Table of Contents
kr
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 10-K
(Mark One)
☒
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2022
or
Commission file number 000-29889
RIGEL PHARMACEUTICALS, INC.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
611 Gateway Boulevard, Suite 900,
South San Francisco, California
(Address of principal executive offices)
94-3248524
(IRS Employer
Identification No.)
94080
(Zip Code)
(650) 624-1100
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class:
Common Stock, par value $.001 per share
Trading Symbol(s)
RIGL
Name of each exchange on which registered:
The Nasdaq Stock Market LLC
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. 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, a smaller reporting company, or an emerging growth company. See the
definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large-accelerated filer ☐
Accelerated filer ☒
Non-accelerated filer ☐
Smaller reporting company ☐
Emerging growth company ☐
If an emerging growth company, 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. ☐
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 prepared or issued its audit report. ☒
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to
previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive
officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by a check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒
The approximate aggregate market value of the Common Stock held by non-affiliates of the registrant, based upon the closing price of the registrant’s common stock as reported on the Nasdaq
Global Select on June 30, 2022, the last business day of the registrant’s most recently completed second fiscal quarter, was $193.7 million. Shares of the registrant’s outstanding common stock held by
each executive officer, director and affiliates of the registrant’s outstanding common stock have been excluded. The determination of affiliate status for the purposes of this calculation is not necessarily
a conclusive determination for other purposes.
As of February 28, 2023, there were 173,653,353 shares of the registrant’s common stock outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Items 10, 11, 12, 13 and 14 of Part III of this Annual Report on Form 10-K incorporate information by reference from the definitive proxy statement for the registrant’s 2023 Annual Meeting of
Stockholders to be filed with the Securities and Exchange Commission pursuant to Regulation 14A not later than 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K.
Table of Contents
TABLE OF CONTENTS
PART I
Item 1.
Item 1A.
Item 1B.
Item 2.
Item 3.
Item 4.
PART II
Item 5.
Item 6.
Item 7.
Item 7A.
Item 8.
Item 9.
Item 9A.
Item 9B.
Item 9C.
PART III
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
PART IV
Item 15.
Item 16.
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
[Reserved]
Management’s Discussion and Analysis of Financial Condition and Results of Operations
Quantitative and Qualitative Disclosures about Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Directors, Executive Officers and Corporate Governance
Executive Compensation
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Certain Relationships and Related Transactions, and Director Independence
Principal Accountant Fees and Services
Exhibits and Financial Statement Schedules
Form 10-K Summary
Signatures
Page
4
40
86
86
86
86
87
87
88
89
101
102
138
138
140
140
140
140
140
140
140
141
141
141
145
146
Table of Contents
FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains statements indicating expectations about future performance and other forward-
looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), Section 21E of the
Securities Exchange Act of 1934, as amended (the Exchange Act), and the Private Securities Litigation Reform Act of 1995, that involve
risks and uncertainties. We usually use words such as “may,” “will,” “would,” “should,” “could,” “expect,” “plan,” “anticipate,”
“might,” “believe,” “estimate,” “predict,” “intend,” or the negative of these terms or similar expressions to identify these forward-looking
statements. These statements appear throughout this Annual Report on Form 10-K and are statements regarding our current expectations,
beliefs or intent, primarily with respect to our operations and related industry developments. Examples of these statements include, but are
not limited to: our expectations regarding the impact of the global COVID-19 pandemic; our business and scientific strategies; risks and
uncertainties associated with the commercialization and marketing of our products in the United Stated (US) and outside the US; risks that
the US Food and Drug Administration (FDA), European Medicines Agency (EMA) or other regulatory authorities may make adverse
decisions regarding our products; the progress of our and our collaborators’ product development programs, including clinical testing, and
the timing of results thereof; our corporate collaborations and revenues that may be received from our collaborations and the timing of
those potential payments; our expectations with respect to regulatory submissions and approvals; our drug discovery technologies; our
research and development expenses; protection of our intellectual property and our intention to vigorously enforce our intellectual property
rights; sufficiency of our cash and capital resources and the need for additional capital; and our operations and legal risks. You should not
place undue reliance on these forward-looking statements. Our actual results could differ materially from those anticipated in these
forward-looking statements for many reasons, including as a result of the risks and uncertainties discussed in “Part I, Item 1A, Risk
Factors” of this Annual Report on Form 10-K. Any forward-looking statement speaks only as of the date on which it is made, and we
undertake no obligation to update any forward-looking statement to reflect events or circumstances after the date on which the statement is
made or to reflect the occurrence of unanticipated events, except as required by applicable law. New factors emerge from time to time, and
it is not possible for us to predict which factors will arise. In addition, we cannot assess the impact of each factor 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.
