrictions on drug
manufacturer marketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians.
Data Privacy and Security
We may also be subject to data privacy and security regulation by both the federal government and the states in which we conduct
our business. HIPAA, as amended by the Health Information Technology and Clinical Health Act, or HITECH, and their respective
implementing regulations, including the final omnibus rule published on January 25, 2013, imposes specified requirements relating to
the privacy, security and transmission of individually identifiable health information. Among other things, HITECH makes HIPAA’s
privacy and security standards directly applicable to “business associates,” defined as independent contractors or agents of covered
entities that create, receive, maintain or transmit protected health information in connection with providing a service for or on behalf of
a covered entity. HITECH also increased the civil and criminal penalties that may be imposed against covered entities, business
associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in
federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions. In
addition, state laws govern the privacy and security of personal health information in certain circumstances, many of which differ from
each other in significant ways, thus complicating compliance efforts.
PRC Regulation of Foreign Currency Exchange, Offshore Investment and State-Owned Assets
PRC Foreign Currency Exchange
Foreign currency exchange regulation in China is primarily governed by the following rules:
• Foreign Currency Administration Rules (1996), as last amended on August 5, 2008, or the Exchange Rules; and
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• Administration Rules of the Settlement, Sale and Payment of Foreign Exchange (1996), or the Administration Rules.
Under the Exchange Rules, the renminbi is convertible for current account items, including the distribution of dividends, interest
payments, trade and service-related foreign exchange transactions. Conversion of renminbi for capital account items, such as direct
investment, loan, security investment and repatriation of investment, however, is still subject to the SAFE.
Under the Administration Rules, foreign-invested enterprises may only buy, sell and/or remit foreign currencies at those banks
authorized to conduct foreign exchange business after providing valid commercial documents and, in the case of capital account item
transactions, obtaining approval from the SAFE. Capital investments by foreign-invested enterprises outside of China are also subject
to limitations, which include approvals by the MOFCOM, the SAFE and the NDRC.
Pursuant to the Circular on Further Improving and Adjusting the Direct Investment Foreign Exchange Administration Policies, or
Circular 59, promulgated by the SAFE on November 19, 2012 and became effective on December 17, 2012, approval is not required
for the opening of and payment into foreign exchange accounts under direct investment, for domestic reinvestment with legal income
of foreign investors in China. Circular 59 also simplified the capital verification and confirmation formalities for Chinese foreign
invested enterprises and the foreign capital and foreign exchange registration formalities required for the foreign investors to acquire
the equities of Chinese party and other items. Circular 59 further improved the administration on exchange settlement of foreign
exchange capital of Chinese foreign invested enterprises.
Foreign Exchange Registration of Offshore Investment by PRC Residents
In July 2014, the SAFE issued the Notice on Relevant Issues Concerning Foreign Exchange Administration for PRC Residents to
Engage in Offshore Investment and Financing and Round Trip Investment via Special Purpose Vehicles, or Circular 37, and its
implementation guidelines, which abolishes and supersedes the SAFE’s Circular on Relevant Issues Concerning Foreign Exchange
Administration for PRC Residents to Engage in Financing and Round Trip Investment via Overseas Special Purpose Vehicles, or
Circular 75. Pursuant to Circular 37 and its implementation guidelines, PRC residents (including PRC institutions and individuals) must
register with local branches of the SAFE in connection with their direct or indirect offshore investment in an overseas special purpose
vehicle, or SPV, directly established or indirectly controlled by PRC residents for the purposes of offshore investment and financing
with their legally owned assets or interests in domestic enterprises, or their legally owned offshore assets or interests. Such PRC residents
are also required to amend their registrations with the SAFE when there is a significant change to the SPV, such as changes of the PRC
individual resident’s increase or decrease of its capital contribution in the SPV, or any share transfer or exchange, merger, division of
the SPV. Failure to comply with the registration procedures set forth in Circular 37 may result in restrictions being imposed on the
foreign exchange activities of the relevant onshore company, including the payment of dividends and other distributions to its offshore
parent or affiliate, the capital inflow from the offshore entities and settlement of foreign exchange capital, and may also subject relevant
onshore company or PRC residents to penalties under PRC foreign exchange administration regulations.
In February 2012, the SAFE promulgated the Notices on Issues Concerning the Foreign Exchange Administration for Domestic
Individuals Participating in Stock Incentive Plans of Overseas Publicly Listed Companies. Based on this regulation, directors,
supervisors, senior management and other employees of domestic subsidiaries or branches of a company listed on an overseas stock
market who are PRC citizens or who are non-PRC citizens residing in China for a continuous period of not less than one year, subject
to a few exceptions, are required to register with the SAFE or its local counterparts by following certain procedures if they participate
in any stock incentive plan of the company listed on an overseas stock market. Foreign exchange income received from the sale of shares
or dividends distributed by the overseas listed company may be remitted into a foreign currency account of such PRC citizen or be
exchanged into renminbi. Our PRC citizen employees who have been granted share options have been subject to these rules due to our
admission to trading on the AIM market of the London Stock Exchange and the listing of our ADSs on Nasdaq.
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Regulation on Investment in Foreign-invested Enterprises
Pursuant to PRC law, the registered capital of a limited liability company is the total capital contributions subscribed for by all the
shareholders as registered with the company registration authority. A foreign-invested enterprise also has a total investment limit that is
approved by or filed with the MOFCOM or its local counterpart by reference to both its registered capital and expected investment scale.
The difference between the total investment limit and the registered capital of a foreign-invested enterprise or the cross-border financing
risk weighted balance calculated based on a formula by the PBOC represents the foreign debt financing quota to which it is entitled
(i.e., the maximum amount of debt which the company may borrow from a foreign lender). A foreign-invested enterprise is required to
obtain approval from or file with the MOFCOM or its local counterpart for any increases to its total investment limit. In accordance
with these regulations, we and our joint venture partners have contributed financing to our PRC subsidiaries and joint ventures in the
form of capital contributions up to the registered capital amount and/or in the form of shareholder loans up to the foreign debt quota.
According to the financing needs of our PRC subsidiaries and joint ventures, we and our joint venture partners have requested and
received approvals from the government authorities for increases to the total investment limit for certain of our PRC subsidiaries and
joint ventures from time to time. As a result, these regulations have not had a material impact to date on our ability to finance such
entities.
Regulation on Dividend Distribution
The principal regulations governing distribution of dividends paid by wholly foreign-owned enterprises include:
• Company Law of the PRC (1993), as amended in 1999, 2004, 2005, 2013 and 2018;
• Foreign Investment Law of the PRC; and
•
Implementation Rules for the Foreign Investment Law.
• Under these laws and regulations, foreign-invested enterprises in China may pay dividends only out of their accumulated
profits, if any, determined in accordance with PRC accounting standards and regulations. In addition, a wholly foreign-owned
enterprise in China is required to set aside at least 10.0% of its after-tax profit based on PRC accounting standards each year to
its general reserves until the accumulative amount of such reserves reach 50.0% of its registered capital. These reserves are not
distributable as cash dividends. The board of directors of a foreign-invested enterprise has the discretion to allocate a portion
of its after-tax profits to staff welfare and bonus funds, which may not be distributed to equity owners except in the event of
liquidation.
Filings and Approvals Relating to State-Owned Assets
Pursuant to applicable PRC state-owned assets administration laws and regulations, incorporating a joint venture that will have
investments of assets that are both state-owned and non-state-owned and investing in an entity that was previously owned by a
state-owned enterprise require the performance of an assessment of the relevant state-owned assets and the filing of the assessment
results with the competent state-owned assets administration, finance authorities or other regulatory authorities and, if applicable, the
receipt of approvals from such authorities.
Our joint venture partners were required to perform a state-owned asset assessment when Shanghai Hutchison Pharmaceuticals and
Hutchison Baiyunshan were incorporated and our joint venture partners contributed state-owned assets, and when we invested in
Hutchison Sinopharm, which was previously wholly-owned by Sinopharm, a state-owned enterprise. In all three instances, our joint
venture partners have informed us that they have duly filed the relevant state-owned asset assessment results with, and obtained the
requisite approvals from, the relevant governmental authorities as required by the foregoing laws and regulations. Accordingly, we
believe that such joint ventures are in full compliance with all applicable laws and regulations governing the administration of
state-owned assets, although we are currently unable to obtain copies of certain filing and approval documents of our joint venture
partners due to their internal confidentiality constraints. We have not received any notice of warning or been subject to any penalty or
other disciplinary action from the relevant governmental authorities with respect to the applicable laws and regulations governing the
administration of state-owned assets.
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C. Organizational Structure
The chart below shows our organizational structure, including our principal subsidiaries and joint ventures, as of March 1, 2021.
Notes:
(1) Employees and former employees of Hutchison MediPharma Limited hold the remaining 0.2% shareholding in Hutchison
MediPharma Holdings Limited.
(2) Held through Hutchison MediPharma (HK) Investment Limited, a 100.0% subsidiary of Hutchison MediPharma Holdings Limited.
Hutchison MediPharma Limited’s revenue generated by sales of, and royalties, manufacturing costs and services fees paid in
connection with, our current and future internally developed drug candidates are allocated to the Oncology/Immunology operations.
(3) Our Other Ventures also include: (i) Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited (in which
the Company holds 50.0% through our 80.0% owned subsidiary Hutchison BYS (Guangzhou) Holding Limited), a non-consolidated
joint venture with Guangzhou Baiyunshan Pharmaceutical Holdings Co. Limited which holds the other 50.0%, and (ii) Hutchison
Hain Organic Holdings Limited, a consolidated joint venture with The Hain Celestial Group, Inc., which wholly-owns Hutchison
Hain Organic (Hong Kong) Limited and Hutchison Hain Organic (Guangzhou) Limited.
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(4) Held through our 100.0% subsidiary Shanghai Hutchison Chinese Medicine (HK) Investment Limited. Shanghai Pharmaceuticals
Holding Co., Limited is the other 50.0% joint venture partner.
(5) Sinopharm Group Co. Limited is the other 49.0% joint venture partner.
D. Property, Plants and Equipment
We are headquartered in Hong Kong where we have our main administrative offices. Our joint ventures, Shanghai Hutchison
Pharmaceuticals and Hutchison Baiyunshan, operate two large-scale research and development and manufacturing facilities for which
they have obtained land use rights and property ownership certificates.
Shanghai Hutchison Pharmaceuticals has a 78,000 square meter facility outside of Shanghai.
Hutchison Baiyunshan’s facilities are in Guangzhou on a 59,000 square meter site and Bozhou on a 230,000 square meter site. In
2020, Hutchison Baiyunshan surrendered for deregistration its land use rights for an unused portion of its Guangzhou property to the
local government for cash consideration. Hutchison Baiyunshan also operates cultivation sites through its subsidiary in Heilongjiang
province in China.
Our and our joint ventures’ manufacturing operations consist of bulk manufacturing and formulation, fill, and finishing activities
that produce products and drug candidates for both clinical and commercial purposes. Our manufacturing capabilities have a large
operation scale for our own-brand products. We and our joint ventures manufacture and sell about 4.9 billion doses of medicines a year,
in the aggregate, through our well-established manufacturing base. See “—Other Ventures—Shanghai Hutchison Pharmaceuticals” and
“—Other Ventures—Hutchison Baiyunshan” for more details on our manufacturing operations.
Please also see “—Other Ventures—Shanghai Hutchison Pharmaceuticals” and “—Other Ventures—Hutchison Baiyunshan” for
more details on the new facilities of Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan mentioned above.
Additionally, we rent and operate a 2,107 square meter GMP-certified manufacturing facility for fruquintinib and surufatinib in
Suzhou, Jiangsu Province in Eastern China, and own a 5,024 square meter facility in Shanghai which houses research and development
operations. We lease 7,036 square meters of office space in Shanghai which houses Hutchison MediPharma’s management and staff.
In 2020, we entered into a 50-year land use rights agreement for a 28,771 square meter site in Shanghai. We have commenced
construction of a new almost 55,000 square meter large-scale manufacturing facility for innovative drugs on the site.
We also lease a 26,989 square foot facility in Florham Park, New Jersey where we house our U.S.-based clinical, regulatory and
commercial management and staff.
ITEM 4A. UNRESOLVED STAFF COMMENTS
None
ITEM 5. OPERATING AND FINANCIAL REVIEW AND PROSPECTS
You should read the following discussion and analysis of our financial condition and results of operations together with Item 3.A.
“Selected Financial Data,” our consolidated financial statements and the related notes and our non-consolidated joint ventures’
consolidated financial statements and the related notes appearing elsewhere in this annual report. This report contains forward-looking
statements within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the
Exchange Act, including, without limitation, statements regarding our expectations, beliefs, intentions or future strategies that are
signified by the words “expect,” “anticipate,” “intend,” “believe,” or similar language. All forward-looking statements included in
this annual report are based on information available to us on the date hereof, and we assume no obligation to update any such forward-
looking statements. In evaluating our business, you should carefully consider the information provided under Item 3.D. “Risk Factors.”
Actual results could differ materially from those projected in the forward-looking statements.
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A. Operating Results.
Overview
We are a global commercial-stage biopharmaceutical company focused on the discovery, development and commercialization of
targeted therapies and immunotherapies for the treatment of patients with cancer and immunological diseases. We conduct our business
through our Oncology/Immunology and Other Ventures operations.
Through our Oncology/Immunology operations, our team of approximately 600 scientists and staff has created and developed a
deep portfolio of ten drug candidates. In China, we have brought two of our internally developed drugs, fruquintinib (Elunate) and
surufatinib (Sulanda), to patients, and we have filed for marketing authorization for a third, savolitinib. All three drugs are also in late-
stage development outside of China, with the most advanced being surufatinib for which we are filing a rolling NDA in the United
States. We have six additional drug candidates in earlier stage clinical development and several advanced preclinical drug candidates.
These drug candidates are being developed to treat a wide spectrum of diseases, including solid tumors, hematological malignancies
and immunological diseases which we believe may address significant unmet medical needs and represent large commercial
opportunities. Our success in research and development has led to partnerships with leading global pharmaceutical companies, including
AstraZeneca and Eli Lilly. We and our collaboration partners have invested over $970 million in our Oncology/Immunology operations
as of December 31, 2020, with almost all of these funds used for research and development expenses for the development of our drug
candidates. Net loss attributable to our company from our Oncology/Immunology operations was $102.4 million, $127.4 million and
$175.5 million for the years ended December 31, 2018, 2019 and 2020, respectively.
In addition, we have built large-scale and profitable drug marketing and distribution platforms through the joint ventures and
subsidiaries in our Other Ventures, which primarily manufacture, market and distribute prescription drugs and consumer health products
in China. Net income attributable to our company generated from our Other Ventures was $41.4 million, $41.5 million and $72.8 million
for the years ended December 31, 2018, 2019 and 2020, respectively. In addition to helping to fund our Oncology/Immunology
operations, we anticipate that we will be able to utilize the know-how from our Other Ventures to support the launch of our internally
developed Oncology/Immunology products in China. Our Other Ventures also include our businesses focused on consumer health
products, which is a profitable and cash flow generating business selling primarily over-the-counter pharmaceutical products (through
our non-consolidated joint venture Hutchison Baiyunshan) and a range of health-focused consumer products.
Our consolidated revenue was $214.1 million, $204.9 million and $228.0 million for the years ended December 31, 2018, 2019 and
2020, respectively. Net loss attributable to our company was $74.8 million, $106.0 million and $125.7 million for the years ended
December 31, 2018, 2019 and 2020, respectively.
Basis of Presentation
Our consolidated statements of operations data presented herein for the years ended December 31, 2020, 2019 and 2018 and our
consolidated balance sheet data presented herein as of December 31, 2020 and 2019 have been derived from our audited consolidated
financial statements, which were prepared in accordance with U.S. GAAP, and should be read in conjunction with those statements
which are included elsewhere in this annual report.
As a consequence of our recent commercialization of both Elunate and Sulanda and the possible approval and launch of savolitinib,
we have changed the manner in which we report results in our financial statements. Effective from the year ended December 31, 2020,
we will report two segments, (1) Oncology/Immunology, covering all activities related to oncology/immunology including sales,
marketing, manufacturing and research and development with respect to our drugs and drug candidates; and (2) Other Ventures, which
includes all other Hutchmed businesses. We have retrospectively revised prior period information to conform to current period
presentation in the financial information contained in this annual report.
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Our Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan joint ventures under our Other Ventures operations and our
Nutrition Science Partners joint venture under our Oncology/Immunology operations (until December 9, 2019 when it was purchased
by us and became our consolidated subsidiary) are accounted for under the equity accounting method as non-consolidated entities in our
consolidated financial statements, and their consolidated financial statements were prepared in accordance with IFRS as issued by the
IASB and audited under auditing standards generally accepted in the U.S. and included elsewhere in this annual report. We have two
strategic business units, Oncology/Immunology and Other Ventures, that offer different products and services. The presentation of
financial data for our business units excludes certain unallocated costs attributed to expenses incurred by our corporate head office. For
more information on our corporate structure, see Item 4.A. “History and Development of the Company.”
Research and Development Expenses
Factors Affecting our Results of Operations
We believe our ability to successfully develop innovative drug candidates through our Oncology/Immunology operations will be
the primary factor affecting our long-term competitiveness, as well as our future growth and development. Creating high quality global
first-in-class or best-in-class drug candidates requires significant investment of resources over a prolonged period of time, and a core
part of our strategy is to continue making sustained investments in this area. As a result of this commitment, our pipeline of drug
candidates has been steadily advancing and expanding, six of which are in global clinical development. For more information on the
nature of the efforts and steps necessary to develop our drug candidates, see Item 4.B. “Business Overview—Our Clinical Pipeline” and
“Business Overview—Regulation.”
The drug candidates of our Oncology/Immunology operations are still in development, and we have incurred and will continue to
incur significant research and development costs for pre-clinical studies and clinical trials. We expect that our research and development
expenses will significantly increase in future periods in line with the advancement and expansion of the development of our drug
candidates.
Oncology/Immunology expenses include:
•
•
•
•
•
employee compensation related expenses, including salaries, benefits and equity compensation expense;
expenses incurred for payments to CROs, investigators and clinical trial sites that conduct our clinical studies;
the cost of acquiring, developing, and manufacturing clinical study materials;
facilities, depreciation, and other expenses, which include office leases and other overhead expenses; and
costs associated with pre-clinical activities and regulatory operations.
Research and development costs incurred by our Oncology/Immunology operations totaled $114.2 million, $138.2 million and
$174.8 million for the years ended December 31, 2018, 2019 and 2020, respectively, representing approximately 53.3%, 67.4% and
76.7% of our total consolidated revenue for the respective period. These figures do not include payments made by our collaboration
partners directly to third parties to help fund the research and development of our drug candidates.
We have historically been able to fund the research and development expenses for our Oncology/Immunology operations via a
range of sources, including payments received from our collaboration partners, cash flows generated from and dividend payments from
our Other Ventures, the proceeds raised from our initial public offering on the AIM market of the London Stock Exchange, our initial
public offering and follow-on offerings on Nasdaq, investments from other third parties and bank borrowings.
This diversified approach to funding allows us to not depend on any one method of funding for our research and development
activities, thereby reducing the risk that sufficient financing will be unavailable as we continue to accelerate the development of our
drug candidates.
For more information on the research and development expenses incurred for the development of our drug candidates, see “—Key
Components of Results of Operations—Cost of Revenues and Operating Expenses—Research and Development Expenses.”
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Our Ability to Commercialize Our Drug Candidates
Our ability to generate revenue from our drug candidates depends on our ability to successfully complete clinical trials for our drug
candidates and obtain regulatory approvals for them in the United States, Europe, China and other major markets.
We believe that our risk-balanced strategy of focusing on drug development for novel but relatively well-characterized targets and
for validated targets, in combination with our development of multiple drug candidates concurrently and testing them for multiple
indications and in combinations with other drugs, enhances the likelihood that our research and development efforts will yield successful
drug candidates. Nonetheless, we cannot be certain if any of our drug candidates will receive regulatory approvals. Even if such
approvals are granted, we will need to thereafter establish manufacturing supply and engage in extensive marketing prior to generating
any revenue from such drugs. The effectiveness of our marketing will depend on the efforts of our dedicated oncology team in China
and the United States, the latter of which we are currently in the process of setting up. The ultimate commercial success of our drugs
will depend on their acceptance by patients, the medical community and third-party payors and their ability to compete effectively with
other therapies on the market.
To date, fruquintinib and surufatinib have been approved for sale. We have incurred a total of approximately $13.5 million in capital
expenditures between 2013 and 2020 to establish a standard manufacturing (formulation) facility in Suzhou, China, which now produces
commercial supplies of Elunate (the brand name for fruquintinib ) and Sulanda (the brand name for surufatinib). Beginning in October
2020, we assumed responsibility for the development and execution of all on-the-ground medical detailing, promotion and local and
regional marketing activities in China for Elunate. Surufatinib is marketed by us without the support of a collaboration partner. However,
we have a limited history of successfully commercializing our internally developed drug candidates, which makes it difficult to evaluate
our future prospects.
The competitive environment is also an important factor with the commercial success of our potential global first-in-class products,
such as savolitinib and HMPL-523, depending on whether we are able to gain regulatory approvals and quickly bring such products to
market ahead of competing drug candidates being developed by other companies.
For our drug candidates where we retain all rights worldwide, which currently include surufatinib, HMPL-523, HMPL-689, epitinib,
HMPL-453 and HMPL-306, if they remain unpartnered, we will be able to retain all the profits if any of them are successfully
commercialized, though we will need to bear all the costs associated with such drug candidates. Conversely, as discussed below, for our
drug candidates which are subject to collaboration partnerships, our collaboration partners provide funding for development of the drug
candidates but are entitled to retain a significant portion of any revenue generated by such drug candidates.
Our Collaboration Partnerships
Our results of operations have been, and we expect them to continue to be, affected by our collaborations with third parties for the
development and commercialization of certain of our drug candidates. Currently, these include savolitinib (collaboration with
AstraZeneca) and fruquintinib (collaboration with Eli Lilly). In addition to providing us with clinical and regulatory support, the
payments received from these collaborations have been critical to our ability to develop and quickly advance the pre-clinical and clinical
studies of multiple drug candidates concurrently.
In particular, our partners cover a portion of our research and development costs for drug candidates developed in collaboration
with them. For example, under our collaboration agreement with AstraZeneca, it is responsible for a significant portion of the
development costs for savolitinib. However, in August 2016 and December 2020, we and AstraZeneca amended our collaboration
agreement whereby we agreed to contribute additional funding for the research and development of savolitinib in return for a larger
share of the upside if and when savolitinib is approved. Under our original collaboration agreement with Eli Lilly, it was responsible for
a significant portion of all fruquintinib development costs in China. Under the terms of our December 2018 amendment to this
agreement, we are responsible for all development costs for fruquintinib in new life cycle indications. In July 2020, we amended our
collaboration with Eli Lilly to assume responsibility for all on-the-ground medical detailing, promotion and local and regional marketing
activities in China for Elunate, thereby expanding its potential economic value to our company.
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In addition, under our licensing, co-development and commercialization agreements with AstraZeneca and Eli Lilly, we received
upfront payments upon our entry into such agreements and milestone payments upon the achievement of certain development, regulatory
and commercial milestones payments for our provision of research and development services for the relevant drug candidate as well as
royalties and revenue from products sales of Elunate which we manufacture and sell to Eli Lilly at cost. Revenue recognized in our
consolidated financial statements from such agreements with AstraZeneca and Eli Lilly totaled $33.4 million, $26.3 million and $29.7
million for the years ended December 31, 2018, 2019 and 2020, respectively.
The achievement of milestones for our drug candidates, which is dependent on the outcome of clinical studies, is subject to a high
degree of uncertainty and, as a result, we cannot reasonably estimate when we can expect to receive future milestone payments, or at
all. For more information on our revenue recognition policies, see “—Critical Accounting Policies and Significant Judgments and
Estimates—Revenue recognition— Oncology/Immunology.” If we are unable to achieve development milestones for our drug
candidates or if our partners were to terminate their collaborative agreements with us, payments for research and development services
could also be affected.
AstraZeneca and Eli Lilly are entitled to a significant proportion of any future revenue from commercialization of our drug
candidates developed in collaboration with them, as well as a degree of influence over the clinical development process for such drug
candidates. For more information regarding our collaboration agreements, see Item 4.B. “Business Overview—Overview of Our
Collaborations.”
China Government Insurance Reimbursement and Drug Pricing Policies
Our revenue is affected by the sales volume and pricing of our current and future internally developed drug candidates, if approved.
Eligible participants in the government-sponsored medical insurance programs in China are entitled to reimbursement for varying
percentages of the cost for any medicines that are included in applicable reimbursement lists. Factors that affect the inclusion of
medicines in China’s NRDL and any other applicable reimbursement list may include whether the medicine is consumed in large
volumes and commonly prescribed for clinical use in China and whether it is considered to be important in meeting the basic healthcare
needs of the general public. For more information, see Item 4.B. “Business Overview—Coverage and Reimbursement—PRC Coverage
and Reimbursement.” The inclusion of a medicine in the NRDL or other applicable reimbursement lists can substantially improve the
sales volume of the medicine due to the availability of third-party reimbursements; while, on the other hand, subjects it to price controls
in the form of fixed retail prices or retail price ceilings, as well as periodical price adjustments by the regulatory authorities. Such price
controls, especially downward price adjustments, may negatively affect the retail price of our drug candidates. On balance, we believe
that, if priced appropriately, the benefit of the inclusion of our drug candidates in the NRDL and other applicable reimbursement lists
outweighs the cost of such inclusion. Starting on January 1, 2020, Elunate was included on China’s NRDL at a 63% discount to its initial
retail price, paving the way to significantly broaden access for advanced CRC patients and rapidly build penetration in China in the
coming years.
Revenue from our Other Ventures, including the revenue of our non-consolidated joint ventures Shanghai Hutchison
Pharmaceuticals and Hutchison Baiyunshan, is affected by the sales volume and pricing of their own-brand prescription and over-the-
counter pharmaceutical products as well as third-party pharmaceutical products. The sales volume of the products sold by these
businesses is driven in part by the level of Chinese government spending on healthcare and the coverage of Chinese government medical
insurance schemes, which is correlated with patient reimbursements for drug purchases, all of which have increased significantly in
recent years as part of healthcare reforms in China. The sales volume of pharmaceutical products in China is also influenced by their
representation on the NRDL, which determines eligibility for drug reimbursement, as well as their representation on the National
Essential Medicines List, which mandates distribution of drugs in China. Substantially all pharmaceutical products manufactured and
sold by Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan in 2020 were capable of being reimbursed under the NRDL as
of December 31, 2020. In addition, among these two joint ventures an aggregate of 46 drugs, of which nine were in active production
as of December 31, 2020, have been included on the National Essential Medicines List. She Xiang Bao Xin pills, Shanghai Hutchison
Pharmaceuticals’ top-selling drug, is one of the few proprietary drugs included on the National Essential Medicines List.
The NRDL and the National Essential Medicines List are subject to revision by the government from time to time, and our results
could be materially and adversely affected if any of our products are removed from the NRDL or the National Essential Medicines List.
For more information, see Item 3.D. “Risk Factors—Risks Relating to Other Ventures and Sales of Our Commercial-stage Drug
Candidates—Reimbursement may not be available for the products currently sold through our Other Ventures operations or our drug
candidates in China, the United States or other countries, which could diminish our sales or affect our profitability.”
152
The sale prices of certain pharmaceutical products sold by the joint ventures in our Other Ventures are also subject to Chinese
government’s price controls. In April 2014, the China National Development and Reform Commission, or the NDRC, announced a new
LPDL, aimed at making certain low-price pharmaceuticals more profitable for manufacturers to produce. The LPDL established caps
for the daily cost of chemical pharmaceuticals at less than RMB3.0 ($0.46) per day and of traditional Chinese medicine pharmaceuticals
at less than RMB5.0 ($0.76) per day. The LPDL gives manufacturers flexibility to increase prices within the caps and exempts LPDL
pharmaceuticals from hospital tenders. As of the end of 2020, Hutchison Baiyunshan’s two top-selling products, Fu Fang Dan Shen
tablets and Banlangen, cost consumers RMB1.9 ($0.29) per day and RMB2.4 ($0.37) per day, respectively, and Shanghai Hutchison
Pharmaceuticals’ two top-selling products, She Xiang Bao Xin pills and Danning tablets, cost RMB3.6 ($0.55) per day and RMB4.3
($0.66) per day, respectively, each below the established caps for traditional Chinese medicine pharmaceuticals under the LPDL. As a
result, we do not expect the LPDL to exert downward pressure on the pricing of these products unless the government makes significant
downward adjustments to the LPDL price caps in the future.
Subject to customer demand, we have the ability to increase the prices for these products under the current LPDL price caps. For
example, during 2016 we began to phase in, on a province-by-province basis, a 30% price increase for She Xiang Bao Xin pills from
RMB2.7 ($0.41) per day to RMB3.5 ($0.53) per day. We further increased the price to RMB3.6 ($0.55) per day in 2020. In addition,
the pricing of Shanghai Hutchison Pharmaceuticals’ prescription drugs is influenced by the outcomes of periodic provincial and
municipal tender processes organized by the various provincial or municipal government agencies in China. For more information, see
Item “Business Overview—Coverage and Reimbursement—PRC Coverage and Reimbursement.”
Ability to Effectively Market Own Brand and Third Party Drugs
A key component of the operations of Other Ventures is the extensive prescription drugs marketing network operated by our joint
ventures Shanghai Hutchison Pharmaceuticals and Hutchison Sinopharm, which includes approximately 2,300 medical sales
representatives covering hospitals in about 320 cities and towns in China. Our results of operations are impacted by the effectiveness
of this network, including the ability of Shanghai Hutchison Pharmaceuticals to generate sales of She Xiang Bao Xin pills, which
represented approximately 85%, 88% and 90% of its total revenue for the years ended December 31, 2018, 2019 and 2020, respectively.
In addition, in recent years Hutchison Sinopharm has been increasingly focused on providing distribution and commercialization
services for prescription drugs licensed from third parties, and we are building an oncology sales and marketing team which we plan to
utilize for our internally developed drugs for which we have commercialization rights, if approved.
If the marketing efforts of these joint ventures to doctors and hospitals are not successful, our revenue and profitability may be
negatively affected. Moreover, if we are unsuccessful in marketing any third party drugs, it may adversely affect our ability to enter
into commercialization arrangements on acceptable terms, gain rights to market additional third-party drugs or prevent us from
expanding the geographic scope of existing arrangements.
Seasonality
The results of operations of our Other Ventures are also affected by seasonal factors. Our Other Ventures operations typically
experience higher profits in the first half of the year due to the sale cycles of our distributors, whereby they typically increase their
inventories at the beginning of each year. In addition, in the second half of each year, our Other Ventures operations typically spend
more on marketing activities to help reduce such inventory held by distributors. We do not experience material seasonal variations in
the results of our Oncology/Immunology operations.
Overall Economic Growth and Consumer Spending Patterns
The results of operations and growth of our Other Ventures, in particular for sales of consumer health products, depend in part on
continuing economic growth and increasing income and health awareness of consumers in Asia. Although economic growth in China
has slowed in recent periods, it achieved an annual growth rate in real gross domestic product of approximately 1.9% in 2020 according
to the International Monetary Fund. As per capita disposable income has increased, consumer spending has also increased, and
consumers in China have tended to be more health conscious and to spend more on organic and natural products for their families’
health and well-being. However, if customer demand for such products does not achieve the levels we expect, whether due to slowing
economic conditions, changing consumer tastes or otherwise, the results of operations and growth of our Other Ventures operations
could be materially and adversely affected.
153
Critical Accounting Policies and Significant Judgments and Estimates
Our discussion and analysis of operating results and financial condition are based upon our consolidated financial statements. The
preparation of consolidated financial statements requires us to estimate the effect of various matters that are inherently uncertain as of
the date of the consolidated financial statements. Each of these required estimates varies with regard to the level of judgment involved
and its potential impact on our reported financial results. Estimates are deemed critical when a different estimate could have reasonably
been used or where changes in the estimates are reasonably likely to occur from period to period, and a different estimate would
materially impact our financial position, changes in financial position or results of operations. Our significant accounting policies are
discussed under note 3 to our consolidated financial statements included in this annual report. We believe the following critical
accounting policies are affected by significant judgments and estimates used in the preparation of our consolidated financial statements
and that the judgments and estimates are reasonable.
Revenue recognition—Oncology/Immunology
Our Oncology/Immunology reportable segment principally generates revenue from license and collaboration contracts as well as
revenues related to the sale of drug products developed by our subsidiary Hutchison MediPharma. The license and collaboration
contracts generally contain multiple performance obligations including (1) the license to the commercialization rights of a drug
compound and (2) the research and development services for each specified treatment indication, which are accounted for separately if
they are distinct, i.e. if a product or service is separately identifiable from other items in the arrangement and if a customer can benefit
from it on its own or with other resources that are readily available to the customer.
The transaction price generally includes fixed and variable consideration in the form of upfront payment, research and development
cost reimbursements, contingent milestone payments and sales-based royalties. Contingent milestone payments are not included in the
transaction price until it becomes probable that a significant reversal of revenue will not occur, which is generally when the specified
milestone is achieved. The allocation of the transaction price to each performance obligation is based on the relative standalone selling
prices of each performance obligation determined at the inception of the contract. We estimate the standalone selling prices based on
the income approach.
Control of the license to the drug compounds transfers at the inception date of the collaboration agreements and consequently,
amounts allocated to this performance obligation are generally recognized at a point in time. Conversely, research and development
services for each specified indication are performed over time and amounts allocated to these performance obligations are generally
recognized over time using cost inputs as a measure of progress. We have determined that research and development expenses provide
an appropriate depiction of measure of progress for the research and development services. Changes to estimated cost inputs may result
in a cumulative catch-up adjustment. Royalty revenues are recognized as future sales occur as they meet the requirements for the sales-
usage based royalty exception.
Deferred revenue is recognized if allocated consideration is received in advance of the rendering of research and development
services. Accounts receivable is recognized based on the terms of the contract and when we have an unconditional right to bill the
customer, which is generally when research and development services are rendered.
Revenue recognition from the sales of goods and provision of services for drug products developed by our Oncology/Immunology
operations follows the revenue recognition policies in our Other Ventures operations below.
Revenue recognition — Other Ventures
Our Other Ventures reportable segment principally generates revenue from (1) sales of goods, which are the manufacture or
purchase and distribution of pharmaceutical products and other consumer health products and (2) provision of services, which are the
provision of sales, distribution and marketing services to pharmaceutical manufacturers. We evaluate whether we are the principal or
agent for these contracts. Where we obtain control of the goods for distribution, we are the principal (i.e. recognizes sales of goods on a
gross basis). Where we do not obtain control of the goods for distribution, we are the agent (i.e. recognizes provision of services on a
net basis). Control is primarily evidenced by taking physical possession and inventory risk of the goods.
154
Revenue from sales of goods is recognized when the customer takes possession of the goods. We have determined that this usually
occurs upon completed delivery of the goods to the customer site. The amount of revenue recognized is adjusted for expected sales
incentives as stipulated in the contract, which are generally issued to customers as direct discounts at the point of sale or indirectly in
the form of rebates. Sales incentives are estimated using the expected value method. Additionally, sales are generally made with a
limited right of return under certain conditions. Revenues are recorded net of provisions for sales discounts and returns.
Revenue from provision of services is recognized when the benefits of the services transfer to the customer over time, which is
based on the proportionate value of services rendered as determined under the terms of the relevant contract. Additionally, when the
amounts that can be invoiced correspond directly with the value to the customer for performance completed to date, we recognize
revenue from provision of services based on amounts that can be invoiced to the customer.
Share-based Compensation
We recognize share-based compensation expense on share options granted to employees and directors based on their estimated
grant date fair value using the polynomial model. Determining the fair value of share options requires the use of highly subjective
assumptions. This polynomial pricing model uses various inputs to measure fair value, including estimated market value of our
underlying ordinary shares at the grant date, contractual terms, estimated volatility, risk-free interest rates and expected dividend yields.
The assumptions in determining the fair value of share options are highly subjective and represent our best estimates, which involve
inherent uncertainties and the application of judgment. As a result, if factors change and different assumptions are used, our level of
share-based compensation could be materially different in the future.
We recognize share-based compensation expense in the consolidated statements of operations on a graded vesting basis over the
requisite service period, and account for forfeitures as they occur.
Impairment of Long-lived Assets
We evaluate the recoverability of long-lived assets in accordance with authoritative guidance on accounting for the impairment or
disposal of long-lived assets.
We evaluate long-lived assets for impairment whenever events or changes in circumstances indicate that the carrying value of these
assets may not be recoverable. Indicators that we consider in deciding when to perform an impairment review include significant under-
performance of a business or product line in relation to expectations, significant negative industry or economic trends, and significant
changes or planned changes in our use of the assets.
If indicators of impairment exist, the first step of the impairment test is performed to assess if the carrying value of the net assets
exceeds the undiscounted cash flows of the assets. If yes, the second step of the impairment test is performed in order to determine if
the carrying value of the net assets exceeds the fair value. If yes, impairment is recognized for the excess.
Impairment of Goodwill
Goodwill represents the excess of the purchase price plus fair value of non-controlling interests over the fair value of identifiable
assets and liabilities acquired. Goodwill is not amortized, but is tested for impairment at the reporting unit level on at least an annual
basis or when an event occurs or circumstances change that would more likely than not reduce the fair value of a reporting unit below
its carrying amount. When performing an evaluation of goodwill impairment, we have the option to first assess qualitative factors, such
as significant events and changes to expectations and activities that may have occurred since the last impairment evaluation, to determine
if it is more likely than not that goodwill might be impaired.
If as a result of the qualitative assessment, that it is more likely than not that the fair value of the reporting unit is less than its
carrying amount, the quantitative fair value test is performed to determine if the fair value of the reporting unit exceeds its carrying
value. If the carrying value of the net assets assigned to the reporting unit exceeds the fair value of the reporting unit, an impairment
loss shall be recognized in an amount equal to that excess, limited to the total amount of goodwill allocated to that reporting unit.
155
Our quantitative fair value test uses the income method to estimate a reporting unit's fair value. The income method is based on a
discounted future cash flow approach that uses the following assumptions and inputs: revenue, based on assumed growth rates; costs;
and discount rates based on a reporting unit's weighted average cost of capital as determined by considering the observable weighted
average cost of capital of comparable companies. Our estimates of revenue growth and costs are based on historical data, various internal
estimates, and a variety of external sources. These estimates are developed as part of our routine planning process. We test the
reasonableness of the inputs and outcomes of our discounted cash flow analysis against available comparable market data. A reporting
unit's carrying value represents the assignment of various assets and liabilities, excluding certain assets and liabilities, such as cash and
cash equivalents, short-term investments, and debt. We performed the goodwill impairment test and determined that the fair values of
the reporting units exceeded their carrying values and considered that impairment was not necessary for any reporting unit.
Impairment of Equity Method investments
Our equity method investments represent our investments in our non-consolidated joint ventures. All of these are in non-marketable
equity investments. Non-marketable equity investments are inherently risky, and their success depends on their ability to generate
revenues, remain profitable, operate efficiently and raise additional funds and other key business factors. The companies could fail or
not be able to raise additional funds when needed, or they may receive lower valuations with less favorable investment terms. These
events could cause our investments to become impaired. In addition, financial market volatility could negatively affect our ability to
realize value in our investments through liquidity events such as initial public offerings, mergers, and private sales.
We consider if our equity method investments are impaired when events or circumstances suggest that their carrying amounts may
not be recoverable. An impairment charge would be recognized in earnings for a decline in value that is determined to be other-than-
temporary. This is based on our quantitative and qualitative analysis, which includes assessing the severity and duration of the
impairment and the likelihood of recovery before disposal. The investments are recorded at fair value only if impairment is recognized.
The recognition of impairment and measurement of fair value requires significant judgment and includes a qualitative and quantitative
analysis of events or circumstances that impact the fair value of the investment. Qualitative analysis of our investments involves
understanding our investee's revenue and earnings trends relative to pre-defined milestones and overall business prospects, the
technological feasibility of our investee's products and technologies, the general market conditions in the investee's industry or
geographic area including adverse regulatory or economic changes, and the management and governance structure of the investee. We
did not identify any events or circumstances that would suggest that the carrying amount of each of our equity method investments may
not be recoverable and we consider impairment was not necessary.
Revenues
Key Components of Results of Operations
We derive our consolidated revenue primarily from (i) the sales of goods and services to Eli Lilly as well as royalties on in-market
sales of Elunate by Eli Lilly, (ii) licensing and collaboration projects conducted by our Oncology/Immunology operations, which
generate revenue in the form of upfront payments, milestone payments, payments received for providing research and development
services for our collaboration projects; and (iii) the sales of goods and services by our Other Ventures, which generate revenue from the
distribution and marketing of prescription pharmaceutical and consumer health products.
156
The following table sets forth the components of our consolidated revenue for the years indicated, which does not include the
revenue from our non-consolidated joint ventures which are included in our Other Ventures, Shanghai Hutchison Pharmaceuticals and
Hutchison Baiyunshan. Our revenues from research and development projects for related parties is attributable to income for research
and development services that we received primarily from Shanghai Hutchison Pharmaceuticals and Nutrition Science Partners, our
former non-consolidated joint venture with Nestlé Health Science. Our revenue from sales to related parties is attributable to sales by
our Other Ventures to indirect subsidiaries of CK Hutchison.
Revenues
Oncology/Immunology:
Goods—third parties
Services:
Collaboration R&D—third parties
Services—Commercialization—third parties
R&D services—related parties
Other collaboration revenue:
Royalties—third parties
Licensing—third parties
Subtotal
Other Ventures:
Goods—third parties
Goods—related parties
Services—third parties
Subtotal
Total
2020
Year Ended December 31,
2019
2018
$’000
%
$’000
%
$’000
%
11,329
9,771
3,734
491
4,890
—
30,215
192,277
5,484
—
197,761
227,976
5.0
4.3
1.7
0.2
2.1
—
13.3
84.3
2.4
—
86.7
100.0
8,113
4.0
3,324
15,532
—
494
7.6
—
0.2
2,653
—
26,792
1.3
—
13.1
17,681
—
7,832
261
12,135
41,233
167,877
7,637
2,584
178,098
204,890
81.9
3.7
1.3
86.9
100.0
152,910
8,306
11,660
172,876
214,109
1.5
8.3
—
3.7
0.1
5.7
19.3
71.4
3.9
5.4
80.7
100.0
Revenue from Oncology/Immunology primarily comprises revenue from Elunate in China. The revenue we generate from Elunate
is primarily comprised of revenue from the sales of Elunate to Eli Lilly which we manufacture and sell at cost, promotion and marketing
services to Eli Lilly and royalty revenue. Additionally, Oncology/Immunology revenue also comprises revenue recognized in our
consolidated financial statements under licensing, co-development and commercialization agreements for upfront, milestone and
research and development services payments for our drug candidates developed in collaboration with AstraZeneca and Eli Lilly.
Revenue from our Other Ventures primarily comprises revenue from prescription drugs including the commercial services, logistics
and distribution business of our consolidated Hutchison Sinopharm joint venture with Sinopharm, a leading distributor of pharmaceutical
and healthcare products and a leading supply chain service provider in China. Hutchison Sinopharm was historically a distributor of
AstraZeneca’s quetiapine tablets (under the Seroquel trademark) and recorded commercialization services revenue under a fee-for-
service model. However, in May 2019, our distribution of Seroquel was terminated.
Revenue from our Other Ventures also comprises revenue from sales of organic and natural products by Hutchison Hain Organic,
Zhi Ling Tong infant nutrition and other health supplement products manufactured by Hutchison Healthcare and distributed through
Hutchison Sinopharm, and certain third-party consumer products distributed and marketed by Hutchison Consumer Products.
The revenue of our non-consolidated joint venture, Shanghai Hutchison Pharmaceuticals, the accounts of which are prepared in
accordance with IFRS as issued by the IASB and whose revenue is not included in our consolidated revenue, was $275.7 million, $272.1
million and $276.4 million for the years ended December 31, 2018, 2019 and 2020, respectively. Shanghai Hutchison Pharmaceuticals
is a joint venture with Shanghai Pharmaceuticals, a leading pharmaceuticals company in China, and primarily focuses on the manufacture
and sale of prescription pharmaceutical products in China. We and Shanghai Pharmaceuticals each own 50% of this joint venture. We
have the right to nominate the general manager and other management of this joint venture and run its day-to-day operations. The effect
of Shanghai Hutchison Pharmaceuticals on our consolidated financial results is discussed below under “—Equity in Earnings of Equity
Investees.”
157
The revenue of our non-consolidated joint venture, Hutchison Baiyunshan, the accounts of which are prepared in accordance with
IFRS as issued by the IASB and whose revenue is not included in our consolidated revenue, was $215.8 million, $215.4 million and
$232.4 million for the years ended December 31, 2018, 2019 and 2020, respectively. Hutchison Baiyunshan is a joint venture with
Guangzhou Baiyunshan, a leading China-based pharmaceutical company, and primarily focuses on the manufacture and distribution of
over-the-counter pharmaceutical products in China. Our interest in Hutchison Baiyunshan is held through an 80%-owned subsidiary of
ours, Hutchison BYS (Guangzhou) Holding Limited, which owns 50% of that joint venture, with the other 50% interest held by
Guangzhou Baiyunshan. The effect of Hutchison Baiyunshan on our consolidated financial results is discussed under “—Equity in
Earnings of Equity Investees.”
Cost of Revenues and Operating Expenses
Cost of Revenues
Our cost of revenues are primarily attributable to the cost of revenues of Hutchison Sinopharm and Hutchison MediPharma. Our
cost of revenues to related parties is attributable to sales to indirect subsidiaries of CK Hutchison. The following table sets forth the
components of our cost of revenues attributable to third parties and related parties for the years indicated.
Cost of Revenues
Costs of goods—third parties
Costs of goods—related parties
Costs of services—third parties
Total
Research and Development Expenses
2020
Year Ended December 31,
2019
2018
$’000
%
$’000
%
$’000
%
178,828
3,671
6,020
188,519
94.9
1.9
3.2
100.0
152,729
5,494
1,929
160,152
95.4
3.4
1.2
100.0
129,346
5,978
8,620
143,944
89.9
4.2
5.9
100.0
Our research and development expenses are attributable to our Oncology/Immunology operations. These costs primarily comprise
the cost of research and development for our drug candidates, including clinical trial related costs such as payments to third-party CROs,
personnel compensation and related costs, and other research and development expenses. The following table sets forth the components
of our research and development expenses and the clinical trial related costs incurred for the development of our main drug candidates
for the years indicated.
R&D Expenses
Oncology/Immunology:
Savolitinib (targeting MET)
Fruquintinib (targeting VEGFR1/2/3)
Surufatinib (targeting VEGFR/FGFR1/CSF-1R)
Epitinib (targeting EGFRm+ with brain metastasis)
Theliatinib (targeting EGFR wild-type)
HMPL-523 (targeting Syk)
HMPL-689 (targeting PI3Kδ)
HMPL-453 (targeting FGFR)
HMPL-306 (targeting IDH 1/2)
Others and government grant
Total clinical trial related costs
Personnel compensation and related costs
Other research and development costs
Total
2020
%
$’000
Year Ended December 31,
2019
%
$’000
2018
%
$’000
5,341
28,254
32,106
808
(74)
7,422
7,383
1,356
5,389
17,884
105,869
63,542
5,365
174,776
3.1
16.2
18.4
0.5
—
4.2
4.2
0.8
3.1
10.1
60.6
36.3
3.1
100.0
14,630
19,488
23,809
(1,841)
138
18,338
5,938
1,948
—
5,329
87,777
46,246
4,167
138,190
10.6
14.1
17.2
(1.3)
0.1
13.3
4.3
1.4
—
3.8
63.5
33.5
3.0
11,749
17,423
20,996
3,448
1,399
7,562
2,113
2,082
2
6,919
73,693
35,340
5,128
100.0 114,161
10.3
15.3
18.4
3.0
1.2
6.6
1.8
1.8
—
6.1
64.5
31.0
4.5
100.0
158
The following table summarizes our research and development expenses by location for the years indicated.
PRC
U.S. and others
Total
2020
%
63.8
36.2
100.0
$’000
111,473
63,303
174,776
Year Ended December 31,
2019
%
$’000
116,479
21,711
138,190
$’000
84.3 109,584
4,577
15.7
100.0 114,161
2018
%
96.0
4.0
100.0
In addition to the research and development costs shown above, the table below summarizes the research and development costs
and impairment provision incurred by our former non-consolidated Nutrition Science Partners joint venture, primarily in relation to the
development of our drug candidate HMPL-004/HM004-6599. The losses incurred by this joint venture during the periods indicated
were reflected on our consolidated statements of operations in the equity in earnings of equity investees line item. Nutrition Science
Partners did not have any operating activities for the years ended December 31, 2019 and 2020. On December 9, 2019, we acquired the
remaining 50% shareholding in Nutrition Science Partners from our joint venture partner for approximately $8.1 million, representing
the cash balance at that time; and, therefore, Nutrition Science Partners has been included in our consolidated group since that date. The
consolidated financial statements of Nutrition Science Partners are prepared in accordance with IFRS as issued by the IASB and are
presented separately elsewhere in this annual report. For more information on this joint venture, see “—Equity in Earnings of Equity
Investees.”
Nutrition Science Partners
HMPL-004/HM004-6599 related development costs
Other costs
Other income
Impairment provision
Profit/(loss) for the period/year
Equity in earnings of equity investee attributable to our company
Period Ended December 9, Year Ended December 31,
2019
2018
$’000
%
$’000
%
—
(51)
250
—
199
100
—
(25.6)
125.6
—
100.0
50.0
(2,420)
(5,966)
188
(30,000)
(38,198)
(19,099)
6.4
15.6
(0.5)
78.5
100.0
50.0
We cannot determine with certainty the duration and completion costs of the current or future pre-clinical or clinical studies of our
drug candidates or if, when, or to what extent we will generate revenues from the commercialization and sale of any of our drug
candidates that obtain regulatory approval. We may never succeed in achieving regulatory approval for any of our drug candidates
currently under development. The duration, costs, and timing of clinical studies and development of our drug candidates will depend on
a variety of factors, including:
•
•
•
•
•
the scope, rate of progress and expense of our ongoing as well as any additional clinical studies and other research and
development activities;
future clinical study results;
uncertainties in clinical study enrollment rate;
significant and changing government regulation; and
the timing and receipt of any regulatory approvals.
A change in the outcome of any of these variables with respect to the development of a drug candidate could mean a significant
change in the costs and timing associated with the development of that drug candidate.
For more information on the risks associated with the development of our drug candidates, see Item 3.D. “Risk Factors—Risks
Relating to Our Oncology/Immunology Operations and Development of Our Drug Candidates—All of our drug candidates, other than
fruquintinib and surufatinib in China, are still in development. If we are unable to obtain regulatory approval and ultimately
commercialize our drug candidates, or if we experience significant delays in doing so, our business will be materially harmed.”
159
Selling Expenses
The following table sets forth the components of our selling expenses for the years indicated.
Selling Expenses
Oncology/Immunology
Other Ventures
Total
2020
%
$’000
Year Ended December 31,
2019
%
$’000
2018
%
$’000
237
11,097
11,334
2.1
97.9
100.0
—
13,724
13,724
—
100.0
100.0
—
17,736
17,736
—
100.0
100.0
Our selling expenses primarily comprise sales and marketing expenses and related personnel expenses incurred by our Other
Ventures in their distribution and marketing of pharmaceutical and consumer health products. It also includes selling expenses incurred
by our Oncology/Immunology operations by Hutchison MediPharma for sales of Elunate to third parties other than Eli Lilly.
Administrative Expenses
The following table sets forth the components of our administrative expenses for the years indicated.
Administrative expenses are also incurred by our corporate head office, which are not allocated to either Oncology/Immunology or
Other Ventures.
Administrative Expenses
Oncology/Immunology
Other Ventures
Corporate Head Office
Total
2020
Year Ended December 31,
2019
2018
$’000
%
$’000
%
$’000
%
19,144
6,129
24,742
50,015
38.3
12.3
49.4
100.0
12,189
5,292
21,729
39,210
31.1
13.5
55.4
100.0
9,662
4,564
16,683
30,909
31.3
14.7
54.0
100.0
Oncology/Immunology’s administrative expenses primarily comprise the salaries and benefits of administrative staff, office leases
and other overhead expenses incurred by Hutchison MediPharma.
Our Other Ventures’ administrative expenses primarily comprise the salaries and benefits of administrative staff, office leases and
other overhead expenses incurred by Hutchison Sinopharm, Hutchison Hain Organic and Hutchison Healthcare.
Our corporate head office administrative expenses primarily comprise the salaries and benefits of our corporate head office
employees and directors, office leases and other overhead expenses.
Equity in Earnings of Equity Investees
We have historically derived a significant portion of our net income from our equity in earnings of equity investees, which was
primarily attributable to two of our Other Ventures’ non-consolidated joint ventures, Shanghai Hutchison Pharmaceuticals and
Hutchison Baiyunshan, partially offset by losses at our former non-consolidated joint venture, Nutrition Science Partners. Our equity in
earnings of equity investees, net of tax, contributed by the non-consolidated joint ventures in our Other Ventures, Shanghai Hutchison
Pharmaceuticals and Hutchison Baiyunshan, was $38.3 million, $40.6 million and $79.1 million for the years ended December 31, 2018,
2019 and 2020, respectively. Equity in earnings of Hutchison Baiyunshan for the year ended December 31, 2020 included a one-time
gain of $36.0 million from land compensation for a return of land-use rights to the Guangzhou government.
160
Our equity in earnings of equity investees, net of tax, contributed by Oncology/Immunology was a loss of $19.0 million, income of
$0.1 million and a loss of $0.1 million for the years ended December 31, 2018, 2019 and 2020, respectively. The loss for the year ended
December 31, 2018 was primarily attributable to losses at Nutrition Science Partners, which had incurred research and development
expenses for the drug candidate HMPL-004/HM004-6599 and the full impairment provision of its $30.0 million intangible asset of
which our attributable portion was $15.0 million. On December 9, 2019, we acquired our joint venture partner’s 50% shareholding in
Nutrition Science Partners, after which Nutrition Science Partners became our consolidated subsidiary.
The following table shows the revenue of Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan for the years indicated.
Nutrition Science Partners did not have revenue for any of the years presented. The consolidated financial statements of these joint
ventures are prepared in accordance with IFRS as issued by the IASB and are presented separately elsewhere in this annual report.
Revenue
Other Ventures:
Shanghai Hutchison Pharmaceuticals
Hutchison Baiyunshan
Total
2020
Year Ended December 31,
2019
2018
$’000
%
$’000
%
$’000
%
276,354
232,368
508,722
54.3
45.7
100.0
272,082
215,403
487,485
55.8
44.2
100.0
275,649
215,838
491,487
56.1
43.9
100.0
The following table shows the amount of equity in earnings of equity investees, net of tax, of our non-consolidated joint ventures
for the years indicated.
Equity in earnings of equity investees, net of tax
Oncology/Immunology:
Nutrition Science Partners(1)
Others
Other Ventures:
Shanghai Hutchison Pharmaceuticals
Hutchison Baiyunshan(2)
Total
2020
%
$’000
Year Ended December 31,
2019
%
$’000
2018
%
$’000
—
(97)
—
(0.1)
100
47
0.3
0.1
(19,099)
118
(98.8)
0.6
33,502
45,641
79,046
42.4
57.7
100.0
30,654
9,899
40,700
75.3
24.3
100.0
29,884
8,430
19,333
154.6
43.6
100.0
(1) On December 9, 2019, we acquired our joint venture partner’s 50% shareholding in Nutrition Science Partners, after which Nutrition
Science Partners became our consolidated subsidiary.
(2) The amount for the year ended December 31, 2020 includes a one-time gain of $36.0 million from land compensation for a return
of land use rights to the Guangzhou government.
161
Results of Operations
The following table sets forth a summary of our consolidated results of operations for the years indicated, both in absolute amounts
and as percentages of our revenues. This information should be read together with our consolidated financial statements and related
notes included elsewhere in this annual report. Our operating results in any period are not necessarily indicative of the results that may
be expected for any future period.