RISK FACTOR SUMMARY
Investing in our securities involves a high degree of risk. Below is a summary of the material factors that make an investment in
our common stock speculative or risky. This summary does not address all of the risks that we face. Additional discussion of the risks
summarized in this risk factor summary, as well as other risks that we face, can be found below under the heading “Part 1, Item 1A, Risk
Factors” and should be carefully considered, together with other information in this Form 10-K and our other filings with the SEC, before
making an investment decision regarding our common stock.
● Our prospects are highly dependent on our first commercial product, TAVALISSE® (fostamatinib disodium hexahydrate) and our
recently launched second commercial product REZLIDHIA™ (olutasidenib). To the extent that the commercial success of our
products in the US and respective territories outside of the US is diminished or is not commercially successful, our business,
financial condition and results of operations may be adversely affected, and the price of our common stock may decline.
● We may not be able to successfully develop or commercialize our product candidates if problems arise in the clinical testing and
approval process. There is a high risk that drug discovery and development efforts might not generate successful product
candidates. If the results of our clinical trials do not meet the primary efficacy endpoints, or if the top-line data from the results of
our clinical trials may not ultimately meet the requirements for an NDA approval by the FDA and other national regulatory
authorities, the commercial prospects of our business may be harmed, and our ability to generate product revenues may be delayed
or eliminated.
● Even if we, or any of our collaborative partners, are able to continue to commercialize our products or any product candidate that
we, or they, develop, the product may become subject to unfavorable pricing regulations, unfavorable health technology
assessments (HTA) assessment, third-party payor reimbursement practices or labeling restrictions, all of which may vary from
country to country and any of which could harm our business.
2
Table of Contents
● If we are unable to successfully market and distribute our products and retain experienced commercial personnel, our business will
be substantially harmed.
● Our business was adversely affected and could be materially and adversely affected in the future by the evolving effects of the
COVID-19 pandemic as a result of the potential future impacts on our commercialization efforts, supply chain, regulatory, clinical
development and corporate development activities and other business operations, in addition to the impact of a global economic
slowdown.
● We are subject to stringent and evolving privacy and information security laws, regulations, rules, policies and contractual
obligations, and changes in such laws, regulations, rules, policies, contractual obligations and our actual or perceived failure to
comply with such requirements could subject us to significant investigations, fines, penalties, and claims, any of which may have a
material adverse effect on our business, financial condition, results of operations or prospects.
● If manufacturers obtain approval for generic versions of our products, or of products with which we compete, our business may be
harmed.
● Unforeseen safety issues could emerge with our products that could require us to change the prescribing information to add
warnings, limit use of the product, and/or result in litigation. Any of these events could have a negative impact on our business.
● We rely and may continue to rely on third party distribution facilities for the sale of our products and potential sale of any of our
product candidates. If any or all of them become subject to adverse findings from inspections or face other difficulties to operate,
then the distribution of our products may be interrupted or otherwise adversely affected.
● We lack the capability to manufacture compounds for clinical development and we intend to rely on third parties for commercial
supply, manufacturing and distribution, if any, of our product candidates which receive regulatory approval and we may be unable
to obtain required material or product in a timely manner, at an acceptable cost or at a quality level required to receive regulatory
approval.