2020
Year Ended December 31,
2019
2018
Revenues
Cost of revenues
Research and development expenses
Selling expenses
Administrative expenses
Other income
Income tax expense
Equity in earnings of equity investees, net of tax
Net loss
Net loss attributable to our company
Cayman Islands
Taxation
%
%
%
$’000
227,976
(188,519)
(174,776)
(11,334)
(50,015)
6,934
(4,829)
79,046
(115,517)
(125,730)
100.0
(82.7)
(76.7)
(5.0)
(21.9)
3.0
(2.1)
34.7
(50.7)
(55.2)
$’000
204,890
(160,152)
(138,190)
(13,724)
(39,210)
5,281
(3,274)
40,700
(103,679)
(106,024)
100.0
(78.2)
(67.4)
(6.7)
(19.1)
2.6
(1.6)
19.9
(50.6)
(51.7)
$’000
214,109
(143,944)
(114,161)
(17,736)
(30,909)
5,986
(3,964)
19,333
(71,286)
(74,805)
100.0
(67.2)
(53.3)
(8.3)
(14.4)
2.8
(1.9)
9.0
(33.3)
(34.9)
Hutchison China MediTech Limited is incorporated in the Cayman Islands. The Cayman Islands currently levies no taxes on profits,
income, gains or appreciation earned by individuals or corporations. In addition, our payment of dividends, if any, is not subject to
withholding tax in the Cayman Islands. For more information, see Item 10.E. “Taxation—Overview of Tax Implications of Various
Other Jurisdictions—Cayman Islands Taxation.”
People’s Republic of China
Our subsidiaries and joint ventures incorporated in the PRC are governed by the EIT Law and regulations. Under the EIT Law, the
standard EIT rate is 25% on taxable profits as reduced by available tax losses. Tax losses may be carried forward to offset any taxable
profits for the following five years (ten years for those with HNTE status, with effective from 1 January 2018). Hutchison MediPharma
and our non-consolidated joint ventures, Shanghai Hutchison Pharmaceutical and Hutchison Baiyunshan, have been successful in their
respective applications to renew their HNTE status for three years from January 1, 2020 to December 31, 2022. Accordingly, these
entities are eligible for a preferential EIT rate of 15% for the years ended December 31, 2020, 2021 and 2022. Hutchison MediPharma
(Suzhou) Limited, a wholly owned subsidiary of Hutchison MediPharma, was granted the HNTE status for three years from January 1,
2018 to December 31, 2020, and is preparing to apply to renew its status for another three years.
For more information, see Item 10.E. “Taxation—Taxation in the PRC.” Please also see Item. 3 “Key Information—Risk Factors—
Other Risks and Risks Relating to Doing Business in China—Our business benefits from certain PRC government tax incentives. The
expiration of, changes to, or our PRC subsidiaries/joint ventures failing to continuously meet the criteria for these incentives could have
a material adverse effect on our operating results by significantly increasing our tax expenses.”
Hong Kong
Hutchison China MediTech Limited and certain of its subsidiaries are subject to Hong Kong Profits Tax laws and regulations. Hong
Kong has a two-tiered Profits Tax rates regime under which the first HK$2.0 million ($0.3 million) of assessable profits of qualifying
corporations will be taxed at 8.25%, with the remaining assessable profits taxed at 16.5%. Hong Kong Profits Tax has been provided
for at the relevant rates on the estimated assessable profits less estimated available tax losses, if any, of these entities as applicable.
162
According to the EIT Law, dividends declared after January 1, 2008 and paid by PRC foreign-invested enterprises to their non-PRC
parent companies will be subject to PRC withholding tax at 10% unless there is a tax treaty between the PRC and the jurisdiction in
which the overseas parent company is a tax resident and which specifically exempts or reduces such withholding tax, and such tax
exemption or reduction is approved by the relevant PRC tax authorities. Pursuant to the Arrangement, if the shareholder of the PRC
enterprise is a Hong Kong tax resident and directly holds a 25% or more equity interest in the PRC enterprise and is considered to be
the beneficial owner of dividends paid by the PRC enterprise, such withholding tax rate may be lowered to 5%, subject to approvals by
the relevant PRC tax authorities. For more information, see Item 10.E. “Taxation—Taxation in the PRC” and “Taxation—Overview of
Tax Implications of Various Other Jurisdictions—Hong Kong Taxation.”
Year Ended December 31, 2020 Compared to Year Ended December 31, 2019
Revenues
Our revenue increased by 11.3% from $204.9 million for the year ended December 31, 2019 to $228.0 million for the year ended
December 31, 2020, which was caused by increased revenue from both Oncology/Immunology and Other Ventures operations.
Revenue from Oncology/Immunology increased by 12.8% from $26.8 million for the year ended December 31, 2019 to $30.2
million for the year ended December 31, 2020, primarily due to an increase in revenue related to the sale of Elunate from $10.8 million
for the year ended December 31, 2019 (of which $2.7 million was royalty revenue and $8.1 was revenue from sales to Eli Lilly) to $20.0
million for the year ended December 31, 2020 (of which $4.9 million was royalty revenue, $11.3 million was revenue from sales of
goods primarily to Eli Lilly and $3.8 million was revenue from promotion and marketing services to Eli Lilly which commenced in
October 2020) as a result of the inclusion of Elunate in the 2020 China NRDL. This increase was offset in part by a decrease in revenue
related to collaboration research and development services from $15.5 million for the year ended December 31, 2019 to $9.8 million for
the year ended December 31, 2020 as there was less clinical activity subject to reimbursement from our collaboration partners.
Revenue from our Other Ventures increased by 11.0% from $178.1 million for the year ended December 31, 2019 to $197.8 million
for the year ended December 31, 2020, primarily due to an increase in sales of prescription drug products. Revenue from sales of
prescription drugs increased by 14.9% from $143.7 million for the year ended December 31, 2019 to $165.1 million for the year ended
December 31, 2020 primarily due to increased sales by our consolidated joint venture Hutchison Sinopharm. This increase was offset
in part by a decrease in sales of consumer health products which decreased by 4.9% from $34.4 million for the year ended December
31, 2019 to $32.7 million for the year ended December 31, 2020. This decrease was primarily attributable to decreased sales of infant
nutrition products.
Our Other Ventures’ results of operations are affected by seasonality. For more information, see “—Factors Affecting our Results
of Operations—Other Ventures—Seasonality.”
Cost of Revenues
Our cost of revenues increased by 17.7% from $160.2 million for the year ended December 31, 2019 to $188.5 million for the year
ended December 31, 2020. This increase was primarily due to increased sales by our Other Ventures. Our cost of revenues increased at
a higher rate than revenue due to an increased proportion of sales of lower margin products by Hutchison Sinopharm. As a result, cost
of revenues as a percentage of our revenues increased from 78.2% to 82.7% across these periods.
Research and Development Expenses
Our research and development expenses incurred by Oncology/Immunology increased by 26.5% from $138.2 million for the year
ended December 31, 2019 to $174.8 million for the year ended December 31, 2020, which was primarily attributable to a $18.1 million
increase in payments to CROs and other clinical trial related costs and a $18.5 million increase in employee compensation related and
other costs. These increased costs were due to a significant expansion of clinical activities in the U.S. and rapid organizational growth
to support such expansion. In particular, this increase was attributable to the expansion of the fruquintinib, surufatinib, HMPL-306,
epitinib and HMPL-689 development programs. As a result, research and development expenses as a percentage of our revenue
increased from 67.4% to 76.7% across these periods.
163
Selling Expenses
Our selling expenses decreased by 17.4% from $13.7 million for the year ended December 31, 2019 to $11.3 million for the year
ended December 31, 2020, primarily due to decreased marketing activities after the COVID-19 outbreak. Selling expenses as a
percentage of our revenues from our Other Ventures decreased from 7.7% to 5.6% across these periods.
Administrative Expenses
Our administrative expenses increased by 27.6% from $39.2 million for the year ended December 31, 2019 to $50.0 million for the
year ended December 31, 2020. This was primarily due to $7.0 million increase in administrative expenses incurred by
Oncology/Immunology, which was mainly related to increased staff cost to support the expansion of our clinical activities. There was
also an increase of $3.0 million in administrative expenses incurred by our corporate head office for organizational expansion.
Administrative expenses as a percentage of our revenues increased from 19.1% to 21.9% across these periods.
Other Income
We had net other income of $5.3 million for the year ended December 31, 2019, compared to net other income of $6.9 million for
the year ended December 31, 2020. The increase was primarily due to foreign currency exchange gains of $3.0 million, offset in part
by a decline in interest income of $1.7 million due to lower bank deposit rates.
Income Tax Expense
Our income tax expense increased from $3.3 million for the year ended December 31, 2019 to $4.8 million for the year ended
December 31, 2020 primarily due to the accrual of withholding tax on the undistributed earnings in relation to the gain on return of land
by Hutchison Baiyunshan.
Equity in Earnings of Equity Investees
Our equity in earnings of equity investees, net of tax, increased by 94.2% from $40.7 million for the year ended December 31, 2019
to $79.0 million for the year ended December 31, 2020. This change was primarily due to the one-time gain on return of land recorded
by Hutchison Baiyunshan of which our attributable portion recorded to equity in earnings of equity investees was $36.0 million for the
year ended December 31, 2020.
Shanghai Hutchison Pharmaceuticals
The following table shows a summary of the results of operations of Shanghai Hutchison Pharmaceuticals for the years indicated.
The consolidated financial statements of Shanghai Hutchison Pharmaceuticals are prepared in accordance with IFRS as issued by the
IASB and are presented separately elsewhere in this annual report.
Revenue
Cost of sales
Selling expenses
Administrative expenses
Taxation charge
Profit for the year
Equity in earnings of equity investee attributable to our company
Year Ended December 31,
2020
2019
($’000)
276,354
(72,163)
(111,892)
(17,907)
(10,833)
67,020
33,502
%
100.0
(26.1)
(40.5)
(6.5)
(3.9)
24.3
12.1
($’000)
272,082
(77,313)
(110,591)
(14,761)
(11,015)
61,301
30,654
%
100.0
(28.4)
(40.6)
(5.4)
(4.0)
22.5
11.3
Shanghai Hutchison Pharmaceuticals’ revenue increased by 1.6% from $272.1 million for the year ended December 31, 2019 to
$276.4 million for the year ended December 31, 2020, primarily due to an increase in sales of She Xiang Bao Xin pills, a vasodilator
used in the treatment of heart conditions. Sales of She Xiang Bao Xin pills increased by 4.4% from $239.5 million for the year ended
December 31, 2019 to $250.0 million for the year ended December 31, 2020. Additionally, revenue from Shanghai Hutchison
Pharmaceutical’s distribution business decreased from $11.1 million for the year ended December 31, 2019 to $5.4 million for the year
ended December 31, 2020, primarily due to lower provision of services after the discontinuation of our distribution of Seroquel.
164
Cost of sales decreased by 6.7% from $77.3 million for the year ended December 31, 2019 to $72.2 million for the year ended
December 31, 2020, primarily due to the discontinuation of our distribution of Seroquel. Additionally, our revenue increased at a higher
rate than cost of sales due to an increased proportion of sales of higher margin She Xiang Bao Xin pills.
Selling expenses increased by 1.2% from $110.6 million for the year ended December 31, 2019 to $111.9 million for the year ended
December 31, 2020, in line with the increase in revenues.
Administrative expenses increased by 21.3% from $14.8 million for the year ended December 31, 2019 to $17.9 million for the
year ended December 31, 2020, primarily due to an increase in research and development expenses for new products.
Taxation charge decreased by 1.7% from $11.0 million for the year ended December 31, 2019 to $10.8 million for the year ended
December 31, 2020, primarily due to more tax concessions received in the year ended December 31, 2020.
As a result of the foregoing, profit increased by 9.3% from $61.3 million for the year ended December 31, 2019 to $67.0 million
for the year ended December 31, 2020. Our equity in earnings of equity investees contributed by this joint venture was $30.7 million
and $33.5 million for the years ended December 31, 2019 and 2020, respectively.
Hutchison Baiyunshan
The following table shows a summary of the results of operations of Hutchison Baiyunshan for the years indicated. The consolidated
financial statements of Hutchison Baiyunshan are prepared in accordance with IFRS as issued by the IASB and are presented separately
elsewhere in this annual report.
Revenue
Cost of sales
Selling expenses
Administrative expenses
Gain on return of land
Taxation charge
Profit attributable to equity holders of Hutchison Baiyunshan
Equity in earnings of equity investee attributable to our company
Year Ended December 31,
2020
2019
($’000)
232,368
(115,564)
(74,066)
(25,664)
84,667
(16,494)
91,276
45,641
%
100.0
(49.7)
(31.9)
(11.0)
36.4
(7.1)
39.3
19.6
($’000)
215,403
(100,279)
(74,013)
(23,817)
—
(3,634)
19,792
9,899
%
100.0
(46.6)
(34.4)
(11.1)
—
(1.7)
9.2
4.6
Hutchison Baiyunshan’s revenue increased by 7.9% from $215.4 million for the year ended December 31, 2019 to $232.4 million
for the year ended December 31, 2020, primarily due to an increase in sales of Banlangen, an anti-viral product, after the COVID-19
outbreak.
Cost of sales increased by 15.2% from $100.3 million for the year ended December 31, 2019 to $115.6 million for the year ended
December 31, 2020, primarily due to an increase in raw material costs for Banlangen.
Selling expenses remained stable at $74.0 million and $74.1 million for the years ended December 31, 2019 and 2020, respectively.
Administrative expenses increased by 7.8% from $23.8 million for the year ended December 31, 2019 to $25.7 million for the year
ended December 31, 2020, primarily due to an increase in general overhead costs incurred.
Taxation charge increased by 354% from $3.6 million for the year ended December 31, 2019 to $16.5 million for the year ended
December 31, 2020, primarily due to a tax of $12.7 million on a one-time gain on return of land for the year ended December 31, 2020.
As a result of the foregoing and the one-time gain on return of land of $84.7 million related to land compensation received from the
Guangzhou government, profit attributable to equity holders of Hutchison Baiyunshan increased by 361% from $19.8 million for the
year ended December 31, 2019 to $91.3 million for the year ended December 31, 2020. Our equity in earnings of equity investees
contributed by this joint venture was $9.9 million and $45.6 million for the years ended December 31, 2019 and 2020, respectively.
165
Nutrition Science Partners
Nutrition Science Partners became our consolidated subsidiary subsequent to December 9, 2019. The following table shows a
summary of the results of operations of Nutrition Science Partners for the period indicated during which it was a non-consolidated joint
venture. The consolidated financial statements of Nutrition Science Partners are prepared in accordance with IFRS as issued by the
IASB and are presented separately elsewhere in this annual report.
Revenue
Profit for the period
Equity in earnings of equity investee attributable to our company
Period Ended December 9, 2019
($’000)
%
—
199
100
—
100.0
50.0
Nutrition Science Partners had no revenues and a profit of $0.2 million for the period ended December 9, 2019. Our equity in
earnings of equity investees contributed by this joint venture was income of $0.1 million for the period ended December 9, 2019.
For more information on the financial results of our non-consolidated joint ventures, see “—Key Components of Results of
Operations— Equity in Earnings of Equity Investees.”
Net Loss
As a result of the foregoing, our net loss increased from $103.7 million for the year ended December 31, 2019 to $115.5 million for
the year ended December 31, 2020. Net loss attributable to our company increased from $106.0 million for the year ended December
31, 2019 to $125.7 million for the year ended December 31, 2020.
Year Ended December 31, 2019 Compared to Year Ended December 31, 2018
For a discussion of our results of operations for the year ended December 31, 2019 compared with the year ended December 31,
2018, see “Item 5. Operating and Financial Review and Prospects — A. Operating Results — Year Ended December 31, 2019 Compared
to Year Ended December 31, 2018” of our annual report on Form 20-F for the fiscal year ended December 31, 2019, filed with the SEC
on March 3, 2020.
B. Liquidity and Capital Resources.
To date, we have taken a multi-source approach to fund our operations, including through cash flows generated and dividend
payments from our Other Ventures, service and milestone and upfront payments from our Oncology/Immunology collaboration partners,
and bank borrowings. Since our founding, we have received various financial support from CK Hutchison in the form of undertakings
for bank borrowings, as well as investments from other third parties, proceeds from our listings on the AIM market of the London Stock
Exchange in 2006 and the Nasdaq Global Select Market in 2016 and our follow-on offerings in 2017 and 2020.
Our Oncology/Immunology operations have historically not generated significant profits or have operated at a net loss, as creating
potential global first-in-class or best-in-class drug candidates requires a significant investment of resources over a prolonged period of
time. As a result, we anticipate that we may need additional financing for our Oncology/Immunology operations in future periods. See
Item 3.D. “Risk Factors—Risks Relating to Our Oncology/Immunology Operations and Development of Our Drug Candidates—
Historically, our in house research and development division, known as our Oncology/Immunology operations, has not generated
significant profits or has operated at a net loss. Our future profitability is dependent on the successful commercialization of our drug
candidates.”
As of December 31, 2020, we had cash and cash equivalents and short-term investments of $435.2 million and unutilized bank
facilities of $69.4 million. Substantially all of our bank deposits are at major financial institutions, which we believe are of high credit
quality. As of December 31, 2020, we had $26.9 million in bank loans, all of which was related to a term loan from HSBC. The total
weighted average cost of bank borrowings for the year ended December 31, 2020 was 1.89% per annum. For additional information,
see “—Loan Facilities.”
166
Certain of our subsidiaries and non-consolidated joint ventures, including those registered as wholly foreign-owned enterprises in
China, are required to set aside at least 10.0% of their after-tax profits to their general reserves until such reserves reach 50.0% of their
registered capital. There is no fixed percentage of after-tax profit required to be set aside for the general reserves for our PRC joint
ventures. Profit appropriated to the reserve funds for our subsidiaries and non-consolidated joint ventures incorporated in the PRC was
approximately $15,000, $51,000 and $44,000 for the years ended December 31, 2018, 2019 and 2020, respectively. In addition, as a
result of PRC regulations restricting dividend distributions from such reserve funds and from a company’s registered capital, our PRC
subsidiaries are restricted in their ability to transfer a certain amount of their net assets to us as cash dividends, loans or advances. This
restricted portion amounted to $0.2 million as of December 31, 2020. Although we do not currently require any such dividends, loans
or advances from our PRC subsidiaries to fund our operations, should we require additional sources of liquidity in the future, such
restrictions may have a material adverse effect on our liquidity and capital resources. For more information, see Item 4.B. “Business
Overview—Regulation—PRC Regulation of Foreign Currency Exchange, Offshore Investment and State-Owned Assets—Regulation
on Investment in Foreign invested Enterprises—Regulation on Dividend Distribution.”
In addition, our non-consolidated joint ventures held an aggregate of $89.1 million in cash and cash equivalents and no bank
borrowings as of December 31, 2020. These cash and cash equivalents are only accessible by us through dividend payments from these
joint ventures. The level of dividends declared by these joint ventures is subject to agreement each year between us and our joint venture
partners based on the profitability and working capital needs of the joint ventures. As a result, we cannot guarantee that these joint
ventures will continue to pay dividends to us in the future at the same rate we have enjoyed in the past, or at all, which may have a
material adverse effect on our liquidity and capital resources. For more information, see Item 3.D. “Risk Factors—Risks Relating to
Other Ventures and Sales of Our Commercial-stage Drug Candidates—As a significant portion of the operations of our Other Ventures
is conducted through joint ventures, we are largely dependent on the success of our joint ventures and our receipt of dividends or other
payments from our joint ventures for cash to fund our operations.”
We believe that our current levels of cash and cash equivalents, short-term investments, along with cash flows from operations,
dividend payments and unutilized bank borrowings, will be sufficient to meet our anticipated cash needs for at least the next 12 months.
However, we may require additional financing in order to fund all of the clinical development efforts that we plan to undertake to
accelerate the development of our clinical-stage drug candidates. For more information, see Item 3.D. “Risk Factors—Risks Relating
to Our Financial Position and Need for Capital.”
Cash Flow Data:
Net cash used in operating activities
Net cash (used in)/generated from investing activities
Net cash generated from/(used in) financing activities
Net increase in cash and cash equivalents
Effect of exchange rate changes
Cash and cash equivalents at beginning of the year
Cash and cash equivalents at end of the year
Net Cash used in Operating Activities
Year Ended December 31,
2020
(62,066)
(125,441)
296,434
108,927
5,546
121,157
235,630
2019
($’000)
(80,912)
119,028
(1,493)
36,623
(1,502)
86,036
121,157
2018
(32,847)
43,752
(8,231)
2,674
(1,903)
85,265
86,036
Net cash used in operating activities was $80.9 million for the year ended December 31, 2019, compared to net cash used in
operating activities of $62.1 million for the year ended December 31, 2020. The net change of $18.8 million was primarily attributable
to an increase in dividends received from Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan of $58.6 million from $28.1
million for the year ended December 31, 2019 to $86.7 million for the year ended December 31, 2020. The net change was partially
offset by higher net losses, primarily due to an increase in research and development expenses of $36.6 million from $138.2 million for
the year ended December 31, 2019 to $174.8 million for the year ended December 31, 2020.
167
Net cash used in operating activities was $32.8 million for the year ended December 31, 2018, compared to net cash used in
operating activities of $80.9 million for the year ended December 31, 2019. The net change of $48.1 million was primarily attributable
to the increase in net loss of $32.4 million from $71.3 million for the year ended December 31, 2018, which included our company’s
$15.0 million share of Nutrition Science Partner’s non-cash impairment provision, to $103.7 million for the year ended December 31,
2019. Additionally, the net change was also a result of a decrease in dividends received from equity investees of $7.1 million from
$35.2 million for the year ended December 31, 2018 to $28.1 million for the year ended December 31, 2019. The net change was
partially offset by the effects of changes in working capital. In particular, there was a $26.0 million increase in other payables, accruals
and advance receipts for the year ended December 31, 2019, as compared to a $16.3 million increase for the year ended December 31,
2018.
Net Cash (used in)/generated from Investing Activities
Net cash generated from investing activities was $119.0 million for the year ended December 31, 2019, compared to net cash used
in investing activities of $125.4 million for the year ended December 31, 2020. The net change of $244.4 million was primarily
attributable to a net withdrawal of deposits in short-term investments of $118.9 million for the year ended December 31, 2019 compared
to a net deposit in short-term investments of $103.5 million for the year ended December 31, 2020. The net change was also attributable
to a purchase of leasehold land of $11.6 million in Shanghai.
Net cash generated from investing activities was $43.8 million for the year ended December 31, 2018, compared to net cash
generated from investing activities of $119.0 million for the year ended December 31, 2019. The net change of $75.2 million was
primarily attributable to net withdrawal of deposits in short-term investments of $58.1 million for the year ended December 31, 2018
compared to the net withdrawal of deposits in short-term investments of $118.9 million for the year ended December 31, 2019. The net
change was also attributable to the acquisition of 50% shareholding of Nutrition Science Partners held by our joint venture partner,
which resulted in a net cash inflow of $8.7 million.
Net Cash generated from/(used in) Financing Activities
Net cash used in financing activities was $1.5 million for the year ended December 31, 2019, compared to net cash generated from
financing activities of $296.4 million for the year ended December 31, 2020. The net change of $297.9 million was primarily attributable
to net proceeds of $310.0 million from our follow-on offering in the United States in January 2020 and private placements in July 2020
and November 2020.
Net cash used in financing activities was $8.2 million for the year ended December 31, 2018, compared to net cash used in financing
activities of $1.5 million for the year ended December 31, 2019. The net change of $6.7 million was primarily attributable to purchases
of ADSs by our company for the settlement of certain equity awards totaling $0.3 million for the year ended December 31, 2019 as
compared to $5.5 million for the year ended December 31, 2018, as well as the repayment of a $1.6 million loan to a non-controlling
shareholder of a subsidiary in the year ended December 31, 2018.
Loan Facilities
In November 2018, our subsidiary Hutchison China MediTech (HK) Limited, or HCM HK, renewed a three-year revolving loan
facility with HSBC. The facility amount of this loan is HK$234.0 million ($30.0 million) with an interest rate at the Hong Kong Inter-
bank Offered Rate, or HIBOR, plus 0.85% per annum. This credit facility is guaranteed by us and includes certain financial covenant
requirements. No amount was drawn from this loan facility as of December 31, 2020.
In August 2018, HCM HK entered into a credit facility agreement with each of Bank of America, N.A. and Deutsche Bank AG for
the provision of unsecured credit facilities in the aggregate amount of HK$507.0 million ($65.0 million). The credit facility with Bank
of America, N.A. is a HK$351.0 million ($45.0 million) revolving loan facility, with a term of 24 months and an interest rate at HIBOR
plus 1.35% per annum. The credit facility with Deutsche Bank AG is a HK$156.0 million ($20.0 million) revolving loan facility with
a term of 24 months and an interest rate at HIBOR plus 1.35% per annum. Each of these credit facilities expired in August 2020.
168
In February 2017, HCM HK entered into a credit facility agreement with each of Bank of America, N.A. and Deutsche Bank AG
for the provision of unsecured credit facilities in the aggregate amount of HK$546.0 million ($70.0 million). The credit facility with
Bank of America, N.A. included (i) a HK$156.0 million ($20.0 million) term loan facility and (ii) a HK$195.0 million ($25.0 million)
revolving loan facility, both with a term of 18 months and an interest rate at HIBOR plus 1.25% per annum. The term loan was drawn
from this credit facility in March 2017 and repaid and terminated in May 2018. The credit facility with Deutsche Bank AG included (i)
a HK$78.0 million ($10.0 million) term loan facility and (ii) a HK$117.0 million ($15.0 million) revolving loan facility, both with a
term of 18 months and an interest rate at HIBOR plus 1.25% per annum. The term loan was drawn from this credit facility in August
2017 and repaid and terminated in May 2018. Both revolving loan facilities were terminated in August 2018.
In November 2017, our subsidiary Hutchison China MediTech Finance Holdings Limited entered into facility agreements with
Scotiabank (Hong Kong) Limited for the provision of unsecured credit facilities in the aggregate amount of HK$400.0 million ($51.3
million). The credit facilities included (i) a HK$210.0 million ($26.9 million) 3-year term loan facility and (ii) a HK$190.0 million
($24.4 million) 18-month revolving loan facility. The term loan bore interest at HIBOR plus 1.50% per annum. The revolving loan
facility bore interest at HIBOR plus 1.25% per annum. These credit facilities were guaranteed by us and included certain financial
covenant requirements. The term loan was drawn in May 2018 and was fully repaid in June 2019. The revolving loan facility expired
in May 2019.
In May 2019, HCM HK entered into additional credit facility arrangements with HSBC for the provision of unsecured credit
facilities in the aggregate amount of HK$400.0 million ($51.3 million). The 3-year credit facilities include (i) a HK$210.0 million
($26.9 million) term loan facility and (ii) a HK$190.0 million ($24.4 million) revolving loan facility, both with an interest rate at HIBOR
plus 0.85% per annum. These credit facilities are guaranteed by us and include certain financial covenant requirements. In October
2019, we drew down HK$210.0 million ($26.9 million) from the term loan facility and as of December 31, 2020, no amount was drawn
from the revolving loan facility.
In August 2020, HCM HK entered into a 24-month revolving credit facility with Deutsche Bank AG in the amount of HK$117.0
million ($15.0 million) with an interest rate of HIBOR plus 4.5% per annum. This revolving facility is guaranteed by us and includes
certain financial covenant requirements. As of December 31, 2020, no amount was drawn from the revolving loan facility.
Our non-consolidated joint ventures Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan had no bank borrowings
outstanding as of December 31, 2020.
Capital Expenditures
We had capital expenditures of $6.4 million, $8.6 million and $19.6 million, for the years ended December 31, 2018, 2019 and
2020, respectively. Our capital expenditures during these periods were primarily used for the purchases of property, plant and equipment
to expand the Hutchison MediPharma research facilities and the manufacturing facility in Suzhou, China, and acquiring leasehold land
for a new large-scale manufacturing facility for innovative drugs in Shanghai, China. Our capital expenditures have been primarily
funded by cash flows from operations and proceeds from our initial public and follow-on offerings in the United States and other equity
offerings.
As of December 31, 2020, we had commitments for capital expenditures of approximately $5.1 million, primarily for the
construction of the new manufacturing facility in Shanghai. We expect to fund these capital expenditures through cash flows from
operations, bank borrowings and existing cash resources.
Our non-consolidated joint venture Shanghai Hutchison Pharmaceuticals had capital expenditures of $5.2 million, $4.6 million and
$2.4 million for the years ended December 31, 2018, 2019 and 2020, respectively. These capital expenditures were primarily related to
the improvements of the production facilities in Shanghai. These capital expenditures were primarily funded through cash flows from
operations of Shanghai Hutchison Pharmaceuticals.
Our non-consolidated joint venture Hutchison Baiyunshan had capital expenditures of $5.4 million, $3.4 million and $2.3 million
for the years ended December 31, 2018, 2019 and 2020, respectively. These capital expenditures were primarily related to the
construction and improvements of the production facilities in Guangzhou and Bozhou. These capital expenditures were primarily funded
through cash flows from operations of Hutchison Baiyunshan.
169
C. Research and Development, Patents and Licenses, etc.
Full details of our research and development activities and expenditures are given in the “Business” and “Operating and Financial
Review and Prospects” sections of this annual report above.
D. Trend Information.
Other than as described elsewhere in this annual report, we are not aware of any trends, uncertainties, demands, commitments or
events that are reasonably likely to have a material adverse effect on our revenue, income, profitability, liquidity or capital resources, or
that would cause our reported financial information not necessarily to be indicative of future operation results or financial condition.
E. Off-balance Sheet Arrangements.
We do not currently or during the periods presented have any material off-balance sheet arrangements as defined under the rules of
the SEC.
F. Tabular Disclosure of Contractual Obligations.
The following table sets forth our contractual obligations as of December 31, 2020. Our purchase obligations relate to property,
plant and equipment that are contracted for but not yet paid. Our lease obligations primarily comprise future aggregate minimum lease
payments in respect of various factories, warehouse, offices and other assets under non-cancellable lease agreements.
Bank borrowings
Interest on bank borrowings
Purchase obligations
Lease obligations
Total
Shanghai Hutchison Pharmaceuticals
Total
26,923
393
5,053
12,420
44,789
Payment Due by Period
Less Than
1 Year 1‑3 Years 3‑5 Years
($’000)
26,923
116
—
5,481
32,520
—
277
5,053
3,349
8,679
—
—
—
2,128
2,128
More Than
5 Years
—
—
—
1,462
1,462
The following table sets forth the contractual obligations of our non-consolidated joint venture Shanghai Hutchison Pharmaceuticals
as of December 31, 2020. Shanghai Hutchison Pharmaceuticals’ purchase obligations comprise capital commitments for property, plant
and equipment contracted for but not yet paid. Shanghai Hutchison Pharmaceuticals’ lease obligations primarily comprise future
aggregate minimum lease payments in respect of various offices under non-cancellable lease agreements.
Purchase obligations
Lease obligations
Total
Payment Due by Period
Less Than
1 Year
1‑3 Years 3‑5 Years
More Than
5 Years
902
135
1,037
($’000)
—
19
19
—
—
—
—
—
—
Total
902
154
1,056
170
Hutchison Baiyunshan
The following table sets forth the contractual obligations of our non-consolidated joint venture Hutchison Baiyunshan as of
December 31, 2020. Hutchison Baiyunshan’s purchase obligations comprise capital commitments for property, plant and equipment
contracted for but not yet paid. Hutchison Baiyunshan’s lease obligations primarily comprise future aggregate minimum lease payments
in respect of various warehouses under non-cancellable lease agreements.
Payment Due by Period
Less Than
1 Year 1‑3 Years 3‑5 Years
($’000)
1,633
598
2,231
—
307
307
—
—
—
Total
1,633
905
2,538
More Than
5 Years
—
—
—
Quantitative and Qualitative Disclosures About Market Risk
Purchase obligations
Lease obligations
Total
Foreign Exchange Risk
Most of our revenue and expenses are denominated in renminbi, and our consolidated financial statements are presented in U.S.
dollars. We do not believe that we currently have any significant direct foreign exchange risk and have not used any derivative financial
instruments to hedge our exposure to such risk. Although, in general, our exposure to foreign exchange risks should be limited, the
value of your investment in our ADSs will be affected by the exchange rate between the U.S. dollar and the renminbi because the value
of our business is effectively denominated in renminbi, while the ADSs will be traded in U.S. dollars.
The value of the renminbi against the U.S. dollar and other currencies may fluctuate and is affected by, among other things, changes
in China’s political and economic conditions. The conversion of renminbi into foreign currencies, including U.S. dollars, has been based
on rates set by the PBOC. On July 21, 2005, the PRC government changed its decade-old policy of pegging the value of the renminbi
to the U.S. dollar. Under the revised policy, the renminbi is permitted to fluctuate within a narrow and managed band against a basket
of certain foreign currencies. This change in policy resulted in a more than 20% appreciation of the renminbi against the U.S. dollar in
the following three years. Between July 2008 and June 2010, this appreciation halted, and the exchange rate between the renminbi and
U.S. dollar remained within a narrow band. In June 2010, the PBOC announced that the PRC government would increase the flexibility
of the exchange rate, and thereafter allowed the renminbi to appreciate slowly against the U.S. dollar within the narrow band fixed by
the PBOC. At various times since then, the PBOC has significantly devalued the renminbi against the U.S. dollar. If we decide to convert
renminbi into U.S. dollars for the purpose of making payments for dividends on our ordinary shares or ADSs or for other business
purposes, appreciation of the U.S. dollar against the renminbi would have a negative effect on the U.S. dollar amounts available to us.
Credit Risk
Substantially all of our bank deposits are in major financial institutions, which we believe are of high credit quality. We limit the
amount of credit exposure to any single financial institution. We make periodic assessments of the recoverability of trade and other
receivables and amounts due from related parties. Our historical experience in collection of receivables falls within the recorded
allowances, and we believe that we have made adequate provision for uncollectible receivables.
Interest Rate Risk
We have no significant interest-bearing assets except for bank deposits. Our exposure to changes in interest rates is mainly
attributable to our bank borrowings, which bear interest at floating interest rates and expose us to cash flow interest rate risk. We have
not used any interest rate swaps to hedge our exposure to interest rate risk. We have performed sensitivity analysis for the effects on
our results for the year from changes in interest rates on floating rate borrowings. The sensitivity to interest rates used is based on the
market forecasts available at the end of the reporting period and under the economic environments in which we operate, with other
variables held constant. According to the analysis, the impact on our net loss of a 1.0% interest rate shift would be a maximum
increase/decrease of $0.3 million for the year ended December 31, 2020.
171
Inflation
In recent years, China has not experienced significant inflation, and thus inflation has not had a material impact on our results of
operations. According to the National Bureau of Statistics of China, the Consumer Price Index in China increased by 1.9%, 4.5% and
0.2% in 2018, 2019 and 2020, respectively. Although we have not been materially affected by inflation in the past, we can provide no
assurance that we will not be affected in the future by higher rates of inflation in China.
See Note 3 to our consolidated financial statements included in this annual report for information regarding recent accounting
pronouncements.
Recent Accounting Pronouncements
ITEM 6. DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES
A. Directors and Senior Management.
Below is a list of the names and ages of our directors and officers as of March 1, 2021, and a brief account of the business experience
of each of them. The business address for our directors and officers is c/o Hutchison China MediTech Limited, Level 18, The Metropolis
Tower, 10 Metropolis Drive, Hunghom, Kowloon, Hong Kong.
Name
Simon To
Christian Hogg
Johnny Cheng
Weiguo Su, Ph.D.
Dan Eldar, Ph.D.
Edith Shih
Paul Carter
Karen Ferrante, M.D.
Graeme Jack
Tony Mok, M.D.
May Wang, Ph.D.
Zhenping Wu, Ph.D.
Mark Lee
Position
Executive Director and Chairman
Executive Director and Chief Executive Officer
Executive Director and Chief Financial Officer
Executive Director and Chief Scientific Officer
Age
69
55
54
63
67 Non-executive Director
69 Non-executive Director and Company Secretary
Senior Independent Non-executive Director
60
Independent Non-executive Director
63
Independent Non-executive Director
70
Independent Non-executive Director
60
Senior Vice President, Business Development & Strategic Alliances
57
Senior Vice President, Pharmaceutical Sciences
61
Senior Vice President, Corporate Finance & Development
43
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Simon To has been a director since 2000 and an executive director and the chairman of our board of directors since 2006. He is also
a member of our nomination committee, remuneration committee and technical committee. He is the managing director of Hutchison
Whampoa (China) Limited and has been with Hutchison Whampoa (China) Limited for over 40 years, building its business from a small
trading company to a multi-billion dollar investment group. He has negotiated major transactions with multinational corporations such
as Procter & Gamble, or P&G, Lockheed, Pirelli, Beiersdorf, United Airlines and British Airways. He is currently the chairman of the
board of directors of Gama Aviation Plc and formerly served as independent non-executive director on the boards of China Southern
Airlines Company Limited and Air China Limited. Mr. To’s career in China spans more than 45 years. He is the original founder of the
China healthcare business of Hutchison Whampoa Limited (currently a subsidiary of CK Hutchison) and has been instrumental in its
acquisitions made to date. He received a bachelor’s degree in mechanical engineering from Imperial College, London and a master in
business administration from Stanford University’s Graduate School of Business.
Christian Hogg has been an executive director and our chief executive officer since 2006. He is also a member of our technical
committee. He was a member of our nomination committee from April 2019 to December 2020. He joined the business in 2000, as its
first employee, and has since led all aspects of the creation, implementation and management of our strategy, business and listings. This
includes the establishment of our Oncology/Immunology operations which now have an organization of about 1,200 scientific and
commercial personnel involved in the launch of its first two oncology drugs, Elunate and Sulanda in China, as well as the management
of global clinical development activities on our portfolio of ten in-house discovered novel oncology drug candidates. Furthermore, Mr.
Hogg oversaw the acquisition and operational integration of assets that led to the formation of our Other Ventures operations, which
manufacture, market and distribute prescription drugs and consumer health products, covering an extensive network of hospitals across
China. Prior to joining us, he spent ten years with P&G, starting in the United States in Finance and then Brand Management in the
Laundry and Cleaning Products Division. He then moved to China to manage P&G’s detergent business, followed by a move to Brussels
to run P&G’s global bleach business. Mr. Hogg received a bachelor’s degree in civil engineering from the University of Edinburgh and
a master in business administration from the University of Tennessee.
Johnny Cheng has been an executive director since 2011 and our chief financial officer since 2008. He was a member of our
nomination committee from April 2019 to December 2020. Prior to joining our company, Mr. Cheng was vice president, finance of
Bristol Myers Squibb in China and was a director of Sino-American Shanghai Squibb Pharmaceuticals Ltd. and Bristol-Myers Squibb
(China) Investment Co. Ltd. in Shanghai between late 2006 and 2008. Mr. Cheng started his career as an auditor with Price Waterhouse
(currently PricewaterhouseCoopers) in Australia and then KPMG in Beijing before spending eight years with Nestlé China where he
was in charge of a number of finance and control functions in various operations. Mr. Cheng received a bachelor of economics,
accounting major from the University of Adelaide and is a member of Chartered Accountants Australia and New Zealand.
Weiguo Su has been an executive director since 2017 and has been our executive vice president and chief scientific officer since
2012. He is also a member of our technical committee. He was a member of our nomination committee from April 2019 to December
2020. Dr. Su has headed all drug discovery and research since he joined our company, including master-minding our scientific strategy,
being a key leader of our Oncology/Immunology operations, and responsible for the discovery of each and every small molecule drug
candidate in our product pipeline. Prior to joining our company in 2005, Dr. Su spent 15 years with the U.S. Research and Development
Department of Pfizer, Inc. with his last position as director of the Medicinal Chemistry Department. In March 2017, he was granted the
prestigious award by the China Pharmaceutical Innovation and Research Development Association (PhIRDA) as one of the Most
Influential Drug R&D Leaders in China. Dr. Su received a bachelor of science degree in chemistry from Fudan University in Shanghai.
He completed a Ph.D. and post-doctoral fellowship in chemistry at Harvard University under the guidance of Nobel Laureate Professor
E. J. Corey.
Dan Eldar has been a non-executive director since 2016. He was a member of our nomination committee from April 2019 to
December 2020. He has more than 30 years of experience as a senior executive, leading global operations in telecommunications, water,
biotech and healthcare. He is an executive director of Hutchison Water Israel Ltd (an associated company of CK Hutchison) which
focuses on large scale projects including desalination, wastewater treatment and water reuse. He was formerly an independent non-
executive director of Leumi Card Ltd., a subsidiary of Bank Leumi Le-Israel B.M., one of Israel’s leading credit card companies. Dr.
Eldar holds a Ph.D. degree in government from Harvard University, master of arts degree in government from Harvard University,
master of arts degree in political science and public administration from the Hebrew University of Jerusalem and a bachelor of arts
degree in political science from the Hebrew University of Jerusalem.
173
Edith Shih has been a non-executive director and company secretary of our company since 2006 and company secretary of Group
companies since 2000. She was a member of our nomination committee from April 2019 to December 2020. She is also an executive
director and company secretary of CK Hutchison. She has been with the Cheung Kong (Holdings) Limited group, or CKH, since 1989
and with Hutchison Whampoa Limited, or HWL, from 1991 to 2015. Both CKH and HWL became wholly-owned subsidiaries of CK
Hutchison in 2015. She has acted in various capacities within the HWL group, including head group general counsel and company
secretary of HWL and director and company secretary of HWL subsidiaries and associated companies. Ms. Shih is a non-executive
director of Hutchison Telecommunications Hong Kong Holdings Limited and Hutchison Port Holdings Management Pte. Limited as
the trustee-manager of Hutchison Port Holdings Trust; and a member of board of commissioners of PT Duta Intidaya Tbk. The
aforementioned companies are either the subsidiaries or associated companies of CK Hutchison of which Ms. Shih has oversight. She
has over 35 years of experience in legal, regulatory, corporate finance, compliance and corporate governance fields. She is the immediate
past international president and current member of the executive committee of The Chartered Governance Institute, or CGI, as well as
a past president and current chairperson of various committees and panels of The Hong Kong Institute of Chartered Secretaries, or
HKICS. She is also chairman of the process review panel for the Financial Reporting Council and a panel member of the Securities and
Futures Appeals Tribunal and the immediate past chairman of the governance committee of the Hong Kong Institute of Certified Public
Accountants. Ms. Shih is a solicitor qualified in England and Wales, Hong Kong and Victoria, Australia and a fellow of both the CGI
and HKICS, holding chartered secretary and chartered governance professional dual designations. Ms. Shih holds a bachelor of science
degree in education and a master of arts degree from the University of the Philippines and a master of arts degree and a master of
education degree from Columbia University, New York.
Paul Carter has been a senior independent non-executive director since 2017. He is also the chairman of our remuneration
committee and a member of our audit committee and technical committee. He was a member of our nomination committee from April
2019 to December 2020. He has more than 26 years of experience in the pharmaceutical industry. From 2006 to 2016, Mr. Carter served
in various senior executive roles at Gilead Sciences, Inc., or Gilead, a research-based biopharmaceutical company, with the last position
as executive vice president, commercial operations. In this role, Mr. Carter headed the worldwide commercial organization responsible
for the launch and commercialization of all of Gilead’s products. Prior to joining Gilead, he spent 14 years with GlaxoSmithKline plc
and its group companies, with the last position as regional head of the international business in Asia. He is currently a director of
Mallinckrodt plc and Immatics N.V. He is the chairman of Evox Therapeutics and a retained advisor to several firms active in the life
sciences sector. He was formerly a director of Alder Biopharmaceuticals, Inc. Mr. Carter holds a degree in business studies from the
Ealing School of Business and Management (now merged into University of West London) and is a fellow of the Chartered Institute of
Management Accountants in the United Kingdom.
Karen Ferrante has been an independent non-executive director since 2017. She is also the chairman of our technical committee
and a member of our audit committee. She was a member of our nomination committee from April 2019 to December 2020. She has
more than 26 years of experience in the pharmaceutical industry. She was the former chief medical officer and head of research and
development of Tokai Pharmaceuticals, Inc., a biopharmaceutical company focused on developing and commercializing innovative
therapies for prostate cancer and other hormonally driven diseases. From September 2007 to July 2013, Dr. Ferrante held senior positions
at Millennium Pharmaceuticals, Inc. and its parent company, Takeda Pharmaceutical Company Limited, including chief medical officer
and most recently as oncology therapeutic area and Cambridge USA site head. From 1999 to 2007, she held positions of increasing
responsibility at Pfizer Inc., with the last position as vice president, oncology development. Dr. Ferrante is currently a member of the
board of directors of MacroGenics, Inc. and Cogent Biosciences, Inc. (formerly Unum Therapeutics Inc.). Dr. Ferrante was previously
a director of Baxalta Incorporated until it was acquired by Shire plc in 2016 and a director of Progenics Pharmaceuticals, Inc. until it
was acquired by Lantheus Holdings, Inc. in 2020. She is an author of a number of papers in the field of oncology, an active participant
in academic and professional associations and symposia and holder of several patents. Dr. Ferrante holds a bachelor of science degree
in chemistry and biology from Providence College and a Doctor of Medicine from Georgetown University.
Graeme Jack has been an independent non-executive director since 2017. He is also the chairman of our audit committee and a
member of our nomination committee and remuneration committee. He has more than 40 years of experience in finance and audit. He
retired as partner of PricewaterhouseCoopers in 2006 after a distinguished career with the firm for over 33 years. He is currently an
independent non-executive director of The Greenbrier Companies, Inc. (an international supplier of equipment and services to the freight
rail transportation markets), Hutchison Port Holdings Management Pte. Limited as the trustee-manager of Hutchison Port Holdings
Trust (a developer and operator of deep water container terminals) and of COSCO SHIPPING Development Co., Ltd., formerly known
as “China Shipping Container Lines Company Limited” (an integrated financial services platform principally engaged in vessel and
container leasing). He holds a bachelor of commerce degree from the University of New South Wales, Australia and is a Fellow of the
Hong Kong Institute of Certified Public Accountants and an Associate of Chartered Accountants Australia and New Zealand.
174
Tony Mok has been an independent non-executive director since 2017. He is also the chairman of our nomination committee and a
member of our technical committee. Professor Mok has more than 31 years of experience in clinical oncology with his main research
interest focusing on biomarker and molecular targeted therapy in lung cancer. He is currently Li Shu Fan Medical Foundation named
professor and chairman of department of clinical oncology at The Chinese University of Hong Kong. Professor Mok has contributed to
over 250 articles in international peer-reviewed journals, as well as multiple editorials and textbooks. In October 2018, Professor Mok
was the first Chinese to be bestowed with the European Society for Medical Oncology Lifetime Achievement Award, one of the most
prestigious international honors and recognitions given to cancer researchers, for his contribution to and leadership in lung cancer
research worldwide. He is a non-executive director of AstraZeneca plc, a board director of the ASCO and a steering committee member
of the Chinese Society of Clinical Oncology. He is also the past president of the International Association for the Study of Lung Cancer,
and co-founder of Sanomics Limited and Aurora Tele-Oncology Limited. Professor Mok is also closely affiliated with the oncology
community in China and has been awarded an Honorary Professorship at Guangdong Province People’s Hospital, Guest Professorship
at Peking Union Medical College Hospital and Visiting Professorship at Shanghai Jiao Tong University. He received his bachelor of
medical science degree and a Doctor of Medicine from University of Alberta, Canada. He is also a fellow of the Royal College of
Physicians and Surgeons of Canada, Hong Kong College of Physicians, Hong Kong Academy of Medicine, Royal College of Physicians
of Edinburgh and ASCO.
May Wang is our senior vice president of business development & strategic alliances. Prior to joining our company in 2010, Dr.
Wang spent 16 years with Eli Lilly where she was a director of Eli Lilly’s Lilly Research Laboratories and responsible for establishing
and managing research collaborations in China and across Asia. She holds numerous patents, has published more than 50 peer-reviewed
articles and has given dozens of seminars and plenary lectures. Dr. Wang received a Ph.D. in biochemistry from Purdue University.
Zhenping Wu joined our company in 2008 and has been our senior vice president of pharmaceutical sciences since 2012. Dr. Wu
has over 26 years of experience in drug discovery and development. His past positions include senior director of pharmaceutical sciences
at Phenomix Corporation, a U.S.-based biotechnology company, director of pharmaceutical development at Pfizer Global Research &
Development in California (formerly Agouron Pharmaceuticals) and a group leader at Roche at its Palo Alto site. He is a past chairman
and president of the board of the Sino-American Biotechnology and Pharmaceutical Association. Dr. Wu received a Ph.D. from the
University of Hong Kong and a master in business administration from the University of California at Irvine.
Mark Lee is our senior vice president of corporate finance and development. Prior to joining our company in 2009, he worked in
healthcare investment banking in the United States and Europe since 1998. Based in the New York and London offices of Credit Suisse,
Mr. Lee was involved in the execution and origination of mergers, acquisitions, public and private financings and corporate strategy for
life science companies such as AstraZeneca, Bristol-Myers Squibb and Genzyme, as well as other medical product and service
companies. Mr. Lee received his bachelor’s degree in biochemical engineering with first class honors from University College London,
where he was awarded a Dean’s Commendation. He also received a master of business administration from the Massachusetts Institute
of Technology’s Sloan School of Management.
175
B. Compensation.
Summary Compensation Table
Executive Officer Compensation
The following table sets forth the compensation paid or accrued during the fiscal year ended December 31, 2020 to our chief
executive officer, chief financial officer, chief scientific officer and other executive officers on an aggregate basis.
Name and Principal Position
Christian Hogg
Johnny Cheng
Weiguo Su
Other Executive Officers in the Aggregate
Notes:
Salary
and fees
($)
Bonus(4)
($)
458,076 (1)(2) 897,435
380,141 (3) 371,794
420,894 (2) 735,930
963,480
647,049
Taxable Non-taxable Pension
benefits
benefits
($)
($)
9,936
17,820
9,936
—
6,471
10,000
27,309
6,410
contributions
($)
29,369
27,091
32,229
37,847
Total
($)
1,412,636
788,962
1,205,524
1,682,095
(1) Director’s fees received from the subsidiaries of the Company during the period he served as director that were paid to a subsidiary
or an intermediate holding company of the Company are not included in the amounts above.
(2) Amount includes director’s fees of $75,000.
(3) Amount includes director’s fees of $70,000.
(4) In December 2013 and March 2014, we awarded cash retention bonuses to certain of our executive officers in the aggregate amount
of $2,977,751. Each such executive officer receives portions of his or her retention bonus upon certain dates in the future depending
on when the bonus was granted and, in each case, assuming he or she remains employed by our company on such future dates. No
amounts in relation to such cash retention bonuses were paid in 2020.
Employment Arrangements with our Executive Officers
Offer Letters for Executive Officers at Hutchison China MediTech Limited and Hutchison MediPharma (Hong Kong)
Limited
We have entered into employment offer letters with each of our executive officers who is employed by our Hong Kong subsidiaries,
HCM HK or Hutchison MediPharma (Hong Kong) Limited, namely Mr. Christian Hogg, Mr. Johnny Cheng and Mr. Mark Lee. Under
these our executives receive compensation in the form of salaries, discretionary bonuses, participation in the Hutchison Provident Fund
retirement scheme, medical coverage under the CK Hutchison Group Medical Scheme, personal accident insurance and annual leave.
None of the employment arrangements provide benefits to our executive officers upon termination. We may terminate employment by
giving the executive three months’ prior written notice. The executive officer may also voluntarily terminate his employment with us
upon not less than three months’ prior written notice to us.
Each executive officer has agreed, for the term of employment with us and thereafter, not to disclose or use for his own purposes
any of our and our associated companies’ confidential information that the executive officer may develop or learn in the course of
employment with us. Moreover, each of our executive officers has agreed, for the term of employment with us and for a period of twelve
months thereafter, (i) not to undertake or be employed or interested directly or indirectly anywhere in Hong Kong in any activity which
is similar to and competitive with our company or associated companies in which the executive officer had been involved in the period
of 12 months prior to such termination and (ii) not to solicit for any employees of our company or our joint ventures or orders from any
person, firm or company which was at any time during the 12 months prior to termination of such employment a customer or supplier
of our company or associated companies.
176
Employment Agreements with Executive Officers at Hutchison MediPharma
We have also entered into employment agreements with each of our executive officers who are employed directly by Hutchison
MediPharma, namely Dr. Weiguo Su, Dr. May Wang and Dr. Zhenping Wu. Under these employment agreements, we engage the
executive officer on either an open-ended or a fixed term. Our executive officers receive compensation in the form of salaries,
discretionary bonuses, annual leave, statutory maternity leave and nursing leave.
Under the terms of these agreements, we provide labor protection and work conditions that comply with the safety and sanitation
requirements stipulated by the relevant PRC laws. The employment agreements prohibit the executive officers from engaging in any
conduct and business activities which may compete with the business or interests of Hutchison MediPharma during the term of the
executive officer’s employment. These executive officers also enjoy the Hutchison Provident Fund retirement scheme, medical coverage
under the Hutchison Group Medical Scheme and personal accident insurance.
We may terminate an executive officer’s employment for cause at any time without notice. Termination for cause may include a
serious breach of our internal rules and policies, serious negligence in the executive officer’s performance of his or her duties, an
accusation or conviction of a criminal offence, acquisition of another job which materially affects the executive officer’s ability to
perform his or her duties for our company and other circumstances stipulated by applicable PRC laws. We may terminate an executive
officer’s employment with three months’ prior notice if the executive officer is unable to perform his or her duties (after the expiration
of the prescribed medical treatment period) because of an illness or non-work-related injury or the executive officer is incompetent and
remains incompetent after training or adjustment of his or her position.
The executive officer may voluntarily terminate his or her contract without cause with three months’ prior notice. The executive
officer may also terminate the employment agreement immediately for cause, which includes a failure by us to provide labor protection
and the work conditions as specified under the employment agreement. In case of termination for any reason, we agree to make any
mandatory severance payments required by the relevant PRC labor laws.
Share Options
The following table sets forth information concerning the outstanding equity awards held by our chief executive officer, chief
financial officer, chief scientific officer and other executive officers on an aggregate basis as of December 31, 2020.
Number of
unexercised
shares which are
unexercisable
(#)
Number of
unexercised
options in
the form of
Number of
unexercised
options in
the form of
Shares
Option
exercise ADRs which are ADRs which are exercise
price
($/ADR)
unexercisable
(#)
exercisable
(#)
Option
expiration
date
Name and Principal Position
Christian Hogg
Christian Hogg
Johnny Cheng
Weiguo Su
Weiguo Su
Weiguo Su
Weiguo Su
Weiguo Su
Other Executive Officers in the
Aggregate
Other Executive Officers in the
Aggregate
Other Executive Officers in the
Aggregate
Number of
unexercised
shares which
are
exercisable
(#)
—
—
—
3,000,000
750,000
500,000
—
—
2,936,860
—
—
price
(£/share)
n/a
n/a
n/a
1.97
3.105
4.974
n/a
n/a
—
—
—
—
250,000
500,000
—
—
—
—
—
1.97
n/a
n/a
177
—
—
—
—
—
—
—
—
—
—
—
258,340 22.09 Apr. 27, 2030
7,922 29.00 Dec. 13, 2030
80,380 22.09 Apr. 27, 2030
n/a Dec. 19, 2023
n/a Mar. 26, 2027
n/a Mar. 18, 2028
22.09 Apr. 27, 2030
29.00 Dec. 13, 2030
—
—
—
157,940
3,792
—
n/a Dec. 19, 2023
171,540
22.09 Apr. 27, 2030
8,583 29.00 Dec. 13, 2030
Long-Term Incentive Compensation
The following table sets forth information concerning the outstanding LTIP grants held by our chief executive officer, chief financial
officer, chief scientific officer and other executive officers on an aggregate basis as of December 31, 2020.
Name and Principal Position
Christian Hogg
Johnny Cheng
Weiguo Su
Other Executive Officers in the Aggregate
Maximum
Aggregate
Value of
LTIP awards(1)
$
$
$
$
1,580,193
640,443
1,407,120
1,097,278
(1) The amounts reflected in the table above represent the maximum aggregate value of all LTIP awards outstanding as of December
31, 2020. The LTIP awards are conditional upon the achievement of annual performance targets for the fiscal year 2020. The
amounts reflected in the table above assume the maximum amount that may be paid under these contingent LTIP awards. The LTIP
awards will be settled in a variable number of shares based on a fixed monetary amount awarded upon achievement of performance
targets. An independent third-party trustee who administers the LTIP purchased shares of our company on either the AIM or Nasdaq
market which will be used to settle the LTIP awards. See “Outstanding Awards” for more details.
The following table sets forth a summary of the compensation we paid to our directors other than Christian Hogg, Johnny Cheng
and Weiguo Su during 2020.
Director Compensation
Name of Director
Simon To
Dan Eldar
Edith Shih
Paul Carter
Karen Ferrante
Graeme Jack
Tony Mok
Fees Earned or Received and Vested in 4 years
Value of LTIP Awards
Paid in Cash
($)
80,000(1) $
$
70,000
70,000(2) $
$
117,000
$
102,500
$
104,000
$
84,000
$
$
$
$
$
$
$
at 25% each year
($)
200,000
200,000
200,000
200,000
200,000
200,000
200,000
(1) Such director’s fees were paid to Hutchison Whampoa (China) Limited, a wholly owned subsidiary of CK Hutchison. Director’s
fees received from our subsidiaries during the period he served as director that were paid to a subsidiary or an intermediate holding
company of our company are not included in the amounts above.
(2) Such director’s fees were paid to Hutchison International Limited, a wholly owned subsidiary of CK Hutchison. Director’s fees
received from our subsidiaries during the period she served as director that were paid to a subsidiary or an intermediate holding
company of our company are not included in the amounts above.
Equity Compensation Schemes and Other Benefit Plans
We have two share option schemes. We refer to these collectively as the Option Schemes. Our shareholder adopted the first option
scheme, or the 2005 Option Scheme, in June 2005, and it was subsequently approved by the shareholders of Hutchison Whampoa
Limited, our then majority shareholder, in May 2006 and later amended by our board of directors in March 2007. This share option
scheme expired in 2016. In April 2015, our shareholders adopted the second option scheme, or the 2015 Option Scheme, which was
later approved by the shareholders of CK Hutchison, the ultimate parent of our then majority shareholder, in May 2016.
We also have a long-term incentive scheme which was adopted by our shareholders in April 2015. We refer to this as our LTIP.
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In addition, our subsidiary Hutchison MediPharma Holdings has two share option schemes. We refer to these collectively as the
Hutchison MediPharma Option Schemes. The first Hutchison MediPharma option scheme, or the 2008 Hutchison MediPharma Option
Scheme, was adopted in August 2008 upon approval by its shareholder. The 2008 Hutchison MediPharma Option Scheme was thereafter
amended by the board of directors of Hutchison MediPharma Holdings in April 2011 and expired in 2014. The second Hutchison
MediPharma option scheme, or the 2014 Hutchison MediPharma Option Scheme, was adopted in December 2014 upon approval by its
shareholders.
Our Option Schemes, our LTIP and the 2014 Hutchison MediPharma Option Scheme each terminate on the tenth anniversary of
their adoption. Each may also be terminated by its board of directors at any time. Any termination of a scheme is without prejudice to
the awards outstanding at such time. Options are no longer being granted under the 2005 Option Scheme or the 2008 Hutchison
MediPharma Option Scheme, but outstanding awards under the 2005 Option Scheme continue to be governed by the terms thereof.
The following describes the material terms of our Option Schemes, our LTIP and the Hutchison MediPharma Option Schemes, or
collectively the Schemes.
Awards and Eligible Grantees. The Schemes provide for the award of share options exercisable for ordinary shares of our company
(in the case of the Option Schemes) or ordinary shares of Hutchison MediPharma Holdings (in the case of the Hutchison MediPharma
Option Schemes) to Eligible Employees (as defined in the Option Schemes) or non-executive directors (excluding any independent non-
executive directors under the Option Schemes).
Under our LTIP, awards in the form of contingent rights to receive either shares or cash payments may be granted to the directors
of our company, directors of our subsidiaries and employees of our company, subsidiaries, affiliates or such other companies as
determined by our board of directors in its absolute discretion.
Scheme Administration. Our board of directors has delegated its authority for administering our Option Schemes and our LTIP to
our remuneration committee. The board of directors of Hutchison MediPharma Holdings is responsible for administering the Hutchison
MediPharma Option Schemes. Each such plan administrator has the authority to, among other things, select participants and determine
the amount and terms and conditions of the awards under the applicable Schemes as it deems necessary and proper, subject to the
restrictions described in “—Restrictions on Grants” below.
Restrictions on Grants. Under the Option Schemes, grants may not be made to independent non-executive directors. Furthermore,
those grants may not be made to any of our employees or directors if such person is also a director, chief executive or substantial
shareholder of any of our direct or indirect parent companies which is listed on a stock exchange or any of its associates without approval
by the independent non-executive directors of such parent company (excluding any independent non-executive director who is a
proposed grantee). In addition, approval by our shareholders and the shareholders of such listed parent company is required if an option
grant under our Option Schemes is to be made to a substantial shareholder or independent non-executive director of a listed parent
company or any of its associates and, upon exercise of such grant and any other grants made during the prior 12-month period to that
shareholder, that individual would receive an amount of our ordinary shares equal or greater than 0.1% of our total outstanding shares
or with an aggregate value in excess of HK$5 million (equivalent to $0.6 million as of December 31, 2017). The Hutchison MediPharma
Option Schemes do not contain these restrictions.
In addition, options under our Option Schemes and the Hutchison MediPharma Option Schemes may not be granted to any
individual if, upon the exercise of such options, the individual would receive an amount of shares when aggregated with all other options
granted to such individual under the applicable Scheme in the 12-month period up to and including the grant date, that exceeds 1% of
the total shares outstanding of the company granting the award on such date. In the event a grant of share options would exceed 1% of
the total number of issued shares of Hutchison MediPharma Holdings, our company must also approve the grant. There are no individual
limits under our LTIP.
Under our LTIP, no grant to any director, chief executive or substantial shareholder of our company may be made without the prior
approval of our independent non-executive directors (excluding an independent non-executive director who is a proposed grantee).
Vesting. Vesting conditions of options granted under the Schemes are determined by the respective board of directors at the time of
grant. Any options granted are normally exercisable to the extent vested within the period specified by the applicable Scheme, which
ranges from six to ten years after the date of grant.
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Under our Option Schemes and the Hutchison MediPharma Option Schemes, if a participant has committed any misconduct or any
conduct making such participant’s service terminable for cause, all options (whether vested or unvested) lapse unless the respective
board of directors otherwise determines in its absolute discretion. Options may be exercised to the extent vested where a participant’s
service ceases due to the participant’s death, serious illness, injury, disability, retirement at the applicable retirement age, or earlier if
determined by the participant’s employer, or if a participant’s service ceases for any other reason other than for cause.
Under our LTIP, if a participant’s employment or service with our company or its subsidiaries is terminated for cause or if the
participant breaches certain provisions in our LTIP restricting the transfer of awards by grantees and imposing non-competition
obligations on grantees, all unvested awards are automatically cancelled. Where a participant’s employment or service ceases for any
reason other than the reasons listed above (including due to the participant’s resignation, retirement, death or disability or upon the non-
renewal of such participant’s employment or service agreement other than for cause), our board of directors may determine at its
discretion whether unvested awards shall be deemed vested.
Exercise Price. The exercise price for each share pursuant to the initial options granted under the 2005 Option Scheme was a price
determined by our board of directors at the date of grant, and for grants made thereafter, the exercise price was the Market Value of a
share at the date of grant (as defined in our Option Schemes). The exercise price for each share pursuant to options granted under our
2008 Hutchison MediPharma Option Scheme was a price determined by the board of directors of Hutchison MediPharma Holdings.
The exercise price for each share pursuant to the options granted under the 2015 Option Scheme must be the Market Value of a
share at the date of grant (as defined in our Option Schemes). The exercise price for each share pursuant to options granted under the
2014 Hutchison MediPharma Option Scheme will be determined by the boards of directors of Hutchison MediPharma Holdings at the
date of grant.
Non-transferability of Awards. Awards may not be transferred except in the case of a participant’s death by the terms of each
Scheme.
Takeover or Scheme of Arrangement. In the event of a general or partial offer for the shares of our company (under our Option
Schemes) or Hutchison MediPharma Holdings (under the Hutchison MediPharma Option Schemes), whether by way of takeover, offer,
share repurchase offer, or scheme of arrangement, the affected company is required to use all reasonable endeavors to procure that such
offer is extended to all holders of options granted by such company on the same terms as those applying to shareholders. Both vested
and unvested options may be exercised up until (i) the closing date of any such offer, (ii) the record date for entitlements under a scheme
of arrangement, or (iii) two business days prior to any general meeting of members convened to consider such offer (under the 2014
Hutchison MediPharma Option Scheme), and will lapse thereafter. Certain options may also be exercised on a voluntary winding up of
our company or Hutchison MediPharma Holdings, as the case may be.
Under our LTIP, in the event of a general offer for all the shares of our company, whether by way of takeover or scheme of
arrangement, or if our company is to be voluntarily wound up, our board of directors shall determine in its discretion whether outstanding
unvested awards will vest and the period within which such awards will vest.
Amendment. Our Option Schemes require that amendments of a material nature only be made with the approval of our shareholders.
The Hutchison MediPharma Option Schemes may be altered by the board of directors of our company or Hutchison MediPharma
Holdings, as the case may be, but any amendments which provide a material advantage to grantees cannot take effect without
shareholders’ approval.
Our board of directors may alter our LTIP, but amendments which are of a material nature cannot take effect without shareholders’
approval, unless the changes take effect automatically under the terms of our LTIP.
Authorized Shares. Under our 2015 Option Scheme, our board of directors may “refresh” the scheme limit from time to time
provided that the total number of shares which may be issued upon exercise of all options to be granted under our Option Schemes shall
not exceed 10% of our total shares outstanding on such date. In addition, the limit on the number of shares which may be issued upon
exercise of all outstanding options granted and not yet exercised under the 2015 Option Scheme and any options granted and not yet
exercised under any other schemes must not exceed 10% of the shares of the company in issue from time to time. In April 2020, our
shareholders approved a refresh of the 2015 Option Scheme.
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Following the 2015 Option Scheme refresh discussed above, subject to certain adjustments for share splits, share consolidations
and other changes in capitalization, the maximum number of shares that may be issued upon exercise of all options granted may not in
the aggregate exceed: (i) 5% of our shares outstanding on April 27, 2020 or (ii) 5% of the shares of Hutchison MediPharma Holdings
outstanding on the date of adoption under the 2014 Hutchison MediPharma Option Scheme. Share awards under our LTIP may not
exceed 5% of our shares outstanding on the adoption date of our LTIP.
Outstanding Awards
In the year ended December 31, 2020, we granted options to purchase an aggregate of 15,437,080 ordinary shares, representing
approximately 2.1% of our outstanding share capital, at a weighted average exercise price of £3.71 ($5.01) per share under the 2015
Option Scheme. The options expire 10 years from the date of grant.
As of December 31, 2020, the following options were outstanding:
•
•
options to purchase an aggregate of 1,116,180 ordinary shares, representing approximately 0.2% of our outstanding share
capital, at a weighted average exercise price of £0.55 ($0.74) per ordinary share under the 2005 Option Scheme, and
options to purchase an aggregate of 28,044,810 ordinary shares, representing approximately 3.9% of the outstanding share
capital, at a weighted average exercise price of £3.53 ($4.77) per ordinary share under the 2015 Option Scheme.
In the year ended December 31, 2020, we granted awards under our LTIP to 373 senior managers, executives and directors, giving
them a conditional right to receive ordinary shares to be purchased by the third-party trustee up to an aggregate maximum cash amount
of $39,411,820. These awards are related to the achievement of performance targets. These LTIP awards vest after three years, subject
to the continued employment of the LTIP holder.
In the year ended December 31, 2020, we granted non-performance LTIP awards in a total of $950,000 to three senior executives,
which vests over four years at 25% per year subject to the continued employment of our LTIP holder. We also granted non-performance
LTIP awards of $200,000 each to seven of our directors which are subject to a vesting schedule of 25% per year over four years.
As of December 31, 2020, LTIP awards representing a maximum cash amount of $34,491,924 were outstanding.
C. Board Practices.
Our board of directors consists of ten directors including four executive directors, two non-executive directors and four independent
non-executive directors. Pursuant to a relationship agreement dated April 21, 2006, and amended and restated on June 13, 2019, by and
between our company and Hutchison Whampoa (China) Limited, a parent company of Hutchison Healthcare Holdings Limited, or the
Relationship Agreement, our board of directors must consist of at least one director who is independent of the CK Hutchison group if
Hutchison Whampoa (China) Limited is entitled to cast at least 50% votes eligible to be cast on a poll vote at a general meeting of our
company. The Relationship Agreement will continue in effect until our ordinary shares cease to be traded on the AIM market or the CK
Hutchison group individually or collectively ceases to hold at least 30% of our shares.
Our directors are subject to a three-year term of office and hold office until such time as they wish to retire and not offer themselves
up for re-election, are not re-elected by the shareholders, or are removed from office by special resolution at an annual general meeting
of the shareholders. Under our Articles of Association, a director will be removed from office automatically if, among other things, the
director (i) becomes bankrupt or makes any arrangement or composition with his creditors; or (ii) is found to be or becomes of unsound
mind. For information regarding the period during which our officers and directors have served in their respective positions, please see
Item 6.A. “Directors and Senior Management.”
Our board of directors has established an audit committee, remuneration committee, technical committee and nomination
committee.
Board Committees
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Audit Committee
Our audit committee consists of Graeme Jack, Paul Carter and Karen Ferrante, with Graeme Jack serving as chairman of the
committee. Graeme Jack, Paul Carter and Karen Ferrante each meet the independence requirements under the rules of the Nasdaq Stock
Market and under Rule 10A-3 under the Exchange Act. We have determined that Graeme Jack is an “audit committee financial expert”
within the meaning of Item 407 of Regulation S-K. All members of our audit committee meet the requirements for financial literacy
under the applicable rules and regulations of the SEC and the Nasdaq Stock Market.
Although we are a foreign private issuer, we are required to comply with Rule 10A-3 of the Exchange Act, relating to audit
committee composition and responsibilities. Rule 10A-3 provides that the audit committee must have direct responsibility for the
nomination, compensation and choice of our auditor, as well as control over the performance of their duties, management of complaints
made, and selection of consultants. Under Rule 10A-3, if the governing law or documents of a listed issuer require that any such matter
be approved by the board of directors or the shareholders of the company, the audit committee’s responsibilities or powers with respect
to such matter may instead be advisory. Our Articles of Association provide that the audit committee may only have an advisory role
and appointment of our auditor must be decided by our shareholders at our annual general meeting or at a subsequent extraordinary
general meeting in each year.
The audit committee formally meets at least twice a year and otherwise as required. The audit committee’s purpose is to oversee
our accounting and financial reporting process and the audit of our financial statements. Our audit committee’s primary duties and
responsibilities are to:
• monitor the integrity of our financial statements, our annual and half-year reports and accounts and our announcements of
interim or final results;
•
•
•
provide advice, where requested by the board of directors, on whether the annual report and accounts, taken as a whole, are
fair, balanced and understandable, and provide the information necessary for shareholders to assess our company’s position
and performance, business model and strategy;
review significant financial reporting issues and the judgments which they contain;
review, whenever practicable without being inconsistent with any requirement for prompt reporting under applicable listing
rules, other statements containing financial information such as significant financial returns to regulators and release of price
sensitive information first where board of director approval is required; and
•
review and challenge where necessary:
•
•
the consistency of, and any changes to, accounting policies both on a year-on-year basis and across our company;
the methods used to account for significant or unusual transactions where different approaches are possible;
• whether our company has followed appropriate accounting standards and made appropriate estimates and judgments,
taking into account the views of the external auditor;
•
•
the clarity of the disclosure in our financial reports and the context in which statements are made; and
all material information presented with the financial statements, such as any operating and financial review and any
corporate governance statements (insofar as it relates to the audit and risk management).
In relation to our internal controls and risk management systems, our audit committee, among other things:
•
reviews the effectiveness of our internal control and risk management systems;
182
•
•
•
•
•
reviews the policies and procedures for the identification, assessment and reporting of financial and non-financial risks and our
management of those risks in accordance with the requirements of the Sarbanes-Oxley Act and other applicable laws, rules and
regulations and the applicable requirements of any stock exchange;
approves the appointment and removal of the head of the internal audit function;
ensures our internal audit function has adequate standing and resources and is free from management or other restrictions;
reviews and monitors our executive management’s responsiveness to the findings and recommendations of the internal audit
function; and
reviews with management and our independent auditors the adequacy and effectiveness of our internal control over financial
reporting and disclosure controls and procedures.
In relation to our external auditor, our audit committee, among other things:
•
•
•
•
•
recommends the appointment, reappointment or removal of the external auditor and considers any issues relating to their
resignation, dismissal, remuneration or terms of engagement, subject to approval by the shareholders;
considers and monitors the external auditor’s independence, objectivity and effectiveness;
reviews and monitors the effectiveness of the audit process, considering relevant ethical or professional requirements;
develops and implements policy on the engagement of the external auditor to provide non-audit services, taking into any
relevant ethical guidance; and
pre-approves the external auditors’ annual audit fees and the nature and scope of proposed audit coverage, subject to approval
by our shareholders.
The audit committee is authorized to obtain, at our company’s expense, reasonable outside legal or other professional advice on
any matters within the scope of its responsibilities.
Remuneration Committee
Our remuneration committee consists of Paul Carter, Graeme Jack and Simon To, with Paul Carter serving as chairman of the
committee. The remuneration committee is responsible for considering all material elements of remuneration policy and remuneration
and incentives of our executive directors and key employees with reference to independent remuneration research and professional
advice. The remuneration committee meets formally at least once each year and otherwise as required and make recommendations to
our board of directors on the framework for executive remuneration and on proposals for the granting of share options and other equity
incentives. Our board of directors is responsible for implementing these recommendations and agreeing the remuneration packages of
individual directors. No director is permitted to participate in discussions or decisions concerning his or her own remuneration.
Technical Committee
Our technical committee consists of Karen Ferrante, Paul Carter, Simon To, Christian Hogg, Weiguo Su and Tony Mok, with Karen
Ferrante serving as chairperson of the committee. The technical committee’s responsibility is to consider, from time to time, matters
relating to the technical aspects of the research and development activities of our Oncology/Immunology operations. It invites such
executives as it deems appropriate to participate in meetings from time to time.
183
Nomination Committee
Our nomination committee consists of Tony Mok, Graeme Jack and Simon To, with Tony Mok serving as chairman of the
committee. Our nomination committee reviews the structure, size, diversity profile and skills set of the board against its needs and
makes recommendations on the composition of the board to achieve our corporate strategy as well as promote shareholder value. It
facilitates the board in the conduct of the selection and nomination of directors, makes recommendations to the board on the appointment
or reappointment of directors and succession planning for directors. It also assesses director independence having regard to the criteria
under the applicable corporate governance code, SEC or stock exchange rules.
U.K. Corporate Governance Code
The U.K. Corporate Governance Code 2018 published by the U.K. Financial Reporting Council, or the 2018 Code, is the primary
source of corporate governance standards for all companies with a premium listing on the Official List of the U.K. Financial Conduct
Authority, whether incorporated in the United Kingdom or elsewhere, and it is recognized as a best practice for the largest companies
by market capitalization on the AIM market of the London Stock Exchange. The 2018 Code is comprised of main and supporting
principles of good governance addressing the following areas: (i) board leadership and company purpose; (ii) division of responsibilities;
(iii) board composition, succession and evaluation; (iv) audit, risk and internal control; and (v) remuneration. Together with the U.K.
Financial Reporting Council’s Guidance on Board Effectiveness (published in July 2018), it also includes detailed recommendations
derived from these principles, such as the roles of board chairman and chief executive officer should not be exercised by the same
individual and the chairman of the board should ensure that new directors receive a full, formal and tailored induction on joining the
board. The 2018 Code applies to accounting periods beginning on or after January 1, 2019. For the year ended December 31, 2019, we
have voluntarily complied with many of the principles of the U.K. Corporate Governance Code.
Code of Ethics
Our board of directors has adopted a code of ethics to set standards for our directors, officers and employees as are reasonably
necessary to promote (i) honest and ethical conduct, including the ethical handling of actual or apparent conflicts of interest between
personal and professional relationships; (ii) full, fair, accurate, timely and understandable disclosure in the reports and documents that
we file or submit to the applicable stock exchanges, and in any other public communications; (iii) compliance with applicable
governmental and regulatory laws, rules, codes and regulations; (iv) prompt internal reporting of any violations of the code of ethics;
and (v) accountability for adherence to the code of ethics.
Code of Ethics for Business Partners
Our board of directors has adopted a code of ethics for our business partners, including our suppliers, vendors, customers, agents,
contractors, joint venture partners and representatives. This code of ethics contains general guidelines to promote the standards outlined
in our internal code of ethics as described above.
Complaints Procedures
Our board of directors has adopted procedures for the confidential receipt, retention, and treatment of complaints from, or concerns
raised by, employees regarding accounting, internal accounting controls and auditing matters as well as illegal or unethical matters. The
complaint procedures are reviewed by the audit committee from time to time as warranted to ensure their continuing compliance with
applicable laws and listing standards as well as their effectiveness.
Information Security Policy
Our board of directors has adopted an information security policy to define and help communicate the common policies for
information confidentiality, integrity and availability to be applied to us and our joint ventures. The purpose of the information security
policy is to ensure business continuity by preventing and minimizing the impact of security risks within our company and our joint
ventures. Our information security policy applies to all of our and our joint ventures’ business entities across all countries. It applies to
the creation, communication, storage, transmission and destruction of all different types of information. It applies to all forms of
information, including but not limited to electronic copies, hardcopy, and verbal disclosures whether in person, over the telephone, or
by other means.
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Code on Dealings in Shares
Our board of directors has adopted a policy on the handling of material inside information, consisting of information which is either
“inside information” under the EU Market Abuse Regulation (Regulation (EU) 596/2014), or MAR, or “material non-public
information” under U.S. law. This policy, among other things, prohibits any employees, directors, other persons discharging managerial
responsibilities or their connected persons dealing in our securities or their derivatives, or those of our collaborators, business partners,
suppliers and customers, while in possession of material inside information. Certain members of our senior management or staff,
including persons discharging managerial responsibilities, and their connected persons are subject to additional compliance requirements
which are outlined in the code (including but not limited to obtaining written pre-clearance from designated members of management
prior to any dealing in any such securities is allowed).
Board Diversity Policy
Our board of directors has established a board diversity policy as our board of directors recognizes the benefits of a board of directors
that possesses a balance of skills, experience, expertise, independence and knowledge and diversity of perspectives appropriate to the
requirements of our businesses.
We maintain that appointment to our board of directors should be based on merit that complements and expands the skills,
experience, expertise, independence and knowledge of the board of directors as a whole, taking into account gender, age, professional
experience and qualifications, cultural and educational background, and any other factors that our board of directors might consider
relevant and applicable from time to time towards achieving a diverse board of directors.
D. Employees.
As of December 31, 2018, 2019 and 2020, we had 714, 853 and 1,280 full-time employees, respectively. None of our employees
are represented by labor unions or covered by collective bargaining agreements. The number of employees by function as of the end of
the period for our fiscal years ended December 31, 2018, 2019 and 2020 was as follows:
By Function:
Oncology/Immunology
Other Ventures
Corporate Head Office
Total
2020
2019
2018
643
594
43
1,280
500
315
38
853
418
267
29
714
As of December 31, 2020, a total of 347 employees on our Oncology/Immunology research and development team have M.D. or
Ph.D. degrees. Additionally, our Other Ventures joint venture Shanghai Hutchison Pharmaceuticals employed a total of 2,898 full time
employees, and Hutchison Baiyunshan employed a total of 1,700 full time employees and 1,864 outsourced contract staff, who are
mostly sales representatives and manufacturing employees as of December 31, 2020. Their employees are represented by labor unions
and covered by collective bargaining agreements. To date, neither Shanghai Hutchison Pharmaceuticals nor Hutchison Baiyunshan has
experienced any strikes, labor disputes or industrial actions which had a material effect on their business, and consider their relations
with the union and our employees to be good.
E. Share Ownership.
See Item 6.B. “Compensation” and Item 7 “Major Shareholders and Related Party Transactions.”
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ITEM 7. MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS
A. Major Shareholders.
We had 727,722,215 ordinary shares outstanding as of March 1, 2021. The following table and accompanying footnotes set forth
information relating to the beneficial ownership of our ordinary shares as of December 31, 2020 by:
•
•
•
each person, or group of affiliated persons, known by us to beneficially own more than 5% of our outstanding ordinary shares;
each of our directors; and
each of our named executive officers.
Our major shareholders do not have voting rights that are different from our shareholders in general. Beneficial ownership is
determined in accordance with the rules and regulations of the SEC.
Name of beneficial owner
Executive Officers and Directors:**
Christian Hogg
Johnny Cheng
Simon To
Edith Shih
Weiguo Su
Dan Eldar
Tony Mok
Paul Carter
Karen Ferrante
Graeme Jack
May Wang
Zhenping Wu
Mark Lee
All Executive Officers and Directors as a Group
Principal Shareholders:
Hutchison Healthcare Holdings Limited(4)
Capital International Investors(5)
General Atlantic Singapore HCM Pte. Ltd.(6)
Notes:
Number of
Ordinary
Share held
Number of
American
Depositary
Share held
Appropriate
percent of Issued
Share Capital**
10,938,020
2,561,460
1,800,000
700,000
4,750,000(2)
19,000
—
35,240
—
—
*(2)
*(2)
*(2)
23,766,250(3)
332,478,770
2,306,477
36,666,670(7)
132,620(1)
34,496(1)
133,237
100,000
111,146(1)
8,993
10,002
—
5,785
3,000
*(1)
*(1)
*(1)
596,116(1)
—
10,130,453
—
1.59%
*
*
*
*
*
*
*
*
*
*
*
*
3.68%
45.69%
7.27%
5.04%
* Less than 1% of our total outstanding ordinary shares.
** Percentage of beneficial ownership of each listed person or group is based on 727,722,215 ordinary shares outstanding as of
March 1, 2021.
(1) Amount includes ADSs vested under the LTIP and ADSs issuable upon vesting of options within 60 days of March 1, 2021.
(2) Amount includes ordinary shares issuable upon vesting of options within 60 days of March 1, 2021.
(3) Amount includes ordinary shares and ordinary shares issuable upon vesting of options within 60 days of March 1, 2021 held by our
executive officers and directors as group.
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(4) Hutchison Healthcare Holdings Limited, a British Virgin Islands company, is an indirect wholly owned subsidiary of CK Hutchison,
a company incorporated in the Cayman Islands and listed on the Hong Kong Stock Exchange. The registered address of Hutchison
Healthcare Holdings Limited is Vistra Corporate Services Centre, Wickhams Cay II, Road Town, Tortola VG1110, British Virgin
Islands.
(5) Based on information included in the Schedule 13G filed by Capital International Investors on February 16, 2021.
(6) Based on information included in the Schedule 13D filed by General Atlantic Singapore HCM Pte. Ltd. and affiliated entities on
July 6, 2020.
(7) Includes 16,666,670 ordinary shares that may be issued pursuant to a warrant, which is exercisable, in part or in whole, at any time
after July 2, 2020 and ending on January 3, 2022.
As of March 1, 2021, based on public filings with the SEC and on AIM, there are 3 major shareholders holding 5% or more of our
ordinary shares or ADSs representing ordinary shares, except as described above. As of March 1, 2021, there were three ordinary
shareholders of record with an address in the United States. Deutsche Bank Trust Company America, as depositary of our ADS program,
held 269,543,005 ordinary shares as of that date in the name of DB London (Investors Services) Nominees Limited.
To our knowledge, except as disclosed above, we are not owned or controlled, directly or indirectly, by another corporation, by any
foreign government or by any other natural or legal person or persons, severally or jointly. To our knowledge, there are no arrangements
the operation of which may at a subsequent date result in us undergoing a change in control. Our major shareholders do not have different
voting rights than any of our other shareholders.
B. Related Party Transactions.
Letters of awareness with respect to loans
Relationship with CK Hutchison
CK Hutchison has provided letters of awareness to certain of our lenders stating that it is aware that loan facilities have been
provided to us and that its current intention is that for so long as amounts are outstanding under such loan facilities, it will not reduce its
direct or indirect shareholding in our company to below 40% of our issued share capital while such loans are outstanding.
Relationship Agreement with the CK Hutchison group
We entered into a relationship agreement dated April 21, 2006, which was amended and restated on June 13, 2019 with effect from
June 3, 2015, with Hutchison Whampoa (China) Limited, which is an indirect wholly owned subsidiary of CK Hutchison, with a view
to ensuring that our company is capable of carrying on its business independently of the CK Hutchison group. We refer to this agreement
as the Relationship Agreement. The Relationship Agreement provides, among other things, that all transactions between any of us or
our joint ventures, on the one hand, and the CK Hutchison group, on the other hand, will be on an arm’s length basis, on normal
commercial terms and in a manner consistent with the AIM Rules. The Relationship Agreement further provides that the approval of
our board of directors shall be required for any transaction between any of us or our joint ventures, on one hand, and the CK Hutchison
group, on the other hand, and that in approving any such transaction, our board of directors must consist of at least one director who is
independent of CK Hutchison. Our board of directors must consist of at least one director who is independent of the CK Hutchison
group if Hutchison Whampoa (China) Limited is entitled to cast at least 50% votes eligible to be cast on a poll vote at a general meeting
of our company, see Item 6.C. “Directors, Senior Management and Employees—Board Practices.” Hutchison Whampoa (China) Limited
has also agreed to procure that each member of the Hutchison Whampoa (China) Limited group will not exercise its voting rights and
powers so as to amend our Memorandum or Articles of Association in a manner which is inconsistent with the Relationship Agreement.
The Relationship Agreement will continue until the first to occur of: (i) our shares ceasing to be traded on the AIM market or (ii) the
CK Hutchison group individually or collectively cease to hold or control the exercise of at least 30% or more of the rights to vote at our
general meetings.
187
Products sold to group companies of CK Hutchison
We have entered into agreements with members of the CK Hutchison group, including the retail grocery and pharmacy chains
PARKnSHOP and Watsons which are owned and operated by the A.S. Watson Group, an indirect subsidiary of CK Hutchison, in respect
of the distribution of certain of our consumer health products. For the year ended December 31, 2020, sales of our products to members
of the CK Hutchison group amounted to $5.5 million. In addition, for the year ended December 31, 2020, we paid approximately $0.3
million to members of the CK Hutchison group for the provision of marketing services associated with these products. Our sales to CK
Hutchison group companies are made pursuant to purchase orders issued by each purchaser periodically, the terms of which are on an
arm’s length basis on normal commercial terms.
See Item 3.D. “Risk Factors—Risks Relating to Our Dependence on Third Parties—There is no assurance that the benefits currently
enjoyed by virtue of our association with CK Hutchison will continue to be available” for more information on the risks associated with
our relationship with CK Hutchison’s group companies.
Intellectual property licensed by the CK Hutchison group
We conduct our business using trademarks with various forms of the “Hutchison”, “Chi-Med”, “Hutchison China MediTech”,
“Hutchmed”, “Elunate” and “Sulanda” brands, the logo used by Hutchison MediPharma, as well as domain names incorporating some
or all of these trademarks. We have entered into a brand license agreement dated April 21, 2006 (as amended and restated on June 13,
2019 with effect from June 3, 2015) with Hutchison Whampoa Enterprises Limited, which is an indirect wholly owned subsidiary of
CK Hutchison, pursuant to which we have been granted a non-exclusive, non-transferrable, royalty-free right to use the “Hutchison”,
“Hutchison China MediTech”, “Chi-Med”, “Hutchmed” trademarks, domain names and other intellectual property rights owned by the
CK Hutchison group in connection with the operation of our business worldwide. We refer to this amended and restated agreement as
the Brand License Agreement. We are also permitted to sub-license such intellectual property rights to our affiliates.
The Brand License Agreement contains provisions on quality control pursuant to which we are obliged to use the brands and related
materials in compliance with the brand guidelines, industry best practice and other quality directives issued by Hutchison Whampoa
Enterprises Limited from time to time. Under this agreement, we assign all intellectual property rights, including future copyrights in
any works incorporating brand-related material or translations thereof, to Hutchison Whampoa Enterprises Limited (subject to any third-
party rights).
Hutchison Whampoa Enterprises Limited may terminate the Brand License Agreement (or any sub-license) if, among other things,
we commit a material breach of the agreement, or within any twelve-month period aggregate direct or indirect shareholding in our
company held by Hutchison Whampoa Limited, our indirect shareholder, is reduced to less than 40%, 30% or 20%. On termination of
the Brand License Agreement, we (and any sub-licensees) must immediately cease using the brands and are obliged to withdraw from
the sale of any products bearing the brands; provided that if the agreement is terminated following a change in Hutchison Whampoa
Limited’s aggregate direct or indirect shareholding in our company, we will have a six-month transitional period during which we can
continue to use the licensed rights. Hutchison Whampoa Limited’s interest in our company is less than 20%, but we do not anticipate
that Hutchison Whampoa Enterprises Limited will terminate such license in the foreseeable future.
Hutchison Whampoa Enterprises Limited has also granted a royalty-free license to use the Hutchison name and associated
trademarks to Hutchison Baiyunshan. The license has a term equal to the operational period of the joint venture but may be terminated
by the licensor if, among other things, Hutchison Baiyunshan is in breach of the terms of the license and fails to remedy that breach after
an arbitration award is issued against Hutchison Baiyunshan, the joint venture agreement terminates, or our company’s interest in
Hutchison Baiyunshan falls below 50%.
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Sharing of services with the CK Hutchison group
Pursuant to an amended and restated services agreement dated January 1, 2016 between us and Hutchison Whampoa (China)
Limited, an indirect wholly owned subsidiary of CK Hutchison, we share certain services with and receive operational support from the
CK Hutchison group including, among others, legal and regulatory services, company secretarial support services, tax and internal audit
services, shared use of accounting software system and related services, participation in the CK Hutchison group’s pension, medical and
insurance plans, participation in the CK Hutchison group’s procurement projects with third-party vendors/suppliers, other staff benefits
and staff training services, company functions and activities and operation advisory and support services. We refer to this amended and
restated agreement as the Services Agreement. The Services Agreement replaces our prior services agreement with Hutchison Whampoa
(China) Limited, dated April 21, 2006, which had substantially similar terms. We pay a management fee to Hutchison Whampoa (China)
Limited for the provision of such services. In addition, we make payments under the Services Agreement to Hutchison Whampoa (China)
Limited for our executive offices in Hong Kong. Furthermore, pursuant to the terms of the Services Agreement, Hutchison Whampoa
(China) Limited charges us management fees and other costs through Hutchison Healthcare Holdings Limited, its wholly owned
subsidiary.
The Services Agreement may be terminated by either party by giving three months’ written notice. Hutchison Whampoa (China)
Limited may also immediately terminate if its shareholding in our company falls below 30%. The services provided under the Services
Agreement are provided on an arm’s length basis, on normal commercial terms.
Any amount unpaid after 30 days accrues interest at the rate of 1.5% per annum. In the year ended December 31, 2020, we paid a
management fee of approximately $1.0 million under the Services Agreement. As of December 31, 2020, we had $0.4 million in unpaid
fees outstanding to Hutchison Whampoa (China) Limited.
Director and Executive Officer Compensation
Agreements with Our Directors and Executive Officers
See Item 6.B. “Compensation—Executive Officer Compensation” and “Compensation—Director Compensation” for a discussion
of our compensation of directors and executive officers.
Equity Compensation
See Item 6.B. “Compensation—Equity Compensation Schemes and Other Benefit Plans.”
Employment Agreements
We have entered into employment agreements with our executive officers. For more information regarding these agreements, see
Item 6.B. “Compensation—Executive Officer Compensation—Employment Arrangements with our Executive Officers.”
Indemnification Agreements
We have entered into indemnification agreements with each of our directors and executive officers. We also maintain a general
liability insurance policy which covers certain liabilities of our directors and executive officers arising out of claims based on acts or
omissions in their capabilities as directors or officers.
C. Interests of Experts and Counsel.
Not applicable.
ITEM 8. FINANCIAL INFORMATION
A. Consolidated Financial Statements and Other Financial Information.
See Item 18 “Financial Statements.”
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A.7 Legal Proceedings.
There are no material legal proceedings pending or, to our knowledge, threatened against us. From time to time we become subject
to legal proceedings and claims in the ordinary course of our business, including claims of alleged infringement of patents and other
intellectual property rights. Such legal proceedings or claims, even if not meritorious, could result in the expenditure of significant
financial and management resources.
A.8 Dividend Policy.
We have never declared or paid dividends on our ordinary shares. We currently expect to retain all future earnings for use in the
operation and expansion of our business and do not have any present plan to pay any dividends. The declaration and payment of any
dividends in the future will be determined by our board of directors in its discretion, and will depend on a number of factors, including
our earnings, capital requirements, overall financial condition, and contractual restrictions.
B. Significant Changes.
We have not experienced any significant changes since the date of our audited consolidated financial statements included in this
annual report.
ITEM 9. THE OFFER AND LISTING
Not applicable except for Item 9.A.4 and Item 9.C.
Our ADSs are listed on the Nasdaq Global Select and our ordinary shares are admitted to trading on the AIM market of the London
Stock Exchange under the symbol “HCM.” Our ticker symbol will remain unchanged after our corporate name change as described
under “Item 4.A. History and Development of the Company.”
ITEM 10. ADDITIONAL INFORMATION
A. Share Capital.
Not applicable.
B. Memorandum and Articles of Association.
The information contained in Exhibit 2.4 to our annual report on Form 20-F/A filed with the SEC on April 29, 2020 is incorporated
herein by reference.
C. Material Contracts.
Except as otherwise disclosed in this annual report (including the exhibits hereto), we are not currently, and have not been in the
last two years, party to any material contract, other than contracts entered into in the ordinary course of our business.
D. Exchange Controls.
Foreign currency exchange in the PRC is primarily governed by the Foreign Exchange Administration Rules issued by the State
Council on January 29, 1996 and effective as of April 1, 1996 (and amended on January 14, 1997 and August 5, 2008) and the
Regulations of Settlement, Sale and Payment of Foreign Exchange which came into effect on July 1, 1996.
Under the Foreign Exchange Administration Rules, renminbi is freely convertible for current account items, including the
distribution of dividends payments, interest payments, and trade and service-related foreign exchange transactions. Conversion of
renminbi for capital account items, such as direct investment, loans, securities investment and repatriation of investment, however, is
still generally subject to the approval or verification of the SAFE.
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Under the Regulations of Settlement, Sale and Payment of Foreign Exchange, foreign invested enterprises including wholly foreign
owned enterprises, may buy, sell or remit foreign currencies only at those banks that are authorized to conduct foreign exchange business
after providing such banks with valid commercial supporting documents and, in the case of capital account item transactions, after
obtaining approvals from the SAFE. Capital investments by foreign invested enterprises outside the PRC are also subject to limitations,
which include approvals by the MOFCOM, the SAFE and the NDRC.
In March 2015, the SAFE released the Circular on Reforming the Management Approach regarding the Foreign Exchange Capital
Settlement of Foreign-invested Enterprises, or FIEs, or the Foreign Exchange Capital Settlement Circular, which became effective from
June 1, 2015. This circular replaced the SAFE’s previous related circulars, including the Circular on Issues Relating to the Improvement
of Business Operation with Respect to the Administration of Foreign Exchange Capital Payment and Settlement of Foreign Invested
Enterprises. The Foreign Exchange Capital Settlement Circular clarifies that FIEs may settle a specified proportion of their foreign
exchange capital in banks at their discretion, and may choose the timing for such settlement. The proportion of foreign exchange capital
to be settled at FIEs’ discretion for the time being is 100% and the SAFE may adjust the proportion in due time based on the situation
of international balance of payments. The circular also stipulates that FIEs’ usage of capital and settled foreign exchange capital shall
comply with relevant provisions concerning foreign exchange control and be subject to the management of a negative list. The FIEs’
capital and Renminbi capital gained from the settlement of foreign exchange capital may not be directly or indirectly used for expenditure
beyond the business scope of the FIEs or as prohibited by laws and regulations of the PRC. Such capital also may not be directly or
indirectly used for issuing renminbi entrusted loans except as permitted by the business scope of the FIE, for repaying inter-enterprise
borrowings including any third-party advance, or for repaying the bank loans denominated in renminbi that have been sub-lent to a third
party.
In addition, the payment of dividends by entities established in the PRC is subject to limitations. Regulations in the PRC currently
permit payment of dividends only out of accumulated profits as determined in accordance with accounting standards and regulations in
the PRC. Each of our PRC subsidiaries and joint ventures that is a domestic company is also required to set aside at least 10.0% of its
after-tax profit based on PRC accounting standards each year to its general reserves or statutory capital reserve fund until the
accumulative amount of such reserves reach 50.0% of its respective registered capital. These restricted reserves are not distributable as
cash dividends. In addition, if any of our PRC subsidiaries or joint ventures incurs debt on its own behalf in the future, the instruments
governing the debt may restrict its ability to pay dividends or make other distributions to us.
For more information about foreign exchange control, see Item 3.D. “Risk Factors—Other Risks and Risks Relating to Doing
Business in China—Restrictions on currency exchange may limit our ability to receive and use our revenue effectively.”
E. Taxation
The following is a general summary of certain PRC, Hong Kong, Cayman Islands and U.S. federal income tax consequences
relevant to the acquisition, ownership and disposition of our ADSs. The discussion is not intended to be, nor should it be construed as,
legal or tax advice to any particular individual. The discussion is based on laws and relevant interpretations thereof in effect as of
March 1, 2021, all of which are subject to change or different interpretations, possibly with retroactive effect. The discussion does not
address U.S. state or local tax laws, or tax laws of jurisdictions other than the PRC, Hong Kong, the Cayman Islands and the United
States. You should consult your own tax advisors with respect to the consequences of acquisition, ownership and disposition of our
ADSs and ordinary shares.
191
PRC Enterprise Income Tax
Taxation in the PRC
Under the EIT Law, which was promulgated on March 16, 2007 and subsequently amended on February 24, 2017 and December
29, 2018, and its implementation rules which became effective on January 1, 2008, the standard tax rate of 25% applies to all enterprises
(including FIEs) with exceptions in special situations if relevant criteria are met and subject to the approval of the PRC tax authorities.
An enterprise incorporated outside of the PRC whose “de facto management bodies” are located in the PRC is considered a “resident
enterprise” and will be subject to a uniform EIT rate of 25% on its global income. In April 2009, the SAT, in Circular 82, specified
certain criteria for the determination of what constitutes “de facto management bodies.” If all of these criteria are met, the relevant
foreign enterprise will be deemed to have its “de facto management bodies” located in the PRC and therefore be considered a resident
enterprise in the PRC. These criteria include: (a) the enterprise’s day-to-day operational management is primarily exercised in the PRC;
(b) decisions relating to the enterprise’s financial and human resource matters are made or subject to approval by organizations or
personnel in the PRC; (c) the enterprise’s primary assets, accounting books and records, company seals, and board and shareholders’
meeting minutes are located or maintained in the PRC; and (d) 50% or more of voting board members or senior executives of the
enterprise habitually reside in the PRC. In addition, an enterprise established outside the PRC which meets all of the aforesaid
requirements is expected to make an application for the classification as a “resident enterprise” and this will ultimately be confirmed by
the province-level tax authority. Although Circular 82 only applies to foreign enterprises that are majority-owned and controlled by PRC
enterprises, not those owned and controlled by foreign enterprises or individuals, the determining criteria set forth in Circular 82 may
be adopted by the PRC tax authorities as the test for determining whether the enterprises are PRC tax residents, regardless of whether
they are majority-owned and controlled by PRC enterprises. However, it is not entirely clear how the PRC tax authorities will determine
whether a non-PRC entity (that has not already been notified of its status for EIT purposes) will be classified as a “resident enterprise”
in practice.
Except for our PRC subsidiaries and joint ventures incorporated in China, we believe that none of our entities incorporated outside
of China is a PRC resident enterprise for PRC tax purposes. However, the tax resident status of an enterprise is subject to determination
by the PRC tax authorities, and uncertainties remain with respect to the interpretation of the term “de facto management body.”
If a non-PRC enterprise is classified as a “resident enterprise” for EIT purposes, any dividends to be distributed by that enterprise
to non-PRC resident shareholders or ADS holders or any gains realized by such investors from the transfer of shares or ADSs may be
subject to PRC tax. If the PRC tax authorities determine that we should be considered a PRC resident enterprise for EIT purposes, any
dividends payable by us to our non-PRC resident enterprise shareholders or ADS holders, as well as gains realized by such investors
from the transfer of our shares or ADSs may be subject to a 10% withholding tax, unless a reduced rate is available under an applicable
tax treaty. Furthermore, if we are considered a PRC resident enterprise for EIT purposes, it is unclear whether our non-PRC individual
shareholders (including our ADS holders) would be subject to any PRC tax on dividends or gains obtained by such non-PRC individual
shareholders. If any PRC tax were to apply to dividends realized by non-PRC individuals, it would generally apply at a rate of up to
20% unless a reduced rate is available under an applicable tax treaty.
According to the EIT Law, dividends declared after January 1, 2008 and paid by PRC FIEs to their non-PRC parent companies will
be subject to PRC withholding tax at 10% unless there is a tax treaty between the PRC and the jurisdiction in which the overseas parent
company is a tax resident and which specifically exempts or reduces such withholding tax, and such tax exemption or reduction is
approved by the relevant PRC tax authorities. Pursuant to the Arrangement, if the non-PRC immediate holding company is a Hong Kong
tax resident and directly holds a 25% or more equity interest in the PRC enterprise and is considered to be the beneficial owner of
dividends paid by the PRC enterprise, such withholding tax rate may be lowered to 5%, subject to approval by the relevant PRC tax
authorities in accordance with relevant tax regulations upon the assessment of beneficial ownership.
192
Value Added Tax
The Interim Regulations of the PRC on VAT, or the VAT Regulations, came into effect on January 1, 2009 (subsequently amended
on February 6, 2016 and November 19, 2017). Pursuant to the VAT Regulations, VAT is imposed on the goods sold in or imported into
the PRC and on processing, repair and replacement services provided within the PRC.
The MOF, and the SAT jointly promulgated the Circular on Comprehensively Promoting the Pilot Program of the Collection of
VAT in Lieu of Business Tax, or the 2016 VAT Circular, on March 23, 2016, which came into effect on May 1, 2016. Pursuant to the
2016 VAT Circular, the sale of services, intangible assets or real property within the PRC (including when either party of a transaction
is within the PRC unless in specified situations) is subject to VAT instead of Business Tax, with VAT rates being 6%, 11% or 17% and
could be zero for certain specified cross border taxable items/services, in accordance with the relevant regulations. Certain specified
technology transfer/development related income are exempt from VAT, subject to approval of relevant tax authorities. According to the
Notice of the MOF and the SAT on Adjusting VAT Rates, which was promulgated on April 4, 2018 and became effective on May 1,
2018, the VAT rates are revised to 6%, 10% or 16%. The Public Notice regarding certain Policies for Deepening the VAT Reform was
promulgated on March 20, 2019 and became effective on April 1, 2019, whereby VAT rates are further revised to 6%, 9% or 13%.
A Municipal Maintenance Tax, together with Education Surcharge and a Local Education Surcharge, are payable at a rate, in
aggregate, of 6% to 12% of the VAT paid.
Cayman Islands Taxation
Overview of Tax Implications of Various Other Jurisdictions
According to our Cayman Islands counsel, Conyers Dill & Pearman, the Cayman Islands currently levies no taxes on individuals
or corporations based upon profits, income, gains or appreciation and there is no taxation in the nature of inheritance tax or estate duty.
There are no other taxes likely to be material to us levied by the government of the Cayman Islands except for stamp duties which may
be applicable on instruments executed in, or brought within the jurisdiction of the Cayman Islands. The Cayman Islands is a party to a
double tax treaty entered into with the United Kingdom in 2010 but it is otherwise not a party to any double tax treaties that are applicable
to any payments made to or by our company. There are no exchange control regulations or currency restrictions in the Cayman Islands.
Pursuant to the Tax Concessions Act of the Cayman Islands, Hutchison China MediTech Limited has obtained an undertaking: (a)
that no law which is enacted in the Cayman Islands imposing any tax to be levied on profits or income or gains or appreciations shall
apply to us or our operations; and (b) that the aforesaid tax or any tax in the nature of estate duty or inheritance tax shall not be payable
(i) on its shares, debentures or other obligations or (ii) by way of the withholding in whole or in part of any relevant payment as defined
in the Tax Concessions Act.
The undertaking is for a period of twenty years from December 31, 2020.
Hong Kong Taxation
Profits Tax
Hutchison China MediTech Limited is a Hong Kong tax resident. Hong Kong tax residents are subject to Hong Kong Profits Tax
in respect of profits arising in or derived from Hong Kong at the current rate of 16.5% (except portions eligible for the two-tiered profits
tax as discussed above). Dividend income earned by a Hong Kong tax resident is generally not subject to Hong Kong Profits Tax.
Hong Kong tax on shareholders and ADS holders
No tax is payable in Hong Kong in respect of dividends paid by a Hong Kong tax resident to their shareholders, including our ADS
holders.
Hong Kong Profits Tax will not be payable by our shareholders, including our ADS holders (other than shareholders / ADS holders
carrying on a trade, profession or business in Hong Kong and holding the shares / ADSs for trading purposes), on any capital gains made
on the sale or other disposal of the ADSs. Shareholders, including our ADS holders, should take advice from their own professional
advisors as to their particular tax position.
193
No Hong Kong Stamp Duty is payable by our shareholders, including our ADS holders.
U.S. Taxation
Corporate Tax
Our subsidiary in the United States, Hutchison MediPharma International Inc., which has operations in New Jersey and New York,
is subject to a federal corporate tax of 21%, a New Jersey state income tax of 11.5%, a New York state income tax of 6.5% and other
local taxes.
Material U.S. Federal Income Tax Considerations with Respect to Ordinary Shares and ADSs
The following summary, subject to the limitations set forth below, describes the material U.S. federal income tax consequences for
a U.S. Holder (as defined below) of the acquisition, ownership and disposition of ordinary shares and ADSs. It is not a comprehensive
description of all tax considerations that may be relevant to a particular person’s decision to acquire securities. This discussion is limited
to U.S. Holders who hold such ordinary shares or ADSs as capital assets within the meaning of Section 1221 of the Internal Revenue
Code of 1986, as amended, or the Code, for tax purposes (generally, property held for investment). For purposes of this summary, a
“U.S. Holder” is a beneficial owner of an ordinary share or ADS that is for U.S. federal income tax purposes:
•
•
•
•
a citizen or individual resident of the United States;
a corporation (or any other entity treated as a corporation for U.S. federal income tax purposes) organized in or under the laws
of the United States or any state thereof, or the District of Columbia;
an estate the income of which is subject to U.S. federal income taxation regardless of its source; or
a trust if (i) it has a valid election in effect to be treated as a U.S. person for U.S. federal income tax purposes or (ii) a U.S.
court can exercise primary supervision over its administration and one or more U.S. persons have the authority to control all of
its substantial decisions.
Except as explicitly set forth below, this summary does not address aspects of U.S. federal income taxation that may be applicable
to U.S. Holders subject to special rules, including:
•
•
•
•
•
•
•
•
•
banks or other financial institutions;
insurance companies;
real estate investment trusts;
regulated investment companies;
grantor trusts;
tax-exempt organizations;
persons holding our ordinary shares or ADSs through a partnership (including an entity or arrangement treated as a partnership
for U.S. federal income tax purposes) or S corporation;
dealers or traders in securities, commodities or currencies;
persons whose functional currency is not the U.S. dollar;
• U.S. expatriates and certain former citizens or former long-term residents of the United States;
194
•
•
•
persons required under Section 451(b) of the Code to conform to the timing of income accruals with respect to our ADSs or
the ordinary shares represented by such ADSs;
persons holding our ordinary shares or ADSs as part of a position in a straddle or as part of a hedging, conversion or integrated
transaction for U.S. federal income tax purposes; or
direct, indirect or constructive owners of 10% or more of our equity (by vote or value).
In addition, this summary does not address the U.S. federal estate and gift tax or the alternative minimum tax consequences of the
acquisition, ownership, and disposition of our ordinary shares or ADSs. We have not received nor do we expect to seek a ruling from
the U.S. Internal Revenue Service, or the IRS, regarding any matter discussed herein. No assurance can be given that the IRS would not
assert, or that a court would not sustain, a position contrary to any of those set forth below. Each prospective investor should consult its
own tax advisors with respect to the U.S. federal, state, local and non-U.S. tax consequences of acquiring, owning and disposing of our
ordinary shares and ADSs.
This discussion is based on the Code, U.S. Treasury Regulations promulgated thereunder and administrative and judicial
interpretations thereof, and the income tax treaty between the PRC and the United States, or the U.S.- PRC Tax Treaty, each as available
and in effect on the date hereof, all of which are subject to change or differing interpretations, possibly with retroactive effect, which
could affect the tax consequences described herein. In addition, this summary assumes representations made by the depositary to us in
the deposit agreement are true and assumes that the deposit agreement, and all other related agreements, will be performed in accordance
with their terms.
If an entity or arrangement treated as a partnership for U.S. federal income tax purposes holds our ordinary shares or ADSs, the tax
treatment of the partnership and a partner in such partnership generally will depend on the status of the partner and the activities of the
partnership. Such partner or partnership should consult its own tax advisors as to the U.S. federal income tax consequences of acquiring,
owning and disposing of our ordinary shares or ADSs.
PROSPECTIVE INVESTORS SHOULD CONSULT THEIR OWN TAX ADVISORS WITH REGARD TO THE PARTICULAR
TAX CONSEQUENCES APPLICABLE TO THEIR SITUATIONS AS WELL AS THE APPLICATION OF ANY U.S. FEDERAL,
STATE, LOCAL, NON-U.S. OR OTHER TAX LAWS, INCLUDING GIFT AND ESTATE TAX LAWS.
ADSs
A U.S. Holder of ADSs will generally be treated, for U.S. federal income tax purposes, as the owner of the underlying ordinary
shares that such ADSs represent. Accordingly, no gain or loss will be recognized if a U.S. Holder exchanges ADSs for the underlying
shares represented by those ADSs.
The U.S. Treasury has expressed concern that parties to whom ADSs are released before shares are delivered to the depositary or
intermediaries in the chain of ownership between holders and the issuer of the security underlying the ADSs, may be taking actions that
are inconsistent with the claiming of foreign tax credits by U.S. Holders of ADSs. These actions would also be inconsistent with the
claiming of the reduced rate of tax, described below, applicable to dividends received by certain non-corporate U.S. Holders.
Accordingly, the creditability of non-U.S. withholding taxes (if any), and the availability of the reduced tax rate for dividends received
by certain non-corporate U.S. Holders, each described below, could be affected by actions taken by such parties or intermediaries. For
purposes of the discussion below, we assume that intermediaries in the chain of ownership between the holder of an ADS and us are
acting consistently with the claim of U.S. foreign tax credits by U.S. Holders.
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Taxation of Dividends
As described in “Dividend Policy” above, we do not currently anticipate paying any distributions on our ordinary shares or ADSs
in the foreseeable future. However, to the extent there are any distributions made with respect to our ordinary shares or ADSs, and
subject to the discussion under “—Passive Foreign Investment Company Considerations” below, the gross amount of any such
distribution (including withheld taxes, if any) made out of our current or accumulated earnings and profits (as determined for U.S.
federal income tax purposes) will generally be taxable to a U.S. Holder as ordinary dividend income on the date such distribution is
actually or constructively received. Distributions in excess of our current and accumulated earnings and profits will be treated as a non-
taxable return of capital to the extent of the U.S. Holder’s adjusted tax basis in the ordinary shares or ADSs, as applicable, and thereafter
as capital gain. However, because we do not maintain calculations of our earnings and profits in accordance with U.S. federal income
tax accounting principles, U.S. Holders should expect to treat distributions paid with respect to our ordinary shares and ADSs as
dividends. Dividends paid to corporate U.S. Holders generally will not qualify for the dividends received deduction that may otherwise
be allowed under the Code. This discussion assumes that distributions made by us, if any, will be paid in U.S. dollars.
Dividends paid to a non-corporate U.S. Holder by a “qualified foreign corporation” may be subject to reduced rates of U.S. federal
income taxation if certain holding period and other requirements are met. A qualified foreign corporation generally includes a foreign
corporation (other than a PFIC) if (1) its ordinary shares (or ADSs backed by ordinary shares) are readily tradable on an established
securities market in the United States or (2) it is eligible for benefits under a comprehensive U.S. income tax treaty that includes an
exchange of information program and which the U.S. Treasury Department has determined is satisfactory for these purposes.
IRS guidance indicates that our ADSs (which are listed on the Nasdaq Global Select Market) are readily tradable for purposes of
satisfying the conditions required for these reduced tax rates. We do not expect, however, that our ordinary shares will be listed on an
established securities market in the United States and therefore do not believe that any dividends paid on our ordinary shares that are
not represented by ADSs currently meet the conditions required for these reduced tax rates. There can be no assurance that our ADSs
will be considered readily tradable on an established securities market in subsequent years.
The United States does not have a comprehensive income tax treaty with the Cayman Islands. However, in the event that we were
deemed to be a PRC resident enterprise under the EIT Law (see “—Taxation in the PRC” above), although no assurance can be given,
we might be considered eligible for the benefits of the U.S.-PRC Tax Treaty for purposes of these rules. U.S. Holders should consult
their own tax advisors regarding the availability of the reduced tax rates on dividends paid with respect to our ordinary shares or ADSs
in light of their particular circumstances.
Non-corporate U.S. Holders will not be eligible for reduced rates of U.S. federal income taxation on any dividends received from
us if we are a PFIC in the taxable year in which such dividends are paid or in the preceding taxable year unless, under certain
circumstances, the “deemed sale election” described below under “—Passive Foreign Investment Company Considerations—Status as
a PFIC” has been made.