● Any product for which we have obtained regulatory approval, or for which we obtain approval in the future, is subject to, or will be
subject to, extensive ongoing regulatory requirements by the FDA, EMA and other comparable regulatory authorities, and if we fail
to comply with regulatory requirements or if we experience unanticipated problems with our products, we may be subject to
penalties, we will be unable to generate revenue from the sale of such products, our potential for generating positive cash flow will
be diminished, and the capital necessary to fund our operations will be increased.
● If our corporate collaborations or license agreements are unsuccessful, or if we fail to form new corporate collaborations or license
agreements, our research and development efforts could be delayed.
● Our success is dependent on intellectual property rights held by us and third parties, and our interest in such rights is complex and
uncertain.
● If a dispute arises regarding the infringement or misappropriation of the proprietary rights of others, such dispute could be costly
and result in delays in our research and development activities, partnering and commercialization activities.
● If our competitors develop technologies that are more effective than ours, our commercial opportunity will be reduced or
eliminated.
● If product liability lawsuits are successfully brought against us, we may incur substantial liabilities and may be required to limit
commercialization of our products.
3
Table of Contents
PART I
Item 1. Business
Overview
We are a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve
the lives of patients with hematologic disorders and cancer. Our pioneering research focuses on signaling pathways that are critical to
disease mechanisms.
Our first product approved by the FDA is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only approved oral spleen
tyrosine kinase (SYK) inhibitor, for the treatment of adult patients with chronic immune thrombocytopenia (ITP) who have had an
insufficient response to a previous treatment. The product is also commercially available in Europe and the United Kingdom (UK) (as
TAVLESSE), and in Canada and Israel (as TAVALISSE) for the treatment of chronic ITP in adult patients.
Our second FDA approved product is REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with relapsed or
refractory (R/R) acute myeloid leukemia (AML) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation as detected by an FDA-
approved test. We began our commercialization of REZLIDHIA (olutasidenib) in December 2022. We in-licensed olutasidenib from Forma
Therapeutics, Inc. (Forma), with exclusive, worldwide rights for its development, manufacturing and commercialization
We conducted a Phase 3 clinical trial evaluating fostamatinib for the treatment of warm autoimmune hemolytic anemia (wAIHA)
and announced that we did not file a supplemental New Drug Application (sNDA) for this indication considering the top-line data results
and guidance received from the FDA. We announced the completion of the FOCUS Phase 3 clinical trial of fostamatinib for the treatment
of hospitalized high-risk patients with COVID-19. Fostamatinib is currently being studied in a National Institute of Health (NIH)/National
Heart, Lung, and Blood Institute (NHLBI) sponsored Accelerating COVID-19 Therapeutic Inventions and Vaccines Phase 2/3 trial
(ACTIV-4 Host Tissue Trial) for the treatment of COVID-19 in hospitalized patients.
Our other clinical programs include our interleukin receptor-associated kinase (IRAK) inhibitor program, and a receptor-
interacting serine/threonine-protein kinase (RIPK1) inhibitor program in clinical development with partner Eli Lilly and Company (Lilly).
In addition, we have product candidates in clinical development with partners BerGenBio ASA (BerGenBio) and Daiichi Sankyo (Daiichi).
Business Updates
TAVALISSE in ITP
In 2022, our net product sales of TAVALISSE were $75.8 million, a 20% increase compared to 2021. The increase in our net
product sales was primarily driven by the increase in quantities sold as well as the increase in price per bottle of TAVALISSE. These
increases were partially offset by the increase in revenue reserves mainly due to higher rebates on recent contracts entered with certain
Pharmacy Benefits Managers (PBMs), and higher government program rebates. Our first quarter net sales are typically impacted by the first
quarter reimbursement issues such as the resetting of co-pays and the Medicare donut hole.
We continue to deploy resources to enable our field-based employees to engage with health care providers, either in-person or
virtually. These engagements have enabled our field team to cover existing prescribers, as well as develop relationships with new
prescribers to appropriately market TAVALISSE. In the third quarter of 2021, we expanded our sales force by increasing our number of
territories.