In the event that we were deemed to be a PRC resident enterprise under the EIT Law (see “—Taxation in the PRC” above), U.S.
Holders might be subject to PRC withholding taxes on dividends paid by us. In that case, subject to certain conditions and limitations,
such PRC withholding tax may be treated as a foreign tax eligible for credit against a U.S. Holder’s U.S. federal income tax liability
under the U.S. foreign tax credit rules. For purposes of calculating the U.S. foreign tax credit, dividends paid on our ordinary shares or
ADSs, will be treated as income from sources outside the United States and will generally constitute passive category income. If a U.S.
Holder is eligible for U.S.-PRC Tax Treaty benefits, any PRC taxes on dividends will not be creditable against such U.S. Holder’s U.S.
federal income tax liability to the extent such tax is withheld at a rate exceeding the applicable U.S.-PRC Tax Treaty rate. An eligible
U.S. Holder who does not elect to claim a foreign tax credit for PRC tax withheld may instead be eligible to claim a deduction, for U.S.
federal income tax purposes, in respect of such withholding but only for the year in which such U.S. Holder elects to do so for all
creditable foreign income taxes. The U.S. foreign tax credit rules are complex. U.S. Holders should consult their own tax advisors
regarding the foreign tax credit rules in light of their particular circumstances.
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Taxation of Capital Gains
Subject to the discussion below in “—Passive Foreign Investment Company Considerations,” upon the sale, exchange, or other
taxable disposition of our ordinary shares or ADSs, a U.S. Holder generally will recognize gain or loss in an amount equal to the
difference between the amount realized on such sale or exchange (determined in the case of sales or exchanges in currencies other than
U.S. dollars by reference to the spot exchange rate in effect on the date of the sale or exchange or, if sold or exchanged on an established
securities market and the U.S. Holder is a cash basis taxpayer or an electing accrual basis taxpayer, the spot exchange rate in effect on
the settlement date) and the U.S. Holder’s adjusted tax basis in such ordinary shares or ADSs determined in U.S. dollars. A U.S. Holder’s
initial tax basis will be the U.S. Holder’s U.S. dollar purchase price for such ordinary shares or ADSs.
Assuming we are not a PFIC and have not been treated as a PFIC during the U.S. Holder’s holding period for its ordinary shares or
ADSs, such gain or loss will be capital gain or loss. Under current law, capital gains of non-corporate U.S. Holders derived with respect
to capital assets held for more than one year are generally eligible for reduced rates of taxation. The deductibility of capital losses is
subject to limitations. Capital gain or loss, if any, recognized by a U.S. Holder generally will be treated as U.S. source income or loss
for U.S. foreign tax credit purposes. U.S. Holders are encouraged to consult their own tax advisors regarding the availability of the U.S.
foreign tax credit in consideration of their particular circumstances.
If we were treated as a PRC resident enterprise for EIT Law purposes and PRC tax were imposed on any gain (see “—Taxation in
the PRC” above), and if a U.S. Holder is eligible for the benefits of the U.S.-PRC Tax Treaty, the holder may be able to treat such gain
as PRC source gain under the treaty for U.S. foreign tax credit purposes. A U.S. Holder will be eligible for U.S.-PRC Tax Treaty benefits
if (for purposes of the treaty) such holder is a resident of the United States and satisfies the other requirements specified in the U.S.-
PRC Tax Treaty. Because the determination of treaty benefit eligibility is fact-intensive and depends upon a holder’s particular
circumstances, U.S. Holders should consult their tax advisors regarding U.S.-PRC Tax Treaty benefit eligibility. U.S. Holders are also
encouraged to consult their own tax advisors regarding the tax consequences in the event PRC tax were to be imposed on a disposition
of ordinary shares or ADSs, including the availability of the U.S. foreign tax credit and the ability and whether to treat any gain as PRC
source gain for the purposes of the U.S. foreign tax credit in consideration of their particular circumstances.
Additional Tax on Net Investment Income
An additional 3.8% tax is imposed on the “net investment income” of certain U.S. citizens and resident aliens, and on the
undistributed “net investment income” of certain estates and trusts. Among other items, “net investment income” would generally
include dividends on and gains from the sale or other disposition of ordinary shares or ADSs. You should consult your own tax advisor
regarding the application of this tax.
Passive Foreign Investment Company Considerations
Status as a PFIC. The rules governing PFICs can result in adverse tax consequences to U.S. Holders. We generally will be
classified as a PFIC for U.S. federal income tax purposes if, for any taxable year, either: (1) 75% or more of our gross income consists
of certain types of passive income, or (2) the average value (determined on a quarterly basis), of our assets that produce, or are held for
the production of, passive income is 50% or more of the value of all of our assets.
Passive income generally includes dividends, interest, rents and royalties (other than certain rents and royalties derived in the active
conduct of a trade or business), annuities and gains from assets that produce passive income. If a non-U.S. corporation owns at least
25% by value of the stock of another corporation, the non-U.S. corporation is treated for purposes of the PFIC tests as owning its
proportionate share of the assets of the other corporation and as receiving directly its proportionate share of the other corporation’s
income. Under this rule, we should be deemed to own a proportionate share of the assets and to have received a proportionate share of
the income of our principal subsidiaries, including Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
and Shanghai Hutchison Pharmaceuticals Limited, for purposes of the PFIC determination.
Additionally, if we are classified as a PFIC in any taxable year with respect to which a U.S. Holder owns ordinary shares or ADSs,
we generally will continue to be treated as a PFIC with respect to such U.S. Holder in all succeeding taxable years, regardless of whether
we continue to meet the tests described above, unless the U.S. Holder makes the “deemed sale election” described below. Furthermore,
if we are treated as a PFIC, then one or more of our subsidiaries may also be treated as PFICs.
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Based on certain estimates of our gross income and gross assets (which estimates are inherently imprecise) and the nature of our
business, we do not believe that we are currently a PFIC. Notwithstanding the foregoing, the determination of whether we are a PFIC is
made annually and depends on particular facts and circumstances (such as the valuation of our assets, including goodwill and other
intangible assets) and also may be affected by the application of the PFIC rules, which are subject to differing interpretations. The fair
market value of our assets is expected to depend, in part, upon (a) the market price of our ADSs, which is likely to fluctuate, and (b) the
composition of our income and assets, which will be affected by how, and how quickly, we spend any cash that is raised in any financing
transaction. In light of the foregoing, no assurance can be provided that we are not currently a PFIC or that we will not become a PFIC
in any future taxable year. Prospective investors should consult their own tax advisors regarding our PFIC status.
U.S. federal income tax treatment of a shareholder of a PFIC. If we are classified as a PFIC for any taxable year during which
a U.S. Holder owns ordinary shares or ADSs, the U.S. Holder, absent certain elections (including the mark-to-market and QEF elections
described below), generally will be subject to adverse rules (regardless of whether we continue to be classified as a PFIC) with respect
to (1) any “excess distributions” (generally, any distributions received by the U.S. Holder on its ordinary shares or ADSs in a taxable
year that are greater than 125% of the average annual distributions received by the U.S. Holder in the three preceding taxable years or,
if shorter, the U.S. Holder’s holding period) and (2) any gain realized on the sale or other disposition, including a pledge, of such
ordinary shares or ADSs.
Under these rules (a) the excess distribution or gain will be allocated ratably over the U.S. Holder’s holding period, (b) the amount
allocated to the current taxable year and any taxable year prior to the first taxable year in which we are classified as a PFIC will be taxed
as ordinary income and (c) the amount allocated to each other taxable year during the U.S. Holder’s holding period in which we were
classified as a PFIC (i) will be subject to tax at the highest rate of tax in effect for the applicable category of taxpayer for that year and
(ii) will be subject to an interest charge at a statutory rate with respect to the resulting tax attributable to each such other taxable year. In
addition, non-corporate U.S. Holders will not be eligible for reduced rates of taxation on any dividends received from us if we are a
PFIC in the taxable year in which such dividends are paid or in the preceding taxable year.
If we are classified as a PFIC, a U.S. Holder will generally be treated as owning a proportionate amount (by value) of stock or
shares owned by us in any direct or indirect subsidiaries that are also PFICs and will be subject to similar adverse rules with respect to
any distributions we receive from, and dispositions we make of, the stock or shares of such subsidiaries. U.S. Holders are urged to
consult their tax advisors about the application of the PFIC rules to any of our subsidiaries.
If we are classified as a PFIC and then cease to be so classified, a U.S. Holder may make an election (a “deemed sale election”) to
be treated for U.S. federal income tax purposes as having sold such U.S. Holder’s ordinary shares or ADSs on the last day of our taxable
year during which we were a PFIC. A U.S. Holder that makes a deemed sale election would then cease to be treated as owning stock in
a PFIC. However, gain recognized as a result of making the deemed sale election would be subject to the adverse rules described above
and loss would not be recognized.
PFIC “mark-to-market” election. In certain circumstances, a holder of “marketable stock” of a PFIC can avoid certain of the
adverse rules described above by making a timely mark-to-market election with respect to such stock. For purposes of these rules
“marketable stock” is stock which is “regularly traded” (traded in greater than de minimis quantities on at least 15 days during each
calendar quarter) on a “qualified exchange” or other market within the meaning of applicable U.S. Treasury Regulations. A “qualified
exchange” includes a national securities exchange that is registered with the SEC.
A U.S. Holder that makes a timely mark-to-market election must include in gross income, as ordinary income, for each taxable year
that we are a PFIC an amount equal to the excess, if any, of the fair market value of the U.S. Holder’s ordinary shares or ADSs that are
“marketable stock” at the close of the taxable year over the U.S. Holder’s adjusted tax basis in such ordinary shares or ADSs. An electing
U.S. Holder may also claim an ordinary loss deduction for the excess, if any, of the U.S. Holder’s adjusted tax basis in such ordinary
shares or ADSs over their fair market value at the close of the taxable year, but this deduction is allowable only to the extent of any net
mark-to-market gains previously included in income pursuant to the timely mark-to-market election. The adjusted tax basis of a U.S.
Holder’s ordinary shares or ADSs with respect to which the timely mark-to-market election applies would be adjusted to reflect amounts
included in gross income or allowed as a deduction because of such election. If a U.S. Holder makes an effective mark-to-market election
with respect to our ordinary shares or ADSs, gains from an actual sale or other disposition of such ordinary shares or ADSs in a year in
which we are a PFIC would be treated as ordinary income, and any losses incurred on such sale or other disposition would be treated as
ordinary losses to the extent of any net mark-to-market gains previously included in income.
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If we are classified as a PFIC for any taxable year in which a U.S. Holder owns ordinary shares or ADSs but before a timely mark-
to-market election is made, the adverse PFIC rules described above will apply to any mark-to-market gain recognized in the year the
election is made. Otherwise, a timely mark-to-market election will be effective for the taxable year for which the election is made and
all subsequent taxable years unless the ordinary shares or ADSs are no longer regularly traded on a qualified exchange or the IRS
consents to the revocation of the election. Our ADSs are listed on the Nasdaq Global Select Market, which is a qualified exchange or
other market for purposes of the mark-to-market election. Consequently, if the ADSs continue to be so listed, and are “regularly traded”
for purposes of these rules (for which no assurance can be given) we expect that the mark-to-market election would be available to a
U.S. Holder with respect to our ADSs.
A mark-to-market election is not permitted for the shares of any of our subsidiaries that are also classified as PFICs. Prospective
investors should consult their own tax advisors regarding the availability of, and the procedure for, and the effect of making, a mark-to-
market election, and whether making the election would be advisable, including in light of their particular circumstances.
PFIC “QEF” election. In some cases, a shareholder of a PFIC can avoid the interest charge and the other adverse PFIC tax
consequences described above by obtaining certain information from the PFIC and by making a timely QEF election to be taxed currently
on its share of the PFIC’s undistributed income. We do not, however, expect to provide the information regarding our income that would
be necessary in order for a U.S. Holder to make a timely QEF election if we were classified as a PFIC.
PFIC information reporting requirements. If we are classified as a PFIC in any year with respect to a U.S. Holder, such U.S.
Holder will be required to file an annual information return on IRS Form 8621 regarding distributions received on, and any gain realized
on the disposition of, our ordinary shares and ADSs, and certain U.S. Holders will be required to file an annual information return (also
on IRS Form 8621) relating to their ownership interest.
NO ASSURANCE CAN BE GIVEN THAT WE ARE NOT CURRENTLY A PFIC OR THAT WE WILL NOT BECOME A PFIC
IN THE FUTURE. U.S. HOLDERS SHOULD CONSULT THEIR OWN TAX ADVISORS WITH RESPECT TO THE OPERATION
OF THE PFIC RULES AND RELATED REPORTING REQUIREMENTS IN LIGHT OF THEIR PARTICULAR
CIRCUMSTANCES, INCLUDING THE ADVISABILITY AND EFFECTS OF MAKING ANY ELECTION THAT MAY BE
AVAILABLE.
Backup Withholding and Information Reporting and Filing Requirements
Backup withholding and information reporting requirements may apply to distributions on, and proceeds from the sale or disposition
of, ordinary shares and ADSs that are held by U.S. Holders. The payor will be required to withhold tax (currently at a rate of 24%) on
such payments made within the United States, or by a U.S. payor or a U.S. intermediary (and certain subsidiaries thereof) to a U.S.
Holder, other than an exempt recipient, if the U.S. Holder is not otherwise exempt and:
•
•
•
•
the holder fails to furnish the holder’s taxpayer identification number, which for an individual is ordinarily his or her social
security number;
the holder furnishes an incorrect taxpayer identification number;
the applicable withholding agent is notified by the IRS that the holder previously failed to properly report payments of interest
or dividends; or
the holder fails to certify under penalties of perjury that the holder has furnished a correct taxpayer identification number and
that the IRS has not notified the holder that the holder is subject to backup withholding.
Backup withholding is not an additional tax. Amounts withheld as backup withholding may be credited against a U.S. Holder’s
U.S. federal income tax liability (if any) or refunded provided the required information is furnished to the IRS in a timely manner. U.S.
Holders should consult their tax advisors regarding their qualification for an exemption from backup withholding and the procedures
for obtaining such an exemption.
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Certain U.S. Holders of specified foreign financial assets with an aggregate value in excess of the applicable dollar threshold are
required to report information relating to their holding of ordinary shares or ADSs, subject to certain exceptions (including an exception
for shares held in accounts maintained by certain financial institutions) with their tax returns for each year in which they hold such
interests. U.S. Holders should consult their own tax advisors regarding the information reporting obligations that may arise from their
acquisition, ownership or disposition of our ordinary shares or ADSs.
THE ABOVE DISCUSSION DOES NOT COVER ALL TAX MATTERS THAT MAY BE OF IMPORTANCE TO A
PARTICULAR INVESTOR. PROSPECTIVE INVESTORS ARE STRONGLY URGED TO CONSULT THEIR OWN TAX
ADVISORS ABOUT THE TAX CONSEQUENCES OF AN INVESTMENT IN OUR ORDINARY SHARES OR ADSs.
F. Dividends and Payment Agents.
Not applicable.
G. Statement by Experts.
Not applicable.
H. Documents on Display.
We are subject to the informational requirements of the Exchange Act and are required to file reports and other information with
the SEC. Shareholders may access our reports and other information filed with the SEC by viewing them on the SEC’s website, at
www.sec.gov. We also make available on our website’s investor relations page, free of charge, our annual report and the text of our
reports on Form 6-K, including any amendments to these reports, as well as certain other SEC filings, as soon as reasonably practicable
after they are electronically filed with or furnished to the SEC. The address for our investor relations page is www.chi-med.com/
shareholder-information. The information contained on our website is not incorporated by reference in this annual report.
We are a “foreign private issuer” as such term is defined in Rule 405 under the Securities Act, and are not subject to the same
requirements that are imposed upon U.S. domestic issuers by the SEC. Under the Exchange Act, we are subject to reporting obligations
that, in certain respects, are less detailed and less frequent than those of U.S. domestic reporting companies. As a result, we do not file
the same reports that a U.S. domestic issuer would file with the SEC, although we are required to file or furnish to the SEC the continuous
disclosure documents that we are required to file on the AIM market of the London Stock Exchange.
We will furnish Deutsche Bank Trust Company Americas, the depositary of our ADSs, with our annual reports, which will include
a review of operation and annual audited consolidated financial statements prepared in conformity with U.S. GAAP, and all notices of
shareholders’ meetings and other reports and communications that are made generally available to our shareholders. The depositary will
make such notices, reports and communications available to holders of ADSs and, upon our requests, will mail to all record holders of
ADSs the information contained in any notice of a shareholders’ meeting received by the depositary from us.
I. Subsidiary information
Not applicable.
ITEM 11. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
Please see Item 5.F. “Operating and Financial Review and Prospects—Quantitative and Qualitative Disclosures About Market
Risk.”
ITEM 12. DESCRIPTION OF SECURITIES OTHER THAN EQUITY SECURITIES
A. Debt Securities
Not applicable.
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B. Warrants and Rights.
Not applicable.
C. Other Securities.
Not applicable.
D. American Depositary Shares.
Fees and charges our ADS holders may have to pay
ADS holders will be required to pay the following service fees to Deutsche Bank Trust Company America, the depositary of our
ADS program, and certain taxes and governmental charges (in addition to any applicable fees, expenses, taxes and other governmental
charges payable on the deposited securities represented by ADSs):
Service
• To any person to which ADSs are issued or to any person to which a distribution is made in
respect of ADS distributions pursuant to stock dividends or other free distributions of stock,
bonus distributions, stock splits or other distributions (except where converted to cash)
Fees
Up to $0.05 per ADS issued
• Cancellation or withdrawal of ADSs, including the case of termination of the deposit agreement Up to $0.05 per ADS cancelled
• Distribution of cash dividends
• Distribution of cash entitlements (other than cash dividends) and/or cash proceeds from the sale
Up to $0.05 per ADS held
Up to $0.05 per ADS held
of rights, securities and other entitlements
• Distribution of ADSs pursuant to exercise of rights
• Depositary services
Up to $0.05 per ADS held
Up to $0.05 per ADS held on
the applicable record date(s)
established by the depositary
bank (an annual fee)
ADS holders will also be responsible to pay certain fees and expenses incurred by the depositary bank and certain taxes and
governmental charges (in addition to any applicable fees, expenses, taxes and other governmental charges payable on the deposited
securities represented by any of your ADSs) such as:
• Fees for the transfer and registration of ordinary shares charged by the registrar and transfer agent for the ordinary shares in the
Cayman Islands (i.e., upon deposit and withdrawal of ordinary shares).
• Expenses incurred for converting foreign currency into U.S. dollars.
• Expenses for cable, telex and fax transmissions and for delivery of securities.
• Taxes and duties upon the transfer of securities, including any applicable stamp duties, any stock transfer charges or
withholding taxes (i.e., when ordinary shares are deposited or withdrawn from deposit).
• Fees and expenses incurred in connection with the delivery or servicing of ordinary shares on deposit.
• Fees and expenses incurred in connection with complying with exchange control regulations and other regulatory requirements
applicable to ordinary shares, ordinary shares deposited securities, ADSs and ADRs.
• Any applicable fees and penalties thereon.
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The depositary fees payable upon the issuance and cancellation of ADSs are typically paid to the depositary bank by the brokers
(on behalf of their clients) receiving the newly issued ADSs from the depositary bank and by the brokers (on behalf of their clients)
delivering the ADSs to the depositary bank for cancellation. The brokers in turn charge these fees to their clients. Depositary fees payable
in connection with distributions of cash or securities to ADS holders and the depositary services fee are charged by the depositary bank
to the holders of record of ADSs as of the applicable ADS record date.
The depositary fees payable for cash distributions are generally deducted from the cash being distributed or by selling a portion of
distributable property to pay the fees. In the case of distributions other than cash (i.e., share dividends, rights), the depositary bank
charges the applicable fee to the ADS record date holders concurrent with the distribution. In the case of ADSs registered in the name
of the investor (whether certificated or uncertificated in direct registration), the depositary bank sends invoices to the applicable record
date ADS holders. In the case of ADSs held in brokerage and custodian accounts (via DTC), the depositary bank generally collects its
fees through the systems provided by DTC (whose nominee is the registered holder of the ADSs held in DTC) from the brokers and
custodians holding ADSs in their DTC accounts. The brokers and custodians who hold their clients’ ADSs in DTC accounts in turn
charge their clients’ accounts the amount of the fees paid to the depositary banks.
In the event of refusal to pay the depositary fees, the depositary bank may, under the terms of the deposit agreement, refuse the
requested service until payment is received or may set off the amount of the depositary fees from any distribution to be made to the ADS
holder.
The depositary has agreed to pay certain amounts to us in exchange for its appointment as depositary. We may use these funds
towards our expenses relating to the establishment and maintenance of the ADR program, including investor relations expenses, or
otherwise as we see fit. In 2020, we did not collect any reimbursements from the depositary for expenses related to the administration
and maintenance of the facility.
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ITEM 13. DEFAULTS, DIVIDEND ARREARAGES AND DELINQUENCIES
PART II
None.
ITEM 14. MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS
A-D. Material Modifications to the Rights of Security Holders; Assets Securing Securities; Trustees; Paying Agents
None.
E. Use of Proceeds
Not applicable.
ITEM 15. CONTROLS AND PROCEDURES
A. Evaluation of Disclosure Controls and Procedures.
As required by Rule 13a-15 under the Exchange Act, management, including our chief executive officer and our chief financial
officer, has evaluated the effectiveness of our disclosure controls and procedures as of the end of the period covered by this report.
Disclosure controls and procedures refer to controls and other procedures designed to ensure that information required to be disclosed
in the reports we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods
specified in the rules and forms of the SEC. Disclosure controls and procedures include, without limitation, controls and procedures
designed to ensure that information required to be disclosed by us in our reports that we file or submit under the Exchange Act is
accumulated and communicated to management, including our principal executive and principal financial officers, or persons
performing similar functions, as appropriate to allow timely decisions regarding our required disclosure. Based on such evaluation, our
management has concluded that, as of December 31, 2020, our disclosure controls and procedures were effective.
B. Management’s Annual Report on Internal Control over Financial Reporting.
Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as defined in
Rule 13a-15(f) and 15d-15(f) promulgated under the Securities Exchange Act of 1934. Internal control over financial reporting is a
process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of consolidated
financial statements in accordance with U.S. GAAP and includes those policies and procedures that (1) pertain to the maintenance of
records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of a company’s assets; (2) provide
reasonable assurance that transactions are recorded as necessary to permit preparation of consolidated financial statements in accordance
with generally accepted accounting principles, and that a company’s receipts and expenditures are being made only in accordance with
authorizations of a company’s management and directors; and (3) provide reasonable assurance regarding prevention or timely detection
of unauthorized acquisition, use, or disposition of a company’s assets that could have a material effect on the consolidated financial
statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Projections of
any evaluation of effectiveness of our internal control over financial reporting to future periods are subject to the risk that controls may
become inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
Our management, with the participation of our chief executive officer and chief financial officer, has assessed the effectiveness of
our internal control over financial reporting as of December 31, 2020. In making this assessment, our management used the criteria set
forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in Internal Control-Integrated Framework
(2013 Framework). Based on this assessment, management concluded that our internal control over financial reporting was effective as
of December 31, 2020.
203
C. Attestation Report of the Independent Registered Public Accounting Firm.
Our independent registered public accounting firm, PricewaterhouseCoopers, has audited the effectiveness of our internal control
over financial reporting as of December 31, 2020, as stated in its report, which appears on page F-2 of this annual report.
D. Changes in Internal Control over Financial Reporting.
There were no changes in our internal controls over financial reporting during the fiscal year ended December 31, 2020 that have
materially and adversely affected, or are reasonably likely to materially and adversely affect, our internal control over financial reporting.
ITEM 16. RESERVED
ITEM 16A. AUDIT COMMITTEE FINANCIAL EXPERTS
Our audit committee consists of Graeme Jack, Paul Carter and Karen Ferrante, with Graeme Jack serving as chairman of the
committee. Graeme Jack, Paul Carter and Karen Ferrante each meet the independence requirements under the rules of the Nasdaq Stock
Market and under Rule 10A-3 under the Exchange Act. We have determined that Graeme Jack is an “audit committee financial expert”
within the meaning of Item 407 of Regulation S-K. All members of our audit committee meet the requirements for financial literacy
under the applicable rules and regulations of the SEC and the Nasdaq Stock Market. For information relating to qualifications and
experience of each audit committee member, see Item 6. “Directors, Senior Management and Employees.”
ITEM 16B. CODE OF ETHICS
Our board of directors has adopted a code of ethics applicable to all of our employees, officers and directors, including our principal
executive officer, principal financial officer, principal accounting officer or controller, and persons performing similar functions. This
code is intended to qualify as a “code of ethics” within the meaning of the applicable rules of the SEC. Our code of ethics is available
on our website at www.chi-med.com/shareholder-information/terms-of-reference-policies/code-of-ethics/. Information contained on, or
that can be accessed through, our website is not incorporated by reference into this annual report. See Item 6.C. “Board Practices—Code
of Ethics” for more information.
ITEM 16C. PRINCIPAL ACCOUNTANT FEES AND SERVICES
Principal Accountant Fees and Services
The following table summarizes the fees charged by PricewaterhouseCoopers for certain services rendered to our company,
including some of our subsidiaries and joint ventures, during 2019 and 2020.
Audit fees(1)
Tax fees(2)
Other service fees(3)
Total(4)
Notes:
For the year ended
December 31,
2020
2019
(in thousands)
3,289
45
90
3,424
3,586
51
90
3,727
(1) “Audit fees” means the aggregate fees billed in each of the fiscal years for professional services rendered by
PricewaterhouseCoopers for the audit of our annual financial statements and review of our interim financial statements,
filing of our Form F-3 and S-8 and professional services paid by us in connection with follow-on offerings in the United
States and preparation for other capital market transactions.
(2) “Tax fees” means the aggregate fees billed in each of the fiscal years for professional services rendered by
PricewaterhouseCoopers for tax compliance and tax advice.
204
(3) “Other service fees” means the aggregate fees billed for professional services rendered by PricewaterhouseCoopers for
information technology system and security review.
(4) The fees disclosed are exclusive of out-of-pocket expenses and taxes on the amounts paid, which totaled approximately
$237,000 and $164,000 in 2019 and 2020, respectively.
Audit Committee Pre-approval Policies and Procedures
Our audit committee reviews and pre-approves the scope and the cost of audit services related to us and permissible non-audit
services performed by the independent auditors, other than those for de minimis services which are approved by the audit committee
prior to the completion of the audit. All of the services related to our company provided by PricewaterhouseCoopers listed above have
been approved by the audit committee.
ITEM 16D. Exemptions From The Listing Standards For Audit Committees
Not applicable.
ITEM 16E. Purchases of Equity Securities by the Issuer and Affiliated Purchasers
None.
ITEM 16F. CHANGE IN REGISTRANT’S CERTIFYING ACCOUNTANT
Not applicable.
ITEM 16G. CORPORATE GOVERNANCE
As permitted by Nasdaq, in lieu of the Nasdaq corporate governance rules, but subject to certain exceptions, we may follow the
practices of our home country which for the purpose of such rules is the Cayman Islands. Certain corporate governance practices in the
Cayman Islands may differ significantly from corporate governance listing standards as, except for general fiduciary duties and duties
of care, Cayman Islands law has no corporate governance regime which prescribes specific corporate governance standards. For
example, we follow Cayman Islands corporate governance practices in lieu of the corporate governance requirements of the Nasdaq
Global Select Market in respect of the following:
(i)
the majority independent director requirement under Section 5605(b)(1) of the Nasdaq listing rules,
(ii) the requirement under Section 5605(d) of the Nasdaq listing rules that a remuneration committee comprised solely of
independent directors governed by a remuneration committee charter oversee executive compensation, and
(iii) the requirement under Section 5605(e) of the Nasdaq listing rules that director nominees be selected or recommended for
selection by either a majority of the independent directors or a nominations committee comprised solely of independent
directors.
Cayman Islands law does not impose a requirement that our board of directors consist of a majority of independent directors. Nor
does Cayman Islands law impose specific requirements on the establishment of a remuneration committee or nominating committee or
nominating process. We voluntarily comply with certain principles of the U.K. Corporate Governance Code. See Item 6.C. “Board
Practice—U.K. Corporate Governance Code” for more details.
ITEM 16H. MINE SAFETY DISCLOSURE
Not applicable.
205
PART III
ITEM 17. FINANCIAL STATEMENTS
See Item 18 “Financial Statements.”
ITEM 18. FINANCIAL STATEMENTS
Our consolidated financial statements and the consolidated financial statements of our two non-consolidated joint ventures,
Shanghai Hutchison Pharmaceuticals and Hutchison Baiyunshan, and our former non-consolidated joint venture Nutrition Science
Partners, are included at the end of this annual report.
206
ITEM 19. EXHIBITS
EXHIBIT INDEX
1.1
2.1
2.2
2.3
2.4
2.5
4.1*+
4.2+
4.3+
4.4+
4.5+
4.6
4.7
4.8
4.9+
Amended and Restated Memorandum and Articles of Association of Hutchison China MediTech Limited (incorporated
by reference to Exhibit 1.2 to our annual report on Form 20-F/A filed with the SEC on April 29, 2020)
Form of Deposit Agreement and all holders and beneficial owners of ADSs issued thereunder (incorporated by reference
to Exhibit 4.1 to Amendment No. 4 to our Registration Statement on Form F-1 (file no. 333-207447) filed with the SEC
on March 4, 2016)
Form of American Depositary Receipt (incorporated by reference to Exhibit 4.1 to Amendment No. 4 to our Registration
Statement on Form F-1 (file no. 333-207447) filed with the SEC on March 4, 2016)
Form of Specimen Certificate for Ordinary Shares (incorporated by reference to Exhibit 4.3 to Amendment No. 2 to our
Registration Statement on Form F-1 (file no. 333-207447) filed with the SEC on February 11, 2016)
Description of Ordinary Shares (incorporated by reference to Exhibit 2.4 to our annual report on Form 20-F/A filed with
the SEC on April 29, 2020)
Description of American Depositary Shares (incorporated by reference to Exhibit 2.5 to our annual report on Form 20-
F/A filed with the SEC on April 29, 2020)
Amended and Restated License and Collaboration Agreement by and between Hutchison MediPharma Limited and
AstraZeneca AB (publ) dated as of December 7, 2020
Amended and Restated Exclusive License and Collaboration Agreement by and among Hutchison MediPharma
Limited, Eli Lilly Trading (Shanghai) Company Limited and Hutchison China MediTech Limited dated as of October
8, 2013 (incorporated by reference to Exhibit 4.2 to our annual report on Form 20-F/A filed with the SEC on May 30,
2019)
First Amendment to the Amended and Restated Exclusive License and Collaboration Agreement by and among Lilly
(Shanghai) Management Company Limited, Hutchison MediPharma Limited and Hutchison China MediTech Limited
dated as of December 18, 2018 (incorporated by reference to Exhibit 4.16 to our annual report on Form 20-F filed with
the SEC on March 11, 2019)
English translation of Sino-Foreign Joint Venture Contract by and between Guangzhou Baiyunshan Pharmaceutical
Holdings Company Limited and Hutchison Chinese Medicine (Guangzhou) Investment Limited dated as of November
28, 2004 (incorporated by reference to Exhibit 4.5 to our annual report on Form 20-F/A filed with the SEC on May 30,
2019)
English translation of Sino-Foreign Joint Venture Contract by and between Shanghai Traditional Chinese Medicine Co.,
Ltd. and Hutchison Chinese Medicine (Shanghai) Investment Limited dated as of January 6, 2001 (incorporated by
reference to Exhibit 4.6 to our annual report on Form 20-F/A filed with the SEC on May 30, 2019)
English translation of First Amendment to Sino-Foreign Joint Venture Contract by and between Shanghai Traditional
Chinese Medicine Co., Ltd. and Hutchison Chinese Medicine (Shanghai) Investment Limited dated as of July 12, 2001
(incorporated by reference to Exhibit 10.15 to our Registration Statement on Form F-1 (file no. 333-207447) filed with
the SEC on October 16, 2015)
English translation of Second Amendment to Sino-Foreign Joint Venture Contract by and between Shanghai Traditional
Chinese Medicine Co., Ltd. and Shanghai Hutchison Chinese Medicine (HK) Investment Limited dated as of November
5, 2007 (incorporated by reference to Exhibit 10.16 to our Registration Statement on Form F-1 (file no. 333-207447)
filed with the SEC on October 16, 2015)
English translation of Third Amendment to Sino-Foreign Joint Venture Contract by and between Shanghai Traditional
Chinese Medicine Co., Ltd. and Shanghai Hutchison Chinese Medicine (HK) Investment Limited dated as of June 19,
2012 (incorporated by reference to Exhibit 10.17 to our Registration Statement on Form F-1 (file no. 333-207447) filed
with the SEC on October 16, 2015)
English translation of Fourth Amendment to Sino-Foreign Joint Venture Contract by and between Shanghai Traditional
Chinese Medicine Co., Ltd. and Shanghai Hutchison Chinese Medicine (HK) Investment Limited dated as of March 8,
2013 (incorporated by reference to Exhibit 4.10 to our annual report on Form 20-F/A filed with the SEC on May 30,
2019)
207
4.10
4.11
4.12
4.13
4.14*+
8.1*
12.1*
12.2*
13.1*
13.2*
15.1*
15.2*
15.3*
15.4*
15.5*
101.INS*
101.SCH*
101.CAL*
101.LAB*
101.PRE*
101.DEF*
104*
English translation of Sino-Foreign Joint Venture Contract by and between Sinopharm Group Co. Ltd. and Hutchison
Chinese Medicine GSP (HK) Holdings Limited dated as of December 18, 2013 (incorporated by reference to Exhibit
4.11 to our annual report on Form 20-F/A filed with the SEC on May 30, 2019)
Form of Executive Employment Agreement for Hutchison China MediTech (HK) Limited executive officers
(incorporated by reference to Exhibit 10.23 to our Registration Statement on Form F-1 (file no. 333-207447) filed with
the SEC on October 16, 2015)
English translation of Form of Executive Employment Agreement for Hutchison MediPharma Limited executive
officers (incorporated by reference to Exhibit 10.24 to our Registration Statement on Form F-1 (file no. 333-207447)
filed with the SEC on October 16, 2015)
Form of Indemnification Agreement for Directors and Officers (incorporated by reference to Exhibit 10.25 to our
Registration Statement on Form F-1 (file no. 333-207447) filed with the SEC on October 16, 2015)
Second Amendment to the Amended and Restated Exclusive License and Collaboration Agreement by and among Lilly
(Shanghai) Management Company Limited, Hutchison MediPharma Limited and Hutchison China MediTech Limited
dated as of July 28, 2020
List of Significant Subsidiaries of the Company
Certification of Chief Executive Officer Required by Rule 13a-14(a)
Certification of Chief Financial Officer Required by Rule 13a-14(a)
Certification of Chief Executive Officer Required by Rule 13a-14(b) and Section 1350 of Chapter 63 of Title 18 of the
United States Code
Certification of Acting Chief Financial Officer Required by Rule 13a-14(b) and Section 1350 of Chapter 63 of Title 18
of the United States Code
Consent of PricewaterhouseCoopers, an independent registered accounting firm, regarding the consolidated financial
statements of Hutchison China MediTech Limited
Consent of PricewaterhouseCoopers, an independent registered accounting firm, regarding the consolidated financial
statements of Nutrition Science Partners Limited
Consent of PricewaterhouseCoopers Zhong Tian LLP, independent accountants, regarding the consolidated financial
statements of Shanghai Hutchison Pharmaceuticals Limited
Consent of PricewaterhouseCoopers Zhong Tian LLP, independent accountants, regarding the consolidated financial
statements of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Consent of Conyers Dill & Pearman
XBRL Instance Document
XBRL Taxonomy Extension Schema Document
XBRL Taxonomy Extension Calculation Linkbase Document
XBRL Taxonomy Extension Label Linkbase Document
XBRL Taxonomy Extension Presentation Linkbase Document
XBRL Taxonomy Extension Definitions Linkbase Document
Cover Page Interactive Data File (embedded within the Inline XBRL document)
* Filed herewith.
† Furnished herewith.
+ Portions of the exhibit have been omitted because they are both (i) not material and (ii) would likely cause competitive harm to the
company if publicly disclosed.
208
The registrant hereby certifies that it meets all of the requirements for filing on annual report on Form 20-F and that it has duly
caused and authorized the undersigned to sign this annual report on its behalf.
SIGNATURES
Date: March 4, 2021
Hutchison China MediTech Limited
By:
/s/ CHRISTIAN HOGG
Name: Christian Hogg
Title: Chief Executive Officer
209
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Audited Consolidated Financial Statements of Hutchison China MediTech Limited
Report of Independent Registered Public Accounting Firm
As at December 31, 2020 and December 31, 2019:
Consolidated Balance Sheets
For the Years Ended December 31, 2020, 2019 and 2018:
Consolidated Statements of Operations
Consolidated Statements of Comprehensive Loss
Consolidated Statements of Changes in Shareholders’ Equity
Consolidated Statements of Cash Flows
Notes to the Consolidated Financial Statements
Audited Consolidated Financial Statements of Shanghai Hutchison Pharmaceuticals Limited
Report of Independent Auditors
For the Years Ended December 31, 2020, 2019 and 2018:
Consolidated Income Statements
Consolidated Statements of Comprehensive Income
As at December 31, 2020 and December 31, 2019:
Consolidated Statements of Financial Position
For the Years Ended December 31, 2020, 2019 and 2018:
Consolidated Statements of Changes in Equity
Consolidated Statements of Cash Flows
Notes to the Consolidated Financial Statements
Audited Consolidated Financial Statements of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company
Limited
Report of Independent Auditors
For the Years Ended December 31, 2020, 2019 and 2018:
Consolidated Income Statements
Consolidated Statements of Comprehensive Income
As at December 31, 2020 and December 31, 2019:
Consolidated Statements of Financial Position
For the Years Ended December 31, 2020, 2019 and 2018:
Consolidated Statements of Changes in Equity
Consolidated Statements of Cash Flows
Notes to the Consolidated Financial Statements
Audited Consolidated Financial Statements of Nutrition Science Partners Limited
Report of Independent Auditors
For the Period Ended December 9, 2019 and the Year Ended December 31, 2018:
Consolidated Income Statements
Consolidated Statements of Comprehensive Income/(Loss)
As at December 9, 2019:
Consolidated Statement of Financial Position
For the Period Ended December 9, 2019 and the Year Ended December 31, 2018:
Consolidated Statements of Changes in Equity
Consolidated Statements of Cash Flows
Notes to the Consolidated Financial Statements
F-1
F-2
F-4
F-5
F-6
F-7
F-8
F-9
F-48
F-49
F-50
F-51
F-52
F-53
F-54
F-75
F-76
F-77
F-78
F-79
F-80
F-81
F-107
F-108
F-109
F-110
F-111
F-112
F-113
Report of Independent Registered Public Accounting Firm
To the Board of Directors and Shareholders of Hutchison China MediTech Limited
Opinions on the Financial Statements and Internal Control over Financial Reporting
We have audited the accompanying consolidated balance sheets of Hutchison China MediTech Limited and its subsidiaries (the
“Company”) as of December 31, 2020 and 2019, and the related consolidated statements of operations, of comprehensive loss, of
changes in shareholders’ equity and of cash flows for each of the three years in the period ended December 31, 2020, including the
related notes (collectively referred to as the “consolidated financial statements”). We also have audited the Company’s internal control
over financial reporting as of December 31, 2020, based on criteria established in Internal Control–Integrated Framework (2013) issued
by the Committee of Sponsoring Organizations of the Treadway Commission (COSO).
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position
of the Company as of December 31, 2020 and 2019, and the results of its operations and its cash flows for each of the three years in the
period ended December 31, 2020 in conformity with accounting principles generally accepted in the United States of America. Also in
our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31,
2020, based on criteria established in Internal Control–Integrated Framework (2013) issued by the COSO.
Basis for Opinions
The Company’s management is responsible for these consolidated financial statements, for maintaining effective internal control
over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting, included in Management’s
Annual Report on Internal Control over Financial Reporting appearing under Item 15 of Form 20-F. Our responsibility is to express
opinions on the Company’s consolidated financial statements and on the Company’s internal control over financial reporting based on
our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB)
and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable
rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the
audits to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether
due to error or fraud, and whether effective internal control over financial reporting was maintained in all material respects.
Our audits of the consolidated financial statements included performing procedures to assess the risks of material misstatement of
the consolidated financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such
procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated financial statements.
Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating
the overall presentation of the consolidated financial statements. Our audit of internal control over financial reporting included obtaining
an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating
the design and operating effectiveness of internal control based on the assessed risk. Our audits also included performing such other
procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for our opinions.
Definition and Limitations of Internal Control over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability
of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting
principles. A company’s internal control over financial reporting includes those policies and procedures that (i) pertain to the
maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the
company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in
accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in
accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding
prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect
on the financial statements.
F-2
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of
changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
Critical Audit Matters
The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial
statements that was communicated or required to be communicated to the audit committee and that (i) relates to accounts or disclosures
that are material to the consolidated financial statements and (ii) involved our especially challenging, subjective, or complex judgments.
The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a
whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on
the accounts or disclosures to which it relates.
Principal versus agent assessment on revenue recognition
As described in Note 20 to the consolidated financial statements, promotion and marketing (“P&M”) service income arising from
the Company’s Marketed Products of US$3.7 million was recorded for the license and collaboration agreement with Eli Lilly (“Lilly”)
for the year ended December 31, 2020, representing 2% of the Company’s total revenue and no revenue was recognized for the sales
from Lilly to the ultimate customers (“Subsequent Sales Transactions”). Management assessed the principal versus agent considerations
under Accounting Standards Codification 606, Revenue from Contracts with Customers, in particular the control of the goods before
delivery to the ultimate customers and inventory risk, and concluded that while the Company is the manufacturer of Elunate that were
being sold to Lilly, and also provides the P&M service for Lilly’s sales to the customers since October 2020, it did not alter the principal
versus agent considerations that Lilly is the principal for the Subsequent Sales Transactions, and the P&M service is accounted for as a
distinct performance obligation and recognized over time based on the amounts that can be invoiced to Lilly.
The principal considerations for our determination that performing procedures relating to the principal versus agent assessment on
revenue recognition is a critical audit matter are (i) there was significant judgment by management when assessing whether the P&M
service is a distinct performance obligation and determining whether the Company or Lilly is the principal for the Subsequent Sales
Transactions, which in turn led to a high degree of auditor judgement and significant audit effort in performing procedures to evaluate
audit evidence including the analysis made by management and (ii) the gross versus net impact to the presentation and disclosure of
revenue is material.
Addressing the matter involved performing procedures and evaluating audit evidence, in connection with forming our overall
opinion on the consolidated financial statements. These procedures included testing the effectiveness of internal controls relating to the
revenue recognition process, including controls over assessing whether the P&M service is a distinct performance obligation,
management’s assessment on principal versus agent considerations and the quantification of P&M service income recorded in the
consolidated statement of operation. The procedures also included, among others, (i) evaluating the contractual terms of the relevant
agreements, (ii) testing management’s process for determining the appropriate revenue recognition policy based on the contractual terms
identified in the relevant agreements, (iii) evaluating management’s assessment on principal versus agent considerations, (iv) testing of
P&M service income recorded in the consolidated statement of operation and (v) assessing the appropriateness of the presentation and
disclosure of revenue in the consolidated financial statements.
/s/ PricewaterhouseCoopers
Hong Kong
March 4, 2021
We have served as the Company’s auditor since 2005, which includes periods before the Company became subject to SEC reporting
requirements.
F-3
Hutchison China MediTech Limited
Consolidated Balance Sheets
(in US$’000, except share data)
Assets
Current assets
Cash and cash equivalents
Short-term investments
Accounts receivable—third parties
Accounts receivable—related parties
Other receivables, prepayments and deposits
Amounts due from related parties
Inventories
Total current assets
Property, plant and equipment
Right-of-use assets
Deferred tax assets
Investments in equity investees
Amount due from a related party
Other non-current assets
Total assets
Liabilities and shareholders’ equity
Current liabilities
Accounts payable
Other payables, accruals and advance receipts
Lease liabilities
Income tax payable
Deferred revenue
Amounts due to a related party
Total current liabilities
Lease liabilities
Deferred tax liabilities
Long-term bank borrowings
Deferred revenue
Other non-current liabilities
Total liabilities
Commitments and contingencies
Company’s shareholders’ equity
Ordinary shares; $0.10 par value; 1,500,000,000 shares authorized; 727,722,215 and
666,906,450 shares issued at December 31, 2020 and 2019 respectively
Additional paid-in capital
Accumulated losses
Accumulated other comprehensive income/(loss)
Total Company’s shareholders’ equity
Non-controlling interests
Total shareholders’ equity
Total liabilities and shareholders’ equity
Note
2020
2019
December 31,
5
6
7
23(ii)
8
23(ii)
9
10
11
24(ii)
12
23(ii)
13
14
15
11
24(iii)
20
23(ii)
11
24(ii)
16
20
17
18
235,630
199,546
46,648
1,222
26,786
1,142
19,766
530,740
24,170
8,016
1,515
139,505
—
20,172
724,118
31,612
120,882
2,785
1,120
1,597
401
158,397
6,064
5,063
26,861
484
8,300
205,169
121,157
96,011
41,410
1,844
15,769
24,623
16,208
317,022
20,855
5,516
815
98,944
16,190
5,780
465,122
23,961
81,624
3,216
1,828
2,106
366
113,101
3,049
3,158
26,818
133
5,960
152,219
72,772
822,458
(415,591)
4,477
484,116
34,833
518,949
724,118
66,691
514,904
(289,734)
(3,849)
288,012
24,891
312,903
465,122
The accompanying notes are an integral part of these consolidated financial statements.
F-4
Hutchison China MediTech Limited
Consolidated Statements of Operations
(in US$’000, except share and per share data)
Revenues
Goods—third parties
—related parties
Services—commercialization—third parties
—collaboration research and development—third parties
—research and development—related parties
Other collaboration revenue—royalties—third parties
—licensing—third parties
Total revenues
Operating expenses
Costs of goods—third parties
Costs of goods—related parties
Costs of services—commercialization—third parties
Research and development expenses
Selling expenses
Administrative expenses
Total operating expenses
Other income/(expense)
Interest income
Other income
Interest expense
Other expense
Total other income/(expense)
Loss before income taxes and equity in earnings of equity investees
Income tax expense
Equity in earnings of equity investees, net of tax
Net loss
Less: Net income attributable to non-controlling interests
Net loss attributable to the Company
Losses per share attributable to the Company—basic and diluted (US$
per share)
Number of shares used in per share calculation—basic and diluted
Note
2020
Year Ended December 31,
2019
2018
23(i)
23(i)
20
21
26
26
24(i)
12
203,606
5,484
3,734
9,771
491
4,890
—
227,976
(178,828)
(3,671)
(6,020)
(174,776)
(11,334)
(50,015)
(424,644)
(196,668)
3,236
4,600
(787)
(115)
6,934
(189,734)
(4,829)
79,046
(115,517)
(10,213)
(125,730)
175,990
7,637
2,584
15,532
494
2,653
—
204,890
(152,729)
(5,494)
(1,929)
(138,190)
(13,724)
(39,210)
(351,276)
(146,386)
4,944
1,855
(1,030)
(488)
5,281
(141,105)
(3,274)
40,700
(103,679)
(2,345)
(106,024)
156,234
8,306
11,660
17,681
7,832
261
12,135
214,109
(129,346)
(5,978)
(8,620)
(114,161)
(17,736)
(30,909)
(306,750)
(92,641)
5,978
1,798
(1,009)
(781)
5,986
(86,655)
(3,964)
19,333
(71,286)
(3,519)
(74,805)
25
25
(0.18)
(0.16)
697,931,437 665,683,145
(0.11)
664,263,820
The accompanying notes are an integral part of these consolidated financial statements.
F-5
Hutchison China MediTech Limited
Consolidated Statements of Comprehensive Loss
(in US$’000)
Net loss
Other comprehensive income/(loss)
Foreign currency translation gain/(loss)
Total comprehensive loss
Less: Comprehensive income attributable to non-controlling interests
Total comprehensive loss attributable to the Company
2020
(115,517)
Year Ended December 31,
2019
(103,679)
2018
(71,286)
9,530
(105,987)
(11,413)
(117,400)
(4,331)
(108,010)
(1,620)
(109,630)
(6,626)
(77,912)
(2,566)
(80,478)
The accompanying notes are an integral part of these consolidated financial statements.
F-6
Hutchison China MediTech Limited
Consolidated Statements of Changes in Shareholders’ Equity
(in US$’000, except share data in ’000)
Ordinary
Shares
Number
664,470
—
2,107
Ordinary
Shares
Value
66,447
—
211
Additional
Paid-in
Capital
496,960
—
2,952
Losses
(108,184)
(74,805)
—
Total
Accumulated
Company’s
Other
Accumulated Comprehensive Shareholders’
Income/(Loss)
Equity
As at January 1, 2018
Net (loss)/income
Issuances in relation to share option exercises
Share-based compensation
Share options
Long-term incentive plan (“LTIP”)
LTIP—treasury shares acquired and held by Trustee
Dividend declared to a non-controlling shareholder of a
subsidiary
Transfer between reserves
Foreign currency translation adjustments
As at December 31, 2018
Impact of change in accounting policy (Note 3)
As at January 1, 2019
Net (loss)/income
Issuances in relation to share option exercises
Share-based compensation
Share options
LTIP
LTIP—treasury shares acquired and held by Trustee
Transfer between reserves
Foreign currency translation adjustments
As at December 31, 2019
Net (loss)/income
Issuance in relation to public offering
Issuances in relation to private investment in public equity
(“PIPE”)
Issuance costs
Issuances in relation to share option exercises
Share-based compensation
Share options
LTIP
LTIP—treasury shares acquired and held by Trustee
Dividends declared to non-controlling shareholders of
subsidiaries
Purchase of additional interests in a subsidiary of an equity
investee (Note 12)
Transfer between reserves
Foreign currency translation adjustments
As at December 31, 2020
—
—
—
—
—
—
—
666,577
—
666,577
—
329
—
—
—
—
—
—
666,906
—
23,669
36,667
—
480
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
66,658
—
66,658
—
33
—
—
—
—
—
—
66,691
—
2,366
3,667
—
48
—
—
—
—
—
—
—
—
7,885
3,224
11,109
(5,451)
—
15
—
505,585
—
505,585
—
218
7,157
2,239
9,396
(346)
51
—
514,904
—
115,975
196,333
(8,317)
545
8,727
7,203
15,930
(12,904)
—
(52)
44
—
—
—
—
—
—
(15)
—
(183,004)
(655)
(183,659)
(106,024)
—
—
—
—
—
(51)
—
(289,734)
(125,730)
—
—
—
—
—
—
—
—
—
(83)
(44)
—
727,722
72,772
822,458
(415,591)
Non-
controlling
Interests
23,230
3,519
—
460,653
(74,805)
3,163
7,885
3,224
11,109
(5,451)
—
—
(5,673)
388,996
(655)
388,341
(106,024)
251
7,157
2,239
9,396
(346)
—
(3,606)
288,012
(125,730)
118,341
200,000
(8,317)
593
8,727
7,203
15,930
(12,904)
18
9
27
—
(2,564)
—
(953)
23,259
(16)
23,243
2,345
—
16
12
28
—
—
(725)
24,891
10,213
—
—
—
—
10
16
26
—
Total
Shareholders’
Equity
483,883
(71,286)
3,163
7,903
3,233
11,136
(5,451)
(2,564)
—
(6,626)
412,255
(671)
411,584
(103,679)
251
7,173
2,251
9,424
(346)
—
(4,331)
312,903
(115,517)
118,341
200,000
(8,317)
593
8,737
7,219
15,956
(12,904)
5,430
—
—
—
—
—
—
—
—
(5,673)
(243)
—
(243)
—
—
—
—
—
—
—
(3,606)
(3,849)
—
—
—
—
—
—
—
—
—
—
—
(1,462)
(1,462)
(4)
—
8,330
4,477
(139)
—
8,330
484,116
(35)
—
1,200
34,833
(174)
—
9,530
518,949
The accompanying notes are an integral part of these consolidated financial statements.
F-7
Hutchison China MediTech Limited
Consolidated Statements of Cash Flows
(in US$’000)
Net cash used in operating activities
Investing activities
Purchases of property, plant and equipment
Purchase of leasehold land
Payment on leasehold land deposit
Deposits in short-term investments
Proceeds from short-term investments
Purchase of a subsidiary company
Cash acquired in purchase of a subsidiary company
Investment in an equity investee
Net cash (used in)/generated from investing activities
Financing activities
Proceeds from issuance of ordinary shares
Purchases of treasury shares
Dividends paid to non-controlling shareholders of subsidiaries
Repayment of loan to a non-controlling shareholder of a subsidiary
Proceeds from bank borrowings
Repayment of bank borrowings
Payment of issuance costs
Net cash generated from/(used in) financing activities
Net increase in cash and cash equivalents
Effect of exchange rate changes on cash and cash equivalents
Note
27
13
13
19(ii)
Cash and cash equivalents
Cash and cash equivalents at beginning of year
Cash and cash equivalents at end of year
Supplemental disclosure for cash flow information
Cash paid for interest
Cash paid for tax, net of refunds
Supplemental disclosure for non-cash activities
(Decrease)/increase in accruals made for purchases of property, plant and equipment
Accrual made for purchase of leasehold land
Vesting of treasury shares for LTIP
24(iii)
13
19(ii)
Year Ended December 31,
2019
(80,912)
2020
(62,066)
2018
(32,847)
(7,949)
(11,631)
(2,326)
(732,908)
629,373
—
—
—
(125,441)
318,934
(12,904)
(1,462)
—
—
—
(8,134)
296,434
108,927
5,546
114,473
(8,565)
—
—
(478,140)
597,044
(8,080)
16,769
—
119,028
251
(346)
(1,282)
—
26,807
(26,923)
—
(1,493)
36,623
(1,502)
35,121
121,157
235,630
86,036
121,157
815
5,940
(57)
355
4,828
917
3,249
1,068
—
944
(6,364)
—
—
(903,551)
961,667
—
—
(8,000)
43,752
3,868
(5,451)
(1,282)
(1,550)
26,923
(30,000)
(739)
(8,231)
2,674
(1,903)
771
85,265
86,036
979
3,752
138
—
731
The accompanying notes are an integral part of these consolidated financial statements.
F-8
1. Organization and Nature of Business
Hutchison China MediTech Limited
Notes to the Consolidated Financial Statements
Hutchison China MediTech Limited (the “Company”) and its subsidiaries (together the “Group”) are principally engaged in
researching, developing, manufacturing and marketing pharmaceutical products. The Group and its equity investees have research and
development facilities and manufacturing plants in the People’s Republic of China (the “PRC”) and sell their products mainly in the
PRC, including Hong Kong. In addition, the Group has established international operations in the United States of America (the “U.S.”)
and Europe.
The Company was incorporated in the Cayman Islands on December 18, 2000 as an exempted company with limited liability under
the Companies Law (2000 Revision), Chapter 22 of the Cayman Islands. The address of its registered office is P.O. Box 309, Ugland
House, Grand Cayman, KY1-1104, Cayman Islands.
The Company’s ordinary shares are listed on the AIM market of the London Stock Exchange, and its American depositary shares
(“ADS”), each representing five ordinary shares, are traded on the Nasdaq Global Select Market.
Liquidity
As at December 31, 2020, the Group had accumulated losses of US$415,591,000 primarily due to its spending in drug research and
development activities. The Group regularly monitors current and expected liquidity requirements to ensure that it maintains sufficient
cash balances and adequate credit facilities to meet its liquidity requirements in the short and long term. As at December 31, 2020, the
Group had cash and cash equivalents of US$235,630,000, short-term investments of US$199,546,000 and unutilized bank borrowing
facilities of US$69,359,000. Short-term investments comprised of bank deposits maturing over three months. The Group’s operating
plan includes the continued receipt of dividends from certain of its equity investees. Dividends received from equity investees for the
years ended December 31, 2020, 2019 and 2018 were US$86,708,000, US$28,135,000 and US$35,218,000 respectively.
Based on the Group’s operating plan, the existing cash and cash equivalents, short-term investments and unutilized bank borrowing
facilities are considered to be sufficient to meet the cash requirements to fund planned operations and other commitments for at least
the next twelve months (the look-forward period used), and it is appropriate for the Group to prepare the consolidated financial
statements on a going concern basis.
F-9
2. Particulars of Principal Subsidiaries and Equity Investees
Name
Subsidiaries
Hutchison MediPharma Limited (“HMPL”)
Place of
establishment
and
operations
Equity interest
attributable to
the Group
December 31,
2020
2019
Principal activities
PRC
99.75 % 99.75 % Research, development, manufacture and
commercialization of pharmaceutical
products
Hutchison MediPharma International Inc.
U.S.
99.75 % 99.75 % Provision of professional, scientific and
Hutchison Whampoa Sinopharm Pharmaceuticals
PRC
50.87 % 50.87 %
(Shanghai) Company Limited (“HSPL”)
technical support services
Provision of sales, distribution and
marketing services to pharmaceutical
manufacturers
Hutchison Hain Organic (Hong Kong) Limited
Hong Kong
50 %
50 % Wholesale and trading of healthcare and
(“HHOL”) (note (a))
Hutchison Healthcare Limited
PRC
100 %
100 %
consumer products
Manufacture and distribution of
healthcare products
Hutchison Consumer Products Limited
Hong Kong
100 %
100 % Wholesale and trading of healthcare and
consumer products
Equity investees
Shanghai Hutchison Pharmaceuticals Limited
(“SHPL”)
Hutchison Whampoa Guangzhou Baiyunshan Chinese
Medicine Company Limited (“HBYS”) (note (b))
PRC
PRC
50 %
50 %
Manufacture and distribution of
prescription drug products
40 %
40 % Manufacture and distribution of over-the-
counter drug products
Notes:
(a) HHOL is regarded as a subsidiary of the Company, as while both its shareholders have equal representation at the board, in the
event of a deadlock, the Group has a casting vote and is therefore able to unilaterally control the financial and operating policies of
HHOL.
(b) The 50% equity interest in HBYS is held by an 80% owned subsidiary of the Group. The effective equity interest of the Group in
HBYS is therefore 40% for the years presented.
3. Summary of Significant Accounting Policies
Principles of Consolidation and Basis of Presentation
The accompanying consolidated financial statements reflect the accounts of the Company and all of its subsidiaries in which a
controlling interest is maintained. Investments in equity investees over which the Group has significant influence are accounted for
using the equity method. All inter-company balances and transactions have been eliminated in consolidation. The consolidated financial
statements have been prepared in conformity with generally accepted accounting principles in U.S. (“U.S. GAAP”).
Use of Estimates
The preparation of consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and
assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of
the consolidated financial statements and the reported amounts of revenues and expenses during the reporting period.
F-10
Foreign Currency Translation
The Company’s presentation currency is the U.S. dollar (“US$”). The financial statements of the Company and its subsidiaries with
a functional currency other than the US$ have been translated into the Company’s presentation currency. All assets and liabilities of the
subsidiaries are translated using year-end exchange rates and revenues and expenses are translated at average exchange rates for the
year. Translation adjustments are reflected in accumulated other comprehensive (loss)/income in shareholders’ equity.
Net foreign currency exchange gains of US$3,265,000 and US$246,000 and net foreign exchanges losses of US$233,000 were
recorded in other income and other expense in the consolidated statements of operations for the years ended December 31, 2020, 2019
and 2018 respectively.
Cash and Cash Equivalents
The Group considers all highly liquid investments purchased with original maturities of three months or less to be cash equivalents.
Cash and cash equivalents consist primarily of cash on hand and bank deposits and are stated at cost, which approximates fair value.
Short-term Investments
Short-term investments include deposits placed with banks with original maturities of more than three months but less than one
year.
Concentration of Credit Risk
Financial instruments that potentially expose the Group to concentrations of credit risk consist primarily of cash and cash
equivalents, short-term investments, accounts receivable, other receivables and amounts due from related parties.
The Group places substantially all of its cash and cash equivalents and short-term investments in major financial institutions, which
management believes are of high credit quality. The Group has a practice to limit the amount of credit exposure to any particular financial
institution.
The Group has no significant concentration of credit risk. The Group has policies in place to ensure that sales are made to customers
with an appropriate credit history and the Group performs periodic credit evaluations of its customers. Normally the Group does not
require collateral from trade debtors.
Foreign Currency Risk
The Group’s operating transactions and its assets and liabilities in the PRC are mainly denominated in Renminbi (“RMB”), which
is not freely convertible into foreign currencies. The Group’s cash and cash equivalents denominated in RMB are subject to government
controls. The value of the RMB is subject to fluctuations from central government policy changes and international economic and
political developments that affect the supply and demand of RMB in the foreign exchange market. In the PRC, certain foreign exchange
transactions are required by law to be transacted only by authorized financial institutions at exchange rates set by the People’s Bank of
China (the “PBOC”). Remittances in currencies other than RMB by the Group in the PRC must be processed through the PBOC or other
PRC foreign exchange regulatory bodies which require certain supporting documentation in order to complete the remittance.
Accounts Receivable
Accounts receivable are stated at the amount management expects to collect from customers based on their outstanding invoices.
The allowance for credit losses reflects the Group’s current estimate of credit losses expected to be incurred over the life of the
receivables. The Group considers various factors in establishing, monitoring, and adjusting its allowance for credit losses including the
aging of the accounts and aging trends, the historical level of charge-offs, and specific exposures related to particular customers. The
Group also monitors other risk factors and forward-looking information, such as country risk, when determining credit limits for
customers and establishing adequate allowances for credit losses. Accounts receivable are written off after all reasonable means to
collect the full amount (including litigation, where appropriate) have been exhausted.
F-11
Inventories
Inventories are stated at the lower of cost or net realizable value. Cost is determined using the weighted average cost method. The
cost of finished goods comprises raw materials, direct labor, other direct costs and related production overheads (based on normal
operating capacity). Net realizable value is the estimated selling price in the ordinary course of business, less applicable variable selling
expenses. A provision for excess and obsolete inventory will be made based primarily on forecasts of product demand and production
requirements. The excess balance determined by this analysis becomes the basis for excess inventory charge and the written-down value
of the inventory becomes its cost. Written-down inventory is not written up if market conditions improve.
Property, Plant and Equipment
Property, plant and equipment consist of buildings, leasehold improvements, plant and equipment, furniture and fixtures, other
equipment and motor vehicles. Property, plant and equipment are stated at cost, net of accumulated depreciation. Depreciation is
computed using the straight-line method over the estimated useful lives of the depreciable assets.
Buildings
Plant and equipment
Furniture and fixtures, other equipment and
motor vehicles
Leasehold improvements
20 years
5-10 years
4-5 years
Shorter of (a) 5 years or (b) remaining term of lease
Additions and improvements that extend the useful life of an asset are capitalized. Repairs and maintenance costs are expensed
as incurred.
Impairment of Long-Lived Assets
The Group evaluates the recoverability of long-lived assets in accordance with authoritative guidance on accounting for the
impairment or disposal of long-lived assets. The Group evaluates long-lived assets for impairment whenever events or changes in
circumstances indicate that the carrying value of these assets may not be recoverable. If indicators of impairment exist, the first step of
the impairment test is performed to assess if the carrying value of the net assets exceeds the undiscounted cash flows of the assets. If
yes, the second step of the impairment test is performed in order to determine if the carrying value of the net assets exceeds the fair
value. If yes, impairment is recognized for the excess.
Leasehold Land
Leasehold land represents fees paid to acquire the right to use the land on which various plants and buildings are situated for a
specified period of time from the date the respective right was granted and are stated at cost less accumulated amortization and
impairment loss, if any. Amortization is computed using the straight-line basis over the lease period of 50 years.
Goodwill
Goodwill represents the excess of the purchase price plus fair value of non-controlling interests over the fair value of identifiable
assets and liabilities acquired. Goodwill is not amortized, but is tested for impairment at the reporting unit level on at least an annual
basis or when an event occurs or circumstances change that would more likely than not reduce the fair value of a reporting unit below
its carrying amount. When performing an evaluation of goodwill impairment, the Group has the option to first assess qualitative factors,
such as significant events and changes to expectations and activities that may have occurred since the last impairment evaluation, to
determine if it is more likely than not that goodwill might be impaired. If as a result of the qualitative assessment, that it is more likely
than not that the fair value of the reporting unit is less than its carrying amount, the quantitative fair value test is performed to determine
if the fair value of the reporting unit exceeds its carrying value.
Other Intangible Assets
Other intangible assets with finite useful lives are carried at cost less accumulated amortization and impairment loss, if any.
Amortization is computed using the straight-line basis over the estimated useful lives of the assets.
F-12
Borrowings
Borrowings are recognized initially at fair value, net of debt issuance costs incurred. Borrowings are subsequently stated at
amortized cost; any difference between the proceeds (net of debt issuance costs) and the redemption value is recognized in the
consolidated statements of operations over the period of the borrowings using the effective interest method.
Ordinary Shares
The Company’s ordinary shares are stated at par value of US$0.10 per ordinary share. The difference between the consideration
received, net of issuance cost, and the par value is recorded in additional paid-in capital.
Treasury Shares
The Group accounts for treasury shares under the cost method. The treasury shares are purchased for the purpose of the LTIP and
held by a trustee appointed by the Group (the “Trustee”) prior to vesting.
Share-Based Compensation
Share options
The Group recognizes share-based compensation expense on share options granted to employees and directors based on their
estimated grant date fair value using the Polynomial model. This Polynomial pricing model uses various inputs to measure fair value,
including estimated market value of the Company’s underlying ordinary shares at the grant date, contractual terms, estimated volatility,
risk-free interest rates and expected dividend yields. The Group recognizes share-based compensation expense in the consolidated
statements of operations on a graded vesting basis over the requisite service period, and accounts for forfeitures as they occur.
Share options are classified as equity-settled awards. Share-based compensation expense, when recognized, is charged to the
consolidated statements of operations with the corresponding entry to additional paid-in capital.
LTIP
The Group recognizes the share-based compensation expense on the LTIP awards based on a fixed or determinable monetary
amount on a straight-line basis for each annual tranche awarded over the requisite period. For LTIP awards with performance targets,
prior to their determination date, the amount of LTIP awards that is expected to vest takes into consideration the achievement of the
performance conditions and the extent to which the performance conditions are likely to be met. Performance conditions vary by awards,
including targets for shareholder returns, free cash flows, revenues, net profit after taxes and/or the achievement of clinical and regulatory
milestones.
These LTIP awards are classified as liability-settled awards before the determination date (i.e. the date when the achievement of
any performance conditions are known), as they settle in a variable number of shares based on a determinable monetary amount, which
is determined upon the actual achievement of performance targets. As the extent of achievement of the performance targets is uncertain
prior to the determination date, a probability based on management’s assessment of the achievement of the performance targets has been
assigned to calculate the amount to be recognized as an expense over the requisite period.
After the determination date or if the LTIP awards have no performance conditions, the LTIP awards are classified as equity-settled
awards. If the performance target is achieved, the Group will pay the determined monetary amount to the Trustee to purchase ordinary
shares of the Company or the equivalent ADS. Any cumulative compensation expense previously recognized as a liability will be
transferred to additional paid-in capital, as an equity-settled award. If the performance target is not achieved, no ordinary shares or ADS
of the Company will be purchased and the amount previously recorded in the liability will be reversed and included in the consolidated
statements of operations.
F-13
Defined Contribution Plans
The Group’s subsidiaries in the PRC participate in a government-mandated multi-employer defined contribution plan pursuant to
which certain retirement, medical and other welfare benefits are provided to employees. The relevant labor regulations require the
Group’s subsidiaries in the PRC to pay the local labor and social welfare authority’s monthly contributions at a stated contribution rate
based on the monthly basic compensation of qualified employees. The relevant local labor and social welfare authorities are responsible
for meeting all retirement benefits obligations and the Group’s subsidiaries in the PRC have no further commitments beyond their
monthly contributions. The contributions to the plan are expensed as incurred.
The Group also makes payments to other defined contribution plans for the benefit of employees employed by subsidiaries outside
the PRC. The defined contribution plans are generally funded by the relevant companies and by payments from employees.
The Group’s contributions to defined contribution plans for the years ended December 31, 2020, 2019 and 2018 amounted to
US$2,660,000, US$3,479,000 and US$2,878,000 respectively.
Revenue Recognition
Revenue is measured based on consideration specified in a contract with a customer, and excludes any sales incentives and amounts
collected on behalf of third parties. Taxes assessed by a governmental authority that are both imposed on and concurrent with a specific
revenue-producing transaction, that are collected by the Group from a customer, are also excluded from revenue. The Group recognizes
revenue when it satisfies a performance obligation by transferring control over a good, service or license to a customer.
Nature of goods and services
The following is a description of principal activities, separated by reportable segments, from which the Company generates its
revenue:
(i) Oncology/Immunology
The Oncology/Immunology reportable segment principally generates revenue from license and collaboration contracts as well as
revenues related to the sale of Marketed Products developed from Oncology/Immunology (which was represented under
Oncology/Immunology in these consolidated financial statements; refer to Note 26). The license and collaboration contracts generally
contain multiple performance obligations including (1) the license to the commercialization rights of a drug compound and (2) the
research and development services for each specified treatment indication, which are accounted for separately if they are distinct, i.e. if
a product or service is separately identifiable from other items in the arrangement and if a customer can benefit from it on its own or
with other resources that are readily available to the customer.
The transaction price generally includes fixed and variable consideration in the form of upfront payment, research and development
cost reimbursements, contingent milestone payments and sales-based royalties. Contingent milestone payments are not included in the
transaction price until it becomes probable that a significant reversal of revenue will not occur, which is generally when the specified
milestone is achieved. The allocation of the transaction price to each performance obligation is based on the relative standalone selling
prices of each performance obligation determined at the inception of the contract. The Group estimates the standalone selling prices
based on the income approach. Control of the license to the drug compounds transfers at the inception date of the collaboration
agreements and consequently, amounts allocated to this performance obligation are generally recognized at a point in time. Conversely,
research and development services for each specified indication are performed over time and amounts allocated to these performance
obligations are generally recognized over time using cost inputs as a measure of progress. The Group has determined that research and
development expenses provide an appropriate depiction of measure of progress for the research and development services. Changes to
estimated cost inputs may result in a cumulative catch-up adjustment. Royalty revenues are recognized as future sales occur as they
meet the requirements for the sales-usage based royalty exception.
Deferred revenue is recognized if allocated consideration is received in advance of the Group rendering research and development
services. Accounts receivable is recognized based on the terms of the contract and when the Group has an unconditional right to bill the
customer, which is generally when research and development services are rendered.
F-14
Revenue recognition from the sales of goods and provision of services for Marketed Products developed from
Oncology/Immunology follows revenue recognition policies in Other Ventures below.
(ii) Other Ventures
The Other Ventures reportable segment principally generates revenue from (1) sales of goods, which are the manufacture or
purchase and distribution of pharmaceutical products and other consumer health products, and (2) provision of services, which are the
provision of sales, distribution and marketing services to pharmaceutical manufacturers. The Group evaluates whether it is the principal
or agent for these contracts. Where the Group obtains control of the goods for distribution, it is the principal (i.e. recognizes sales of
goods on a gross basis). Where the Group does not obtain control of the goods for distribution, it is the agent (i.e. recognizes provision
of services on a net basis). Control is primarily evidenced by taking physical possession and inventory risk of the goods.
Revenue from sales of goods is recognized when the customer takes possession of the goods. This usually occurs upon completed
delivery of the goods to the customer site. The amount of revenue recognized is adjusted for expected sales incentives as stipulated in
the contract, which are generally issued to customers as direct discounts at the point-of-sale or indirectly in the form of rebates. Sales
incentives are estimated using the expected value method. Additionally, sales are generally made with a limited right of return under
certain conditions. Revenues are recorded net of provisions for sales discounts and returns.
Revenue from provision of services is recognized when the benefits of the services transfer to the customer over time, which is
based on the proportionate value of services rendered as determined under the terms of the relevant contract. Additionally, when the
amounts that can be invoiced correspond directly with the value to the customer for performance completed to date, the Group recognizes
revenue from provision of services based on amounts that can be invoiced to the customer.
Deferred revenue is recognized if consideration is received in advance of transferring control of the goods or rendering of services.
Accounts receivable is recognized if the Group has an unconditional right to bill the customer, which is generally when the customer
takes possession of the goods or services are rendered. Payment terms differ by subsidiary and customer, but generally range from 45
to 180 days from the invoice date.
Research and Development Expenses
Research and development costs are expensed as incurred.
Collaborative Arrangements
The Group enters into collaborative arrangements with collaboration partners that fall under the scope of Accounting Standards
Codification (“ASC”) 808, Collaborative Arrangements (“ASC 808”). The Group records all expenditures for such collaborative
arrangements in research and development expenses as incurred, including payments to third party vendors and reimbursements to
collaboration partners, if any. Reimbursements from collaboration partners are recorded as reductions to research and development
expenses and accrued when they can be contractually claimed.
Government Grants
Grants from governments are recognized at their fair values. Government grants that are received in advance are deferred and
recognized in the consolidated statements of operations over the period necessary to match them with the costs that they are intended to
compensate. Government grants in relation to the achievement of stages of research and development projects are recognized in the
consolidated statements of operations when amounts have been received and all attached conditions have been met. Non-refundable
grants received without any further obligations or conditions attached are recognized immediately in the consolidated statements of
operations.
F-15
Leases
Summary of impact of applying ASC 842
The Group applied ASC 842 to its various leases at the date of initial application of January 1, 2019. As a result, the Group has
changed its accounting policy for leases as detailed below. The core principle of ASC 842 is that a lessee should recognize the assets
and liabilities that arise from leases. Therefore, the Group recognizes in the consolidated balance sheets liabilities to make lease payments
(the lease liabilities) and right-of-use assets representing its right to use the underlying assets for their lease terms. The Group applied
ASC 842 using the optional transition method by recognizing the cumulative effect as an adjustment to opening accumulated losses as
at January 1, 2019. The comparative information prior to January 1, 2019 has not been adjusted and continues to be reported under
ASC 840, Leases (“ASC 840”).
The Group assessed lease agreements as at January 1, 2019 under ASC 842, except for short-term leases. The Group elected the
short-term lease exception for leases with a term of 12 months or less and recognizes lease expenses for such leases on a straight-line
basis over the lease term and does not recognize right-of-use assets or lease liabilities accordingly. As a result of this assessment, the
Group recorded an aggregate US$0.7 million in additional lease expenses as a cumulative adjustment to opening accumulated losses
upon adoption. Additionally, the Group recognized right-of-use assets and lease liabilities of US$5.7 million and US$6.4 million
respectively as at January 1, 2019.
The lease liabilities were measured at the present value of the remaining lease payments, discounted using the lessees’ incremental
borrowing rate as at January 1, 2019. The Group’s weighted average incremental borrowing rate applied on January 1, 2019 was 3.97%
per annum.
A reconciliation of the Group’s reported operating lease commitments as at December 31, 2018 and the Group’s lease liabilities
recognized upon adoption of ASC 842 as at January 1, 2019 is as follows:
Operating lease commitments as at December 31, 2018 (note (a))
Less: Leases not commenced as at January 1, 2019
Less: Short‑term leases
Add: Adjustment as a result of the treatment for a termination option (note (b))
Less: Discount under the lessees’ incremental borrowing rate as at January 1, 2019
Lease liabilities recognized as at January 1, 2019
(in US$’000)
8,835
(3,676)
(5)
1,409
(206)
6,357
Notes:
(a) Future aggregate minimum payments under non-cancellable operating leases under ASC 840 were as follows:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Between 3 to 4 years
Between 4 to 5 years
Later than 5 years
Total minimum lease payments
December 31,
2018
(in US$’000)
3,026
2,735
1,056
882
810
326
8,835
(b) The Group leases its corporate offices in Hong Kong through a support service agreement with an indirect subsidiary
of CK Hutchison Holdings Limited (“CK Hutchison”), which is the Company’s indirect major shareholder. The
support service agreement may be terminated by giving 3-month advance notice; therefore, there was no lease
commitment beyond the 3-month advance notice period as at December 31, 2018. This termination option is not
considered probable of exercise for the purposes of applying ASC 842.
F-16
The Group recognized right-of-use assets as at January 1, 2019 measured at their carrying amounts as if ASC 842 had been applied
since their commencement dates, but discounted using the lessees’ incremental borrowing rate as at January 1, 2019.
Recognized right-of-use assets upon adoption were as follows:
Offices
Factories
Others
(in US$’000)
4,877
383
487
5,747
There were no adjustments to net cash generated from/(used in) operating activities, investing activities or financing activities in
the consolidated statement of cash flows.
In applying ASC 842 for the first time, the Group has used the following practical expedients permitted by the standard: (i) no
reassessment of whether any expired or existing contracts are or contain leases; (ii) no reassessment of the lease classification for any
expired or existing leases; (iii) the exclusion of initial direct costs for the measurement of the right-of-use assets at the date of initial
application; and (iv) the use of hindsight in determining the lease term where the contract contains options to extend or terminate the
lease.
Updated accounting policy—ASC 842
In an operating lease, a lessee obtains control of only the use of the underlying asset, but not the underlying asset itself. An operating
lease is recognized as a right-of-use asset with a corresponding liability at the date which the leased asset is available for use by the
Group. The Group recognizes an obligation to make lease payments equal to the present value of the lease payments over the lease term.
The lease terms may include options to extend or terminate the lease when it is reasonably certain that the Group will exercise that
option.
Lease liabilities include the net present value of the following lease payments: (i) fixed payments; (ii) variable lease payments; and
(iii) payments of penalties for terminating the lease if the lease term reflects the lessee exercising that option, if any. Lease liabilities
exclude the following payments that are generally accounted for separately: (i) non-lease components, such as maintenance and security
service fees and value added tax, and (ii) any payments that a lessee makes before the lease commencement date. The lease payments
are discounted using the interest rate implicit in the lease or if that rate cannot be determined, the lessee’s incremental borrowing rate
being the rate that the lessee would have to pay to borrow the funds in its currency and jurisdiction necessary to obtain an asset of similar
value, economic environment and terms and conditions.
An asset representing the right to use the underlying asset during the lease term is recognized that consists of the initial measurement
of the operating lease liability, any lease payments made to the lessor at or before the commencement date less any lease incentives
received, any initial direct cost incurred by the Group and any restoration costs.
After commencement of the operating lease, the Group recognizes lease expenses on a straight-line basis over the lease term. The
right-of-use asset is subsequently measured at cost less accumulated amortization and any impairment provision. The amortization of
the right-of-use asset represents the difference between the straight-line lease expense and the accretion of interest on the lease liability
each period. The interest amount is used to accrete the lease liability and to amortize the right-of-use asset. There is no amount recorded
as interest expense.
Payments associated with short-term leases are recognized as lease expenses on a straight-line basis over the period of the leases.
Subleases of right-of-use assets are accounted for similar to other leases. As an intermediate lessor, the Group separately accounts
for the head-lease and sublease unless it is relieved of its primary obligation under the head-lease. Sublease income is recorded on a
gross basis separate from the head-lease expenses. If the total remaining lease cost on the head-lease is more than the anticipated sublease
income for the lease term, this is an indicator that the carrying amount of the right-of-use asset associated with the head-lease may not
be recoverable, and the right-of-use asset will be assessed for impairment.
F-17
Prior accounting policy — ASC 840
Leases in which a significant portion of the risks and rewards of ownership are retained by the lessor are classified as operating
leases. Payments made under operating leases are charged to the consolidated statements of operations on a straight-line basis over the
period of the leases.
Total operating lease rentals for factories and offices for the year ended December 31, 2018 amounted to US$3,759,000. Sublease
rentals for the year ended December 31, 2018 amounted to US$254,000.
Income Taxes
The Group accounts for income taxes under the liability method. Under the liability method, deferred income tax assets and
liabilities are determined based on the differences between the financial reporting and income tax bases of assets and liabilities and are
measured using the income tax rates that will be in effect when the differences are expected to reverse. A valuation allowance is recorded
when it is more likely than not that some of the net deferred income tax asset will not be realized.
The Group accounts for an uncertain tax position in the consolidated financial statements only if it is more likely than not that the
position is sustainable based on its technical merits and consideration of the relevant tax authority’s widely understood administrative
practices and precedents. If the recognition threshold is met, the Group records the largest amount of tax benefit that is greater than
50 percent likely to be realized upon ultimate settlement.
The Group recognizes interest and penalties for income taxes, if any, under income tax payable on its consolidated balance sheets
and under other expenses in its consolidated statements of operations.
Losses Per Share
Basic losses per share is computed by dividing net loss attributable to the Company by the weighted average number of outstanding
ordinary shares in issue during the year. Weighted average number of outstanding ordinary shares in issue excludes treasury shares.
Diluted losses per share is computed by dividing net loss attributable to the Company by the weighted average number of
outstanding ordinary shares in issue and dilutive ordinary share equivalents outstanding during the year. Dilutive ordinary share
equivalents include ordinary shares and treasury shares issuable upon the exercise or settlement of share-based awards or warrants issued
by the Company using the treasury stock method. The computation of diluted losses per share does not assume conversion, exercise, or
contingent issuance of securities that would have an anti-dilutive effect.
Segment Reporting
Operating segments are reported in a manner consistent with the internal reporting provided to the chief executive officer who is
the Group’s chief operating decision maker. The chief operating decision maker reviews the Group’s internal reporting in order to assess
performance and allocate resources and determined that the Group’s reportable segments are as disclosed in Note 26.
Profit Appropriation and Statutory Reserves
The Group’s subsidiaries and equity investees established in the PRC are required to make appropriations to certain
non-distributable reserve funds.
In accordance with the relevant laws and regulations established in the PRC, the Company’s subsidiaries registered as wholly-
owned foreign enterprise have to make appropriations from their after-tax profits (as determined under generally accepted accounting
principles in the PRC (“PRC GAAP”)) to reserve funds including general reserve fund, enterprise expansion fund and staff bonus and
welfare fund. The appropriation to the general reserve fund must be at least 10% of the after-tax profits calculated in accordance with
PRC GAAP. Appropriation is not required if the general reserve fund has reached 50% of the registered capital of the company.
Appropriations to the enterprise expansion fund and staff bonus and welfare fund are made at the respective company’s discretion. For
the Group’s equity investees, the amount of appropriations to these funds are made at the discretion of their respective boards.
F-18
In addition, Chinese domestic companies must make appropriations from their after-tax profits as determined under PRC GAAP to
non-distributable reserve funds including statutory surplus fund and discretionary surplus fund. The appropriation to the statutory surplus
fund must be 10% of the after-tax profits as determined under PRC GAAP. Appropriation is not required if the statutory surplus fund
has reached 50% of the registered capital of the company. Appropriation to the discretionary surplus fund is made at the respective
company’s discretion.
The use of the general reserve fund, enterprise expansion fund, statutory surplus fund and discretionary surplus fund is restricted to
the offsetting of losses or increases to the registered capital of the respective company. The staff bonus and welfare fund is a liability in
nature and is restricted to fund payments of special bonus to employees and for the collective welfare of employees. All these reserves
are not permitted to be transferred to the company as cash dividends, loans or advances, nor can they be distributed except under
liquidation.
Recent Accounting Pronouncements
The Group has adopted ASU 2016-13 Financial Instruments – Credit Losses (Topic 326): Measurement of Credit Losses on
Financial Instruments (“ASU 2016-13”) on January 1, 2020, which replaced the incurred loss methodology with an expected loss
methodology that was referred to as the current expected credit loss (“CECL”) methodology. The measurement of expected credit losses
under the CECL methodology was applicable to financial assets measured at amortized cost, including cash and cash equivalents, short-
term investments, accounts receivable and other receivables. The adoption of ASU 2016-13 did not have a material impact on the
Group’s consolidated financial statements.
The Group has adopted ASU 2017-04 – Goodwill and Other (Topic 350): Simplifying the Test for Goodwill Impairment (“ASU
2017-04”) on January 1, 2020, which eliminated step two from the goodwill impairment test and instead requires an entity to recognize
an impairment charge for the amount by which the carrying value exceeds the reporting unit’s fair value, limited to the total amount of
goodwill allocated to that reporting unit. The Group applied ASU 2017-04 prospectively and the adoption did not have a material impact
on the Group’s consolidated financial statements.
Amendments that have been issued by the Financial Accounting Standards Board or other standards-setting bodies that do not
require adoption until a future date are not expected to have a material impact on the Group’s consolidated financial statements.
4. Fair Value Disclosures
The following table presents the Group’s financial instruments by level within the fair value hierarchy under ASC 820, Fair Value
Measurement:
As at December 31, 2020
Cash and cash equivalents
Short-term investments
As at December 31, 2019
Cash and cash equivalents
Short-term investments
Fair Value Measurement Using
Level 1
Level 2
Level 3
Total
(in US$’000)
235,630
199,546
121,157
96,011
—
—
—
—
—
—
235,630
199,546
—
—
121,157
96,011
Accounts receivable, other receivables, amounts due from related parties, accounts payable, other payables and amounts due to
related parties are carried at cost, which approximates fair value due to the short-term nature of these financial instruments, and are
therefore excluded from the above table. Bank borrowings are floating rate instruments and carried at amortized cost, which
approximates their fair values, and are therefore excluded from the above table.
F-19
5. Cash and Cash Equivalents
Cash at bank and on hand (note (a))
Bank deposits maturing in three months or less (note (a))
Denominated in:
US$ (note (b))
RMB (note (b))
UK Pound Sterling (“£”) (note (b))
Hong Kong dollar (“HK$”)
Euro
Notes:
December 31,
2020
2019
(in US$’000)
87,828
147,802
235,630
85,990
35,167
121,157
164,201
64,258
954
5,907
310
235,630
84,911
27,768
335
8,143
—
121,157
(a) The weighted average effective interest rate on bank deposits for the years ended December 31, 2020 and 2019 was
1.12% per annum and 2.15% per annum respectively.
(b) Certain cash and bank balances denominated in RMB, US$ and £ were deposited with banks in the PRC. The
conversion of these balances into foreign currencies is subject to the rules and regulations of foreign exchange control
promulgated by the PRC government.
6. Short-term Investments
Bank deposits maturing over three months (note)
Denominated in:
US$
RMB
HK$
December 31,
2020
2019
(in US$’000)
187,961
612
10,973
199,546
73,986
—
22,025
96,011
Note: The weighted average effective interest rate on bank deposits for the years ended December 31, 2020 and 2019 was
1.06% per annum and 2.65% per annum respectively (with maturities ranging from 91 to 180 days and 91 to 129 days
respectively).
7. Accounts Receivable—Third Parties
Accounts receivable from contracts with customers, net of allowance for credit losses, consisted of the following:
Accounts receivable, gross
Allowance for credit losses
Accounts receivable, net
December 31,
2020
2019
(in US$’000)
46,743
(95)
46,648
41,426
(16)
41,410
Substantially all accounts receivable are denominated in RMB, US$ and HK$ and are due within one year from the end of the
reporting periods. The carrying values of accounts receivable approximate their fair values due to their short-term maturities.
F-20
Movements on the allowance for credit losses:
As at January 1
Increase in allowance for credit losses
Decrease in allowance due to subsequent collection
Write-off
Exchange difference
As at December 31
8. Other receivables, prepayments and deposits
Other receivables, prepayments and deposits consisted of the following:
2020
16
95
(18)
—
2
95
2019
(in US$’000)
41
16
(41)
—
—
16
2018
258
21
(223)
(1)
(14)
41
Prepayments
Purchase rebates
Leasehold land deposit (Note 13)
Deposits
Value-added tax receivables
Interest receivables
Others
9. Inventories
Inventories, net of provision for excess and obsolete inventories, consisted of the following:
Raw materials
Finished goods
December 31,
2020
2019
(in US$’000)
7,038
191
930
905
14,957
283
2,482
26,786
3,767
173
—
898
8,760
537
1,634
15,769
December 31,
2020
2019
(in US$’000)
4,502
15,264
19,766
2,274
13,934
16,208
F-21
10. Property, Plant and Equipment
Property, plant and equipment consisted of the following:
Buildings
Leasehold
improvements
Plant
and
equipment
Furniture
and
fixtures,
other
equipment
and motor
vehicles
Construction
in progress
Total
2,212
—
—
—
160
2,372
1,406
112
—
108
1,626
17,022
269
(3,103)
1,014
1,144
16,346
8,304
2,701
(3,051)
698
8,652
746
7,694
(in US$’000)
4,474
59
(3)
789
324
5,643
1,155
484
(1)
109
1,747
3,896
19,571
2,993
(1,846)
913
1,409
23,040
12,487
2,646
(1,815)
938
14,256
928
4,571
—
(2,716)
267
3,050
—
—
—
—
—
44,207
7,892
(4,952)
—
3,304
50,451
23,352
5,943
(4,867)
1,853
26,281
8,784
3,050
24,170
Buildings
Leasehold
improvements
Plant
and
equipment
Furniture
and
fixtures,
other
equipment
and motor
vehicles
Construction
in progress
Total
2,272
—
—
—
(60)
2,212
1,330
114
—
(38)
1,406
806
13,684
587
—
3,103
(352)
17,022
6,244
2,270
—
(210)
8,304
8,718
(in US$’000)
3,218
247
—
1,096
(87)
4,474
782
402
—
(29)
1,155
3,319
16,643
3,470
(812)
755
(485)
19,571
11,470
2,058
(720)
(321)
12,487
625
5,329
—
(4,954)
(72)
928
—
—
—
—
—
36,442
9,633
(812)
—
(1,056)
44,207
19,826
4,844
(720)
(598)
23,352
7,084
928
20,855
Cost
As at January 1, 2020
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2020
Accumulated depreciation
As at January 1, 2020
Depreciation
Disposals
Exchange differences
As at December 31, 2020
Net book value
As at December 31, 2020
Cost
As at January 1, 2019
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2019
Accumulated depreciation
As at January 1, 2019
Depreciation
Disposals
Exchange differences
As at December 31, 2019
Net book value
As at December 31, 2019
Depreciation for the year ended December 31, 2018 was US$3,486,000.
F-22
11. Leases
Leases consisted of the following:
Right‑of‑use assets
Offices (note)
Factories
Warehouse
Others
Total right‑of‑use assets
Lease liabilities—current
Lease liabilities—non‑current
Total lease liabilities
December 31,
2020
2019
(in US$’000)
6,789
945
197
85
8,016
2,785
6,064
8,849
5,281
112
—
123
5,516
3,216
3,049
6,265
Note: Includes US$2.0 million right-of-use asset for corporate offices in Hong Kong that is leased through May 2024 in
which the contract has a termination option with 3-month advance notice. The termination option was not recognized as
part of the right-of-use asset and lease liability as it was uncertain that the Group will exercise such option.
Lease activities are summarized as follows:
Lease expenses:
Short‑term leases with lease terms equal or less than 12 months
Leases with lease terms greater than 12 months (note)
Sublease rental income
Cash paid on lease liabilities
Non-cash: Lease liabilities recognized from obtaining right-of-use assets
Non-cash: Lease liabilities changed in relation to modifications
Year Ended December 31,
2020
2019
(in US$’000)
323
3,400
3,723
—
3,340
3,098
2,259
311
3,702
4,013
61
3,886
3,197
744
Note: Lease expenses for the year ended December 31, 2019 includes US$0.3 million in accelerated amortization on a
right-of-use asset for retail space in the United Kingdom leased through May 2022. The Group had subleased the retail
space through May 2022 to a third-party and in December 2019, the sublease was discontinued and the Group recorded
accelerated amortization after determining that additional sublease rental income was uncertain.
Lease contracts are typically within a period of 1 to 8 years. The weighted average remaining lease term and the weighted average
discount rate as at December 31, 2020 was 3.72 years and 3.87% respectively. The weighted average remaining lease term and the
weighted average discount rate as at December 31, 2019 was 2.80 years and 4.10% respectively.
F-23
Future lease payments are as follows:
Lease payments:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Between 3 to 4 years
Between 4 to 5 years
Later than 5 years
Total lease payments (note)
Less: Discount factor
Total lease liabilities
December 31,
2020
(in US$’000)
3,059
2,429
2,222
1,046
216
484
9,456
(607)
8,849
Note: Excludes future lease payments on a lease not commenced as at December 31, 2020 in the aggregate amount of
US$2.9 million.
12. Investments in Equity Investees
Investments in equity investees consisted of the following:
HBYS
SHPL
Other
December 31,
2020
2019
(in US$’000)
59,712
79,408
385
139,505
22,271
76,226
447
98,944
Particulars regarding the principal equity investees are disclosed in Note 2. The equity investees are private companies and there
are no quoted market prices available for their shares.
Summarized financial information for the significant equity investees HBYS and SHPL, both under Other Ventures segment, is
as follows:
(i) Summarized balance sheets
Current assets
Non-current assets
Current liabilities
Non-current liabilities
Net assets
Non-controlling interests
HBYS
SHPL
December 31,
2020
2019
2020
2019
177,888
95,731
(137,179)
(16,034)
120,406
(982)
119,424
(in US$’000)
124,704
95,096
(124,051)
(48,690)
47,059
(2,518)
44,541
175,965
93,361
(109,873)
(6,739)
152,714
—
152,714
141,268
91,098
(79,533)
(6,074)
146,759
—
146,759
F-24
(ii) Summarized statements of operations
Revenue
Gross profit
Interest income
Finance cost
Profit before taxation
Income tax expense (note (b))
Net income
Non-controlling interests
Net income attributable to the shareholders of equity investee
Notes:
HBYS(note a)
2020
2019
2018
2020
Year Ended December 31,
(in US$’000)
232,368
116,804
271
(5)
107,715
(16,494)
91,221
62
91,283
215,403
115,124
160
(16)
22,926
(3,634)
19,292
505
19,797
215,838
113,137
81
(152)
20,703
(4,227)
16,476
384
16,860
276,354
204,191
975
—
77,837
(10,833)
67,004
—
67,004
SHPL
2019
272,082
194,769
582
—
72,324
(11,015)
61,309
—
61,309
2018
275,649
192,939
673
—
69,138
(9,371)
59,767
—
59,767
(a) In June 2020, HBYS entered into an agreement with the government to return the land use right for a plot of land in Guangzhou to
the government for cash consideration of up to RMB683.0 million (approximately US$101.2 million) (the “Land Compensation
Agreement”). In November 2020, HBYS completed all material obligations as stipulated in the Land Compensation Agreement
including the deregistration of the land use right certificate. Therefore, HBYS has recorded the return of leasehold land to the
government for RMB569.2 million (approximately US$86.1 million), resulting in a gain of RMB559.7 million (approximately
US$84.7 million) after deducting costs of RMB1.7 million (approximately US$0.3 million) to HBYS or RMB475.7 million, net of
tax (approximately US$72.0 million). The remaining RMB113.8 million (approximately US$17.4 million) of cash consideration is
conditional upon the receipt of a completion confirmation from the government within 12 months from the date of the Land
Compensation Agreement and therefore has not been recognized as at December 31, 2020.
(b) The main entities within each of the HBYS and SHPL groups have been granted the High and New Technology Enterprise
(“HNTE”) status (the latest renewal of this status covers the years from 2020 to 2022). These entities were eligible to use a
preferential income tax rate of 15% for the year ended December 31, 2020 on this basis.
For the years ended December 31, 2020 and 2019, other equity investees had net losses of approximately US$194,000 and net
income of approximately US$294,000 respectively. For the year ended December 31, 2018, other equity investees had net losses of
approximately US$37,962,000, primarily from Nutrition Science Partners Limited (“NSPL”) which incurred research and development
expenses and recorded an impairment provision of US$30,000,000 on its intangible assets. In December 2019, the Group acquired the
remaining 50% shareholding in NSPL from the equity investee partner and, after the acquisition, it became a subsidiary.
(iii) Reconciliation of summarized financial information
Reconciliation of the summarized financial information presented to the carrying amount of investments in equity investees is
as follows:
2020
HBYS
2019
2018
2020
(in US$’000)
SHPL
2019
2018
Opening net assets after non-controlling interests as at January 1
Impact of change in accounting policy (ASC 842-Leases)
Net income attributable to the shareholders of equity investee
Purchase of additional interests in a subsidiary of an equity investee
(note)
Dividends declared
Other comprehensive income/(loss)
Closing net assets after non-controlling interests as at December 31
Group’s share of net assets
Goodwill
Carrying amount of investments as at December 31
44,541
—
91,283
(347)
(20,756)
4,703
119,424
59,712
—
59,712
121,984
(19)
19,797
—
(93,957)
(3,264)
44,541
22,271
—
22,271
110,616
—
16,860
—
—
(5,492)
121,984
60,992
—
60,992
146,759
—
67,004
—
(72,179)
11,130
152,714
76,357
3,051
79,408
131,778
(2)
61,309
—
(41,654)
(4,672)
146,759
73,380
2,846
76,226
132,731
—
59,767
—
(54,923)
(5,797)
131,778
65,889
2,923
68,812
Note: During the year ended December 31, 2020, HBYS acquired an additional 30% interest in a subsidiary and after the acquisition, it
became a wholly owned subsidiary of HBYS.
F-25
The equity investees had the following capital commitments:
Property, plant and equipment
Contracted but not provided for
13. Other Non-Current Assets
Leasehold land (note)
Goodwill
Leasehold land deposit (note)
Long term prepayment
Other intangible asset
Deferred issuance cost
December 31,
2020
(in US$’000)
2,535
December 31,
2020
2019
(in US$’000)
13,121
3,307
1,396
950
227
1,171
20,172
1,110
3,112
—
1,103
275
180
5,780
Note: In December 2020, HMPL acquired a land use right in Shanghai for consideration of US$12.0 million. In addition,
a leasehold land deposit amounting to US$2.3 million was required to be paid to the government which is refundable upon
reaching specific milestones for the construction of a manufacturing plant on the land. US$0.9 million was included in
other receivables, prepayments and deposits (Note 8) and US$1.4 million was included in other non-current assets based
on the expected timing of the specific milestones.
14. Accounts Payable
Accounts payable—third parties
Accounts payable—non-controlling shareholders of subsidiaries (Note 23(iv))
December 31,
2020
2019
(in US$’000)
26,756
4,856
31,612
19,598
4,363
23,961
Substantially all accounts payable are denominated in RMB and US$ and due within one year from the end of the reporting period.
The carrying values of accounts payable approximate their fair values due to their short-term maturities.
15. Other Payables, Accruals and Advance Receipts
Other payables, accruals and advance receipts consisted of the following:
Accrued salaries and benefits
Accrued research and development expenses
Accrued selling and marketing expenses
Accrued administrative and other general expenses
Deferred government grants
Deposits
Others
F-26
December 31,
2020
2019
(in US$’000)
21,982
72,697
5,747
10,319
374
1,408
8,355
120,882
13,258
48,531
3,337
8,411
445
1,778
5,864
81,624
16. Bank Borrowings
Bank borrowings consisted of the following:
Non-current
December 31,
2020
2019
(in US$’000)
26,861
26,818
The weighted average interest rate for outstanding bank borrowings for the years ended December 31, 2020 and 2019 was 1.89%
per annum and 3.30% per annum respectively. The carrying amounts of the Group’s bank borrowings were denominated in HK$.
(i) 3-year revolving loan facility and 3-year term loan and revolving loan facilities
In November 2018, the Group through its subsidiary, renewed a 3-year revolving loan facility with a bank in the amount of
HK$234,000,000 (US$30,000,000) with an interest rate at the Hong Kong Interbank Offered Rate (“HIBOR”) plus 0.85% per annum.
This credit facility is guaranteed by the Company. As at December 31, 2020 and 2019, no amount has been drawn from the revolving
loan facility.
In May 2019, the Group through its subsidiary, entered into a separate facility agreement with the bank for the provision of
additional unsecured credit facilities in the aggregate amount of HK$400,000,000 (US$51,282,000). The 3-year credit facilities include
(i) a HK$210,000,000 (US$26,923,000) term loan facility and (ii) a HK$190,000,000 (US$24,359,000) revolving loan facility, both
with an interest rate at HIBOR plus 0.85% per annum, and an upfront fee of HK$819,000 (US$105,000) on the term loan. These credit
facilities are guaranteed by the Company. The term loan was drawn in October 2019 and is due in May 2022. As at December 31, 2020
and 2019, no amount has been drawn from the revolving loan facility.
(ii) 2-year revolving loan facilities
In August 2018, the Group through its subsidiary, entered into two separate facility agreements with banks for the provision of
unsecured credit facilities in the aggregate amount of HK$507,000,000 (US$65,000,000). The first credit facility was a HK$351,000,000
(US$45,000,000) revolving loan facility, with a term of 2 years and an interest rate at HIBOR plus 1.35% per annum. The second credit
facility was a HK$156,000,000 (US$20,000,000) revolving loan facility, with a term of 2 years and an interest rate at HIBOR plus
1.35% per annum. These credit facilities were guaranteed by the Company. No amount has been drawn from either of the revolving loan
facilities. Both loan facilities expired in August 2020.
In August 2020, the Group through its subsidiary, entered into a 2-year revolving loan facility with a bank in the amount of
HK$117,000,000 (US$15,000,000) with an interest rate at HIBOR plus 4.5% per annum. This credit facility is guaranteed by the
Company. As at December 31, 2020, no amount has been drawn from the revolving loan facility.
(iii) 3-year term loan and 18-month revolving loan facilities
In November 2017, the Group through its subsidiary, entered into facility agreements with a bank for the provision of unsecured
credit facilities in the aggregate amount of HK$400,000,000 (US$51,282,000). The credit facilities included (i) a HK$210,000,000
(US$26,923,000) 3-year term loan facility and (ii) a HK$190,000,000 (US$24,359,000) 18-month revolving loan facility. The term loan
bore interest at HIBOR plus 1.50% per annum and an upfront fee of HK$1,575,000 (US$202,000). The revolving loan facility bore
interest at HIBOR plus 1.25% per annum. These credit facilities were guaranteed by the Company. The term loan was drawn in May
2018 and was fully repaid in June 2019. The revolving loan facility expired in May 2019.
F-27
The Group’s bank borrowings are repayable as from the dates indicated as follows:
December 31,
2020
2019
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
(in US$’000)
—
26,923
—
26,923
—
—
26,923
26,923
As at December 31, 2020 and 2019, the Group had unutilized bank borrowing facilities of HK$541,000,000 (US$69,359,000) and
HK$931,000,000 (US$119,359,000) respectively.
17. Commitments and Contingencies
The Group had the following capital commitments:
Property, plant and equipment
Contracted but not provided for
The Group does not have any other significant commitments or contingencies.
18. Ordinary Shares
As at December 31, 2020, the Company is authorized to issue 1,500,000,000 ordinary shares.
December 31,
2020
(in US$’000)
5,053
On January 27, 2020, the Company issued 22,000,000 ordinary shares in the form of 4,400,000 ADS for gross proceeds of US$110.0
million. On February 10, 2020, the Company issued an additional 1,668,315 ordinary shares in the form of 333,663 ADS for gross
proceeds of US$8.3 million. Issuance costs totaled US$8.0 million.
On July 2, 2020 and July 3, 2020, the Company issued (1) aggregate 20,000,000 ordinary shares and (2) warrants to a third party
for gross proceeds of US$100.0 million through a PIPE. The warrants allow the third party to purchase up to 16,666,670 ordinary shares
of the Company within 18 months of the issuance date for an exercise price of US$6.00 per ordinary share, or an additional US$100.0
million if fully exercised. As the warrants qualify for equity classification, all gross proceeds were recorded to equity. Issuance costs
totaled US$0.2 million.
On November 26, 2020, the Company issued 16,666,670 ordinary shares to a third party for gross proceeds of US$100.0 million
through a PIPE. Issuance costs totaled US$0.1 million.
Each ordinary share is entitled to one vote. The holders of ordinary shares are also entitled to receive dividends whenever funds are
legally available and when declared by the Board of Directors of the Company.
19. Share-based Compensation
(i) Share-based Compensation of the Company
The Company conditionally adopted a share option scheme on June 4, 2005 (as amended on March 21, 2007) and such scheme has
a term of 10 years. It expired in 2016 and no further share options can be granted. Another share option scheme was conditionally
adopted on April 24, 2015 (the “HCML Share Option Scheme”). Pursuant to the HCML Share Option Scheme, the Board of Directors
of the Company may, at its discretion, offer any employees and directors (including Executive and Non-executive Directors but
excluding Independent Non-executive Directors) of the Company, holding companies of the Company and any of their subsidiaries or
affiliates, and subsidiaries or affiliates of the Company share options to subscribe for shares of the Company.
F-28
Pursuant to a resolution passed in the Annual General Meeting on April 27, 2020, the scheme limit of the HCML Share Option
Scheme was refreshed to 34,528,738 ordinary shares, representing 5% of the total issued shares on such date.
As at December 31, 2020, the aggregate number of shares issuable under the HCML Share Option Scheme was 50,663,268 ordinary
shares and the aggregate number of shares issuable under the prior share option scheme which expired in 2016 was 1,116,180 ordinary
shares. The Company will issue new shares to satisfy share option exercises. Additionally, the number of shares authorized but unissued
was 772,277,785 ordinary shares.
Share options granted are generally subject to a four-year vesting schedule, depending on the nature and the purpose of the grant.
Share options subject to the four-year vesting schedule, in general, vest 25% upon the first anniversary of the vesting commencement
date as defined in the grant letter, and 25% every subsequent year. However, certain share option grants may have a different vesting
schedule as approved by the Board of Directors of the Company. No outstanding share options will be exercisable or subject to vesting
after the expiry of a maximum of eight to ten years from the date of grant.
A summary of the Company’s share option activity and related information is as follows:
Outstanding at January 1, 2018
Granted
Exercised
Cancelled
Outstanding at December 31, 2018
Granted
Exercised
Cancelled
Expired
Outstanding at December 31, 2019
Granted
Exercised
Cancelled
Expired
Outstanding at December 31, 2020
Vested and exercisable at December 31, 2019
Vested and exercisable at December 31, 2020
Weighted average
exercise price in
£ per share
Weighted average
remaining
contractual life
(years)
Aggregate
intrinsic value
(in £’000)
43,158
6.29
Number of
share
options
11,264,120
10,606,260
(2,107,080)
(1,208,450)
18,554,850
2,315,000
(329,000)
(1,012,110)
(96,180)
19,432,560
15,437,080
(480,780)
(4,486,200)
(741,670)
29,160,990
10,139,170
11,529,280
1.77
4.69
1.40
4.30
3.31
3.18
0.61
4.61
4.65
3.27
3.71
0.96
3.85
4.62
3.40
2.39
2.73
7.35
15,158
6.67
18,668
7.21
4.89
4.57
35,654
16,654
21,864
In estimating the fair value of share options granted, the following assumptions were used in the Polynomial model for awards
granted in the periods indicated:
Weighted average grant date fair value of share options (in £ per share)
Significant inputs into the valuation model (weighted average):
Exercise price (in £ per share)
Share price at effective date of grant (in £ per share)
Expected volatility (note (a))
Risk-free interest rate (note (b))
Contractual life of share options (in years)
Expected dividend yield (note (c))
Notes:
2020
Year Ended December 31,
2019
1.40
3.71
3.71
42.6%
0.59%
10
0%
1.07
3.18
3.07
38.4%
0.56%
10
0%
2018
1.67
4.69
4.66
37.6%
1.46%
10
0%
(a) The Company calculated its expected volatility with reference to the historical volatility prior to the issuances of share options.
F-29
(b) For share options exercisable into ordinary shares, the risk-free interest rates reference the sovereign yield of the United Kingdom
because the Company’s ordinary shares are currently listed on AIM and denominated in £. For share options exercisable into ADS,
the risk-free interest rates reference the U.S. Treasury yield curves because the Company's ADS are currently listed on the NASDAQ
and denominated in US$.
(c) The Company has not declared or paid any dividends and does not currently expect to do so in the foreseeable future, and therefore
uses an expected dividend yield of zero in the Polynomial model.
The Company will issue new shares to satisfy share option exercises. The following table summarizes the Company’s share option
exercises:
Cash received from share option exercises
Total intrinsic value of share option exercises
2020
Year Ended December 31,
2019
(in US$’000)
251
1,189
593
2,475
3,868
9,394
2018
The Group recognizes compensation expense on a graded vesting approach over the requisite service period. The following table
presents share-based compensation expense included in the Group’s consolidated statements of operations:
Research and development expenses
Selling and administrative expenses
Cost of goods
2018
2020
Year Ended December 31,
2019
(in US$’000)
6,634
539
—
7,173
4,061
4,586
90
8,737
7,280
623
—
7,903
As at December 31, 2020, the total unrecognized compensation cost was US$19,350,000, and will be recognized on a graded vesting
approach over the weighted average remaining service period of 3.23 years.
(ii) LTIP
The Company grants awards under the LTIP to participating directors and employees, giving them a conditional right to receive
ordinary shares of the Company or the equivalent ADS (collectively the “Awarded Shares”) to be purchased by the Trustee up to a cash
amount. Vesting will depend upon continued employment of the award holder with the Group and will otherwise be at the discretion of
the Board of Directors of the Company. Additionally, some awards are subject to change based on annual performance targets prior to
their determination date.
LTIP awards prior to the determination date
Performance targets vary by award, and may include targets for shareholder returns, free cash flows, revenues, net profit after taxes
and the achievement of clinical and regulatory milestones. As the extent of achievement of the performance targets is uncertain prior to
the determination date, a probability based on management’s assessment on the achievement of the performance target has been assigned
to calculate the amount to be recognized as an expense over the requisite period with a corresponding entry to liability.
LTIP awards after the determination date
Upon the determination date, the Company will pay a determined monetary amount, up to the maximum cash amount based on the
actual achievement of the performance target specified in the award, to the Trustee to purchase the Awarded Shares. Any cumulative
compensation expense previously recognized as a liability will be transferred to additional paid-in capital, as an equity-settled award. If
the performance target is not achieved, no Awarded Shares of the Company will be purchased and the amount previously recorded in
the liability will be reversed through share-based compensation expense.
F-30
Granted awards under the LTIP are as follows:
Grant date
August 6, 2018
December 14, 2018
August 5, 2019
October 10, 2019
April 20, 2020
April 20, 2020
April 20, 2020
April 20, 2020
August 12, 2020
August 12, 2020
Notes:
Maximum cash
amount per annum
(in US$ millions)
0.1
1.5
0.7
0.1
5.3
37.4
1.9
0.2
2.1
0.3
Covered
financial years
Performance target
determination date
2018-2019
2019
2019
note (b)
2019
2020
note (b)
note (c)
2020
note (b)
note (a)
note (a)
note (a)
note (b)
note (d)
note (a)
note (b)
note (c)
note (a)
note (b)
(a) The annual performance target determination date is the date of the announcement of the Group’s annual results for the covered
financial year and vesting occurs two business days after the announcement of the Group's annual results for the financial year
falling two years after the covered financial year to which the LTIP award relates.
(b) This award does not stipulate performance targets and is subject to a vesting schedule of 25% on each of the first, second, third and
fourth anniversaries of the date of grant.
(c) This award does not stipulate performance targets and will be vested on the first anniversary of the date of grant.
(d) This award does not stipulate performance targets and vesting occurs two business days after the announcement of the Group's
annual results for the financial year falling two years after the covered financial year to which the LTIP award relates.
The Trustee has been set up solely for the purpose of purchasing and holding the Awarded Shares during the vesting period on
behalf of the Company using funds provided by the Company. On the determination date, if any, the Company will determine the cash
amount, based on the actual achievement of each annual performance target, for the Trustee to purchase the Awarded Shares. The
Awarded Shares will then be held by the Trustee until they are vested.
The Trustee’s assets include treasury shares and funds for additional treasury shares, trustee fees and expenses. The number of
treasury shares (in the form of ordinary shares or ADS of the Company) held by the Trustee were as follows:
As at January 1, 2018
Purchased
Vested
As at December 31, 2018
Purchased
Vested
As at December 31, 2019
Purchased
Vested
As at December 31, 2020
Number of
Cost
treasury shares (in US$’000)
1,957
5,451
(731)
6,677
346
(944)
6,079
12,904
(4,828)
14,155
559,775
795,005
(233,750)
1,121,030
60,430
(240,150)
941,310
3,281,920
(712,555)
3,510,675
Based on the estimated achievement of performance conditions for 2020 financial year LTIP awards, the determined monetary
amount was US$30,355,000 which is recognized to share-based compensation expense over the requisite vesting period to March 2023.
For the years ended December 31, 2020, 2019 and 2018, US$7,038,000, US$262,000 and US$692,000 of the LTIP awards were
forfeited respectively.
F-31
The following table presents the share-based compensation expenses recognized under the LTIP awards:
Research and development expenses
Selling and administrative expenses
Cost of goods
Recorded with a corresponding credit to:
Liability
Additional paid-in capital
2018
2020
Year Ended December 31,
2019
(in US$’000)
2,640
1,779
—
4,419
7,252
3,552
101
10,905
1,000
1,227
—
2,227
7,778
3,127
10,905
2,694
1,725
4,419
764
1,463
2,227
For the years ended December 31, 2020, 2019 and 2018, US$4,092,000, US$526,000 and US$1,770,000 were reclassified from
liability to additional paid-in capital respectively upon LTIP awards reaching the determination date. As at December 31, 2020 and
2019, US$7,089,000 and US$3,403,000 were recorded as liabilities respectively for LTIP awards prior to the determination date.
As at December 31, 2020, the total unrecognized compensation cost was approximately US$28,623,000, which considers expected
performance targets and the amount expected to vest, and will be recognized over the requisite periods.