REZLIDHIA in R/R AML with mIDHI
On December 1, 2022, the FDA approved REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R AML
with a susceptible IDH1 mutation as detected by an FDA-approved test. The recommended dosage of REZLIDHIA is 150 mg taken orally
twice daily until disease progression or unacceptable toxicity. We in-licensed olutasidenib from Forma with exclusive, worldwide rights for
its development, manufacturing and
4
Table of Contents
commercialization. On December 22, 2022, we began the commercialization of REZLIDHIA in the US and made it available to patients. In
2022, we recorded net product sales of $0.9 million from sale of REZLIDHIA. REZLIDHIA is highly synergistic with our existing
hematology-oncology focused commercial and medical affairs infrastructure. We incurred operating expenses in 2022 and will continue to
incur such expenses in the future associated with our commercial launch activities for REZLIDHIA in the US. Specifically, our
commercial efforts focus on targeting hematologists and hematologist-oncologists who manage patients with R/R AML. We also plan to
enter partnerships with third parties to commercialize REZLIDHIA outside the US. For further discussions and other updates on
REZLIDHIA (olutasidenib), refer to “Commercial Products – REZLIDHIA in R/R AML with mIDH1” section below.
Pursuant to the license and transition services agreement with Forma entered on July 27, 2022, Forma provided us an exclusive
license to develop, manufacture and commercialize olutasidenib, Forma’s proprietary inhibitor of mutated IDH1 (mIDH1), for any uses
worldwide, including for the treatment of AML and other malignancies. On October 14, 2022, Novo Nordisk A/S (Novo Nordisk)
announced the completion of the acquisition of Forma. Following this acquisition, Forma became a wholly owned subsidiary of Novo
Nordisk.
In accordance with the terms of the license and transition services agreement, we paid Forma an upfront fee of $2.0 million, with
the potential to pay up to $67.5 million additional payments upon achievement of specified development and regulatory milestones and up
to $165.5 million additional payments upon achievement of certain commercial milestones. In addition, subject to the terms and conditions
of the license and transition services agreement, Forma would be entitled to tiered royalty payments on net sales of licensed products at
percentages ranging from low-teens to mid-thirties, as well as certain portions of our sublicensing revenue, subject to certain standard
reductions and offsets. As of December 31, 2022, certain milestones were met which entitled Forma to receive a $17.5 million milestone
payment, of which, $15.0 million was outstanding and included within accounts payable on our balance sheet. For further discussions of the
license and transition services agreement with Forma, see “Note 4 - Sponsored Research and License Agreements and Government
Contract” to our “Notes to Financial Statements” contained in “Part II, Item 8, Financial Statements and Supplementary Data” of this
Annual Report on Form 10-K.
R289, an Oral IRAK1/4 Inhibitor for Autoimmune, Inflammatory and Hematology-Oncology Diseases
We continue to advance the development of our IRAK1/4 program, completing the evaluation of a new pro-drug formulation of
R835, R289, in single-ascending and multiple ascending dose studies with positive safety results in 2021. In January 2022, we received
clearance from the FDA on our clinical trial design to explore R289 in low-risk MDS. The open-label, Phase 1b trial will determine the
tolerability and preliminary efficacy of R289 in patients with low-risk MDS who are refractory or resistant to prior therapies. In December
2022, we announced that we dosed the first patient in our Phase 1b trial of R289. The Phase 1b trial of R289 is expected to enroll
approximately 22 patients. The primary objective of the trial is safety, with secondary and exploratory objectives to assess preliminary
efficacy and characterize the pharmacokinetic and pharmacodynamic profile of R289. The safety and efficacy data from this Phase 1b trial,
along with the safety and pharmacokinetic/pharmacodynamic data from the completed first-in-human study in heathy volunteers, are
intended to be used to determine the recommended Phase 2 dose for future clinical development of R289 targeting lower-risk MDS.
Fostamatinib in Hospitalized COVID-19 patients
In April 2021, we reported positive top-line results from a multi-center, Phase 2 clinical trial sponsored by the NIH/NHLBI,
evaluating the safety of fostamatinib, our oral SYK inhibitor, for the treatment of hospitalized patients with COVID-19. The trial met its
primary endpoint of safety comparable to standard of care (SoC) and showed broad and consistent improvement in numerous efficacy
endpoints, including mortality, ordinal scale assessment, and number of days in the intensive care unit (ICU). In May 2021, the trial data
were submitted as part of a request for an Emergency Use Authorization (EUA) from the FDA for fostamatinib as a treatment for
hospitalized patients with COVID-19. In August 2021, the FDA informed us that the clinical data submitted from the NIH/NHLBI-
sponsored Phase 2 trial were insufficient to support an EUA. In September 2021, the data from the NIH/NHLBI-sponsored Phase 2 trial
was published in Clinical Infectious Diseases, an official publication of the Infectious Disease Society of America.
5
Table of Contents
In July 2022, we completed the enrollment of our FOCUS Phase 3 clinical trial to evaluate the safety and efficacy of fostamatinib
in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors with 280 patients. The trial had
originally targeted a total of 308 patients; however, we determined the trial would be sufficiently powered with 280 patients to potentially
provide a clinically meaningful result and determine the efficacy and safety of fostamatinib in hospitalized COVID-19 patients. On
November 1, 2022, we announced the top-line results from the FOCUS trial. The trial approached but did not meet statistical significance
(p=0.0603) in the primary efficacy endpoint of the number of days on oxygen through Day 29. All prespecified secondary endpoints in the
study numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment,
and number of days in the ICU. We are evaluating the opportunity and discussing next steps with the FDA and in collaboration with our
partner, the US Department of Defense.
In June 2021, we announced that fostamatinib has been selected for the NIH ACTIV-4 Host Tissue Trial in hospitalized patients
with COVID-19. The ACTIV-4 Host Tissue Trial, initiated and funded by NHLBI, is a randomized, placebo-controlled trial of therapies,
including fostamatinib, targeting the host response to COVID-19 in hospitalized patients. The ACTIV-4 Host Tissue Trial is evaluating
fostamatinib in a targeted population of approximately 600 hospitalized patients with COVID-19, 300 fostamatinib versus 300 placebo. An
interim analysis of the trial was completed by the Data and Safety Monitoring Board with a recommendation for the trial to continue.
Fostamatinib in wAIHA
In June 2022, we announced top-line efficacy and safety data results from our FORWARD study, a Phase 3 pivotal trial of
fostamatinib, an oral SYK inhibitor, in patients with wAIHA, which we initiated in March 2019. We completed the enrollment of our
FORWARD study in November 2021 with 90 patients enrolled and completed the treatment period for the last patient under the study in
April 2022. The results of the trial did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin
response in the overall study population. For more detailed discussions of the results of the trial, refer to “Clinical Stage Programs” section
below. We conducted an in-depth analysis of these data to better understand differences in patient characteristics and outcomes and
submitted these findings to the FDA. In October 2022, we announced that we received guidance from the FDA’s review of these findings.
Based on the result of the trial and the guidance from the FDA, we did not file a supplemental New Drug Application (sNDA) for this
indication.
Global Strategic Partnership with Lilly
We have a global exclusive license and collaboration agreement with Lilly (the Lilly Agreement) entered in February 2021, to
develop and commercialize R552, a RIPK1 inhibitor, for the treatment of non-central nervous system (non-CNS) diseases. In addition, the
collaboration is aimed at developing additional RIPK1 inhibitors for the treatment of central nervous system (CNS) diseases. Pursuant to
the terms of the license agreement, we granted to Lilly the exclusive rights to develop and commercialize R552 and related RIPK1
inhibitors in all indications worldwide.