20. Revenues
The following table presents disaggregated revenue, with sales of goods recognized at a point-in-time and provision of services
recognized over time:
Goods—Marketed Products (note (a))
Goods—Distribution
Services—Commercialization—Marketed Products
—Collaboration Research and Development
—Research and Development
Royalties (note (a))
Third parties
Related parties (Note 23(i))
Oncology/
Immunology
Year Ended December 31, 2020
Other
Ventures
(in US$’000)
11,329
—
3,734
9,771
491
4,890
30,215
29,724
491
30,215
—
197,761
—
—
—
—
197,761
192,277
5,484
197,761
Total
11,329
197,761
3,734
9,771
491
4,890
227,976
222,001
5,975
227,976
F-32
Goods—Marketed Products (note (a))
Goods—Distribution
Services—Commercialization
—Collaboration Research and Development
—Research and Development
Royalties (note (a))
Third parties
Related parties (Note 23(i))
Goods—Marketed Products (note (a))
Goods—Distribution
Services—Commercialization
—Collaboration Research and Development
—Research and Development
Royalties (note (a))
Licenses (note (b))
Third parties
Related parties (Note 23(i))
Notes:
Oncology/
Immunology
Year Ended December 31, 2019
Other
Ventures
(in US$’000)
8,113
—
—
15,532
494
2,653
26,792
26,298
494
26,792
—
175,514
2,584
—
—
—
178,098
170,461
7,637
178,098
Oncology/
Immunology
Year Ended December 31, 2018
Other
Ventures
(in US$’000)
3,324
—
—
17,681
7,832
261
12,135
41,233
33,401
7,832
41,233
—
161,216
11,660
—
—
—
—
172,876
164,570
8,306
172,876
Total
8,113
175,514
2,584
15,532
494
2,653
204,890
196,759
8,131
204,890
Total
3,324
161,216
11,660
17,681
7,832
261
12,135
214,109
197,971
16,138
214,109
(a) Goods—Marketed Products and royalties relate to revenue from an oncology drug developed by the
Oncology/Immunology segment and launched into the market. It was represented under the Oncology/Immunology
segment to align with a change to the segment reporting. Refer to Note 26.
(b) Relates to the proportionate amount of milestone payment allocated to the license to the commercialization rights of
an oncology drug compound transferred at the inception date of the relevant license and collaboration contract. During
the year ended December 31, 2018, the Group received a milestone of US$13.5 million, of which US$12.1 million
was allocated to licenses and US$1.4 million was allocated to services.
The following table presents liability balances from contracts with customers:
Deferred revenue
Current—Oncology/Immunology segment (note (a))
Current—Other Ventures segment (note (b))
Non-current—Oncology/Immunology segment (note (a))
Total deferred revenue (note (c) and (d))
F-33
December 31,
2020
2019
(in US$’000)
1,450
147
1,597
484
2,081
1,753
353
2,106
133
2,239
Notes:
(a) Oncology/Immunology segment deferred revenue relates to the unamortized upfront and milestone payments and
advance consideration received for cost reimbursements, which are attributed to research and development services
that have not yet been rendered as at the reporting date.
(b) Other Ventures segment deferred revenue relates to payments in advance from customers for goods that have not been
transferred and services that have not been rendered to the customer as at the reporting date.
(c) Estimated deferred revenue to be recognized over time as from the date indicated is as follows:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Between 3 to 4 years
December 31,
2020
2019
(in US$’000)
1,597
211
205
68
2,081
2,106
133
—
—
2,239
(d) As at January 1, 2020, deferred revenue was US$2.2 million, of which US$0.9 million was recognized during the year
ended December 31, 2020.
License and collaboration agreement with Eli Lilly
On October 8, 2013, the Group entered into a licensing, co-development and commercialization agreement in China with Eli Lilly
and Company (“Lilly”) relating to Elunate (“Lilly Agreement”), also known as fruquintinib, a targeted oncology therapy for the
treatment of various types of solid tumors. Under the terms of the Lilly Agreement, the Group is entitled to receive a series of payments
up to US$86.5 million, including upfront payments and development and regulatory approval milestones. Development costs after the
first development milestone are shared between the Group and Lilly. Elunate was successfully commercialized in China in November
2018, and the Group receives tiered royalties in the range of 15% to 20% on all sales in China.
In December 2018, the Group entered into various amendments to the Lilly Agreement (the “2018 Amendment”). Under the terms
of the 2018 Amendment, the Group is entitled to determine and conduct future life cycle indications (“LCI”) development of Elunate in
China beyond the three initial indications specified in the Lilly Agreement and will be responsible for all associated development costs.
In return, the Group will receive additional regulatory approval milestones of US$20 million for each LCI approved, for up to three LCI
or US$60 million in aggregate, and will increase tiered royalties to a range of 15% to 29% on all Elunate sales in China upon the
commercial launch of the first LCI. Additionally, through the 2018 Amendment, Lilly has provided consent, and freedom to operate,
for the Group to enter into joint development collaborations with certain third-party pharmaceutical companies to explore combination
treatments of Elunate and various immunotherapy agents. The 2018 Amendment also provided the Group rights to promote Elunate in
provinces that represent 30% to 40% of the sales of Elunate in China upon the occurrence of certain commercial milestones by Lilly.
Such rights were further amended below.
F-34
In July 2020, the Group entered an amendment to the Lilly Agreement (the "2020 Amendment") relating to the expansion of the
Group's role in the commercialization of Elunate across all of China. Under the terms of the 2020 Amendment, the Group is responsible
for providing promotion and marketing services, including the development and execution of all on-the-ground medical detailing,
promotion and local and regional marketing activities, in return for service fees on sales of Elunate made by Lilly. In October 2020, the
Group commenced such promotion and marketing services. In addition, development and regulatory approval milestones for an initial
indication under the Lilly Agreement were increased by US$10 million in lieu of cost reimbursement.
Upfront and cumulative milestone payments according to the Lilly Agreement received up to December 31, 2020 are summarized
as follows:
Upfront payment
Development milestone payments achieved
(in US$’000)
6,500
40,000
Under ASC 606, the Group identified the following performance obligations under the Lilly Agreement: (1) the license for the
commercialization rights to Elunate and (2) the research and development services for the specified indications. The transaction price
includes the upfront payment, research and development cost reimbursements, milestone payments and sales-based royalties. Milestone
payments were not included in the transaction price until it became probable that a significant reversal of revenue would not occur,
which is generally when the specified milestone is achieved. The allocation of the transaction price to each performance obligation was
based on the relative standalone selling prices of each performance obligation determined at the inception of the contract. Based on this
estimation, proportionate amounts of transaction price to be allocated to the license to Elunate and the research and development services
were 90% and 10% respectively. Control of the license to Elunate transferred at the inception date of the agreement and consequently,
amounts allocated to this performance obligation were recognized at inception. Conversely, research and development services for each
specified indication are performed over time and amounts allocated are recognized over time using the prior and estimated future
development costs for Elunate as a measure of progress. Royalties are recognized as future sales occur as they meet the requirements
for the sales-usage based royalty exception.
The 2018 Amendment is a separate contract under ASC 606 as it added distinct research and development services for the LCIs to
the Lilly Agreement. As at December 31, 2020, no LCI regulatory approval milestones were achieved. The 2020 Amendment related to
the promotion and marketing services is a separate contract under ASC 606 as it added distinct services to the Lilly Agreement. Such
promotion and marketing services are recognized over time based on amounts that can be invoiced to Lilly. The 2020 Amendment
related to the additional development and regulatory approval milestone amounts is a modification under ASC 606 as it only affected
the transaction price of research and development services for a specific indication under the Lilly Agreement, and therefore, such
additional milestone amounts will be included in the transaction price accounted under the Lilly Agreement once the specified milestones
are achieved. As at December 31, 2020, no additional development and regulatory approval milestone amounts were achieved.
Revenue recognized under the Lilly Agreement by transaction price type is as follows:
2020
2018
Year Ended December 31,
2019
(in US$’000)
3,910
88
7
2,653
8,113
—
14,771
9,309
122
13,849
261
3,324
—
26,865
1,876
83
32
4,890
11,329
3,734
21,944
Research and development cost reimbursements
Amortization of the upfront payment
Recognition and amortization of the milestone payments (note)
Royalties
Goods—Marketed Products
Promotion and marketing services
F-35
Note: During the years ended December 31, 2020 and 2019, no milestones were achieved. During the year ended December
31, 2018, the Group achieved milestones in relation to the acceptance and approval respectively, of a new drug application
by the National Medical Products Administration of China for Elunate as a treatment of patients with advanced colorectal
cancer.
License and collaboration agreement with AstraZeneca
On December 21, 2011, the Group and AstraZeneca AB (publ) (“AZ”) entered into a global licensing, co-development, and
commercialization agreement for savolitinib (“AZ Agreement”), a novel targeted therapy and a highly selective inhibitor of the c-Met
receptor tyrosine kinase for the treatment of cancer. Under the terms of the AZ Agreement, the Group is entitled to receive a series of
payments up to US$140 million, including upfront payments and development and first-sale milestones. Additionally, the AZ Agreement
contains possible significant future commercial sale milestones. Should savolitinib be successfully commercialized outside China, the
Group would receive tiered royalties from 9% to 13% on all sales outside of China. Should savolitinib be successfully commercialized
in China, the Group would receive fixed royalties of 30% based on all sales in China. Development costs for savolitinib in China will
be shared between the Group and AZ, with the Group continuing to lead the development in China. AZ will lead and pay for the
development of savolitinib for the rest of the world.
In August 2016 (as amended in December 2020), the Group entered into an amendment to the AZ Agreement whereby the Group
shall pay the first approximately US$50 million of phase III clinical trial costs related to developing savolitinib for renal cell carcinoma
("RCC"), and remaining costs will be shared between the Group and AZ. Subject to approval of savolitinib in RCC, the Group would
receive additional tiered royalties on all sales outside of China, with the incremental royalty rates determined based on actual sharing of
development costs.
Upfront and cumulative milestone payments according to the AZ Agreement received up to December 31, 2020 are summarized as
follows:
Upfront payment
Development milestone payments achieved
(in US$’000)
20,000
25,000
Under ASC 606, the Group identified the following performance obligations under the AZ Agreement: (1) the license for the
commercialization rights to savolitinib and (2) the research and development services for the specified indications. The transaction price
includes the upfront payment, research and development cost reimbursements, milestone payments and sales-based royalties. Milestone
payments were not included in the transaction price until it became probable that a significant reversal of revenue would not occur,
which is generally when the specified milestone is achieved. The allocation of the transaction price to each performance obligation was
based on the relative standalone selling prices of each performance obligation determined at the inception of the contract. Based on this
estimation, proportionate amounts of transaction price to be allocated to the license to savolitinib and the research and development
services were 95% and 5% respectively. Control of the license to savolitinib transferred at the inception date of the agreement and
consequently, amounts allocated to this performance obligation were recognized at inception. Conversely, research and development
services for each specified indication are performed over time and amounts allocated are recognized over time using the prior and
estimated future development costs for savolitinib as a measure of progress.
Revenue recognized under the AZ Agreement by transaction price type is as follows:
Research and development cost reimbursements
Amortization of the upfront payment (note (a))
Recognition and amortization of the milestone payments (note (a) and (b))
2020
2018
Year Ended December 31,
2019
(in US$’000)
10,883
302
342
11,527
8,289
(330)
(179)
7,780
5,876
273
387
6,536
Notes:
(a) During the year ended December 31, 2020, estimated costs inputs used for the measure of progress was adjusted to
reflect the additional estimated development costs for phase III clinical trial costs for RCC.
(b) During the years ended December 31, 2020, 2019 and 2018, no milestones were achieved.
F-36
21. Research and Development Expenses
Research and development expenses are summarized as follows:
Clinical trial related costs
Personnel compensation and related costs
Other research and development expenses
2020
2018
Year Ended December 31,
2019
(in US$’000)
87,777
46,246
4,167
73,693
35,340
5,128
174,776 138,190 114,161
105,869
63,542
5,365
The Group has entered into multiple collaborative arrangements under ASC 808 to evaluate the combination of the Group's drug
compounds with the collaboration partners' drug compounds. For the years ended December 31, 2020, 2019 and 2018, the Group has
incurred research and development expenses of US$8,291,000, US$2,921,000 and nil respectively, related to such collaborative
arrangements.
22. Government Grants
Government grants in the Oncology/Immunology segment are primarily given in support of R&D activities and are conditional
upon i) the Group spending a predetermined amount, regardless of success or failure of the research and development projects and/or
ii) the achievement of certain stages of research and development projects being approved by the relevant PRC government authority.
They are refundable to the government if the conditions, if any, are not met. Government grants in the Other Ventures segment are
primarily given to promote local initiatives. These government grants may be subject to ongoing reporting and monitoring by the
government over the period of the grant.
Government grants, which are deferred and recognized in the consolidated statements of operations over the period necessary to
match them with the costs that they are intended to compensate, are recognized in other payable, accruals and advance receipts (Note 15)
and other non-current liabilities. For the years ended December 31, 2020, 2019 and 2018, the Group received government grants of
US$4,724,000, US$8,742,000 and US$1,798,000 respectively.
The government grants were recognized in the consolidated statements of operations as follows:
Research and development expenses
Other income
2018
2020
Year Ended December 31,
2019
(in US$’000)
6,133
780
6,913
1,607
539
2,146
1,422
573
1,995
23. Significant Transactions with Related Parties and Non-Controlling Shareholders of Subsidiaries
The Group has the following significant transactions with related parties and non-controlling shareholders of subsidiaries, which
were carried out in the normal course of business at terms determined and agreed by the relevant parties:
F-37
(i) Transactions with related parties:
Sales to:
Indirect subsidiaries of CK Hutchison
Revenue from research and development services from:
An equity investee
Purchases from:
Equity investees
Rendering of marketing services from:
Indirect subsidiaries of CK Hutchison
An equity investee
Rendering of management services from:
An indirect subsidiary of CK Hutchison
(ii) Balances with related parties included in:
Accounts receivable—related parties
Indirect subsidiaries of CK Hutchison (note (a))
Amounts due from related parties
Equity investees (note (a) and (b))
Amount due from a related party
An equity investee (note (b))
Amounts due to a related party
An indirect subsidiary of CK Hutchison (note (c))
Other deferred income
An equity investee (note (d))
Notes:
2020
Year Ended December 31,
2019
(in US$’000)
2018
5,484
7,637
8,306
491
494
7,832
3,347
2,465
2,827
332
—
332
955
430
2,682
3,112
546
12,703
13,249
931
922
December 31,
2020
2019
(in US$’000)
1,222
1,844
1,142
24,623
—
16,190
401
366
950
1,103
(a) Balances with related parties are unsecured, repayable on demand and interest-free. The carrying values of balances
with related parties approximate their fair values due to their short-term maturities.
(b) As at December 31, 2020 and 2019, the Group had dividend receivables from an equity investee of nil and
US$39,671,000 respectively.
(c) Amounts due to an indirect subsidiary of CK Hutchison are unsecured, repayable on demand and interest-bearing if
not settled within one month.
(d) Other deferred income represents amounts recognized from granting of promotion and marketing rights.
F-38
(iii) Transactions with non-controlling shareholders of subsidiaries:
Sales
Purchases
Interest expense
Dividends declared
(iv) Balances with non-controlling shareholders of subsidiaries included in:
Accounts receivable
Accounts payable
Other non-current liabilities
Loan
24. Income Taxes
(i) Income tax expense
Current tax
HK (note (a))
PRC (note (b))
U.S. and others (note (c))
Total current tax
Deferred income tax
Income tax expense
Notes:
2020
Year Ended December 31,
2018
2019
(in US$’000)
36,500 27,343 19,981
13,936 13,380 15,568
62
2,564
—
1,462
—
—
December 31,
2020
2019
(in US$’000)
6,184
4,856
5,228
4,363
579
579
Year Ended December 31,
2018
2020
2019
(in US$’000)
457
872
219
1,548
3,281
4,829
321
708
636
1,665
1,609
3,274
436
1,293
235
1,964
2,000
3,964
(a) The Company, three subsidiaries incorporated in the British Virgin Islands and its Hong Kong subsidiaries are subject
to Hong Kong profits tax. In March 2018, the Hong Kong two-tiered profits tax rates regime was signed into law under
which the first HK$2.0 million (US$0.3 million) of assessable profits of qualifying corporations will be taxed at 8.25%,
with the remaining assessable profits taxed at 16.5%. Hong Kong profits tax has been provided for at the relevant rates
on the estimated assessable profits less estimated available tax losses, if any, of these entities as applicable.
(b) Taxation in the PRC has been provided for at the applicable rate on the estimated assessable profits less estimated
available tax losses, if any, in each entity. Under the PRC Enterprise Income Tax Law (the “EIT Law”), the standard
enterprise income tax rate is 25%. In addition, the EIT Law provides for a preferential tax rate of 15% for companies
which qualify as HNTE. HMPL and its wholly-owned subsidiary Hutchison MediPharma (Suzhou) Limited qualify
as a HNTE up to December 31, 2022 and 2020 respectively.
F-39
Pursuant to the EIT law, a 10% withholding tax is levied on dividends paid by PRC companies to their foreign
investors. A lower withholding tax rate of 5% is applicable under the China-HK Tax Arrangement if direct foreign
investors with at least 25% equity interest in the PRC companies are Hong Kong tax residents, and meet the conditions
or requirements pursuant to the relevant PRC tax regulations regarding beneficial ownership. Since the equity holders
of the equity investees of the Company are Hong Kong incorporated companies and Hong Kong tax residents, and
meet the aforesaid conditions or requirements, the Company has used 5% to provide for deferred tax liabilities on
retained earnings which are anticipated to be distributed. As at December 31, 2020, 2019 and 2018, the amounts
accrued in deferred tax liabilities relating to withholding tax on dividends were determined on the basis that 100% of
the distributable reserves of the equity investees operating in the PRC will be distributed as dividends.
(c) The Company’s subsidiary in the U.S. with operations in New Jersey and New York states is subject to U.S. taxes,
primarily federal and state taxes, which have been provided for at approximately 21% (federal) and 9% to 16.55%
(state tax) on the estimated assessable profit over the reporting years. Certain income receivable by the Company is
subject to U.S. withholding tax of 30%. One of the Group’s subsidiaries is subject to corporate tax in EU countries at
19% or 20% on the estimated assessable profits in relation to its permanent establishment in these countries in 2020
and/or 2019.
The reconciliation of the Group’s reported income tax expense to the theoretical tax amount that would arise using the tax rates of
the Company against the Group’s loss before income taxes and equity in earnings of equity investees is as follows:
Loss before income taxes and equity in earnings of equity investees
Tax calculated at the statutory tax rate of the Company
Tax effects of:
Different tax rates available in different jurisdictions
Tax valuation allowance
Preferential tax rate difference
Preferential tax deduction and credits
Expenses not deductible for tax purposes
Utilization of previously unrecognized tax losses
Withholding tax on undistributed earnings of PRC entities
Others
Income tax expense
(ii) Deferred tax assets and liabilities
The significant components of deferred tax assets and liabilities are as follows:
Deferred tax assets
Tax losses
Others
Total deferred tax assets
Less: Valuation allowance
Deferred tax assets
Deferred tax liabilities
Undistributed earnings from PRC entities
Others
Deferred tax liabilities
F-40
2020
Year Ended December 31,
2019
(in US$’000)
(141,105)
(23,282)
(189,734)
(31,306)
(86,655)
(14,298)
2018
4,025
46,321
(154)
(18,814)
3,476
(114)
3,962
(2,567)
4,829
2,027
25,498
(177)
(5,444)
4,098
(285)
1,894
(1,055)
3,274
1,349
19,414
—
(5,800)
1,902
(329)
1,983
(257)
3,964
December 31,
2020
2019
(in US$’000)
117,064
6,829
123,893
(122,378)
1,515
68,481
1,733
70,214
(69,399)
815
4,994
69
5,063
3,081
77
3,158
The movements in deferred tax assets and liabilities are as follows:
As at January 1
Utilization of previously recognized withholding tax on undistributed
earnings
(Charged)/Credited to the consolidated statements of operations
Withholding tax on undistributed earnings of PRC entities
Deferred tax on amortization of intangible assets
Deferred tax on provision for assets
Exchange differences
As at December 31
2020
(2,343)
2019
(in US$’000)
(4,256)
2018
(3,819)
2,323
3,390
1,373
(3,962)
18
663
(247)
(3,548)
(1,894)
18
267
132
(2,343)
(1,983)
19
(36)
190
(4,256)
The deferred tax assets and liabilities are offset when there is a legally enforceable right to set off and when the deferred income
taxes relate to the same fiscal authority.
The tax losses can be carried forward against future taxable income and will expire in the following years:
No expiry date
2022
2023
2024
2025
2026
2027
2028
2029
2030
December 31,
2020
2019
(in US$’000)
53,940
195
—
3,998
38,357
51,034
66,555
114,490
186,844
259,163
774,576
40,897
182
—
3,716
35,648
47,661
62,794
106,793
154,454
—
452,145
The Company believes that it is more likely than not that future operations will not generate sufficient taxable income to realize the
benefit of the deferred tax assets. The Company’s subsidiaries have had sustained tax losses, which will expire within five years if not
utilized in the case of PRC subsidiaries (ten years for HNTEs), and which will not be utilized in the case of Hong Kong subsidiaries as
they do not generate taxable profits. Accordingly, a valuation allowance has been recorded against the relevant deferred tax assets arising
from the tax losses.
The table below summarizes changes in the deferred tax valuation allowance:
As at January 1
Charged to consolidated statements of operations
Utilization of previously unrecognized tax losses
Write-off of tax losses
Others
Exchange differences
As at December 31
2020
69,399
46,321
(114)
2019
(in US$’000)
49,021
25,498
(285)
— (3,142)
—
—
(1,693)
6,772
69,399
122,378
2018
31,662
19,414
(329)
—
(105)
(1,621)
49,021
As at December 31, 2020 and 2019, the Group did not have any material unrecognized uncertain tax positions.
F-41
(iii) Income tax payable
As at January 1
Current tax
Withholding tax upon dividend declaration from PRC entities (note (a))
Tax paid (note (b))
Reclassification from non-current withholding tax
Reclassification to prepaid tax
Exchange difference
As at December 31
Notes:
2020
1,828
1,548
2,323
(5,940)
812
485
64
1,120
2019
(in US$’000)
555
1,665
2,581
(2,970)
—
—
(3)
1,828
2018
979
1,964
1,373
(3,752)
—
—
(9)
555
(a) The amount for 2019 excludes a non-current withholding tax of US$0.8 million which is included under other non-
current liabilities.
(b) The amount for 2020 is net of the PRC Enterprise Income Tax (“EIT”) refund of US$0.4 million received by HSPL.
The amount for 2019 excludes the PRC EIT of US$0.3 million prepaid by HSPL which is included under other
receivables, prepayments and deposits.
25. Losses Per Share
(i) Basic losses per share
Basic losses per share is calculated by dividing the net loss attributable to the Company by the weighted average number of
outstanding ordinary shares in issue during the year. Treasury shares held by the Trustee are excluded from the weighted average number
of outstanding ordinary shares in issue for purposes of calculating basic losses per share.
Weighted average number of outstanding ordinary shares in
issue
Net loss attributable to the Company (US$’000)
Losses per share attributable to the Company (US$ per
share)
697,931,437
(125,730)
665,683,145 664,263,820
(74,805)
(106,024)
(0.18)
(0.16)
(0.11)
Year Ended December 31,
2019
2018
2020
(ii) Diluted losses per share
Diluted losses per share is calculated by dividing net loss attributable to the Company by the weighted average number of
outstanding ordinary shares in issue and dilutive ordinary share equivalents outstanding during the year. Dilutive ordinary share
equivalents include shares issuable upon the exercise or settlement of share option, LTIP awards and warrants issued by the Company
using the treasury stock method.
For the years ended December 31, 2020, 2019 and 2018, the share options, LTIP awards and warrants issued by the Company were
not included in the calculation of diluted losses per share because of their anti-dilutive effect. Therefore, diluted losses per share were
equal to basic losses per share for the years ended December 31, 2020, 2019 and 2018.
F-42
26. Segment Reporting
The Group’s operating segments are as follows:
(i) Oncology/Immunology: focuses on discovering, developing, and commercializing targeted therapies and immunotherapies for
the treatment of cancer and immunological diseases. Oncology/Immunology is further segregated into two core business areas:
(a) R&D: comprises research and development activities covering drug discovery, development, manufacturing and regulatory
functions as well as administrative activities to support research and development operations; and
(b) Marketed Products: comprises the sales, marketing, manufacture and distribution of drug developed from research and
development activities.
(ii) Other Ventures: comprises other commercial businesses which include the sales, marketing, manufacture and distribution of
other prescription drugs and over-the-counter pharmaceuticals as well as consumer health products.
The performance of the reportable segments is assessed based on segment operating (loss)/profit.
In the second half of 2020, the Group (1) renamed the Innovation Platform to Oncology/Immunology segment and Commercial
Platform to Other Ventures segment; and began (2) separately presenting R&D activities in the U.S. and other locations under
Oncology/Immunology segment, (3) including the results from manufacturing and commercializing Elunate under Marketed Products
in Oncology/Immunology segment, and (4) aggregating the remaining commercial businesses under Other Ventures segment with Hong
Kong included within the PRC. These changes are consistent with the chief operating decision maker’s view of the business. The
segment information below as at and for the years ended December 31, 2019 and 2018 have been revised so that all segment disclosures
are comparable.
The segment information is as follows:
Year Ended December 31, 2020
Oncology/Immunology
R&D
U.S. and
Others
PRC
Marketed
Products
Other
Ventures
Subtotal
PRC
Subtotal PRC
Unallocated Total
Revenue from external customers
Interest income
Equity in earnings of equity investees, net of tax
Segment operating (loss)/profit
Interest expense
Income tax expense/(credit)
Net (loss)/income attributable to the Company
Depreciation/amortization
Additions to non-current assets (other than financial
10,262
461
(97)
(119,740)
—
402
(120,096)
5,458
—
—
—
(63,482)
—
(642)
(62,683)
119
10,262
461
(97)
(183,222)
—
(240)
(182,779)
5,577
(in US$’000)
19,953
—
—
7,607
—
167
7,282
—
30,215
461
(97)
(175,615)
—
(73)
(175,497)
5,577
197,761
167
79,143
83,888
—
824
72,785
292
—
2,608
—
(18,174)
787
4,078
(23,018)
192
227,976
3,236
79,046
(109,901)
787
4,829
(125,730)
6,061
instruments and deferred tax assets)
22,574
754
23,328
—
23,328
817
1,090
25,235
Oncology/Immunology
December 31, 2020
R&D
U.S. and
Others
PRC
Marketed
Products
Other
Ventures
Subtotal
PRC
Subtotal PRC
Unallocated Total
127,637
22,554
2,782
13,121
—
—
385
9,957
454
1,375
—
—
—
—
137,594
23,008
4,157
13,121
—
—
385
(in US$’000)
5,728
—
—
—
—
—
—
143,322
23,008
4,157
13,121
—
—
385
231,234
688
2,582
—
3,307
227
139,120
349,562
474
1,277
—
—
—
—
724,118
24,170
8,016
13,121
3,307
227
139,505
Total assets
Property, plant and equipment
Right-of-use assets
Leasehold land
Goodwill
Other intangible asset
Investments in equity investees
F-43
Year Ended December 31, 2019
Oncology/Immunology
Marketed
Products
Other
Ventures
R&D
U.S. and
Others
PRC
Subtotal
Revenue from external customers
Interest income
Equity in earnings of equity investees, net of tax
Segment operating (loss)/profit
Interest expense
Income tax expense
Net (loss)/income attributable to the Company
Depreciation/amortization
Additions to non-current assets (other than financial
16,026
322
147
(111,518)
—
63
(111,308)
4,448
—
—
—
(21,785)
—
197
(21,926)
62
16,026
322
147
(133,303)
—
260
(133,234)
4,510
PRC
Subtotal PRC
Unallocated Total
(in US$’000)
10,766
—
—
5,887
—
—
5,872
—
26,792
322
147
(127,416)
—
260
(127,362)
4,510
178,098
109
40,553
45,255
—
939
41,488
264
—
4,513
—
(17,214)
1,030
2,075
(20,150)
168
204,890
4,944
40,700
(99,375)
1,030
3,274
(106,024)
4,942
instruments and deferred tax assets)
8,602
1,308
9,910
—
9,910
2,772
148
12,830
Total assets
Property, plant and equipment
Right-of-use assets
Leasehold land
Goodwill
Other intangible asset
Investments in equity investees
Oncology/Immunology
December 31, 2019
R&D
U.S. and
Others
PRC
Marketed
Products
Other
Ventures
Subtotal
PRC
Subtotal PRC
Unallocated Total
93,332
18,907
1,584
1,110
—
—
447
4,452
515
861
—
—
—
—
97,784
19,422
2,445
1,110
—
—
447
(in US$’000)
813
—
—
—
—
—
—
98,597
19,422
2,445
1,110
—
—
447
170,891
789
2,466
—
3,112
275
98,497
195,634
644
605
—
—
—
—
465,122
20,855
5,516
1,110
3,112
275
98,944
Year Ended December 31, 2018
Oncology/Immunology
R&D
U.S. and
Others
PRC
Marketed
Products
Other
Ventures
Subtotal
PRC
Subtotal PRC
Unallocated Total
Revenue from external customers
Interest income
Equity in earnings of equity investees, net of tax
Segment operating (loss)/profit
Interest expense
Income tax expense
Net (loss)/income attributable to the Company
Depreciation/amortization
Additions to non-current assets (other than financial
37,648
119
(18,981)
(99,992)
—
39
(99,783)
3,326
—
—
—
(4,602)
—
42
(4,632)
8
37,648
119
(18,981)
(104,594)
—
81
(104,415)
3,334
(in US$’000)
3,585
—
—
2,008
—
—
2,003
—
41,233
119
(18,981)
(102,586)
—
81
(102,412)
3,334
172,876
141
38,314
46,990
62
1,662
41,372
195
—
5,718
—
(10,717)
947
2,221
(13,765)
61
214,109
5,978
19,333
(66,313)
1,009
3,964
(74,805)
3,590
instruments and deferred tax assets)
5,133
65
5,198
—
5,198
584
720
6,502
Revenue from external customers is after elimination of inter-segment sales. Sales between segments are carried out at mutually
agreed terms. The amount eliminated attributable to sales between Oncology/Immunology segment and Other Ventures segment was
US$17,059,000, US$3,354,000 and nil for the years ended December 31, 2020, 2019 and 2018 respectively.
There were two customers under Other Ventures segment (with aggregate revenue of US$62,493,000), which accounted for over
10% of the Group’s revenue for the year ended December 31, 2020. There was one customer, under Other Ventures segment (with
revenue of US$27,343,000), which accounted for over 10% of the Group’s revenue for the year ended December 31, 2019. There was
one customer, under Oncology/Immunology segment (with revenue of US$26,865,000), which accounted for over 10% of the Group’s
revenue for the year ended December 31, 2018.
Unallocated expenses mainly represent corporate expenses which include corporate employee benefit expenses and the relevant
share-based compensation expenses. Unallocated assets mainly comprise cash and cash equivalents and short-term investments.
F-44
2018
2020
Year Ended December 31,
2019
(in US$’000)
(99,375)
(1,030)
(3,274)
(66,313)
(1,009)
(3,964)
(115,517) (103,679) (71,286)
(109,901)
(787)
(4,829)
2020
Year Ended December 31,
2019
(in US$’000)
(103,679)
2018
(71,286)
(115,517)
43
6,061
—
85
65
77
8,737
10,905
(79,046)
86,708
(2,197)
(6,149)
(1,111)
(5,315)
622
(9,602)
—
(3,623)
153
7,651
37,437
2,258
(158)
35
(185)
29,273
(62,066)
195
4,942
(17)
17
316
(25)
7,173
4,419
(40,700)
28,135
224
1,679
304
(1,209)
938
(2,452)
(282)
(4,215)
253
(1,664)
26,019
(101)
(709)
(66)
(407)
16,105
(80,912)
76
3,590
—
33
37
(202)
7,903
2,227
(19,333)
35,218
—
1,515
212
(1,564)
1,078
(2,385)
27
(557)
292
1,260
16,286
—
(239)
(6,589)
(446)
7,163
(32,847)
A reconciliation of segment operating loss to net loss is as follows:
Segment operating loss
Interest expense
Income tax expense
Net loss
27. Note to Consolidated Statements of Cash Flows
Reconciliation of net loss for the year to net cash used in operating activities:
Net loss
Adjustments to reconcile net loss to net cash used in operating activities
Amortization of finance costs
Depreciation and amortization
Gain from purchase of a subsidiary
Loss on retirement of property, plant and equipment
Provision for excess and obsolete inventories
Provision for credit losses
Share-based compensation expense—share options
Share-based compensation expense—LTIP
Equity in earnings of equity investees, net of tax
Dividends received from SHPL and HBYS
Changes in right-of-use assets
Unrealized currency translation (gain)/loss
Changes in income tax balances
Changes in working capital
Accounts receivable—third parties
Accounts receivable—related parties
Other receivables, prepayments and deposits
Amounts due from related parties
Inventories
Long-term prepayment
Accounts payable
Other payables, accruals and advance receipts
Lease liabilities
Deferred revenue
Amounts due to related parties
Other
Total changes in working capital
Net cash used in operating activities
F-45
28. Litigation
From time to time, the Group may become involved in litigation relating to claims arising from the ordinary course of business.
The Group believes that there are currently no claims or actions pending against the Group, the ultimate disposition of which could have
a material adverse effect on the Group’s results of operations, financial position or cash flows. However, litigation is subject to inherent
uncertainties and the Group’s view of these matters may change in the future. When an unfavorable outcome occurs, there exists the
possibility of a material adverse impact on the Group’s financial position and results of operations for the periods in which the
unfavorable outcome occurs, and potentially in future periods.
On May 17, 2019, Luye Pharma Hong Kong Ltd. (“Luye”) issued a notice to the Group purporting to terminate a distribution
agreement that granted the Group exclusive commercial rights to Seroquel in the PRC for failure to meet a pre-specified target. The
Group disagrees with this assertion and believes that Luye have no basis for termination. As a result, the Group commenced legal
proceedings in 2019 in order to seek damages. As at December 31, 2020, the legal proceedings are still in progress. Accordingly, no
adjustment has been made to Seroquel-related balances as at December 31, 2020, including accounts receivable, long-term prepayment,
accounts payable and other payables of US$1.2 million, US$1.0 million, US$0.9 million and US$1.2 million respectively.
29. Restricted Net Assets
Relevant PRC laws and regulations permit payments of dividends by the Company’s subsidiaries in the PRC only out of their
retained earnings, if any, as determined in accordance with PRC accounting standards and regulations. In addition, the Company’s
subsidiaries in the PRC are required to make certain appropriations of net after-tax profits or increases in net assets to the statutory
surplus fund prior to payment of any dividends. In addition, registered share capital and capital reserve accounts are restricted from
withdrawal in the PRC, up to the amount of net assets held in each subsidiary. As a result of these and other restrictions under PRC laws
and regulations, the Company’s subsidiaries in the PRC are restricted in their ability to transfer their net assets to the Group in terms of
cash dividends, loans or advances, with restricted portions amounting to US$0.2 million and US$0.3 million as at December 31, 2020
and 2019 respectively, which excludes the Company’s subsidiaries with a shareholders’ deficit. Even though the Group currently does
not require any such dividends, loans or advances from the PRC subsidiaries, for working capital and other funding purposes, the Group
may in the future require additional cash resources from the Company’s subsidiaries in the PRC due to changes in business conditions,
to fund future acquisitions and development, or merely to declare and pay dividends to make distributions to shareholders.
In addition, the Group has certain investments in equity investees in the PRC, where the Group’s equity in undistributed earnings
amounted to US$99.9 million and US$61.6 million as at December 31, 2020 and 2019 respectively.
30. Subsequent Events
The Group evaluated subsequent events through March 4, 2021, which is the date when the consolidated financial statements were
issued.
In January 2021, the Group entered into a contract with a third party contractor for approximately US$46.8 million in connection
with the construction of a factory in Shanghai.
F-46
SHANGHAI HUTCHISON
PHARMACEUTICALS LIMITED
F-47
To the Board of Directors and Shareholders of Shanghai Hutchison Pharmaceuticals Limited
Report of Independent Auditors
We have audited the accompanying consolidated financial statements of Shanghai Hutchison Pharmaceuticals Limited and its
subsidiaries (the “Company”), which comprise the consolidated statements of financial position as of December 31, 2020 and 2019, and
the related consolidated income statements, consolidated statements of comprehensive income, of changes in equity and of cash flows
for each of the three years in the period ended December 31, 2020.
Management’s Responsibility for the Consolidated Financial Statements
Management is responsible for the preparation and fair presentation of the consolidated financial statements in accordance with
International Financial Reporting Standards as issued by the International Accounting Standards Board; this includes the design,
implementation, and maintenance of internal control relevant to the preparation and fair presentation of consolidated financial statements
that are free from material misstatement, whether due to fraud or error.
Auditors’ Responsibility
Our responsibility is to express an opinion on the consolidated financial statements based on our audits. We conducted our audits
in accordance with auditing standards generally accepted in the United States of America. Those standards require that we plan and
perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free from material
misstatement.
An audit involves performing procedures to obtain audit evidence about the amounts and disclosures in the consolidated financial
statements. The procedures selected depend on our judgment, including the assessment of the risks of material misstatement of the
consolidated financial statements, whether due to fraud or error. In making those risk assessments, we consider internal control relevant
to the Company’s preparation and fair presentation of the consolidated financial statements in order to design audit procedures that are
appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control.
Accordingly, we express no such opinion. An audit also includes evaluating the appropriateness of accounting policies used and the
reasonableness of significant accounting estimates made by management, as well as evaluating the overall presentation of the
consolidated financial statements. We believe that the audit evidence we have obtained is sufficient and appropriate to provide a basis
for our audit opinion.
Opinion
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position
of Shanghai Hutchison Pharmaceuticals Limited and its subsidiaries as of December 31, 2020 and 2019, and the results of their
operations and their cash flows for each of the three years in the period ended December 31, 2020 in accordance with International
Financial Reporting Standards as issued by the International Accounting Standards Board.
/s/ PricewaterhouseCoopers Zhong Tian LLP
Shanghai, the People’s Republic of China
March 4, 2021
F-48
Shanghai Hutchison Pharmaceuticals Limited
Consolidated Income Statements
(in US$’000)
Note
5
6
7
15
8
Revenue
Cost of sales
Gross profit
Selling expenses
Administrative expenses
Other net operating income
Operating profit
Finance costs
Profit before taxation
Taxation charge
Profit for the year
Year Ended December 31,
2019
272,082
(77,313)
194,769
(110,591)
(14,761)
2,941
72,358
(42)
72,316
(11,015)
61,301
2020
276,354
(72,163)
204,191
(111,892)
(17,907)
3,473
77,865
(12)
77,853
(10,833)
67,020
2018
275,649
(82,710)
192,939
(111,984)
(14,522)
2,705
69,138
—
69,138
(9,371)
59,767
The accompanying notes are an integral part of these consolidated financial statements.
F-49
Shanghai Hutchison Pharmaceuticals Limited
Consolidated Statements of Comprehensive Income
(in US$’000)
Profit for the year
Other comprehensive income/(loss) that has been or may be reclassified subsequently to
profit or loss:
Exchange translation differences
Total comprehensive income
Year Ended December 31,
2019
61,301
2020
67,020
2018
59,767
11,129
78,149
(4,670)
56,631
(5,797)
53,970
The accompanying notes are an integral part of these consolidated financial statements.
F-50
Shanghai Hutchison Pharmaceuticals Limited
Consolidated Statements of Financial Position
(in US$’000)
Assets
Current assets
Cash and cash equivalents
Trade and bills receivables
Other receivables, prepayments and deposits
Inventories
Total current assets
Property, plant and equipment
Right-of-use assets
Leasehold land
Other intangible asset
Deferred tax assets
Total assets
Liabilities and shareholders’ equity
Current liabilities
Trade payables
Other payables, accruals and advance receipts
Current tax liabilities
Lease liabilities
Total current liabilities
Deferred income
Lease liabilities
Total liabilities
Shareholders’ equity
Share capital
Reserves
Total shareholders’ equity
Total liabilities and shareholders’ equity
Note
2020
2019
December 31,
10
11
12
13
14
15
16
17
18
19
15
15
72,478
18,421
3,392
81,674
175,965
76,932
152
7,021
935
8,315
269,320
11,174
93,534
5,032
133
109,873
6,720
19
116,612
33,382
119,326
152,708
269,320
41,244
24,772
2,935
72,317
141,268
76,576
562
6,707
1,085
6,147
232,345
10,269
66,425
2,395
444
79,533
5,974
100
85,607
33,382
113,356
146,738
232,345
The accompanying notes are an integral part of these consolidated financial statements.
F-51
Shanghai Hutchison Pharmaceuticals Limited
Consolidated Statements of Changes in Equity
(in US$’000)
As at January 1, 2018
Profit for the year
Other comprehensive loss
Exchange translation differences
Total comprehensive (loss)/income
Dividends declared to shareholders
As at December 31, 2018
Impact of change in accounting policy (IFRS 16)
As at January 1, 2019
Profit for the year
Other comprehensive loss
Exchange translation differences
Total comprehensive (loss)/income
Transfer between reserves
Dividends declared to shareholders
As at December 31, 2019
Profit for the year
Other comprehensive income
Exchange translation differences
Total comprehensive income
Transfer between reserves
Dividends declared to shareholders
As at December 31, 2020
Share
capital
33,382
—
—
—
—
33,382
—
33,382
—
—
—
—
—
33,382
—
Exchange General Retained
reserves
Total
earnings
equity
96,436 132,731
59,767
59,767
970
—
reserve
1,943
—
(5,797)
(5,797)
—
(3,854)
—
(3,854)
—
(4,670)
(4,670)
—
—
(8,524)
—
—
—
—
—
59,767
(54,923)
(5,797)
53,970
(54,923)
970 101,280 131,778
(17)
(17)
131,761
101,263
61,301
61,301
—
970
—
—
—
14
—
—
61,301
(14)
(41,654)
(4,670)
56,631
—
(41,654)
984 120,896 146,738
67,020
67,020
—
— 11,129
— 11,129
—
—
—
—
2,605
33,382
—
—
14
—
998
—
67,020
(14)
(72,179)
115,723
11,129
78,149
—
(72,179)
152,708
The accompanying notes are an integral part of these consolidated financial statements.
F-52
Shanghai Hutchison Pharmaceuticals Limited
Consolidated Statements of Cash Flows
(in US$’000)
Operating activities
Net cash generated from operations
Interest received
Income tax paid
Net cash generated from operating activities
Investing activities
Purchase of property, plant and equipment
Proceeds from disposal of property, plant and equipment
Net cash used in investing activities
Financing activities
Dividends paid to shareholders
Lease payments
Net cash used in financing activities
Net increase/(decrease) in cash and cash equivalents
Effect of exchange rate changes on cash and cash equivalents
Cash and cash equivalents
Cash and cash equivalents at beginning of year
Cash and cash equivalents at end of year
Note
20
19
15
Year Ended December 31,
2019
2020
2018
112,609
912
(10,232)
103,289
76,784
518
(13,618)
63,684
(2,437)
63
(2,374)
(4,592)
9
(4,583)
(72,179)
(474)
(72,653)
28,262
2,972
31,234
(41,654)
(595)
(42,249)
16,852
(659)
16,193
54,699
638
(12,158)
43,179
(5,172)
13
(5,159)
(54,667)
—
(54,667)
(16,647)
(1,829)
(18,476)
41,244
72,478
25,051
41,244
43,527
25,051
The accompanying notes are an integral part of these consolidated financial statements.
F-53
Shanghai Hutchison Pharmaceuticals Limited
Notes to the Consolidated Financial Statements
1. General Information
Shanghai Hutchison Pharmaceuticals Limited (the “Company”) and its subsidiaries (together the “Group”) are principally engaged
in manufacturing, selling and distribution of prescription drug products. The Group has manufacturing plants in the People’s Republic
of China (the “PRC”) and sells mainly in the PRC.
The Company was incorporated in the PRC on April 30, 2001 as a Chinese-Foreign Equity joint venture. The Company is jointly
controlled by Shanghai Hutchison Chinese Medicine (HK) Investment Limited (“SHCM(HK)IL”) and Shanghai Traditional Chinese
Medicine Co., Ltd (“SHTCML”).
These consolidated financial statements are presented in United States dollars (“US$”), unless otherwise stated and have been
approved for issue by the Company’s Board of Directors on March 4, 2021.
2. Summary of Significant Accounting Policies
The consolidated financial statements of the Company have been prepared in accordance with International Financial Reporting
Standards (“IFRS”) and interpretations issued by the IFRS Interpretations Committee applicable to companies reporting under IFRS.
The consolidated financial statements comply with IFRS as issued by the International Accounting Standards Board (“IASB”). These
consolidated financial statements have been prepared under the historical cost convention.
During the year, the Group has adopted all of the new and revised standards, amendments and interpretations issued by the IASB
that are relevant to the Group’s operations and mandatory for annual periods beginning January 1, 2020. The adoption of these new and
revised standards, amendments and interpretations did not have any material effects on the Group’s results of operations or financial
position.
The following standards, amendments and interpretations were issued but not yet effective for the financial year ended December
31, 2020 and have not been early adopted by the Group:
IFRS 9, IAS 39, IFRS 7, IFRS 4 and IFRS 16 (Amendments)(1)
IFRS 3 (Amendments)(2)
IAS 16 (Amendments)(2)
IAS 37 (Amendments)(2)
Annual improvement 2018-2020(2)
IAS 1 (Amendments)(3)
IFRS 17(3)
IFRS 10 and IAS 28 (Amendments)(4)
Interest rate benchmark reform – Phase 2
Reference to the Conceptual Framework
Property, Plant and Equipment: Proceeds before Intended Use
Onerous Contracts – Costs of Fulfilling a Contract
Improvements to IFRSs
Classification of Liabilities as Current or Non-current
Insurance Contracts
Sale or Contribution of Assets between an Investor and its
Associate or Joint Venture
(1) Effective for the Group for annual periods beginning on or after January 1, 2021.
(2) Effective for the Group for annual periods beginning on or after January 1, 2022.
(3) Effective for the Group for annual periods beginning on or after January 1, 2023.
(4) Effective date to be determined by the IASB.
The adoption of standards, amendments and interpretations listed above in future periods is not expected to have any material effects
on the Group’s results of operations or financial position.
F-54
(a) Basis of Consolidation
The consolidated financial statements of the Group include the financial statements of the Company and its subsidiaries.
The accounting policies of subsidiaries have been changed where necessary to ensure consistency with the policies adopted by
the Group.
Intercompany transactions, balances and unrealized gains on transactions between group companies are eliminated. Unrealized
losses are also eliminated unless the transaction provides evidence of an impairment of the transferred asset.
(b) Subsidiaries
Subsidiaries are all entities over which the Group has control. The Group controls an entity when the Group is exposed, or has
rights, to variable returns from its involvement with the entity and has the ability to affect those returns through its power to direct the
activities of the entity. In the consolidated financial statements, subsidiaries are accounted for as described in Note 2(a) above.
Subsidiaries are fully consolidated from the date on which control is transferred to the Group. They are de-consolidated from the
date that control ceases.
(c) Foreign Currency Translation
Items included in the financial statements of each of the Group’s companies are measured using the currency of the primary
economic environment in which the entity operates (the “functional currency”). The functional currency of the Company and its
subsidiaries is Renminbi (“RMB”) whereas the consolidated financial statements are presented in US$, which is the Company’s
presentation currency.
Foreign currency transactions are translated into the functional currency using the exchange rates at the dates of the transactions.
Foreign currency gains and losses resulting from the settlement of such transactions and from the translation of monetary assets and
liabilities denominated in foreign currencies at year end exchange rates are generally recognized in the consolidated income statements.
The financial statements of the Company and its subsidiaries are translated into the Company’s presentation currency using the year
end rates of exchange for the statements of financial position items and the average rates of exchange for the year for the income
statement items. Exchange translation differences are recognized directly in other comprehensive income.
(d) Property, Plant and Equipment
Property, plant and equipment other than construction in progress are stated at historical cost less accumulated depreciation and any
accumulated impairment losses. Historical cost includes the purchase price of the asset and any directly attributable costs of bringing
the asset to its working condition and location for its intended use.
Subsequent costs are included in the asset’s carrying amount or recognized as a separate asset, as appropriate, only when it is
probable that future economic benefits associated with the item will flow to the Group and the cost of the item can be measured reliably.
All other repairs and maintenance are charged to the consolidated income statements during the financial period in which they
are incurred.
Depreciation is calculated using the straight-line method to allocate asset costs less accumulated impairment losses over their
estimated useful lives. The principal estimated useful lives are as follows:
Buildings
Leasehold improvements
20 years
Over the unexpired period of the lease or 5 years,
whichever is shorter
Plant and equipment
Furniture and fixtures, other equipment and motor
vehicles
10 years
5 years
F-55
The assets’ useful lives are reviewed and adjusted, if appropriate, at the end of each reporting period. An asset’s carrying amount
is written down immediately to its recoverable amount if the asset’s carrying amount is greater than its estimated recoverable amount.
Gains and losses on disposals are determined by comparing net sales proceeds with the carrying amount of the relevant assets and
are recognized in the consolidated income statements.
(e) Construction in Progress
Construction in progress represents buildings, plant and machinery under construction and pending installation and is stated at cost
less accumulated impairment losses, if any. Cost includes the costs of construction of buildings and the costs of plant and machinery.
No provision for depreciation is made on construction-in-progress until such time as the relevant assets are completed and ready for its
intended use. When the assets concerned are brought into use, the costs are transferred to property, plant and equipment and depreciated
in accordance with the policy as stated in Note 2(d).
(f) Other Intangible Asset
The Group’s other intangible asset represents promotion and marketing rights. Other intangible asset has a definite useful life and
is carried at historical cost less accumulated amortization and accumulated impairment losses, if any. Amortization is calculated using
the straight-line method to allocate its cost over its estimated useful life of ten years.
(g) Research and Development
Research expenditure is recognized as an expense as incurred. Costs incurred on development projects (relating to the design and
testing of new or improved products) are recognized as intangible assets when it is probable that the project will generate future economic
benefits by considering its commercial and technological feasibility, and costs can be measured reliably. Other development
expenditures are recognized as an expense as incurred. Development costs previously recognized as an expense are not recognized as
an asset in a subsequent period. Development costs with a finite useful life that have been capitalized, if any, are amortized on a
straight-line basis over the period of expected benefit not exceeding five years. The capitalized development costs are reviewed for
impairment whenever events or changes in circumstances indicate that the carrying amount of an asset exceeds its recoverable amount.
Where the research phase and the development phase of an internal project cannot be clearly distinguished, all expenditure incurred
on the project is charged to the consolidated income statements.
(h) Impairment of Non-Financial Assets
Assets are reviewed for impairment to determine whether there is any indication that the carrying value of these assets may not be
recoverable and have suffered an impairment loss. If any such indication exists, the recoverable amount of the asset is estimated in order
to determine the extent of the impairment loss, if any. The recoverable amount is the higher of an asset’s fair value less costs to sell and
value in use. Such impairment loss is recognized in the consolidated income statements. Assets that have an indefinite useful life such
as goodwill or intangible assets not ready to use are not subject to amortization and are tested for impairment annually and when there
are indications that the carrying value may not be recoverable.
(i) Inventories
Inventories are stated at the lower of cost or net realizable value. Cost is determined using the weighted average cost method. The
cost of finished goods comprises raw materials, direct labor, other direct costs and related production overheads (based on normal
operating capacity). Net realizable value is the estimated selling price in the ordinary course of business, less applicable variable selling
expenses.
F-56
(j) Trade and Other Receivables
Trade and other receivables are recognized initially at fair value, which is the amount of consideration that is unconditional. Trade
and other receivables solely represent payments of principal and interest, if any, and the Group holds such financial assets with the
objective to collect its contractual cash flows. Therefore, the Group measures them subsequently at amortized cost using the effective
interest method, less any loss allowance. The Group applies the IFRS 9 simplified approach to measuring expected credit losses which
uses a lifetime expected loss allowance for all trade receivables. To measure the expected credit losses, trade receivables have been
grouped based on shared credit risk characteristics and the days past due. All other receivables at amortized cost are considered to have
low credit risk, and the loss allowance recognized during the period was therefore limited to 12 months expected losses. The amount of
the provision is recognized in the consolidated income statements.
(k) Cash and Cash Equivalents
In the consolidated statements of cash flows, cash and cash equivalents include cash on hand, bank deposits and other short-term
highly liquid investments with original maturities of three months or less that are readily convertible to known amounts of cash and
which are subject to an insignificant risk of changes in value, if any.
(l) Financial Liabilities and Equity Instruments
Financial liabilities and equity instruments issued by the Group are classified according to the substance of the contractual
arrangements entered into and the definitions of a financial liability and an equity instrument. Financial liabilities (including trade and
other payables) are initially measured at fair value, and are subsequently measured at amortized cost, using the effective interest method.
An equity instrument is any contract that does not meet the definition of a financial liability and evidences a residual interest in the
assets of the Group after deducting all of its liabilities.
Ordinary shares are classified as equity. Incremental costs, net of tax, directly attributable to the issue of new shares are shown in
equity as a deduction from the proceeds.
(m) Current and Deferred Income Tax
(i) Current income tax
The current income tax charge is calculated on the basis of the tax laws enacted or substantively enacted at the balance sheet date
in the country where the Group operates and generates taxable income. Management periodically evaluates positions taken in tax returns
with respect to situations in which applicable tax regulation is subject to interpretation. It establishes provisions where appropriate on
the basis of amounts expected to be paid to the tax authorities.
(ii) Deferred income tax
Inside basis differences
Deferred income tax is recognized, using the liability method, on temporary differences arising between the tax bases of assets and
liabilities and their carrying amounts in the consolidated financial statements. However, deferred tax liabilities are not recognized if they
arise from the initial recognition of goodwill and deferred income tax is not accounted for if it arises from initial recognition of an asset
or liability in a transaction other than a business combination that at the time of the transaction affects neither accounting nor taxable
profit or loss. Deferred income tax is determined using tax rates (and laws) that have been enacted or substantively enacted by the
balance sheet date and are expected to apply when the related deferred income tax asset is realized or the deferred income tax liability
is settled.
Deferred income tax assets are recognized only to the extent that it is probable that future taxable profit will be available against
which the temporary differences can be utilized. Deferred income tax assets and deferred income tax liabilities are offset when there is
a legally enforceable right to set off and when the deferred income taxes related to the same fiscal authority.
F-57
Outside basis differences
Deferred income tax liabilities are provided on taxable temporary differences arising from investments in subsidiaries, except for
deferred income tax liabilities where the timing of the reversal of the temporary difference is controlled by the Group and it is probable
that the temporary difference will not reverse in the foreseeable future.
Deferred income tax assets are recognized on deductible temporary differences arising from investments in subsidiaries, only to the
extent that it is probable the temporary difference will reverse in the future and there is sufficient taxable profit available against which
the temporary difference can be utilized.
(n) Employee Benefits
The employees of the Group participate in defined contribution retirement benefit plans managed by the relevant municipal and
provincial governments in the PRC. The assets of these plans are held separately from the Group. The Group is required to make monthly
contributions to the plans calculated as a percentage of the employees’ salaries. The municipal and provincial governments undertake
to assume the retirement benefit obligations to all existing and future retired employees under the plans described above. Other than
the monthly contributions, the Group has no further obligations for the payment of the retirement and other post-retirement benefits of
its employees.
(o) Provisions
Provisions are recognized when the Group has a present legal or constructive obligation as a result of past events, it is probable that
an outflow of resources will be required to settle the obligation, and the amount has been reliably estimated. Provisions are not recognized
for future operating losses.
(p) Leases
The IASB has issued IFRS 16, a new standard for leases which replaced IAS 17. The core principle of IFRS 16 is that a lessee
should recognize the assets and liabilities that arise from leases. A lessee should recognize on the statement of financial position a
liability to make lease payments (the lease liability) and a right-of-use asset representing its right to use the underlying asset for the lease
term.
The Group has adopted IFRS 16 retrospectively from January 1, 2019, but has not restated comparatives for the 2018 reporting
period, as permitted under the specific transitional provisions in the standard. The reclassifications and the adjustments arising from the
new leasing rules are therefore recognized in the opening balance sheet on January 1, 2019.
Right-of-use assets were measured on transition as if the new rules had always been applied. As a result, the Group has recognized
a gross up to the consolidated statement of financial position on the date of adoption of US$1.0 million and US$0.9 million in right-of-
use assets and lease liabilities respectively, primarily related to the Group’s various offices under non-cancellable lease agreements that
were accounted as operating leases under IAS 17 as at December 31, 2018.
Under IFRS 16
A lease is recognized as a right-of-use asset with a corresponding liability at the date which the leased asset is available for use by
the Group. The Group recognizes an obligation to make lease payments equal to the present value of the lease payments over the lease
term. The lease terms may include options to extend or terminate the lease when it is reasonably certain that the Group will exercise that
option.
Lease liabilities include the net present value of the following lease payments: (i) fixed payments; (ii) variable lease payments that
depend on an index or a rate; and (iii) payments of penalties for terminating the lease if the lease term reflects the lessee exercising that
option, if any. Lease liabilities exclude the following payments that are generally accounted for separately: (i) non-lease components,
such as maintenance and security service fees and value added tax, and (ii) any payments that a lessee makes before the lease
commencement date. The lease payments are discounted using the interest rate implicit in the lease or if that rate cannot be determined,
the lessee’s incremental borrowing rate being the rate that the lessee would have to pay to borrow the funds in its currency and
jurisdiction necessary to obtain an asset of similar value, economic environment and terms and conditions.
F-58
An asset representing the right to use the underlying asset during the lease term is recognized that consists of the initial measurement
of the lease liability, any lease payments made to the lessor at or before the commencement date less any lease incentives received, any
initial direct cost incurred by the Group and any restoration costs.
After commencement of the lease, each lease payment is allocated between lease liability and finance costs. The finance costs are
recognized over the lease term so as to produce a constant periodic rate of interest on the remaining balance of the lease liability for
each period. The right-of-use asset is depreciated on a straight-line basis over the period of the lease.
Payments associated with short-term leases are recognized as lease expenses on a straight-line basis over the period of the leases.
Leasehold land is accounted under IFRS 16.
The lease liabilities were measured at the present value of the remaining lease payments, discounted using the lessees’ incremental
borrowing rate as at January 1, 2019. The Group’s weighted average incremental borrowing rate applied on January 1, 2019 was 4.75%
per annum.
A reconciliation of the Group’s reported operating lease commitments as at December 31, 2018 and the Group’s lease liabilities
recognized upon adoption of IFRS 16 as at January 1, 2019 was as follows:
Operating lease commitments as at December 31, 2018 (note)
Less: Leases not commenced as at January 1, 2019
Less: Short-term leases
Less: Discount under the lessees’ incremental borrowing rate as at January 1, 2019
Lease liabilities recognized as at January 1, 2019
(in US$’000)
1,241
(187)
(36)
(87)
931
Note: Future aggregate minimum payments under non-cancellable operating leases under IAS 17 were as follows:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Between 3 to 4 years
Between 4 to 5 years
December 31, 2018
(in US$’000)
610
521
98
7
5
1,241
The Group recognized right-of-use assets as at January 1, 2019 measured at their carrying amounts as if IFRS 16 had been applied
since their commencement dates, but discounted using the lessees’ incremental borrowing rate as at January 1, 2019.
Recognized right-of-use assets upon adoption, excluding leasehold land, were offices of US$1.0 million.
There were no adjustments to net cash generated from/(used in) operating activities, investing activities or financing activities in
the consolidated statement of cash flows.
In applying IFRS 16 for the first time, the Group used the following practical expedients permitted by the standard: (i) no
reassessment of whether any expired or existing contracts are or contain leases; (ii) no reassessment of the lease classification for any
expired or existing leases; (iii) the exclusion of initial direct costs for the measurement of the right-of-use assets at the date of initial
application; and (iv) the use of hindsight in determining the lease term where the contract contains options to extend or terminate the
lease.
Under IAS 17
The Group's accounting policy for leases before January 1, 2019 is detailed below.
F-59
Leases in which a significant portion of the risks and rewards of ownership are retained by the lessor are classified as operating
leases. Payments made under operating leases are charged to the consolidated income statements on a straight-line basis over the period
of the leases.
(q) Government Incentives
Incentives from government are recognized at their fair values where there is a reasonable assurance that the incentives will be
received and all attached conditions will be complied with.
Government incentives relating to costs are deferred and recognized in the consolidated income statements over the period necessary
to match them with the costs that they are intended to compensate.
Government grants relating to property, plant and equipment are included in other payables, accruals and advance receipts and
non-current liabilities as deferred income and credited to the consolidated income statements on a straight-line basis over the expected
lives of the related assets.
(r) Revenue and Income Recognition
Revenue is measured based on consideration specified in a contract with a customer, and excludes any sales incentives and amounts
collected on behalf of third parties. Taxes assessed by a governmental authority that are both imposed on and concurrent with a specific
revenue-producing transaction, that are collected by the Group from a customer, are also excluded from revenue. The Group recognizes
revenue when it satisfies a performance obligation by transferring control over a good to a customer.
The Group principally generates revenue from sales of goods. Revenue from sales of goods is recognized when the customer takes
possession of the goods. This usually occurs upon completed delivery of the goods to the customer site. The amount of revenue
recognized is adjusted for expected sales incentives as stipulated in the contract, which are generally issued to customers as direct
discounts at the point-of-sale or indirectly in the form of rebates. Sales incentives are estimated using the expected value method.
Additionally, sales are generally made with a limited right of return under certain conditions. Revenues are recorded net of provisions
for sales discounts and returns.
Revenue from provision of services is recognized when the benefits of the services transfer to the customer over time, which is
based on the proportionate value of services rendered as determined under the terms of the relevant contract. Additionally, when the
amounts that can be invoiced correspond directly with the value to the customer for performance completed to date, the Group recognizes
revenue from provision of services based on amounts that can be invoiced to the customer.
Payments in advance from customers are deferred if consideration is received in advance of transferring control of the goods or
rendering of services. Accounts receivable is recognized if the Group has an unconditional right to bill the customer, which is generally
when the customer takes possession of the goods or services are rendered. Payment terms differ by subsidiary and customer, but
generally range from 45 to 180 days from the invoice date.
(s) Interest Income
Interest income is recognized on a time-proportion basis using the effective interest method.
(t) Segment Reporting
Operating segments are reported in a manner consistent with the internal reporting provided to the chief operating decision makers.
The Company’s Board of Directors, which is responsible for allocating resources and assessing performance of the operating segments,
has been identified as the steering committee that makes strategic decisions.
(u) General Reserves
In accordance with the laws applicable to Foreign Investment Enterprises established in the PRC, the Company makes
appropriations to certain non-distributable reserve funds including the general reserve fund, the enterprise expansion fund and the staff
bonus and welfare fund. The amount of appropriations to these funds are made at the discretion of the Company’s Board of Directors.
F-60
3. Financial Risk Management
(a) Financial risk factors
The Group’s activities expose it to a variety of financial risks, including credit risk and liquidity risk. The Group does not use any
derivative financial instruments for speculative purposes.
(i) Credit risk
The carrying amounts of cash and cash equivalents, trade receivables (including bills receivables) and other receivables included in
the consolidated statements of financial position represent the Group’s maximum exposure to credit risk of the counterparty in relation
to its financial assets.
Substantially all of the Group’s cash and cash equivalents are deposited in major financial institutions, which management believes
are of high credit quality. The Group has a practice to limit the amount of credit exposure to any financial institution.
Bills receivables are mostly settled by state-owned banks or other reputable banks and therefore the management considers that
they will not expose the Group to any significant credit risk.
The Group has no significant concentrations of credit risk. The Group has policies in place to ensure that the sales of products are
made to customers with appropriate credit history and the Group performs periodic credit evaluations of its customers.
Management periodically assesses the recoverability of trade receivables and other receivables. The Group’s historical loss rates
are adjusted to reflect current and forward-looking information on specific factors affecting the ability of the customers to settle the
receivables, and historical experience collecting receivables falls within the recorded allowances.
(ii) Liquidity risk
Prudent liquidity management implies maintaining sufficient cash and cash equivalents and the availability of funding when
necessary. The Group’s policy is to regularly monitor current and expected liquidity requirements to ensure that it maintains sufficient
cash balances and adequate credit facilities to meet its liquidity requirements in the short and long term.
As at December 31, 2020 and 2019, the Group’s current financial liabilities were mainly due for settlement within twelve months
and the Group expects to meet all liquidity requirements.
(b) Capital risk management
The Group’s objectives when managing capital are to safeguard the Group’s ability to provide returns for shareholders and benefits
for other stakeholders and to maintain an optimal capital structure to reduce the cost of capital.
The Group regularly reviews and manages its capital structure to ensure an optimal balance between higher shareholders’ return
that might be possible with higher levels of borrowings and the advantages and security afforded by a sound capital position, and makes
adjustments to the capital structure in light of changes in economic conditions.
The Group monitors capital on the basis of the liabilities to assets ratio. This ratio is calculated as total liabilities divided by total
assets as shown on the consolidated statements of financial position.
F-61
Currently, it is the Group’s strategy to maintain a reasonable liabilities to assets ratio. The liabilities to assets ratio as at
December 31, 2020 and 2019 was as follows:
Total liabilities
Total assets
Liabilities to assets ratio
(c) Fair value estimation
December 31,
2020
2019
(in US$’000)
116,612
269,320
85,607
232,345
43.3 %
36.8 %
The Group does not have any financial assets or liabilities which are carried at fair value. The carrying amounts of the Group’s
current financial assets, including cash and cash equivalents, trade and bills receivables and other receivables, and current financial
liabilities, including trade payables and other payables and accruals, approximate their fair values due to their short-term maturities. The
carrying amounts of the Group’s financial instruments carried at cost or amortized cost are not materially different from their fair values.
The face values less any estimated credit adjustments for financial assets and liabilities with a maturity of less than one year are
assumed to approximate their fair values. The fair value of financial liabilities for disclosure purposes is estimated by discounting the
future contractual cash flows at the current market interest rate that is available to the Group for similar financial instruments.
4. Critical Accounting Estimates and Judgements
Note 2 includes a summary of the significant accounting policies used in the preparation of the consolidated financial statements.
The preparation of consolidated financial statements often requires the use of judgements to select specific accounting methods and
policies from several acceptable alternatives. Furthermore, significant estimates and assumptions concerning the future may be required
in selecting and applying those methods and policies in the consolidated financial statements. The Group bases its estimates and
judgements on historical experience and various other assumptions that it believes are reasonable under the circumstances. Actual results
may differ from these estimates and judgements under different assumptions or conditions.
The following is a review of the more significant assumptions and estimates, as well as the accounting policies and methods used
in the preparation of the consolidated financial statements.
(a) Sales rebates
Certain sales rebates are provided to customers when their business performance for an agreed period within the year and the
whole year meets certain criteria as stipulated in the contracts. Sales rebates are considered variable consideration and the estimate of
sales rebates during the year is based on estimated sales transactions for the entire period stipulated and is subject to change based on
actual performance and collection status.
(b) Useful lives of property, plant and equipment
The Group has made substantial investments in property, plant and equipment. Changes in technology or changes in the intended
use of these assets may cause the estimated period of use or value of these assets to change.
(c) Deferred income tax
Deferred tax is recognized using the liability method on temporary differences arising between the tax bases of assets and liabilities
against which the deductible temporary differences and the carry forward of unused tax losses and tax credits can be utilized. Deferred
income tax assets are recognized only to the extent that it is probable that future taxable profit will be available against which the
temporary differences can be utilized. Where the final outcomes are different from the estimations, such differences will impact the
carrying amount of deferred tax in the period in which such determination is made.
F-62
5. Revenue and Segment Information
Management has reviewed the Group’s internal reporting in order to assess performance and allocate resources, and has determined
that the Group has two reportable operating segments as follows:
—Manufacturing business—manufacture and distribution of drug products
—Distribution business—provision of sales, distribution and marketing services to pharmaceutical manufacturers
The operating segments are strategic business units that offer different products and services. They are managed separately because
each business requires different technology and marketing approaches. The performance of each of the reportable segments is assessed
based on a measure of operating profit/(loss).
The segment information is as follows:
Revenue from external customers
Interest income
Operating profit/(loss)
Finance costs
Depreciation/amortization
Additions to non‑current assets (other than financial instruments
Year Ended December 31, 2020
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
270,954
396
78,069
11
8,670
5,400
579
(204)
1
65
Total
276,354
975
77,865
12
8,735
and deferred tax assets)
3,037
57
3,094
Total segment assets
Revenue from external customers
Interest income
Operating profit/(loss)
Finance costs
Depreciation/amortization
Additions to non‑current assets (other than financial instruments
December 31, 2020
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
261,965
7,355
269,320
Year Ended December 31, 2019
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
260,986
300
74,319
33
7,913
11,096
282
(1,961)
9
185
Total
272,082
582
72,358
42
8,098
and deferred tax assets)
2,958
17
2,975
Total segment assets
December 31, 2019
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
226,976
5,369
232,345
F-63
Revenue from external customers
Interest income
Operating profit
Depreciation/amortization
Additions to non‑current assets (other than financial instruments
Year Ended December 31, 2018
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
252,542
348
66,274
7,500
23,107
325
2,864
5
275,649
673
69,138
7,505
and deferred tax assets)
3,135
3
3,138
Revenue from external customers is after elimination of inter-segment sales. The amount eliminated was US$62.2 million for 2020
(2019: US$60.8 million; 2018: US$82.8 million). Sales between segments are carried out at mutually agreed terms. Revenue from
external customers from the manufacturing business is for sales of goods which are recognized at a point in time. Revenue from external
customers from the distribution business is for provision of services which are recognized over time.
6. Other Net Operating Income
Interest income
Net foreign exchange gain/(loss)
Other operating income
7. Operating Profit
Operating profit
Operating profit is stated after charging/(crediting) the following:
Cost of inventories recognized as expense
Depreciation of property, plant and equipment
(Gain)/Loss on disposal of property, plant and equipment
Amortization of leasehold land
Amortization of other intangible asset
Depreciation charge of right-of-use assets and lease expenses
Movement on the provision for trade receivables
Provision for excess and obsolete inventories
Research and development expense
Auditor’s remuneration
Employee benefit expenses (Note 9)
F-64
2020
Year Ended December 31,
2019
(in US$’000)
2018
975
70
2,428
3,473
582
(20)
2,379
2,941
673
(32)
2,064
2,705
2020
Year Ended December 31,
2019
(in US$’000)
2018
77,865
72,358
69,138
2018
2020
Year Ended December 31,
2019
(in US$’000)
55,653
7,148
11
161
218
724
9
1,062
4,422
194
80,647
47,299
7,878
(2)
160
217
725
(9)
2,447
6,301
198
80,728
53,837
7,109
26
168
228
764
—
79
2,158
173
85,943
8. Taxation Charge
Current tax
Deferred income tax (Note 16)
Taxation charge
2020
Year Ended December 31,
2019
(in US$’000)
10,300
715
11,015
12,520
(1,687)
10,833
2018
13,088
(3,717)
9,371
The taxation charge on the Group’s profit before taxation differs from the theoretical amount that would arise using the Group’s
weighted average tax rate as follows:
Profit before taxation
Tax calculated at the statutory tax rates of respective companies
Tax effects of:
Expenses not deductible for tax purposes
Utilization of unrecognized temporary differences
Tax concession (note)
(Over)/under provision in prior years
Taxation charge
2020
Year Ended December 31,
2019
(in US$’000)
72,316
18,079
77,853
19,463
2018
69,138
17,285
1,137
(938)
(8,753)
(76)
10,833
2,938
(1,669)
(8,541)
208
11,015
4,099
(3,614)
(8,263)
(136)
9,371
Note: The Company has successfully renewed the High and New Technology Enterprise status in 2020. Accordingly, the
Company is subject to a preferential income tax rate of 15% (2019: 15%; 2018: 15%) for 3 years (i.e. 2020, 2021, 2022).
Certain research and development expenses are also eligible for super-deduction such that 175% of qualified expenses
incurred are deductible against taxable profits for tax purposes (2019: 175%; 2018: 175%).
The weighted average tax rate calculated at the statutory tax rates of respective companies for the year was 25% (2019: 25%; 2018:
25%). The effective tax rate for the year was 13.9% (2019: 15.2%; 2018: 13.6%).
9. Employee Benefit Expenses
Wages, salaries and bonuses
Pension costs—defined contribution plans (note)
Staff welfare
2020
Year Ended December 31,
2019
(in US$’000)
60,353
7,689
12,605
80,647
68,226
995
11,507
80,728
2018
65,611
8,437
11,895
85,943
Note: The Group received social security concession of US$7.8 million for the year ended December 31, 2020.
Employee benefit expenses of approximately US$16.4 million (2019: US$18.8 million; 2018: US$23.2 million) are included in
cost of sales.
10. Cash and cash equivalents
Cash and cash equivalents
December 31,
2020
2019
(in US$’000)
72,478
41,244
F-65
The cash and cash equivalents denominated in RMB were deposited with banks in the PRC. The conversion of these RMB
denominated balances into foreign currencies is subject to the rules and regulations of foreign exchange control promulgated by the
PRC government.
11. Trade and Bills Receivables
Trade receivables—third parties
Trade receivables—related parties (Note 22(b))
Bills receivables
December 31,
2020
2019
(in US$’000)
13,996
1,384
3,041
18,421
18,354
696
5,722
24,772
All trade and bills receivables are denominated in RMB and are due within one year from the end of the reporting period. The
carrying values of trade and bills receivables approximate their fair values due to their short-term maturities.
Movements on the provision for trade receivables are as follows:
As at January 1
Increase in provision for trade receivables
Decrease in provision due to subsequent collection
As at December 31
12. Other Receivables, Prepayments and Deposits
Prepayments to suppliers
Interest receivables
Deposits
Others
13. Inventories
Raw materials
Work in progress
Finished goods
2020
9
—
(9)
—
2019
(in US$’000)
—
9
—
9
2018
—
—
—
—
December 31,
2020
2019
(in US$’000)
1,356
171
1,338
527
3,392
1,058
98
1,434
345
2,935
December 31,
2020
2019
(in US$’000)
31,501
32,684
17,489
81,674
29,655
24,164
18,498
72,317
F-66
14. Property, plant and equipment
Cost
As at January 1, 2020
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2020
Accumulated depreciation
As at January 1, 2020
Depreciation
Disposals
Exchange differences
As at December 31, 2020
Net book value
As at December 31, 2020
Cost
As at January 1, 2019
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2019
Accumulated depreciation
As at January 1, 2019
Depreciation
Disposals
Exchange differences
As at December 31, 2019
Net book value
As at December 31, 2019
Buildings
situated in
the PRC
Leasehold
improvements
Plant
and
equipment
Furniture
and
fixtures,
other
equipment
and motor
vehicles
Construction
in progress
Total
68,213
—
—
334
4,933
73,480
11,212
3,493
—
994
15,699
57,781
(in US$’000)
22,606
581
(53)
361
1,678
25,173
8,760
2,786
(35)
777
12,288
9,526
935
(134)
1,155
791
12,273
5,665
1,511
(91)
485
7,570
2,828
1,519
—
(1,850)
188
2,685
1,116
—
—
80
1,196
103,712
3,035
(187)
—
7,629
114,189
27,136
7,878
(126)
2,369
37,257
12,885
4,703
1,489
76,932
539
—
—
—
39
578
383
88
—
33
504
74
Buildings
situated in
the PRC
Leasehold
improvements
Plant
and
equipment
Furniture
and
fixtures,
other
equipment
and motor Construction
in progress
vehicles
(in US$’000)
22,583
334
(41)
337
(607)
22,606
6,786
2,229
(28)
(227)
8,760
7,934
1,511
(170)
500
(249)
9,526
4,614
1,361
(163)
(147)
5,665
3,508
856
—
(1,457)
(79)
2,828
1,146
—
—
(30)
1,116
Total
103,939
2,774
(211)
—
(2,790)
103,712
20,881
7,148
(191)
(702)
27,136
13,846
3,861
1,712
76,576
69,434
—
—
620
(1,841)
68,213
8,035
3,465
—
(288)
11,212
57,001
480
73
—
—
(14)
539
300
93
—
(10)
383
156
F-67
Buildings
situated in
the PRC
Leasehold
improvements
Plant
and
equipment
Furniture
and
fixtures,
other
equipment
and motor Construction
in progress
vehicles
(in US$’000)
23,158
516
(104)
—
(987)
22,583
4,870
2,267
(67)
(284)
6,786
7,574
770
(269)
204
(345)
7,934
3,949
1,132
(267)
(200)
4,614
2,415
1,738
—
(497)
(148)
3,508
1,196
—
—
(50)
1,146
Total
105,718
3,138
(373)
—
(4,544)
103,939
14,984
7,109
(334)
(878)
20,881
15,797
3,320
2,362
83,058
72,070
114
—
293
(3,043)
69,434
4,763
3,603
—
(331)
8,035
61,399
501
—
—
—
(21)
480
206
107
—
(13)
300
180
Cost
As at January 1, 2018
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2018
Accumulated depreciation
As at January 1, 2018
Depreciation
Disposals
Exchange differences
As at December 31, 2018
Net book value
As at December 31, 2018
15. Leases
Leases consisted of the following:
Right-of-use assets
Offices
Lease liabilities—current
Lease liabilities—non-current
Lease activities are summarized as follows:
Lease expenses: Short-term leases with lease terms equal or less than 12 months
Depreciation charge of right-of-use assets
Interest expense (included in finance costs)
Cash paid on lease liabilities
Non-cash: Lease liabilities recognized from obtaining right-of-use assets
Lease contracts are typically within a period of 1 to 5 years. The weighted average remaining lease term and weighted average
discount rate as at December 31, 2020 was 0.89 years (2019: 1.24 years) and 4.75% (2019: 4.75%) respectively.
F-68
December 31,
2020
2019
(in US$’000)
152
133
19
152
562
444
100
544
Year Ended December 31,
2020
2019
(in US$’000)
245
480
12
474
58
153
571
42
595
201
Future lease payments are as follows:
Lease payments:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Total lease payments
Less: Discount factor
Total lease liabilities
16. Deferred Tax Assets
The movements in deferred tax assets are as follows:
December 31,
2020
2019
(in US$’000)
135
19
—
154
(2)
152
460
99
2
561
(17)
544
As at January 1
Credited/(debited) to the consolidated income statements
—Accrued expenses, provisions, deferred income,
accelerated depreciation and other temporary differences
(note)
Exchange differences
As at December 31
2020
2019
(in US$’000)
2018
6,147
7,091
3,594
1,687
481
8,315
(715)
(229)
6,147
3,717
(220)
7,091
Note: During the year ended December 31, 2019, the Group utilized US$0.9 million deferred tax assets which was
recognized during the year ended December 31, 2018 on temporary differences arising from advertising and promotion
expenditures.
The Group’s deferred tax assets are mainly temporary differences including accrued expenses, provisions, deferred income,
accelerated depreciation and other temporary differences. The potential deferred tax assets in respect of tax losses which have not been
recognized in the consolidated financial statements were approximately US$0.7 million as at December 31, 2020 (2019:
US$1.3 million).
These unrecognized tax losses can be carried forward against future taxable income and will expire in the following years:
2020
2021
2022
2023
2024
2025
December 31,
2020
2019
(in US$’000)
—
35
7
2,550
76
7
2,675
39
35
195
4,697
76
—
5,042
F-69
17. Trade Payables
Trade payables—third parties
Trade payables—related parties (Note 22(b))
December 31,
2020
2019
(in US$’000)
8,711
2,463
11,174
6,604
3,665
10,269
All trade payables are denominated in RMB and due within one year from the end of the reporting period. The carrying value of
trade payables approximates their fair values due to their short-term maturities.
18. Other Payables, Accruals and Advance Receipts
Accrued salaries and benefits
Accrued selling and marketing expenses
Value‑added tax and tax surcharge payables
Payments in advance from customers (note)
Others
December 31,
2020
2019
(in US$’000)
17,536
59,930
8,794
2,750
4,524
93,534
12,361
38,477
8,003
4,158
3,426
66,425
Note: Substantially all customer balances as at December 31, 2019 were recognized to revenue during the year ended
December 31, 2020. Additionally, substantially all customer balances as at December 31, 2020 are expected to be
recognized to revenue within one year upon transfer of goods or services as the contracts have an expected duration of
one year or less.
19. Current Tax Liabilities
As at January 1
Current tax (Note 8)
Tax paid
Exchange difference
Transfer to other receivables
As at December 31
2020
2,395
12,520
(10,232)
192
157
5,032
2019
(in US$’000)
5,671
10,300
(13,618)
42
—
2,395
2018
5,341
13,088
(12,158)
(600)
—
5,671
F-70
20. Notes to the Consolidated Statements of Cash Flows
(a) Reconciliation of profit for the year to net cash generated from operations:
Profit for the year
Adjustments to reconcile profit for the year to net cash generated from operations
2020
2019
(in US$’000)
67,020 61,301
2018
59,767
Taxation charge
Finance costs
Interest income
Depreciation on property, plant and equipment
(Gain)/loss on disposal of property, plant and equipment
Amortization of leasehold land
Amortization of other intangible asset
Depreciation charge of right-of-use assets
Provision for excess and obsolete inventories
Movement on the provision for trade receivables
Exchange differences
Changes in working capital:
Trade and bills receivables
Other receivables, prepayments and deposits
Inventories
Trade payables
Other payables, accruals and advance receipts
Deferred income
Total changes in working capital
Net cash generated from operations
10,833 11,015
42
(582)
7,148
11
161
218
571
1,062
9
2,057 (1,439)
12
(975)
7,878
(2)
160
217
480
2,447
(9)
905
6,360
(227)
7,053
(218)
(11,804) (8,459)
3,097
26,511 (3,271)
(935)
22,491 (2,733)
112,609 76,784
746
9,371
—
(673)
7,109
26
168
228
—
79
—
(568)
(9,389)
(216)
(3,892)
(4,601)
(1,003)
(1,707)
(20,808)
54,699
(b) Supplemental disclosure for non-cash activities
During the years ended December 31, 2020, there was an increase in accruals made for purchases of property, plant and equipment
of US$0.6 million (2019 and 2018: a decrease of US$1.8 million and US$2.0 million respectively).
21. Capital commitments
The Group had the following capital commitments:
Property, plant and equipment
Contracted but not provided for
December 31,
2020
(in US$’000)
902
Capital commitments for property, plant and equipment are mainly for improvements to the Group’s plant.
F-71
22. Significant Related Party Transactions
The Group has the following significant transactions with related parties which were carried out in the normal course of business
at terms determined and agreed by the relevant parties:
(a) Transactions with related parties:
2020
Year Ended December 31,
2019
(in US$’000)
2018
Sales of goods to:
—A fellow subsidiary of SHTCML
—A fellow subsidiary of SHCM(HK)IL
Purchase of goods from:
—SHTCML
—Fellow subsidiaries of SHTCML
Rendering of research and development services from:
—A fellow subsidiary of SHCM(HK)IL
Provision of marketing services to:
—A fellow subsidiary of SHTCML
—A fellow subsidiary of SHCM(HK)IL
Leasing office from:
—SHTCML
10,465
2,854
13,319
7,922
1,016
8,938
12,459
2,255
14,714
4,609
3,263
7,872
10,987
2,071
13,058
—
12,219
12,219
491
494
859
2,781
—
2,781
5,045
2,682
7,727
5,917
12,703
18,620
337
335
297
No transactions have been entered into with the directors of the Company (being the key management personnel) during the year
ended December 31, 2020 (2019 and 2018: nil).
(b) Balances with related parties included in:
Trade and bills receivables
—A fellow subsidiary of SHTCML
Other receivables, prepayments and deposits
—A fellow subsidiary of SHTCML
Right-of-use assets
—SHTCML
Trade payables
—SHTCML
— Fellow subsidiaries of SHTCML
Other payables, accruals and advance receipts
—Fellow subsidiaries of SHCM(HK)IL
Lease liabilities
—SHTCML
December 31,
2020
2019
(in US$’000)
1,384
696
946
1,338
87
2,054
409
2,463
986
94
409
3,437
228
3,665
986
424
Balances with related parties are unsecured, interest-free and repayable on demand. The carrying values of balances with related
parties approximate their fair values due to their short-term maturities.
F-72
23. Particulars of Principal Subsidiaries
Place of
establishment
and
operation
Name
Shanghai Shangyao Hutchison
Whampoa GSP Company Limited
PRC
20,000
20,000
Hutchison Heze Bio Resources &
Technology Co., Limited
PRC
1,500
1,500
24. Subsequent Events
Nominal value
of registered
capital
December 31,
Equity
interest
attributable
to the Group
2020
2019
2020
2019
Type of legal entity
Principal activity
(in RMB’000)
100 %
100 %
100 %
100 %
Limited liability
company
Limited liability
company
Distribution of drug
products
Agriculture and sales of
Chinese herbs
The Group evaluated subsequent events through March 4, 2021, which is the date when the consolidated financial statements
were issued.
F-73
HUTCHISON WHAMPOA GUANGZHOU
BAIYUNSHAN CHINESE MEDICINE
COMPANY LIMITED
F-74
Report of Independent Auditors
To the Board of Directors and Shareholders of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine
Company Limited
We have audited the accompanying consolidated financial statements of Hutchison Whampoa Guangzhou Baiyunshan Chinese
Medicine Company Limited and its subsidiaries (the “Company”), which comprise the consolidated statements of financial position as
of December 31, 2020 and 2019, and the related consolidated income statements, consolidated statements of comprehensive income, of
changes in equity and of cash flows for each of the three years in the period ended December 31, 2020.
Management’s Responsibility for the Consolidated Financial Statements
Management is responsible for the preparation and fair presentation of the consolidated financial statements in accordance with
International Financial Reporting Standards as issued by the International Accounting Standards Board; this includes the design,
implementation, and maintenance of internal control relevant to the preparation and fair presentation of consolidated financial statements
that are free from material misstatement, whether due to fraud or error.
Auditors’ Responsibility
Our responsibility is to express an opinion on the consolidated financial statements based on our audits. We conducted our audits
in accordance with auditing standards generally accepted in the United States of America. Those standards require that we plan and
perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free from material
misstatement.
An audit involves performing procedures to obtain audit evidence about the amounts and disclosures in the consolidated financial
statements. The procedures selected depend on our judgment, including the assessment of the risks of material misstatement of the
consolidated financial statements, whether due to fraud or error. In making those risk assessments, we consider internal control relevant
to the Company’s preparation and fair presentation of the consolidated financial statements in order to design audit procedures that are
appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control.
Accordingly, we express no such opinion. An audit also includes evaluating the appropriateness of accounting policies used and the
reasonableness of significant accounting estimates made by management, as well as evaluating the overall presentation of the
consolidated financial statements. We believe that the audit evidence we have obtained is sufficient and appropriate to provide a basis
for our audit opinion.
Opinion
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position
of Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited and its subsidiaries as of December 31, 2020 and
2019, and the results of their operations and their cash flows for each of the three years in the period ended December 31, 2020 in
accordance with International Financial Reporting Standards as issued by the International Accounting Standards Board.
/s/ PricewaterhouseCoopers Zhong Tian LLP
Guangzhou, the People’s Republic of China
March 4, 2021
F-75
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Consolidated Income Statements
(in US$’000)
Revenue
Cost of sales
Gross profit
Selling expenses
Administrative expenses
Other net operating income
Operating profit
Share of (losses)/profits of a joint venture and associated companies, net of tax
Finance costs
Gain on return of land
Gain on divestment of a subsidiary
Profit before taxation
Taxation charge
Profit for the year
Attributable to:
Shareholders of the Company
Non-controlling interests
Note
5
6
7
8
25(b)
9
Year Ended December 31,
2019
215,403
(100,279)
115,124
(74,013)
(23,817)
5,626
22,920
60
(59)
—
—
22,921
(3,634)
19,287
2020
232,368
(115,564)
116,804
(74,066)
(25,664)
6,071
23,145
(84)
(57)
84,667
37
107,708
(16,494)
91,214
2018
215,838
(102,701)
113,137
(70,501)
(25,997)
4,085
20,724
131
(152)
—
—
20,703
(4,227)
16,476
91,276
(62)
91,214
19,792
(505)
19,287
16,860
(384)
16,476
The accompanying notes are an integral part of these consolidated financial statements.
F-76
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Consolidated Statements of Comprehensive Income
(in US$’000)
Profit for the year
Other comprehensive income/(loss) that has been or may be reclassified subsequently to
profit or loss:
Exchange translation differences
Total comprehensive income
Attributable to:
Shareholders of the Company
Non‑controlling interests
Year Ended December 31,
2019
19,287
2020
91,214
2018
16,476
4,728
95,942
(3,353)
15,934
(5,640)
10,836
95,976
(34)
95,942
16,529
(595)
15,934
11,368
(532)
10,836
The accompanying notes are an integral part of these consolidated financial statements.
F-77
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Consolidated Statements of Financial Position
(in US$’000)
Assets
Current assets
Cash and cash equivalents
Trade and bills receivables
Other receivables, prepayments and deposits
Inventories
Total current assets
Property, plant and equipment
Right-of-use assets
Leasehold land
Goodwill
Other intangible assets
Investments in a joint venture and associated companies
Deferred tax assets
Other non-current assets
Total assets
Liabilities and shareholders’ equity
Current liabilities
Trade payables
Other payables, accruals and advance receipts
Dividend payable
Lease liabilities
Current tax liabilities
Total current liabilities
Deferred tax liabilities
Deferred income
Dividend payable
Lease liabilities
Total liabilities
Company’s shareholders’ equity
Share capital
Reserves
Total Company’s shareholders’ equity
Non-controlling interests
Total shareholders’ equity
Total liabilities and shareholder’s equity
Note
2020
2019
December 31,
11
12
13
14
15
16
17
18
19
20
24(b)
16
17
21
24(b)
16
16,602
67,417
50,121
43,748
177,888
60,181
820
8,419
8,751
2,108
584
3,141
11,689
273,581
22,579
98,861
—
568
15,171
137,179
114
15,617
—
303
153,213
24,103
95,283
119,386
982
120,368
273,581
21,421
48,273
8,593
46,417
124,704
60,317
1,525
9,259
8,163
2,375
616
2,323
10,490
219,772
12,699
61,877
46,962
611
1,902
124,051
106
15,244
32,380
960
172,741
24,103
20,410
44,513
2,518
47,031
219,772
The accompanying notes are an integral part of these consolidated financial statements.
F-78
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Consolidated Statements of Changes in Equity
(in US$’000)
Attributable to shareholders of the Company
Non‑
Share
capital
24,103
Exchange General
reserves
131
reserve
6,712
—
—
—
Retained
earnings
79,670
16,860
Total
110,616
16,860
Controlling
interests
3,645
(384)
Total
equity
114,261
16,476
As at January 1, 2018
Profit/(loss) for the year
Other comprehensive loss
Exchange translation differences
Total comprehensive (loss)/income
As at December 31, 2018
Impact of change in accounting policy (IFRS 16)
As at January 1, 2019
Profit/(loss) for the year
Other comprehensive loss
Exchange translation differences
Total comprehensive (loss)/income
Dividends declared to shareholders
As at December 31, 2019
Profit/(loss) for the year
Other comprehensive income
Exchange translation differences
Total comprehensive income/(loss)
Dividends declared to shareholders
Acquisition of additional interest in a subsidiary
(Note 25(a))
Divestment of a subsidiary to non-controlling interest
— (5,492)
— (5,492)
1,220
—
1,220
—
—
24,103
—
24,103
— (3,263)
— (3,263)
—
—
24,103
(2,043)
—
4,700
4,700
—
—
—
—
—
—
—
—
131
—
131
—
—
16,860
96,530
(43)
96,487
19,792
(5,492)
11,368
121,984
(43)
121,941
19,792
(148)
(532)
3,113
—
3,113
(505)
(5,640)
10,836
125,097
(43)
125,054
19,287
—
—
—
19,792
— (93,957)
131
—
22,322
91,276
(3,263)
16,529
(93,957)
44,513
91,276
(90)
(595)
(3,353)
15,934
— (93,957)
47,031
91,214
2,518
(62)
—
—
91,276
—
— (20,756)
4,700
95,976
(20,756)
4,728
28
95,942
(34)
— (20,756)
(9)
(131)
(207)
(347)
(1,537)
(1,884)
(Note 25(b))
As at December 31, 2020
—
24,103
—
2,648
—
—
— 92,635
—
119,386
35
982
35
120,368
The accompanying notes are an integral part of these consolidated financial statements.
F-79
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Consolidated Statements of Cash Flows
(in US$’000)
Operating activities
Net cash generated from operations
Interest received
Finance costs paid
Income tax paid
Net cash generated from operating activities
Investing activities
Purchase of property, plant and equipment
Purchase of intangible asset
Proceeds from return of land
Proceeds from disposal of leasehold land
Proceeds from disposal of property, plant and equipment
Government grants received relating to property, plant and equipment
Net cash generated from/(used in) investing activities
Financing activities
Dividends paid to shareholders
Repayment of advances from shareholder
Acquisition of additional interest in a subsidiary
Lease payments
Net cash used in financing activities
Net (decrease)/increase in cash and cash equivalents
Effect of exchange rate changes on cash and cash equivalents
Cash and cash equivalents
Cash and cash equivalents at beginning of year
Cash and cash equivalents at end of year
Year Ended December 31,
Note
2020
2019
2018
22(a)
8
25(a)
16
60,756
271
(57)
(4,013)
56,957
(2,342)
—
40,422
231
730
963
40,004
26,237
160
(59)
(3,363)
22,975
(3,377)
(356)
—
—
—
950
(2,783)
(100,842)
—
(1,884)
(609)
(103,335)
(6,374)
1,555
(4,819)
(14,615)
—
—
(556)
(15,171)
5,021
(443)
4,578
29,174
81
(152)
(3,729)
25,374
(5,387)
—
—
—
—
1,198
(4,189)
(15,077)
(2,423)
—
(103)
(17,603)
3,582
(582)
3,000
21,421
16,602
16,843
21,421
13,843
16,843
The accompanying notes are an integral part of these consolidated financial statements.
F-80
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited
Notes to the Consolidated Financial Statements
1. General Information
Hutchison Whampoa Guangzhou Baiyunshan Chinese Medicine Company Limited (the “Company”) and its subsidiaries (together
the “Group”) are principally engaged in manufacturing, selling and distribution of over-the-counter drug products. The Group has
manufacturing plants in the People’s Republic of China (the “PRC”) and sells mainly in the PRC.
The Company was incorporated in the PRC on April 12, 2005 as a Chinese-Foreign Equity joint venture. The Company is jointly
controlled by Guangzhou Hutchison Chinese Medicine (HK) Investment Limited (“GZHCMHK”) and Guangzhou Baiyunshan
Pharmaceutical Holdings Company Limited (“GBPHCL”).
These consolidated financial statements are presented in United States dollars (“US$”), unless otherwise stated and have been
approved for issue by the Company’s Board of Directors on March 4, 2021.
2. Summary of Significant Accounting Policies
The consolidated financial statements of the Company have been prepared in accordance with International Financial Reporting
Standards (“IFRS”) and interpretations issued by the IFRS Interpretations Committee applicable to companies reporting under IFRS.
The consolidated financial statements comply with IFRS as issued by the International Accounting Standards Board (“IASB”). These
consolidated financial statements have been prepared under the historical cost convention.
During the year, the Group has adopted all of the new and revised standards, amendments and interpretations issued by the IASB
that are relevant to the Group’s operations and mandatory for annual periods beginning January 1, 2020. The adoption of these new and
revised standards, amendments and interpretations did not have any material effects on the Group’s results of operations or financial
position.
The following standards, amendments and interpretations were issued but not yet effective for the financial year ended
December 31, 2020 and have not been early adopted by the Group:
IFRS 9, IAS 39, IFRS 7, IFRS 4 and IFRS 16 (Amendments)(1)
IFRS 3 (Amendments)(2)
IAS 16 (Amendments)(2)
IAS 37 (Amendments)(2)
Annual improvement 2018-2020(2)
IAS 1 (Amendments)(3)
IFRS 17(3)
IFRS 10 and IAS 28 (Amendments)(4)
Interest rate benchmark reform – Phase 2
Reference to the Conceptual Framework
Property, Plant and Equipment: Proceeds before Intended Use
Onerous Contracts – Costs of Fulfilling a Contract
Improvements to IFRSs
Classification of Liabilities as Current or Non-current
Insurance Contracts
Sale or Contribution of Assets between an Investor and its
Associate or Joint Venture
(1) Effective for the Group for annual periods beginning on or after January 1, 2021.
(2) Effective for the Group for annual periods beginning on or after January 1, 2022.
(3) Effective for the Group for annual periods beginning on or after January 1, 2023.
(4) Effective date to be determined by the IASB.
The adoption of standards, amendments and interpretations listed above in future periods is not expected to have any material effects
on the Group’s results of operations or financial position.
F-81
(a) Basis of Consolidation
The consolidated financial statements of the Group include the financial statements of the Company and its subsidiaries, and also
include the Group’s interests in a joint venture and associated companies on the basis set out in Notes 2(d) and 2(e) below.
The accounting policies of subsidiaries, the joint venture and associated companies have been changed where necessary to ensure
consistency with the policies adopted by the Group.
Intercompany transactions, balances and unrealized gains on transactions between group companies are eliminated. Unrealized
losses are also eliminated unless the transaction provides evidence of an impairment of the transferred asset.
Non-controlling interests represent the interests of outside shareholders in the operating results and net assets of subsidiaries.
(b) Subsidiaries
Subsidiaries are all entities over which the Group has control. The Group controls an entity when the Group is exposed, or has
rights, to variable returns from its involvement with the entity and has the ability to affect those returns through its power to direct the
activities of the entity. In the consolidated financial statements, subsidiaries are accounted for as described in Note 2(a) above.
Subsidiaries are fully consolidated from the date on which control is transferred to the Group. They are de-consolidated from the
date that control ceases.
(c) Transactions with Non-controlling Interests
Transactions with non-controlling interests that do not result in a loss of control are accounted for as transactions with equity owners
of the Group. For purchases from non-controlling interests, the difference between any consideration paid and the relevant share acquired
of the carrying value of net assets of the subsidiary is recorded in equity. Gains or losses on disposals to non-controlling interests are
also recorded in equity.
(d) Joint Arrangements
Investments in joint arrangements are classified either as joint operations or joint ventures depending on the contractual rights and
obligations of each investor. The Group has assessed the nature of its joint arrangement and determined it to be a joint venture. The joint
venture is accounted for using the equity method.
Under the equity method of accounting, the interest in joint venture is initially recognized at cost and adjusted thereafter to recognize
the Group’s share of the post-acquisition profits or losses and movements in other comprehensive income. The Group determines at
each reporting date whether there is any objective evidence that the investment in the joint venture is impaired. If this is the case, the
Group calculates the amount of impairment as the difference between the recoverable amount of the joint venture and its carrying value
and recognizes the amount in the consolidated income statements.
(e) Associated Companies
An associate is an entity, other than a subsidiary or a joint venture, in which the Group has a long-term equity interest and over
which the Group is in position to exercise significant influence over its management, including participation in the financial and
operating policy decisions.
The results and net assets of associates are incorporated in these financial statements using the equity method of accounting, except
when the investment is classified as held for sale, in which case it is accounted for under IFRS 5, Non-current assets held for sale and
discontinued operations. The total carrying amount of such investments is reduced to recognize any identified impairment loss in the
value of individual investments.
F-82
(f) Foreign Currency Translation
Items included in the financial statements of each of the Group’s companies are measured using the currency of the primary
economic environment in which the entity operates (the “functional currency”). The functional currency of the Company and its
subsidiaries, joint venture and associated companies is Renminbi (“RMB”) whereas the consolidated financial statements are presented
in US$, which is the Company’s presentation currency.
Foreign currency transactions are translated into the functional currency using the exchange rates at the dates of the transactions.
Foreign currency gains and losses resulting from the settlement of such transactions and from the translation of monetary assets and
liabilities denominated in foreign currencies at year end exchange rates are generally recognized in the consolidated income statements.
The financial statements of the Company, subsidiaries, joint venture and associated companies are translated into the Company’s
presentation currency using the year end rates of exchange for the statements of financial position items and the average rates of
exchange for the year for the income statement items. Exchange translation differences are recognized directly in other comprehensive
income.
(g) Property, Plant and Equipment
Property, plant and equipment other than construction in progress are stated at historical cost less accumulated depreciation and any
accumulated impairment losses. Historical cost includes the purchase price of the asset and any directly attributable costs of bringing
the asset to its working condition and location for its intended use.
Subsequent costs are included in the asset’s carrying amount or recognized as a separate asset, as appropriate, only when it is
probable that future economic benefits associated with the item will flow to the Group and the cost of the item can be measured reliably.
All other repairs and maintenance are charged to the consolidated income statements during the financial period in which they
are incurred.
Depreciation is calculated using the straight-line method to allocate asset costs less accumulated impairment losses over their
estimated useful lives. The principal estimated useful lives are as follows:
Buildings and facilities
Plant and equipment
Furniture and fixtures, other equipment and motor vehicles
10-30 years
10 years
5 years
The assets’ useful lives are reviewed and adjusted, if appropriate, at the end of each reporting period. An asset’s carrying amount
is written down immediately to its recoverable amount if the asset’s carrying amount is greater than its estimated recoverable amount.
Gains and losses on disposals are determined by comparing net sales proceeds with the carrying amount of the relevant assets and
are recognized in the consolidated income statements.
(h) Construction in Progress
Construction in progress represents buildings, plant and machinery under construction and pending installation and is stated at cost
less accumulated impairment losses, if any. Cost includes the costs of construction of buildings and the costs of plant and machinery.
No provision for depreciation is made on construction in progress until such time as the relevant assets are completed and ready for its
intended use. When the assets concerned are brought into use, the costs are transferred to property, plant and equipment and depreciated
in accordance with the policy as stated in Note 2(g).
(i) Goodwill
Goodwill represents the excess of the cost of an acquisition over the fair value of the Group’s share of the net identifiable assets of
the acquired subsidiary/business at the date of acquisition, or the excess of fair value of business over its fair value of the net identifiable
assets injected into the Company upon its formation. If the cost of acquisition is less than the fair value of the Group’s share of the net
identifiable assets of the acquired subsidiary, the difference is recognized directly in the consolidated income statements.
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Goodwill is retained at the carrying amount as a separate asset, and subject to impairment test annually and when there are
indications that the carrying value may not be recoverable.
The profit or loss on disposal of a subsidiary is calculated by reference to the net assets at the date of disposal including the
attributable amount of goodwill.
(j) Other Intangible Assets
The Group’s other intangible assets mainly include distribution network and drugs licenses contributed from non-controlling
shareholders. Other intangible assets have a definite useful life and are carried at historical cost less accumulated amortization and
accumulated impairment losses, if any. Amortization is calculated using the straight-line method to allocate costs over the estimated
useful lives of ten years.
(k) Research and Development
Research expenditure is recognized as an expense as incurred. Costs incurred on development projects (relating to the design and
testing of new or improved products) are recognized as intangible assets when it is probable that the project will generate future economic
benefits by considering its commercial and technological feasibility, and costs can be measured reliably. Other development
expenditures are recognized as an expense as incurred. Development costs previously recognized as an expense are not recognized as
an asset in a subsequent period. Development costs with a finite useful life that have been capitalized, if any, are amortized on a
straight-line basis over the period of expected benefit not exceeding five years. The capitalized development costs are reviewed for
impairment whenever events or changes in circumstances indicate that the carrying amount of an asset exceeds its recoverable amount.
Where the research phase and the development phase of an internal project cannot be clearly distinguished, all expenditure incurred
on the project is charged to the consolidated income statements.
(l) Impairment of Non-Financial Assets
Assets are reviewed for impairment to determine whether there is any indication that the carrying value of these assets may not be
recoverable and have suffered an impairment loss. If any such indication exists, the recoverable amount of the asset is estimated in order
to determine the extent of the impairment loss, if any. The recoverable amount is the higher of an asset’s fair value less costs to sell and
value in use. Such impairment loss is recognized in the consolidated income statements. Assets that have an indefinite useful life such
as goodwill or intangible assets not ready to use are not subject to amortization and are tested for impairment annually and when there
are indications that the carrying value may not be recoverable.
(m) Non-current Assets (or Disposal Groups) Classified As Held For Sale
Non-current assets (or disposal groups) are classified as held for sale when their carrying amount is to be recovered principally
through a sale transaction and a sale is considered highly probable. The non-current assets (or disposal groups) except for certain assets
as explained below, are stated at the lower of carrying amount and fair value less costs to sell. Deferred tax assets, and financial assets
(other than investments in subsidiaries and associates), which are classified as held for sale, would continue to be measured in accordance
with the policies set out elsewhere in Note 2.
(n) Inventories
Inventories are stated at the lower of cost or net realizable value. Cost is determined using the weighted average cost method. The
cost of finished goods comprises raw materials, direct labor, other direct costs and related production overheads (based on normal
operating capacity). Net realizable value is the estimated selling price in the ordinary course of business, less applicable variable selling
expenses.
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(o) Trade and Other Receivables
Trade and other receivables are recognized initially at fair value, which is the amount of consideration that is unconditional. Trade
and other receivables solely represent payments of principal and interest, if any, and the Group holds such financial assets with the
objective to collect its contractual cash flows. Therefore, the Group measures them subsequently at amortized cost using the effective
interest method, less any loss allowance. The Group applies the IFRS 9 simplified approach to measuring expected credit losses which
uses a lifetime expected loss allowance for all trade receivables. To measure the expected credit losses, trade receivables have been
grouped based on shared credit risk characteristics and the days past due. All other receivables at amortized cost are considered to have
low credit risk, and the loss allowance recognized during the period was therefore limited to 12 months expected losses. The amount of
the provision is recognized in the consolidated income statements.
(p) Cash and Cash Equivalents
In the consolidated statements of cash flows, cash and cash equivalents include cash on hand, bank deposits and other short-term
highly liquid investments with original maturities of three months or less that are readily convertible to known amounts of cash and
which are subject to an insignificant risk of changes in value, if any.
(q) Financial Liabilities and Equity Instruments
Financial liabilities and equity instruments issued by the Group are classified according to the substance of the contractual
arrangements entered into and the definitions of a financial liability and an equity instrument. Financial liabilities (including trade and
other payables) are initially measured at fair value, and are subsequently measured at amortized cost, using the effective interest method.
An equity instrument is any contract that does not meet the definition of financial liability and evidences a residual interest in the assets
of the Group after deducting all of its liabilities.
Ordinary shares are classified as equity. Incremental costs, net of tax, directly attributable to the issue of new shares are shown in
equity as a deduction from the proceeds.
(r) Current and Deferred Income Tax
(i) Current income tax
The current income tax charge is calculated on the basis of the tax laws enacted or substantively enacted at the balance sheet date
in the country where the Group operates and generates taxable income. Management periodically evaluates positions taken in tax returns
with respect to situations in which applicable tax regulation is subject to interpretation. It establishes provisions where appropriate on
the basis of amounts expected to be paid to the tax authorities.
(ii) Deferred income tax
Inside basis differences
Deferred income tax is recognized, using the liability method, on temporary differences arising between the tax bases of assets and
liabilities and their carrying amounts in the consolidated financial statements. However, deferred tax liabilities are not recognized if they
arise from the initial recognition of goodwill and deferred income tax is not accounted for if it arises from initial recognition of an asset
or liability in a transaction other than a business combination that at the time of the transaction affects neither accounting nor taxable
profit or loss. Deferred income tax is determined using tax rates (and laws) that have been enacted or substantively enacted by the
balance sheet date and are expected to apply when the related deferred income tax asset is realized or the deferred income tax liability
is settled.
Deferred income tax assets are recognized only to the extent that it is probable that future taxable profit will be available against
which the temporary differences can be utilized. Deferred income tax assets and deferred income tax liabilities are offset when there is
a legally enforceable right to set off and when the deferred income taxes related to the same fiscal authority.
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Outside basis differences
Deferred income tax liabilities are provided on taxable temporary differences arising from investments in subsidiaries, associates
and joint arrangements, except for deferred income tax liabilities where the timing of the reversal of the temporary difference is
controlled by the Group and it is probable that the temporary difference will not reverse in the foreseeable future. Generally the Group
is unable to control the reversal of the temporary difference for associates. Only when there is an agreement in place that gives the Group
the ability to control the reversal of the temporary difference in the foreseeable future, deferred tax liability in relation to taxable
temporary differences arising from the associate’s undistributed profits is not recognized.
Deferred income tax assets are recognized on deductible temporary differences arising from investments in subsidiaries, associates
and joint arrangements only to the extent that it is probable the temporary difference will reverse in the future and there is sufficient
taxable profit available against which the temporary difference can be utilized.
(s) Employee Benefits
The employees of the Group participate in defined contribution retirement benefit plans managed by the relevant municipal and
provincial governments in the PRC. The assets of these plans are held separately from the Group. The Group is required to make monthly
contributions to the plans, calculated as a percentage of the employees’ salaries. The municipal and provincial governments undertake
to assume the retirement benefit obligations to all existing and future retired employees under the plans described above. Other than
the monthly contributions, the Group has no further obligations for the payment of the retirement and other post-retirement benefits of
its employees.
(t) Provisions
Provisions are recognized when the Group has a present legal or constructive obligation as a result of past events, it is probable that
an outflow of resources will be required to settle the obligation, and the amount has been reliably estimated. Provisions are not recognized
for future operating losses.
(u) Leases
The Group adopted IFRS 16 retrospectively from January 1, 2019, but has not restated comparatives for the 2018 reporting period,
as permitted under the specific transitional provisions in the standard. The reclassifications and the adjustments arising from the new
leasing rules are therefore recognized in the opening balance sheet on January 1, 2019.
Right-of-use assets were measured on transition as if the new rules had always been applied. As a result, the Group has recognized
a gross up to the consolidated statement of financial position on the date of adoption of US$0.6 million and US$0.6 million in right-of-
use assets and lease liabilities respectively, primarily related to the Group’s various warehouses under non-cancellable lease agreements
that were accounted as operating leases under IAS 17 as at December 31, 2018.
Under IFRS 16
A lease is recognized as a right-of-use asset with a corresponding liability at the date which the leased asset is available for use by
the Group. The Group recognizes an obligation to make lease payments equal to the present value of the lease payments over the lease
term. The lease terms may include options to extend or terminate the lease when it is reasonably certain that the Group will exercise that
option.
F-86
Lease liabilities include the net present value of the following lease payments: (i) fixed payments; (ii) variable lease payments that
depend on an index or a rate; and (iii) payments of penalties for terminating the lease if the lease term reflects the lessee exercising that
option, if any. Lease liabilities exclude the following payments that are generally accounted for separately: (i) non-lease components,
such as maintenance and security service fees and value added tax, and (ii) any payments that a lessee makes before the lease
commencement date. The lease payments are discounted using the interest rate implicit in the lease or if that rate cannot be determined,
the lessee’s incremental borrowing rate being the rate that the lessee would have to pay to borrow the funds in its currency and
jurisdiction necessary to obtain an asset of similar value, economic environment and terms and conditions.
An asset representing the right to use the underlying asset during the lease term is recognized that consists of the initial measurement
of the lease liability, any lease payments made to the lessor at or before the commencement date less any lease incentives received, any
initial direct cost incurred by the Group and any restoration costs.
After commencement of the lease, each lease payment is allocated between lease liability and finance costs. The finance costs are
recognized over the lease term so as to produce a constant periodic rate of interest on the remaining balance of the lease liability for
each period. The right-of-use asset is depreciated on a straight-line basis over the period of the lease.
Payments associated with short-term leases are recognized as lease expenses on a straight-line basis over the period of the leases.
Leasehold land is accounted under IFRS 16.
The lease liabilities were measured at the present value of the remaining lease payments, discounted using the lessees’ incremental
borrowing rate as at January 1, 2019. The Group’s weighted average incremental borrowing rate applied on January 1, 2019 was 4.75%
per annum.
A reconciliation of the Group’s reported operating lease commitments as at December 31, 2018 and the Group’s lease liabilities
recognized upon adoption of IFRS 16 as at January 1, 2019 was as follows:
Operating lease commitments as at December 31, 2018 (note)
Less: Short-term leases
Less: Discount under the lessees’ incremental borrowing rate as at January 1, 2019
Lease liabilities recognized as at January 1, 2019
(in US$’000)
1,232
(535)
(60)
637
Note: Future aggregate minimum payments under non-cancellable operating leases under IAS 17 were as follows:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Between 3 to 4 years
December 31, 2018
(in US$’000)
885
144
151
52
1,232
The Group recognized right-of-use assets as at January 1, 2019 measured at their carrying amounts as if IFRS 16 had been applied
since their commencement dates, but discounted using the lessees’ incremental borrowing rate as at January 1, 2019.
Recognized right-of-use assets upon adoption, excluding leasehold land, were warehouses of US$0.6 million.
There were no adjustments to net cash generated from/(used in) operating activities, investing activities or financing activities in
the consolidated statement of cash flows.
F-87
In applying IFRS 16 for the first time, the Group used the following practical expedients permitted by the standard: (i) no
reassessment of whether any expired or existing contracts are or contain leases; (ii) no reassessment of the lease classification for any
expired or existing leases; (iii) the exclusion of initial direct costs for the measurement of the right-of-use assets at the date of initial
application; and (iv) the use of hindsight in determining the lease term where the contract contains options to extend or terminate the
lease.
Under IAS 17
The Group's accounting policy for leases before January 1, 2019 is detailed below.