We are responsible for 20% of the development costs for R552 in the US, Europe, and Japan, up to a specified cap. Lilly is
responsible for funding the remainder of all development activities for R552 and other non-CNS disease development candidates. We have
the right to opt-out of co-funding the R552 development activities in the US, Europe and Japan at two different specified times. If we
exercise our first opt-out right (no later than September 30, 2023), we are required to fund our share of the R552 development activities in
the US, Europe, and Japan up to a maximum funding commitment of $65.0 million through April 1, 2024. Through December 31, 2022,
Lilly billed us $15.1 million of the funding development costs and the amounts were fully paid as of December 31, 2022. Under the Lilly
Agreement, we were responsible for performing and funding initial discovery and identification of CNS disease development candidates,
and following candidate selection, Lilly will be responsible for performing and funding all future development and commercialization of
the CNS disease development candidates. In June 2022, Lilly provided notice of continuance pursuant to the terms of the Lilly Agreement,
whereby Lilly elected its option to lead the identification and selection of CNS penetrant lead candidate.
Lilly is continuing to advance R552, with an initial Phase 2a trial in active rheumatoid arthritis. This initial Phase 2a trial in
approximately 100 patients with moderately to severely active rheumatoid arthritis is anticipated to
6
Table of Contents
begin in the first half of 2023 and will involve global recruitment. RIPK1 is implicated in a broad range of key inflammatory cellular
processes and plays a key role in Tumor Necrosis Factor signaling, especially in the induction of pro-inflammatory necroptosis. The
program also includes RIPK1 compounds that cross the blood-brain barrier (CNS-penetrants) to address neurodegenerative diseases such as
Alzheimer’s disease and Amyotrophic Lateral Sclerosis. The Phase 2a trial analysis is expected by the end of 2024.
Patent Infringement Lawsuit
In June 2022, we received a notice letter regarding an Abbreviated New Drug Application (ANDA) submitted to the FDA by
Annora Pharma Private Limited (Annora), requesting approval to market a generic version of TAVALISSE. On July 25, 2022, we filed a
lawsuit in the United States District Court for the District of New Jersey against Annora and its subsidiaries for infringement of certain of
our US patents. For a more detailed discussion of this litigation matter, see “Part I, Item 3, Legal Proceedings” of this Annual Report on
Form 10-K.
Update on Current and Potential Future Impact of COVID-19 on our Business
The COVID-19 pandemic has adversely impacted, and may continue to adversely impact, our business and operations. The degree
to which the COVID-19 pandemic may affect our business and operations in the future will depend on developments that are highly
uncertain and beyond our knowledge or control. The ultimate potential future impact of the COVID-19 pandemic on our business and
financial condition is highly uncertain and subject to change, and as such, we cannot ascertain the full extent of the impacts on our sales of
our products, our ability to continue to secure new collaborations and support existing collaboration efforts with our partners and our
clinical and regulatory activities. Periodic resurgence of COVID-19 cases negatively impacted and may continue to impact our ability to
grow our product sales. When COVID-19 cases surged, we have observed reduced patient-doctor interactions and our representatives had
fewer visits with health care providers.
We continue to monitor the effects of the COVID-19 pandemic and continues to undertake safety measures to keep our staff,
patients, investigators and stockholders safe. We have a Crisis Management Team (CMT) that implements and monitors our business
continuity plans to prevent or minimize business disruption and ensure the safety and well-being of our personnel. We also have a COVID-
19 Headquarters Policy (Plan) in place to provide guidelines when working onsite. We continue to evaluate the workplace for compliance
with the local, state and federal guidance and may modify or update at any time to ensure the safety of our employees, contractors and
visitors. During the first quarter of 2022, we updated our Plan as we move towards a hybrid schedule, reinstituting more in-person
interactions beginning April 2022. We endeavor to provide the safest and most effective work environment under the circumstances, but we
cannot guarantee that employees who come to the office will not be exposed to COVID-19 while at the office. It will be the responsibility
of all employees to participate and cooperate in safety and cleaning protocols. We expect all employees, contractors, and visitors to our
facility to comply with the Plan. With respect to our supply chain, we did not experience significant disruptions in the supply chain for our
commercial product.