Leases that transfer substantially all the rewards and risks of ownership of the assets to the Group, other than legal title, are accounted
for as finance leases. At the inception of a finance lease, the cost of the leased asset is capitalized at the present value of the minimum
lease payments and recorded together with the obligation, excluding the interest element, to reflect the purchase and financing. Assets
held under capitalized finance leases, including prepaid land lease payments under finance leases, are included in property, plant and
equipment, and depreciated over the shorter of the lease terms and the estimated useful lives of the assets. The finance costs of such
leases are charged to the consolidated income statements so as to provide a constant periodic rate of charge over the lease terms.
Leases in which a significant portion of the risks and rewards of ownership are retained by the lessor are classified as operating
leases. Payments made under operating leases are charged to the consolidated income statements on a straight-line basis over the period
of the leases.
(v) Government Incentives
Incentives from government are recognized at their fair values where there is a reasonable assurance that the incentives will be
received and all attached conditions will be complied with.
Government incentives relating to costs are deferred and recognized in the consolidated income statements over the period necessary
to match them with the costs that they are intended to compensate.
Government grants relating to property, plant and equipment are included in other payables, accruals and advance receipts and
non-current liabilities as deferred income and credited to the consolidated income statements on a straight-line basis over the expected
lives of the related assets.
(w) Revenue and Income Recognition
The Group principally generates revenue from sales of goods. Revenue from sales of goods is recognized when the customer takes
possession of the goods. This usually occurs upon completed delivery of the goods to the customer site. The amount of revenue
recognized is adjusted for expected sales incentives as stipulated in the contract, which are generally issued to customers as direct
discounts at the point-of-sale or indirectly in the form of rebates. Sales incentives are estimated using the expected value method.
Additionally, sales are generally made with a limited right of return under certain conditions. Revenues are recorded net of provisions
for sales discounts and returns.
Revenue from provision of services is recognized when the benefits of the services transfer to the customer over time, which is
based on the proportionate value of services rendered as determined under the terms of the relevant contract. Additionally, when the
amounts that can be invoiced correspond directly with the value to the customer for performance completed to date, the Group recognizes
revenue from provision of services based on amounts that can be invoiced to the customer.
Payments in advance from customers are deferred if consideration is received in advance of transferring control of the goods or
rendering of services. Accounts receivable is recognized if the Group has an unconditional right to bill the customer, which is generally
when the customer takes possession of the goods or services are rendered. Payment terms differ by subsidiary and customer, but
generally range from 45 to 180 days from the invoice date.
(x) Interest income
Interest income is recognized on a time-proportion basis using the effective interest method.
F-88
(y) Segment Reporting
Operating segments are reported in a manner consistent with the internal reporting provided to the chief operating decision-makers.
The Company’s Board of Directors, which is responsible for allocating resources and assessing performance of the operating segments,
has been identified as the steering committee that makes strategic decisions.
(z) General Reserves
In accordance with the laws applicable to Foreign Investment Enterprises established in the PRC, the Company makes
appropriations to certain non-distributable reserve funds including the general reserve fund, the enterprise expansion fund and the staff
bonus and welfare fund. The amount of appropriations to these funds are made at the discretion of the Company’s Board of Directors.
3. Financial Risk Management
(a) Financial risk factors
The Group’s activities expose it to a variety of financial risks, including credit risk and liquidity risk. The Group does not use any
derivative financial instruments for speculative purposes.
(i) Credit risk
The carrying amounts of cash and cash equivalents, trade receivables (including bills receivables) and other receivables included in
the consolidated statements of financial position represent the Group’s maximum exposure to credit risk of the counterparty in relation
to its financial assets.
Substantially all of the Group’s cash and cash equivalents are deposited in major financial institutions, which management believes
are of high credit quality.
Bills receivables are mostly settled by state-owned banks or other reputable banks and therefore the management considers that
they will not expose the Group to any significant credit risk.
The Group has no significant concentrations of credit risk. The Group has policies in place to ensure that the sales of products are
made to customers with appropriate credit history and the Group performs periodic credit evaluations of its customers.
Management periodically assesses the recoverability of trade receivables and other receivables. The Group’s historical loss rates
are adjusted to reflect current and forward-looking information on specific factors affecting the ability of the customers to settle the
receivables, and historical experience collecting receivables falls within the recorded allowances.
(ii) Liquidity risk
Prudent liquidity management implies maintaining sufficient cash and cash equivalents and the availability of funding when
necessary. The Group’s policy is to regularly monitor current and expected liquidity requirements to ensure that it maintains sufficient
cash balances and adequate credit facilities to meet its liquidity requirements in the short and long term.
As at December 31, 2020 and 2019, the Group’s current financial liabilities were mainly due for settlement within twelve months
and the Group expects to meet all liquidity requirements. Additionally, the Group’s financial liabilities include current and non-current
dividends payable to shareholders (refer to Note 24(b)), for which shareholders will only require settlement when sufficient cash and
cash equivalents are available.
(b) Capital risk management
The Group’s objectives when managing capital are to safeguard the Group’s ability to provide returns for shareholders and benefits
for other stakeholders and to maintain an optimal capital structure to reduce the cost of capital.
F-89
The Group regularly reviews and manages its capital structure to ensure an optimal balance between higher shareholders’ return
that might be possible with higher levels of borrowings and the advantages and security afforded by a sound capital position, and makes
adjustments to the capital structure in light of changes in economic conditions.
The Group monitors capital on the basis of the liabilities to assets ratio. This ratio is calculated as total liabilities divided by total
assets as shown on the consolidated statements of financial position.
Currently, it is the Group’s strategy to maintain a reasonable liabilities to assets ratio. The liabilities to assets ratio as at
December 31, 2020 and 2019 was as follows:
Total liabilities
Total assets
Liabilities to assets ratio
(c) Fair value estimation
December 31,
2020
2019
(in US$’000)
153,213
273,581
172,741
219,772
56.0 %
78.6 %
The Group does not have any financial assets or liabilities which are carried at fair value. The carrying amounts of the Group’s
current financial assets, including cash and cash equivalents, trade and bills receivables and other receivables, and current financial
liabilities, including trade payables, and other payables and accruals and dividend payable, approximate their fair values due to their
short-term maturities. The carrying amounts of the Group’s financial instruments carried at cost or amortized cost are not materially
different from their fair values.
The face values less any estimated credit adjustments for financial assets and liabilities with a maturity of less than one year are
assumed to approximate their fair values. The fair value of financial liabilities for disclosure purposes is estimated by discounting the
future contractual cash flows at the current market interest rate that is available to the Group for similar financial instruments.
4. Critical Accounting Estimates and Judgements
Note 2 includes a summary of the significant accounting policies used in the preparation of the consolidated financial statements.
The preparation of consolidated financial statements often requires the use of judgements to select specific accounting methods and
policies from several acceptable alternatives. Furthermore, significant estimates and assumptions concerning the future may be required
in selecting and applying those methods and policies in the consolidated financial statements. The Group bases its estimates and
judgements on historical experience and various other assumptions that it believes are reasonable under the circumstances. Actual results
may differ from these estimates and judgements under different assumptions or conditions.
The following is a review of the more significant assumptions and estimates, as well as the accounting policies and methods used
in the preparation of the consolidated financial statements.
(a) Sales rebates
Certain sales rebates are provided to customers when their business performance for the whole year meets certain criteria as
stipulated in the contracts. Sales rebates are considered variable consideration and the estimate of sales rebates during the year is based
on estimated sales transactions for the entire period stipulated and is subject to change based on actual performance and collection status.
(b) Useful lives of property, plant and equipment
The Group has made substantial investments in property, plant and equipment. Changes in technology or changes in the intended
use of these assets may cause the estimated period of use or value of these assets to change.
F-90
(c) Impairment of non-financial assets
The Group tests at least annually whether goodwill has suffered any impairment. Other non-financial assets are reviewed for
impairment whenever events or changes in circumstances indicate that the carrying amount of the asset exceeds its recoverable amount
in accordance with the accounting policy stated in Note 2(l). The recoverable amount of an asset or a cash-generating unit is determined
based on the higher of the asset’s or the cash-generating unit’s fair value less costs to disposal and value-in-use. The value-in-use
calculation requires the entity to estimate the future cash flows expected to arise from the asset and a suitable discount rate in order to
calculate present value, and the growth rate assumptions in the cash flow projections which has been prepared on the basis of
management’s assumptions and estimates.
(d) Deferred income tax
Deferred tax is recognized using the liability method on temporary differences arising between the tax bases of assets and liabilities
against which the deductible temporary differences and the carry forward of unused tax losses and tax credits can be utilized. Deferred
income tax assets are recognized only to the extent that it is probable that future taxable profit will be available against which the
temporary differences can be utilized. Where the final outcomes are different from the estimations, such differences will impact the
carrying amount of deferred tax in the period in which such determination is made.
(e) Return of land to the government
In June 2020, the Group entered into an agreement with the government to return the land use right for a plot of land in Guangzhou
to the government for cash consideration of up to RMB683.0 million (approximately US$101.2 million) (the “Land Compensation
Agreement”). In November 2020, the Group determined that it had completed the return of land (Note 8). All material obligations as
stipulated in the Land Compensation Agreement had been completed by November 2020, and since there were no further material
obligations to be fulfilled by the Group and there was no recoverability risk on the receivable, control of the land had been passed to the
government. RMB569.2 million (approximately US$86.1 million) of the consideration has been recognized as at December 31, 2020.
The remaining RMB113.8 million (approximately US$17.4 million) conditional consideration will be recognized upon the receipt
of a completion confirmation from the government within 12 months from the date of the Land Compensation Agreement. The remaining
procedures to complete the transaction are administrative processes of the government and are considered perfunctory. If the final
outcome is different from these judgements, it will impact the timing and amount of gain recognized.
5. Revenue and Segment Information
Management has reviewed the Group’s internal reporting in order to assess performance and allocate resources, and has determined
that the Group has two reportable operating segments as follows:
—Manufacturing business—manufacture and distribution of drug products
—Distribution business—provision of sales, distribution and marketing services to pharmaceutical manufacturers
The operating segments are strategic business units that offer different products and services. They are managed separately because
each business requires different technology and marketing approaches. The performance of each of the reportable segments is assessed
based on operating profit.
F-91
The segment information is as follows:
Year Ended December 31, 2020
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
Revenue from external customers
Interest income
Operating profit
Share of losses of joint venture and associated companies, net of tax
Finance costs
Depreciation/amortization
Additions to non‑current assets (other than financial instruments and
deferred tax assets)
215,427
188
20,833
84
51
6,361
16,941 232,368
271
23,145
84
57
6,484
83
2,312
—
6
123
2,432
1
2,433
Total segment assets
Revenue from external customers
Interest income
Operating profit
Share of profits of joint venture and associated companies, net of
tax
Finance costs
Depreciation/amortization
Additions to non‑current assets (other than financial instruments and
deferred tax assets)
December 31, 2020
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
243,578
30,003 273,581
Year Ended December 31, 2019
Manufacturing Distribution
business
PRC
202,852
76
21,738
business
PRC
(in US$’000)
Total
12,551 215,403
160
22,920
84
1,182
60
40
6,411
4,002
—
19
125
60
59
6,536
—
4,002
Total segment assets
December 31, 2019
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
193,732
26,040 219,772
F-92
Revenue from external customers
Interest income
Operating profit
Share of profits of joint venture and associated companies, net of
tax
Finance costs
Depreciation/amortization
Additions to non‑current assets (other than financial instruments and
deferred tax assets)
Year Ended December 31, 2018
Manufacturing Distribution
business
PRC
business
PRC
(in US$’000)
Total
205,949
53
19,988
9,889 215,838
81
20,724
28
736
131
152
5,956
3,471
—
—
9
131
152
5,965
—
3,471
Revenue from external customers is after elimination of inter-segment sales. The amount eliminated was US$0.1 million for 2020
(2019: US$0.7 million; 2018: US$1.9 million). Sales between segments are carried out at mutually agreed terms. Revenue from external
customers is primarily for sales of goods which are recognized at a point in time, except for provision of services which are recognized
over time of US$3.7 million in 2020 (2019: US$3.1 million; 2018: US$3.4 million) and included in the manufacturing business operating
segment.
6. Other Net Operating Income
2018
2020
Year Ended December 31,
2019
(in US$’000)
160
—
(162)
6,226
(598)
5,626
271
166
(643)
6,734
(457)
6,071
81
—
(103)
4,332
(225)
4,085
2020
Year Ended December 31,
2019
(in US$’000)
22,920
2018
20,724
23,145
Interest income
Gain on disposal of leasehold land
Loss on disposal of property, plant and equipment
Other operating income
Other operating expenses
7. Operating Profit
Operating profit
F-93
Operating profit is stated after charging/(crediting) the following:
2020
Year Ended December 31,
2019
(in US$’000)
2018
Cost of inventories recognized as expense
Depreciation of property, plant and equipment
Impairment of property, plant and equipment
Loss on disposal of property, plant and equipment
Gain on disposal of leasehold land
Amortization of leasehold land
Amortization of other intangible assets
Depreciation charge of right-of-use assets and lease expenses
Movements on the provision for trade receivables
Movements on the provision for excess and obsolete inventories
Research and development expense
Auditor’s remuneration
Employee benefit expenses (Note 10)
100,906
5,283
—
643
(166)
236
414
1,438
(20)
474
1,670
88
36,822
85,802 89,939
5,348
5,417
—
525
103
162
—
—
256
230
361
351
1,180
1,227
19
(70)
769
314
823
1,041
81
87
34,634 33,454
8. Gain on return of land
In November 2020, the Group completed all material obligations as stipulated in the Land Compensation Agreement including the
deregistration of the land use right certificate. Therefore, the Group has recorded the return of leasehold land to the government for
RMB569.2 million (approximately US$86.1 million), resulting in a gain of RMB559.7 million (approximately US$84.7 million) after
deducting costs of RMB1.7 million (approximately US$0.3 million) to the Group. As at December 31, 2020, the Group has received
RMB284.6 million (approximately US$40.4 million) and has recorded RMB284.6 million (approximately US$43.4 million) in other
receivables, prepayments and deposits (Note 13). The remaining RMB113.8 million (approximately US$17.4 million) of cash
consideration is conditional upon the receipt of a completion confirmation from the government within 12 months from the date of the
Land Compensation Agreement and therefore has not been recognized as at December 31, 2020.
9. Taxation Charge
Current tax
Deferred income tax (Note 17)
Taxation charge
2018
2020
Year Ended December 31,
2019
(in US$’000)
3,925
(291)
3,634
17,108
(614)
16,494
3,930
297
4,227
The taxation charge on the Group’s profit before taxation differs from the theoretical amount that would arise using the Group’s
weighted average tax rate as follows:
2020
Year Ended December 31,
2019
(in US$’000)
2018
Profit before taxation
Tax calculated at the statutory tax rates of respective companies
Tax effects of:
Expenses not deductible for tax purposes
Tax concession (note)
Tax losses for which no deferred tax assets were recognized
Under/(over) provision in prior years
Others
Taxation charge
F-94
107,708
26,927
22,921 20,703
5,176
5,730
66
(10,454)
339
44
(428)
16,494
56
104
(2,569) (2,159)
1,005
107
(6)
4,227
522
(17)
(88)
3,634
Note: The Company has been granted the High and New Technology Enterprise status. Accordingly, the Company is
subject to a preferential income tax rate of 15% and renewed the status in 2020 (2019: 15%; 2018: 15%). Certain research
and development expenses are also eligible for super-deduction such that 175% (2019: 175%; 2018: 175%) of qualified
expenses incurred are deductible for tax purposes.
The weighted average tax rate calculated at the statutory tax rates of respective companies for the year was 25% (2019: 25%; 2018:
25%). The effective tax rate for the year was 15.3% (2019: 15.9%; 2018: 20.4%).
10. Employee Benefit Expenses
Wages, salaries and bonuses
Pension costs—defined contribution plans
Staff welfare
2020
2018
Year Ended December 31,
2019
(in US$’000)
25,066
8,282
1,286
34,634
23,910
8,408
1,136
33,454
28,380
6,954
1,488
36,822
Employee benefit expenses of approximately US$11.1 million (2019: US$11.4 million; 2018: US$9.2 million) are included in cost
of sales.
11. Cash and Cash Equivalents
Cash and cash equivalents
December 31,
2020
2019
(in US$’000)
16,602
21,421
The cash and cash equivalents denominated in RMB were deposited with banks in the PRC. The conversion of these RMB
denominated balances into foreign currencies is subject to the rules and regulations of foreign exchange control promulgated by the
PRC government.
12. Trade and Bills Receivables
Trade receivables—third parties
Trade receivables—related parties (Note 24(b))
Bills receivables
December 31,
2020
2019
(in US$’000)
1,764
3,485
62,168
67,417
1,896
1,770
44,607
48,273
All trade and bills receivables are denominated in RMB and are due within one year from the end of the reporting period. The
carrying values of trade and bills receivables approximate their fair values due to their short-term maturities.
Movements on the provision for trade receivables are as follows:
As at January 1
Increase in provision for trade receivables
Decrease in provision due to subsequent collection
Exchange differences
As at December 31
2020
19
—
(20)
1
—
2019
(in US$’000)
90
5
(75)
(1)
19
2018
75
78
(59)
(4)
90
The impaired and provided receivables as at December 31, 2019 were aged over 1 year.
F-95
13. Other Receivables, Prepayments and Deposits
Prepayments to suppliers
Value‑added tax receivables
Land compensation receivable
Others
14. Inventories
Raw materials
Work in progress
Finished goods
15. Property, Plant and Equipment
a
Cost
As at January 1, 2020
Additions
Disposals
Disposal of a subsidiary
Transfers
Exchange differences
As at December 31, 2020
Accumulated depreciation
As at January 1, 2020
Depreciation
Disposals
Disposal of a subsidiary
Exchange differences
As at December 31, 2020
Net book value
As at December 31, 2020
December 31,
2020
2019
(in US$’000)
4,784
538
43,414
1,385
50,121
7,098
597
—
898
8,593
December 31,
2020
2019
(in US$’000)
13,063
17,303
13,382
43,748
15,681
15,602
15,134
46,417
Buildings
and
Plant and
facilities equipment
Construction
in progress
Total
Furniture and
fixtures, other
equipment
and motor
vehicles
(in US$’000)
59,099
224
(2,204)
(28)
28
4,148
61,267
14,021
2,201
(926)
(10)
1,082
16,368
25,426
168
(187)
—
502
1,860
27,769
14,096
1,520
(150)
—
1,093
16,559
11,353
651
(522)
(27)
318
842
12,615
8,755
1,562
(464)
(23)
692
10,522
1,311
1,390
97,189
2,433
— (2,913)
(55)
—
—
(848)
6,976
126
103,630
1,979
— 36,872
5,283
—
— (1,540)
(33)
—
—
2,867
— 43,449
44,899
11,210
2,093
1,979
60,181
F-96
Cost
As at January 1, 2019
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2019
Accumulated depreciation
As at January 1, 2019
Depreciation
Disposals
Impairment
Exchange differences
As at December 31, 2019
Net book value
As at December 31, 2019
Cost
As at January 1, 2018
Additions
Disposals
Transfers
Exchange differences
As at December 31, 2018
Accumulated depreciation
As at January 1, 2018
Depreciation
Disposals
Exchange differences
As at December 31, 2018
Net book value
As at December 31, 2018
Buildings
and
Plant and
facilities equipment
Construction
in progress
Total
Furniture and
fixtures, other
equipment
and motor
vehicles
(in US$’000)
61,319
158
(1,005)
227
(1,600)
59,099
12,739
2,299
(887)
241
(371)
14,021
25,866
415
(673)
502
(684)
25,426
12,929
1,569
(294)
267
(375)
14,096
10,700
533
(319)
741
(302)
11,353
7,707
1,549
(287)
17
(231)
8,755
1,423
1,395
99,308
2,501
— (1,997)
—
(2,623)
97,189
(1,470)
(37)
1,311
— 33,375
— 5,417
— (1,468)
525
—
—
(977)
— 36,872
45,078
11,330
2,598
1,311
60,317
Buildings
and
Plant and
facilities equipment
Construction
in progress
Total
Furniture and
fixtures, other
equipment
and motor
vehicles
(in US$’000)
63,378
228
—
399
(2,686)
61,319
10,880
2,406
—
(547)
12,739
26,720
539
(343)
82
(1,132)
25,866
12,110
1,626
(249)
(558)
12,929
8,494
1,607
(47)
1,101
(455)
10,700
6,758
1,316
(38)
(329)
7,707
1,973
1,097
—
(1,582)
(65)
1,423
100,565
3,471
(390)
—
(4,338)
99,308
— 29,748
5,348
—
—
(287)
— (1,434)
— 33,375
48,580
12,937
2,993
1,423
65,933
F-97
16. Leases
Leases consisted of the following:
Right-of-use assets:
Warehouses
Machinery
Lease liabilities—current
Lease liabilities—non-current
Lease activities are summarized as follows:
Lease expenses: Short-term leases with lease terms equal or less than 12
months
Depreciation charge of right-of-use assets
Interest expense (included in finance costs)
Cash paid on lease liabilities
Non-cash: Lease liabilities recognized from obtaining right-of-use assets
December 31,
2020
2019
(in US$’000)
820
—
820
568
303
871
1,268
257
1,525
611
960
1,571
Year Ended
December 31,
2020
2019
(in US$’000)
887
551
57
609
—
689
538
59
556
1,145
Lease contracts are typically within a period of 1 to 6 years. The weighted average remaining lease term and weighted average
discount rate as at December 31, 2020 was 1.56 years (2019: 2.51 years) and 4.75% (2019: 4.77%) respectively.
Future lease payments are as follows:
Lease payments:
Not later than 1 year
Between 1 to 2 years
Between 2 to 3 years
Total lease payments
Less: Discount factor
Total lease liabilities
17. Deferred Tax Assets and Liabilities
Deferred tax assets
Deferred tax liabilities
Net deferred tax assets
December 31,
2020
2019
(in US$’000)
598
307
—
905
(34)
871
671
678
320
1,669
(98)
1,571
December 31,
2020
2019
(in US$’000)
3,141
(114)
3,027
2,323
(106)
2,217
F-98
The movements in net deferred tax assets are as follows:
At January 1
(Debited)/credited to the consolidated income statements
—Tax losses
—Accrued expenses, provisions, depreciation allowances
Exchange differences
At December 31
2020
2,217
2019
(in US$’000)
1,986
(396)
1,010
196
3,027
(27)
318
(60)
2,217
2018
2,375
(867)
570
(92)
1,986
The Group’s deferred tax assets and liabilities are temporary differences including tax losses, accrued expenses, provisions and
depreciation allowances. The potential deferred tax assets in respect of tax losses which have not been recognized in the consolidated
financial statements were approximately US$1.6 million as at December 31, 2020 (2019:US$1.5 million).
These unrecognized tax losses can be carried forward against future taxable income and will expire in the following years:
2020
2021
2022
2023
2024
2025
18. Other Non-Current Assets
Prepayment of leasehold land rights (note)
Others
December 31,
2020
2019
(in US$’000)
—
926
1,836
849
1,334
1,431
6,376
559
873
1,729
792
2,046
—
5,999
December 31,
2020
2019
(in US$’000)
11,160
529
11,689
10,410
80
10,490
Note: Represents prepayments for a land use right. The title of the land is in the process of registration, pending remaining
administrative procedures. The respective prepayments are recorded in other non-current assets until the registration is
completed and title is transferred to the Company. As at December 31, 2020, this process is still in progress and the Group
does not have right to use the land.
19. Trade Payables
Trade payables—third parties
Trade payables—related parties (Note 24(b))
December 31,
2020
2019
(in US$’000)
16,852
5,727
22,579
10,023
2,676
12,699
All trade payables are denominated in RMB and due within one year from the end of the reporting period. The carrying value of
trade payables approximates their fair values due to their short-term maturities.
F-99
20. Other Payables, Accruals and Advance Receipts
Other payables and accruals
Accrued salaries and benefits
Accrued selling and administrative expenses
Value‑added tax and tax surcharge payables
Deposits received
Other payables to manufacturers
Others
Advance receipts
Payments in advance from customers (note)
Deferred government incentives
December 31,
2020
2019
(in US$’000)
4,715
27,872
2,207
5,866
8,794
6,017
55,471
41,963
1,427
43,390
98,861
3,714
15,901
2,471
4,769
11,448
4,831
43,134
17,035
1,708
18,743
61,877
Note: Substantially all customer balances as at December 31, 2019 were recognized to revenue during the year ended
December 31, 2020. Additionally, substantially all customer balances as at December 31, 2020 are expected to be
recognized to revenue within one year upon transfer of goods or services as the contracts have an expected duration of one
year or less.
21. Deferred Income
Deferred government incentives:
Buildings and other non‑current assets
Others
December 31,
2020
2019
(in US$’000)
11,890
3,727
15,617
11,904
3,340
15,244
F-100
22. Notes to the Consolidated Statements of Cash Flows
(a) Reconciliation of profit for the year to net cash generated from operations:
Profit for the year
Adjustments to reconcile profit for the year to net cash generated from
operations
Taxation charge
Finance costs
Interest income
Share of losses/(profits) of a joint venture and associated companies,
net of tax
Depreciation on property, plant and equipment
Depreciation charge of right-of-use assets
Loss on disposal of property, plant and equipment
Gain on return of land
Gain on disposal of leasehold land
Impairment of property, plant and equipment
Amortization of leasehold land
Amortization of other intangible assets
Movement on the provision for trade receivables
Movement on the provision for excess and obsolete inventories
Amortization of deferred income
Gain on divestment of a subsidiary
Exchange differences
Changes in working capital:
Trade and bills receivables
Other receivables, prepayments and deposits
Inventories
Other non-current assets
Trade payables
Other payables, accruals and advance receipts
Total changes in working capital
Net cash generated from operations
(b) Supplemental disclosure for non-cash activities
2020
Year Ended December 31,
2019
(in US$’000)
91,214 19,287 16,476
2018
16,494
57
(271)
3,634
59
(160)
4,227
152
(81)
84
5,283
551
643
(84,667)
(166)
—
236
414
(20)
474
(1,689)
(37)
794
(19,124)
1,902
2,195
—
9,880
36,509
31,362
60,756
(60)
5,417
538
162
—
—
525
230
351
(70)
314
(2,187)
—
(1,120)
(131)
5,348
—
103
—
—
—
256
361
19
769
(1,753)
—
(1,617)
(1,524) (10,330)
1,229
(2,886)
(3,137)
60
(302)
700
119
(2,965)
17,466
5,932
5,045
(683)
29,174
26,237
During the year ended December 31, 2020, there was an increase in accruals made for purchases of property, plant and equipment
of US$0.1 million (2019 and 2018: a decrease of US$0.9 million and US$1.9 million respectively).
23. Capital commitments
The Group had the following capital commitments:
Property, plant and equipment
Contracted but not provided for
December 31,
2020
(in US$’000)
1,633
Capital commitments for property, plant and equipment are mainly for improvements to the Group’s plant.
F-101
24. Significant Related Party Transactions
The Group has the following significant transactions with related parties which were carried out in the normal course of business
at terms determined and agreed by the relevant parties:
(a) Transactions with related parties:
2020
Year Ended December 31,
2019
(in US$’000)
2018
Sales of goods to:
—Fellow subsidiaries of GBPHCL
—A fellow subsidiary of GZHCMHK
Other services income from:
—An equity investee
—Fellow subsidiaries of GBPHCL
Purchase of goods from:
—An equity investee
—Fellow subsidiaries of GBPHCL
Advertising expenses to:
—A fellow subsidiary of GBPHCL
Interest paid to:
—A fellow subsidiary of GBPHCL
—A non-controlling shareholder of a subsidiary
33,535
493
34,028
23,658
210
23,868
23,015
756
23,771
273
6,166
6,439
275
5,913
6,188
—
6,994
6,994
2,317
29,594
31,911
3,216
24,733
27,949
4,349
33,044
37,393
5,733
5,128
7,752
—
5
5
—
16
16
45
21
66
No transactions have been entered into with the directors of the Company (being the key management personnel) during the year
ended December 31, 2020 (2019 and 2018: nil).
F-102
(b) Balances with related parties included in:
Trade and bills receivables
—An equity investee (note (i))
—Fellow subsidiaries of GBPHCL (note (i))
Trade payables
—Fellow subsidiaries of GBPHCL (note (i))
—An equity investee (note (i))
Other receivables—related parties
—Fellow subsidiaries of GBPHCL (note (i))
—An equity investee (note (i))
Other payables, accruals and advance receipts
—Fellow subsidiaries of GZHCMHK (note (i))
—Fellow subsidiaries of GBPHCL (note (i))
—GBPHCL (note (ii))
—An equity investee
Dividend payable - current
—GZHCMHK
—GBPHCL
Dividend payable - non-current
—GZHCMHK
—GBPHCL
Notes:
December 31,
2020
2019
(in US$’000)
305
3,180
3,485
5,043
684
5,727
743
336
1,079
156
5,484
—
—
5,640
—
1,770
1,770
2,579
97
2,676
964
—
964
156
6,154
131
228
6,669
—
—
—
—
—
—
23,481
23,481
46,962
16,190
16,190
32,380
(i) Balances are unsecured, interest-free and repayable on demand. The carrying values of balances with related parties
approximate their fair values due to their short-term maturities.
(ii) Balance is unsecured, interest bearing and repayable on demand. The carrying value of balance with a related party
approximates its fair value due to its short-term maturity.
F-103
25. Particulars of Principal Subsidiaries, a Joint Venture and Associated Companies
Name
Place of
establishment
and
operation
Nominal
value of
registered
capital
Equity
interest
attributable
to the Group
December 31,
2020
2019
(in RMB’000)
2020 2019
Type of legal entity
Principal activity
Hutchison Whampoa Guangzhou Baiyunshan
Chinese Medicine (Bozhou) Co. Ltd
Hutchison Whampoa Guangzhou Baiyunshan
Pharmaceuticals Limited
Hutchison Whampoa Guangzhou Baiyunshan Health
& Wellness Co. Ltd
Hutchison Whampoa Baiyunshan Lai Da
Pharmaceuticals (Shan Tou) Company Limited
("Laida") (note (a))
Fuyang Baiyunshan Hutchison Whampoa Chinese
PRC
100,000
100,000
100 % 100 %
Limited liability company
PRC
10,000
10,000
100 % 100 %
Limited liability company
PRC
10,000
10,000
100 % 100 %
Limited liability company
PRC
10,000
10,000
100 % 70 %
Limited liability company
Medicine Technology Company Limited
PRC
3,650
3,650
75 % 75 %
Limited liability company
Wenshan Baiyunshan Hutchison Whampoa Sanqi
Co. Ltd.
Daqing Baiyunshan Hutchison Whampoa Banlangen
Technology Company Limited
Shen Nong Garden Traditional Chinese Medicine
Museum
Guangzhou Hulu Cultural Communications
Company Limited
Bozhou Baiyunshan Pharmaceuticals Co Ltd
PRC
2,000
2,000
51 % 51 %
Limited liability company
PRC
PRC
PRC
PRC
1,020
1,020
51 % 51 %
Limited liability company
1,000
1,000
100 % 100 % Non‑profit making organization
1,000
— 100 % — %
Limited liability company
500
500
100 % 100 %
Limited liability company
Shen Nong Garden Pharmacy Company Limited
PRC
200
200
100 % 100 %
Limited liability company
Nanyang Baiyunshan Hutchison Whampoa Danshen
R&D Limited ("NYBH") (note (b))
PRC
—
1,000
— % 51 %
Limited liability company
Joint Venture
Qing Yuan Hutchison Whampoa Baiyunshan
Chinese Medicine Company Limited
Associated companies
PRC
1,000
1,000
50 % 50 %
Limited liability company
Linyi Shenghe Jiuzhou Pharmaceuticals Company
Limited
Tibet Linzhi Guangzhou Pharmaceutical
Development Co. Ltd.
PRC
PRC
3,000
3,000
30 % 30 %
Limited liability company
2,000
2,000
20 % 20 %
Limited liability company
Notes:
(a) Acquisition of additional interest in a subsidiary
Manufacture, sales
and distribution of
drug products
Sales and
marketing of drug
products
Health
supplemented food
distribution
Manufacture, sales
and distribution of
drug products
Agriculture and
sales of Chinese
herbs
Agriculture and
sales of Chinese
herbs
Agriculture and
sales of Chinese
herbs
Promote awareness
of Chinese herbs
Promote awareness
of Chinese herbs
Manufacture, sales
and distribution of
drug products
Retail of drug
products, health
foods and
souvenirs
Agriculture and
sales of Chinese
herbs
Agriculture and
sales of Chinese
herbs
Agriculture and
sales of Chinese
herbs
Trading of Chinese
herbs
Laida was a 70% owned subsidiary of the Group. During the year ended December 31, 2020, the Group acquired an additional 30%
interest in Laida for consideration of RMB13.5 million (approximately US$1.9 million) and after the acquisition, it became a
wholly-owned subsidiary of the Group.
(b) Divestment of a subsidiary to non-controlling interest
F-104
In November 2020, the Company completed the divestment of its 51% majority interest in NYBH for consideration of RMB1.
Based on the net liabilities associated with NYBH attributable to the Company of US$72,000, the Company recorded a gain of
US$37,000 upon the divestment.
26. Subsequent Events
The Group evaluated subsequent events through March 4, 2021, which is the date when the consolidated financial statements
were issued.
F-105
NUTRITION SCIENCE PARTNERS LIMITED
F-106
To the Board of Directors and Shareholders of Nutrition Science Partners Limited
Report of Independent Auditors
We have audited the accompanying consolidated financial statements of Nutrition Science Partners Limited and its subsidiary (the
“Company”), which comprise the consolidated statement of financial position as of December 9, 2019, and the related consolidated
income statements, consolidated statements of comprehensive income/(loss), of changes in equity and of cash flows for the period ended
December 9, 2019 and of the year in the period ended December 31, 2018.
Management’s Responsibility for the Consolidated Financial Statements
Management is responsible for the preparation and fair presentation of the consolidated financial statements in accordance with
International Financial Reporting Standards as issued by the International Accounting Standards Board; this includes the design,
implementation, and maintenance of internal control relevant to the preparation and fair presentation of consolidated financial statements
that are free from material misstatement, whether due to fraud or error.
Auditors’ Responsibility
Our responsibility is to express an opinion on the consolidated financial statements based on our audits. We conducted our audits
in accordance with auditing standards generally accepted in the United States of America. Those standards require that we plan and
perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free from material
misstatement.
An audit involves performing procedures to obtain audit evidence about the amounts and disclosures in the consolidated financial
statements. The procedures selected depend on our judgment, including the assessment of the risks of material misstatement of the
consolidated financial statements, whether due to fraud or error. In making those risk assessments, we consider internal control relevant
to the Company’s preparation and fair presentation of the consolidated financial statements in order to design audit procedures that are
appropriate in the circumstances, but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control.
Accordingly, we express no such opinion. An audit also includes evaluating the appropriateness of accounting policies used and the
reasonableness of significant accounting estimates made by management, as well as evaluating the overall presentation of the
consolidated financial statements. We believe that the audit evidence we have obtained is sufficient and appropriate to provide a basis
for our audit opinion.
Opinion
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position
of Nutrition Science Partners Limited and its subsidiary as of December 9, 2019, and the results of their operations and their cash flows
for the period ended December 9, 2019 and of the year in the period ended December 31, 2018, in accordance with International Financial
Reporting Standards as issued by the International Accounting Standards Board.
/s/ PricewaterhouseCoopers
Hong Kong
March 3, 2020
F-107
Nutrition Science Partners Limited
Consolidated Income Statements
(in US$’000)
Service fees charged by a related party
Other research and development costs
Impairment provision
Administrative expenses
Interest income
Profit/(loss) before taxation
Taxation charge
Profit/(loss) for the period/year
Period Ended
December 9,
2019
Note
5
6
7
—
(19)
—
(32)
250
199
—
199
Year Ended
December 31,
2018
(6,973)
(1,361)
(30,000)
(52)
188
(38,198)
—
(38,198)
The accompanying notes are an integral part of these consolidated financial statements.
F-108
Nutrition Science Partners Limited
Consolidated Statements of Comprehensive Income/(Loss)
(in US$’000)
Profit/(loss) for the period/year
Total comprehensive income/(loss) for the period/year
Period Ended
December 9,
2019
199
199
Year Ended
December 31,
2018
(38,198)
(38,198)
The accompanying notes are an integral part of these consolidated financial statements.
F-109
Nutrition Science Partners Limited
Consolidated Statement of Financial Position
(in US$’000)
Assets
Current assets
Cash and cash equivalents
Other receivables
Total assets
Liabilities and shareholders’ equity
Current liabilities
Other payables and accruals
Amounts due to related parties
Total liabilities
Shareholders’ equity
Share capital
Accumulated losses
Total shareholders’ equity
Total liabilities and shareholders’ equity
December 9,
Note
2019
8
9
10
16,769
25
16,794
362
30
392
114,000
(97,598)
16,402
16,794
The accompanying notes are an integral part of these consolidated financial statements.
F-110
Nutrition Science Partners Limited
Consolidated Statements of Changes in Equity
(in US$’000)
As at January 1, 2018
Issuance of share capital
Total comprehensive loss
As at December 31, 2018
Total comprehensive income
As at December 9, 2019
Share
capital
98,000
16,000
–
114,000
–
114,000
Accumulated
losses
(59,599)
–
(38,198)
(97,797)
199
(97,598)
Total
equity
38,401
16,000
(38,198)
16,203
199
16,402
The accompanying notes are an integral part of these consolidated financial statements.
F-111
Nutrition Science Partners Limited
Consolidated Statements of Cash Flows
(in US$’000)
Operating activities
Profit/(loss) for the period/year
Impairment provision
Changes in working capital:
Other receivables
Other payables and accruals
Amounts due to related parties
Net cash used in operating activities
Financing activities
Proceeds from issuance of share capital
Net cash generated from financing activities
Net (decrease)/increase in cash and cash equivalents
Cash and cash equivalents
Cash and cash equivalents at beginning of period/year
Cash and cash equivalents at end of period/year
Period Ended
December 9,
2019
Year Ended
December 31,
2018
Note
6
10
199
—
(25)
(682)
(43)
(551)
—
—
(551)
17,320
16,769
(38,198)
30,000
—
755
(877)
(8,320)
16,000
16,000
7,680
9,640
17,320
The accompanying notes are an integral part of these consolidated financial statements.
F-112
Nutrition Science Partners Limited
Notes to the Consolidated Financial Statements
1. General Information
Nutrition Science Partners Limited (the “Company”) and its subsidiary (together, the “Group”) are principally engaged in the
research and development of pharmaceutical products. The Company was incorporated in Hong Kong on May 28, 2012 as a limited
liability company. The registered office of the Company is located at 48th Floor, Cheung Kong Center, 2 Queen’s Road Central, Hong
Kong.
On November 27, 2012, Hutchison MediPharma (Hong Kong) Limited (“HMPHK”), a subsidiary of Hutchison China MediTech
Limited (“Chi-Med”, which together with its subsidiaries, hereinafter collectively referred to as the “Chi-Med Group”) and Nestlé Health
Science S.A. (“NHS”), a subsidiary of Nestlé S.A. (“Nestlé”), entered into a joint venture agreement (“JV Agreement”). Pursuant to the
JV Agreement, Nestlé agreed to contribute cash of US$30 million and the Chi-Med Group agreed to contribute assets and business
processes including (i) the global development and commercial rights of a novel, oral therapy drug candidate for Inflammatory Bowel
Disease and (ii) the exclusive rights to its extensive botanical library and well-established botanical research and development platform
in the field of gastrointestinal disease into the Company. The Company was jointly owned by HMPHK and NHS with 50% equity
interest each. On December 9, 2019, HMPHK acquired NHS’ 50% shareholding in the Company from NHS (the “Transaction”) and
terminated the JV Agreement. After the Transaction, the Company became a wholly owned subsidiary of HMPHK.
These consolidated financial statements are presented up to the period ended December 9, 2019 when the Company was a non-
consolidated affiliate of Chi-Med for their inclusion in Chi-Med’s annual report on Form 20-F for the fiscal year ended December 31,
2020. These consolidated financial statements are presented in United States dollars (“US$”), unless otherwise stated and have been
approved for issue by the Company’s Board of Directors (the “Board”) on March 4, 2021.
2. Summary of Significant Accounting Policies
The consolidated financial statements of the Company have been prepared in accordance with International Financial Reporting
Standards (“IFRS”) and interpretations issued by the IFRS Interpretations Committee applicable to companies reporting under IFRS.
The consolidated financial statements comply with IFRS as issued by International Accounting Standards Board (“IASB”). These
consolidated financial statements have been prepared under the historical cost convention.
During the period ended December 9, 2019, the Group has adopted all of the new and revised standards, amendments and
interpretations issued by the IASB that are relevant to the Group’s operations and mandatory for the period beginning January 1, 2019.
The adoption of these new and revised standards, amendments and interpretations did not have any material effects on the Group’s
results of operations or financial position.
(a) Basis of Consolidation
The consolidated financial statements of the Group include the financial statements of the Company and its subsidiary. The financial
statements of the subsidiary are prepared for the same reporting period as the Company, using consistent accounting policies. The results
of the subsidiary are consolidated from the date on which the Group obtained control, and will continue to be consolidated until the date
that such control ceases. All intra-group assets and liabilities, equity, income, expenses and cash flows relating to transactions between
members of the Group are eliminated in full on consolidation.
(b) Subsidiary
The subsidiary is an entity over which the Group has control. The Group controls an entity when the Group is exposed to, or has
rights to variable returns from its involvement with the entity and has the ability to affect those returns through its power over the entity.
In the consolidated financial statements, the subsidiary is accounted for as described in Note 2(a) above.
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(c) Foreign Currency Translation
Items included in the financial statements of each of the Group’s companies are measured using the currency of the primary
economic environment in which the entity operates (the “functional currency”). The functional currency of the Company and its
subsidiary as well as the presentation currency of the Group is US$.
Foreign currency transactions are translated into the functional currency using the exchange rates at the dates of the transactions.
Foreign currency gains and losses resulting from the settlement of such transactions and from the translation of monetary assets and
liabilities denominated in foreign currencies at year end exchange rates are generally recognized in the income statement.
(d) Segment Reporting
The Group has one operating segment which conducts research and development activities. All segment assets are located in Hong
Kong. The Board has been identified as the Group’s chief operating decision-maker and reviews the consolidated results of the Group
for the purposes of resource allocation and performance assessment. Therefore, no additional reportable segment and geographical
information has been presented.
(e) Intangible Assets
Intangible assets acquired separately are measured on initial recognition at cost. The useful lives of intangible assets are assessed
to be either finite or indefinite. Intangible assets with finite lives are subsequently amortized over the useful economic life and assessed
for impairment whenever there is an indication that the intangible asset may be impaired. The amortization period and the amortization
method for an intangible asset with a finite useful life are reviewed at least annually. The Group has no intangible assets with indefinite
lives.
(f) Research and Development Costs
All research costs are charged to the consolidated income statements as incurred.
Expenditures incurred on projects to develop new products are capitalized and deferred only when the Group can demonstrate the
technical feasibility of completing the intangible asset so that it will be available for use or sale, its intention to complete and its ability
to use or sell the asset, how the asset will generate future economic benefits, the availability of resources to complete the project and the
ability to measure the expenditure reliably during the development. Product development expenditures which do not meet these criteria
are expensed when incurred.
(g) Cash and Cash Equivalents
In the consolidated statements of cash flows, cash and cash equivalents comprise cash at bank.
(h) Provisions
Provisions are recognized when the Group has a present legal or constructive obligation as a result of past events; it is probable that
an outflow of resources will be required to settle the obligation; and the amount has been reliably estimated. Provisions are not
recognized for future operating losses.
(i) Income Tax
The current tax charge is calculated on the basis of the tax laws enacted or substantively enacted at the balance sheet date in the
countries where the Company and its subsidiary operate and generate taxable income. Management periodically evaluates positions
taken in tax returns with respect to situations in which applicable tax regulation is subject to interpretation and establish provisions
where appropriate on the basis of amounts expected to be paid to the tax authorities.
F-114
3. Financial Risk Management
(i) Financial Risk Factors
The Group’s activities expose it to a variety of financial risks, including credit risk and liquidity risk. The Group does not use any
derivative financial instruments for speculative purposes.
(a) Credit Risk
The carrying amounts of cash and cash equivalents included in the consolidated statements of financial position represent the
Group’s maximum exposure to credit risk of the counterparty in relation to its financial asset. The Group’s bank balance is maintained
with a creditworthy bank with no recent history of default.
(b) Liquidity Risk
The Group’s objective is to maintain a balance between continuity of funding and flexibility through balances with related parties
and shareholders.
As at December 9, 2019, the Group’s current financial liabilities were all contractually due for settlement within twelve months and
the Group expects to meet all liquidity requirements.
(ii) Capital Management
The primary objective of the Group’s capital management is to safeguard the Group’s ability to continue as a going concern.
The Group manages its capital structure and makes adjustments to it in light of changes in economic conditions and the risk
characteristics of the underlying assets. To maintain or adjust the capital structure, the Group may issue new shares. The Group is not
subject to any externally imposed capital requirements. No changes were made to these objectives, policies or processes for managing
capital during the period ended December 9, 2019 and the year ended December 31, 2018.
(iii) Fair Value Estimation
The fair values of the financial asset and liabilities of the Group approximate their carrying amounts largely due to the short term
maturities of these instruments.
4. Critical Accounting Estimates and Judgements
Note 2 includes a summary of the significant accounting policies used in the preparation of the consolidated financial statements.
The preparation of the consolidated financial statements often requires the use of judgements to select specific accounting methods and
policies from several acceptable alternatives. Furthermore, significant estimates and assumptions concerning the future may be required
in selecting and applying those methods and policies in the consolidated financial statements. The Group bases its estimates and
judgements on historical experience and various other assumptions that it believes are reasonable under the circumstances. Actual results
may differ from these estimates and judgements under different assumptions or conditions.
The following is a review of the more significant assumptions and estimates, as well as the accounting policies and methods used
in the preparation of the consolidated financial statements.
F-115
(i) Impairment of intangible asset
The Group tests annually whether an intangible asset not ready for use has incurred any impairment. Assets are reviewed for
impairment whenever events or changes in circumstances indicate that the carrying amount of the assets exceeds its recoverable amount
in accordance with the accounting policy stated in Note 2(e). The recoverable amount of an asset or a cash-generating unit is determined
based on the higher of the asset’s or the cash-generating unit’s fair value less costs to sell and value-in-use. The value-in-use calculation
requires the entity to estimate the future cash flows expected to arise from the asset and a suitable discount rate in order to calculate
present value, and the growth rate assumptions in the cash flow projections which have been prepared on the basis of management’s
assumptions and estimates. The fair value less costs to sell for an asset not traded in an active market is determined using valuation
techniques (level 3 in the fair value hierarchy).
During the year ended December 31, 2018, the Group recorded a full impairment provision of the intangible asset. Refer to Note 6.
5. Significant Related Party Transactions
(i) The Group has the following significant transactions during the period/year with related parties which were carried out in the normal
course of business at terms equivalent to those that prevail in arm’s length transactions and agreed by the relevant parties:
Service fees charged by a subsidiary of Chi-Med
Period Ended
Year Ended
December 9, December 31,
2019
2018
(in US$’000)
—
6,973
On March 25, 2013, Hutchison MediPharma Limited (“HMP”), a subsidiary of Chi-Med, and NHS entered into a research and
development collaboration agreement as contemplated by the JV Agreement for the exclusive rights to conduct research to evaluate and
develop products from HMP’s extensive botanical library and well established botanical research and development platform in the field
of gastrointestinal disease.
On November 19, 2018, the Board decided to put on hold the Company’s research activities pending a strategic review. Refer to
Note 6. On December 9, 2019, the collaboration agreement was terminated along with the JV Agreement.
(ii) Other transaction with related party:
On March 25, 2013, the Company and Nestec Ltd., an affiliate of NHS, entered into an option agreement for the exclusive option
to obtain exclusive royalty-bearing licenses to commercialize certain products in certain territories. The exercise price of the option is
either fixed or subject to negotiation upon the receipt of the exercise notice, depending on the territories.
The option was never exercised and on December 9, 2019, the option agreement was terminated along with the JV Agreement.
(iii) Compensation of key management personnel of the Group:
No compensation was paid by the Group to the key management personnel of the Group in respect of their services rendered to the
Group during the period ended December 9, 2019 and the year ended December 31, 2018.
6. Impairment Provision
On November 19, 2018, the Board reviewed the progress of its drug candidates. After due consideration of the timeline and further
investments required to complete the clinical trials and reach the commercialization stage, it decided to explore alternative strategic
options to maximize the economic returns from the drug candidates. The Group has performed an annual impairment assessment of the
recoverability of the US$30 million intangible asset by comparing its carrying amount to the higher of the asset’s value-in-use or its fair
value less costs to sell. In preparing its assessment, although the Group was in the process of identifying potential buyers or collaboration
partners to maximize its economics returns from the drug candidates, there was no certainty of an available market or that a suitable
buyer or partner can be readily identified. Accordingly, the Group recorded a full impairment provision during the year ended December
31, 2018. During the period ended December 9, 2019, there were no further developments on the drug candidates that would indicate a
reversal of impairment was appropriate.
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7. Taxation Charge
No Hong Kong profits tax has been provided as the Group had no assessable profit for the period ended December 9, 2019 and the
year ended December 31, 2018.
The taxation on the Group’s profit/(loss) before taxation differs from the theoretical account that would arise using the applicable
tax rate as follows:
Profit/(loss) before taxation
Calculated at a taxation rate of 16.5%
Net effect of (income not taxable)/expenses not tax deductible
Taxation charge
8. Cash and Cash Equivalents
Cash at bank
The carrying amounts of the cash and cash equivalents are denominated in US$.
9. Amounts Due to Related Parties
Subsidiaries of Chi-Med
The amounts due to related parties are unsecured, interest free and repayable on demand.
10. Share Capital
Period Ended
Year Ended
December 9, December 31,
2019
2018
(in US$’000)
199
33
(33)
—
(38,198)
(6,303)
6,303
—
December 9,
2019
(in US$’000)
16,769
December 9,
2019
(in US$’000)
30
2019
2018
Number of
shares
(in US$’000)
(in US$’000)
Number of
shares
Issued and fully paid:
Ordinary shares
At January 1
Issuance of shares (note)
At December 9/December 31
57,000
—
57,000
114,000
—
114,000
49,000
8,000
57,000
98,000
16,000
114,000
Note: On April 24, 2018, 8,000 additional ordinary shares of US$2,000 each were issued. They were issued equally to the
two existing shareholders at the time.
11. Directors’ Emoluments
None of the directors received any fees or emoluments from the Group in respect of their services rendered to the Group during the
period ended December 9, 2019 and the year ended December 31, 2018.
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12. Subsidiary
Name
Nutrition Science Partners (UK) Limited
13. Subsequent Events
Place of
establishment
and
operation
United Kingdom
Nominal value
of issued
ordinary share
capital in GBP
As at
December 9,
2019
Equity interest
attributable to
the Group
As at
December 9,
2019
1
100 %
Type of
legal entity
Limited
liability
company
Principal activity
Inactive
The Group evaluated subsequent events through March 4, 2021, which is the date when the consolidated financial statements were
issued.
F-118
INFORMATION FOR
SHAREHOLDERS
LISTING
PRINCIPAL PLACE OF BUSINESS
ADS DEPOSITARY
The ordinary shares of the Company are
listed on the AIM market of the London
Stock Exchange and in the form of American
depositary shares (“ADSs”) on the NASDAQ
Global Select Market. Each ADS represents
ownership of five ordinary shares of the
Company. Additional information and specific
inquiries concerning the ADSs should be
directed to the ADS Depositary at the address
given on this page.
CODE
HCM
FINANCIAL CALENDAR
Closure of Register of Members
April 27, 2021 to April 28, 2021
Annual General Meeting
April 28, 2021
Interim Results Announcement
July 2021
REGISTERED OFFICE
P.O. Box 309, Ugland House
Grand Cayman, KY1-1104
Cayman Islands
Telephone:
Facsimile:
+1 345 949 8066
+1 345 949 8080
48th Floor, Cheung Kong Center
2 Queen’s Road Central
Hong Kong
Telephone:
Facsimile:
+852 2128 1188
+852 2128 1778
PRINCIPAL EXECUTIVE OFFICE
Level 18, The Metropolis Tower
10 Metropolis Drive
Hunghom, Kowloon
Hong Kong
Telephone:
Facsimile:
+852 2121 8200
+852 2121 8281
SHARE REGISTRAR
Computershare Investor Services (Jersey) Limited
13 Castle Street, St. Helier
Jersey, Channel Islands JE1 1ES
Telephone:
Facsimile:
+44 (0)370 707 4040
+44 (0)370 873 5851
CREST DEPOSITARY
Computershare Investor Services PLC
The Pavilions
Bridgwater Road
Bristol BS99 6ZY
United Kingdom
Telephone:
Facsimile:
+44 (0)370 702 0000
+44 (0)370 703 6114
Deutsche Bank Trust Company Americas
60 Wall Street, New York
New York 10005
United States
Telephone:
Facsimile:
+1 212 250 9100
+1 732 544 6346
SHAREHOLDERS CONTACT
Please direct inquiries to:
48th Floor, Cheung Kong Center
2 Queen’s Road Central
Hong Kong
Attn:
Edith Shih
Non-executive Director &
Company Secretary
ediths@ckh.com.hk
+852 2128 1778
E-mail:
Facsimile:
INVESTOR INFORMATION
Corporate press releases, financial reports and
other investor information on the Company are
available online at the Company’s website.
INVESTOR RELATIONS CONTACT
Please direct inquiries to:
E-mail:
Telephone:
Facsimile:
ir@hutch-med.com
+852 2121 8200
+852 2121 8281
WEBSITE ADDRESS
www.hutch-med.com
REFERENCES
Unless the context requires otherwise, references in this Annual Report to the “Group,” the “Company,” “HUTCHMED,” “HUTCHMED Group,” “we,” “us,” and “our,” mean Hutchison China MediTech Limited and its
consolidated subsidiaries and joint ventures unless otherwise stated or indicated by context.
PAST PERFORMANCE AND FORWARD-LOOKING STATEMENTS
The performance and results of operations of the Group contained within this Annual Report are historical in nature, and past performance is no guarantee of future results of the Group. This Annual Report contains
forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by words like “will,”
“expects,” “anticipates,” “future,” “intends,” “plans,” “believes,” “estimates,” “pipeline,” “could,” “potential,” “first-in-class,” “designed to,” “objective,” “guidance,” “pursue,” or similar terms, or by express or implied
discussions regarding potential drug candidates, potential indications for drug candidates or by discussions of strategy, plans, expectations or intentions. You should not place undue reliance on these statements. Such
forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of
these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that any
of our drug candidates will be approved for sale in any market, or that any approvals which are obtained will be obtained at any particular time, or that any such drug candidates will achieve any particular revenue or
net income levels. In particular, management’s expectations could be affected by, among other things: unexpected regulatory actions or delays or government regulation generally; the uncertainties inherent in research
and development, including the inability to meet our key study assumptions regarding enrollment rates, timing and availability of subjects meeting a study’s inclusion and exclusion criteria and funding requirements,
changes to clinical protocols, unexpected adverse events or safety, quality or manufacturing issues; the inability of a drug candidate to meet the primary or secondary endpoint of a study; the impact of the COVID-19
pandemic or other health crises in China or globally; the inability of a drug candidate to obtain regulatory approval in different jurisdictions or gain commercial acceptance after obtaining regulatory approval; global
trends toward health care cost containment, including ongoing pricing pressures; uncertainties regarding actual or potential legal proceedings, including, among others, actual or potential product liability litigation,
litigation and investigations regarding sales and marketing practices, intellectual property disputes, and government investigations generally; and general economic and industry conditions, including uncertainties
regarding the effects of the persistently weak economic and financial environment in many countries and uncertainties regarding future global exchange rates. For further discussion of these and other risks, see
HUTCHMED’s filings with the U.S. Securities and Exchange Commission and on AIM. HUTCHMED is providing the information in this Annual Report as of this date and does not undertake any obligation to update any
forward-looking statements as a result of new information, future events or otherwise.
In addition, this Annual Report contains statistical data and estimates that HUTCHMED obtained from industry publications and reports generated by third-party market research firms. Although HUTCHMED believes
that the publications, reports and surveys are reliable, HUTCHMED has not independently verified the data and cannot guarantee the accuracy or completeness of such data. You are cautioned not to give undue weight
to this data. Such data involves risks and uncertainties and are subject to change based on various factors, including those discussed above.
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2020
ANNUAL
REPORT
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HUTCHISON CHINA MEDITECH LIMITED
和 ⿈ 中 國 醫 藥 科 技 有 限 公 司
(INCORPORATED IN THE CAYMAN ISLANDS WITH LIMITED LIABILITY)