See also “Part I, Item 1A, Risk Factors” of this Annual Report on Form 10-K for additional information on risks and uncertainties
related to the ongoing COVID-19 pandemic.
7
Table of Contents
Strategy
Our goal is to establish ourselves as a successful commercial stage biopharmaceutical company with significant development
capabilities. We aim to expand our commercial business in the US on our own and globally through partnerships. We expanded our
hematology-oncology portfolio with our recently launched commercial product REZLIDHIA, which is highly synergistic with our existing
hematology-oncology focused commercial infrastructure. We continue our research and development of novel therapies designed to
significantly improve the lives of patients with hematological disorders and cancer. We continue to maintain a strong commercial team in
the US to enable us to execute successfully on our commercialization strategy for TAVALISSE in chronic ITP and REZLIDHIA for
treatment of R/R AML patients with a susceptible IDH1 mutation as detected by an FDA-approved test. We entered into partnerships for
the expansion of fostamatinib outside of US, and will be focusing on the further development of the utility of fostamatinib and olutasidenib
in other indications on our own or through our partners. We also aim to expand our development pipeline on our own and/or with
partnerships with pharmaceuticals and biotechnology companies to further develop and market additional product candidates.
In particular, the key elements that we believe are value drivers, which we plan to continue to execute include:
● growing sales of TAVALISSE in the estimated over $2.0 billion global ITP market;
● expanding our hematology-oncology portfolio with REZLIDHIA for treatment of R/R AML patients with a susceptible IDH1
mutation, a well-identified patient population of approximately 1,000 patients, part of an AML market estimated to have an
incidence of 20,000 cases in the US and estimated 120,000 cases globally; and
● expanding our development pipeline on our own and/or with collaboration partner(s).
Our Product Portfolio
The following table summarizes our portfolio:
8
Table of Contents
Commercial Products
TAVALISSE/Fostamatinib in ITP
Disease background. Chronic ITP affects an estimated 81,300 adult patients in the US. In patients with ITP, the immune system
attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. ITP patients can suffer
extraordinary bruising, bleeding and fatigue as a result of low platelet counts. Current therapies for ITP include steroids, blood platelet
production boosters that imitate thrombopoietin (TPO) and splenectomy.
Orally-available fostamatinib program. Taken in tablet form, fostamatinib blocks the activation of SYK inside immune cells. ITP
is typically characterized by the body producing antibodies that attach to healthy platelets in the blood stream. Immune cells recognize
these antibodies and affix to them, which activates the SYK enzyme inside the immune cell, and triggers the destruction of the antibody and
the attached platelet. When SYK is inhibited by fostamatinib, it interrupts this immune cell function and allows the platelets to escape
destruction. The results of our Phase 2 clinical trial, in which fostamatinib was orally administered to 16 adults with chronic ITP, published
in Blood, showed that fostamatinib significantly increased the platelet counts of certain ITP patients, including those who had failed other
currently available agents.
Our Fostamatinib for Immune Thrombocytopenia (FIT) Phase 3 clinical program had a total of 150 ITP patients which were
randomized into two identical multi-center, double-blind, placebo-controlled clinical trials. The patients were diagnosed with persistent or
chronic ITP, and had blood platelet counts consistently below 30,000 per microliter of blood. Two-thirds of the subjects received
fostamatinib orally at 100 mg twice daily (bid) and the other third received placebo on the same schedule. Subjects were expected to remain
on treatment for up to 24 weeks. At week four of treatment, subjects who failed to meet certain platelet counts and met certain tolerability
thresholds could have their dosage of fostamatinib (or corresponding placebo) increased to 150 mg bid. The primary efficacy endpoint of
this program was a stable platelet response by week 24 with platelet counts at or above 50,000 per microliter of blood for at least four of the
final six qualifying blood draws. In August 2015, the FDA granted our request for Orphan Drug designation for fostamatinib for the
treatment of ITP.
In August 2016, we announced the results of the first FIT study, reporting that fostamatinib met the study’s primary efficacy
endpoint. The study showed that 18% of patients receiving fostamatinib achieved a stable platelet response compared to none receiving a
placebo control (p=0.0261). In October 2016, we announced the results of the second FIT study, reporting that the response rate (16% in the
treatment group, versus 4% in the placebo group) was consistent with the first study, although the difference was not statistically
significant. In the ITP double-blind studies, the most commonly-reported adverse reactions occurring in at least 5% of patients treated with
TAVALISSE were diarrhea, hypertension, nausea, dizziness, increased alanine aminotransferase, increased aspartate aminotransferase,
respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia. Serious adverse drug reactions occurring in at least 1% of
patients treated with TAVALISSE in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis.
TAVALISSE was approved by the FDA in April 2018 for the treatment of ITP in adult patients who have had an insufficient
response to a previous treatment, and successfully launched in the US in May 2018. In January 2020, the European Commission (EC)
granted our Marketing Authorization Application (MAA) in Europe for fostamatinib (TAVLESSE) for the treatment of chronic ITP in adult
patients who are refractory to other treatments. In February 2020, Kissei Pharmaceutical Co., Ltd. (Kissei) was granted orphan drug
designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic idiopathic thrombocytopenic
purpura for fostamatinib in chronic ITP. In December 2022, Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) approved the
NDA for fostamatinib in chronic ITP.
A post-hoc analysis from our Phase 3 clinical program in adult patients with chronic ITP, highlighting the potential benefit of using
TAVALISSE in earlier lines of therapy, was published in the British Journal of Haematology in July 2020. Inclusion in one of the leading
peer-reviewed journals in the field of hematology underscores the significance of the 78% (25/32) response rate defined as at least one
platelet count of at least 50,000/µL when TAVALISSE was used as a second-line therapy in our Phase 3 clinical program. Adverse events
were manageable and
9
Table of Contents
consistent with those previously reported with fostamatinib. Our sales force is sharing this data with physicians.
Commercial activities, including sales and marketing
Our marketing and sales efforts are focused on hematologists and hematologist-oncologists in the US who manage chronic adult
ITP patients. We have a fully integrated commercial team consisting of sales, marketing, market access, and commercial operations
functions. Our sales team promotes our products in the US using customary pharmaceutical company practices, and we concentrate our
efforts on hematologists and hematologists-oncologists. Our products are sold initially through third-party wholesale distribution and
specialty pharmacy channels and group purchasing organizations before being ultimately prescribed to patients. To facilitate our
commercial activities in the US, we also enter into arrangements with various third parties, including advertising agencies, market research
firms and other sales-support-related services as needed. We believe that our commercial team and distribution practices are adequate to
ensure that our marketing efforts reach relevant customers and deliver our products to patients in a timely and compliant fashion. Also, to
help ensure that all eligible patients in the US have appropriate access to our products, we have established a reimbursement and patient
support program called Rigel OneCare (ROC). Through ROC, we provide co-pay assistance to qualified, commercially insured patients to
help minimize out-of-pocket costs and also provide free product to uninsured or under-insured patients who meet certain established
clinical and financial eligibility criteria. In addition, ROC is designed to provide reimbursement support, such as information related to
prior authorizations, benefits investigations and appeals.
In addition, our collaborative partner Grifols has launched TAVLESSE in the UK and certain countries in Europe including
Germany, France, Italy and Spain, and continues a phased rollout across the rest of Europe. Also, our collaborative partner Medison has
launched TAVALISSE in Canada and Israel.
Competitive landscape for TAVALISSE
Our industry is intensely competitive and subject to rapid and significant technological change. TAVALISSE is competing with
other existing therapies. In addition, a number of companies are pursuing the development of pharmaceuticals that target the same diseases
and conditions that we are targeting. For example, there are existing therapies and drug candidates in development for the treatment of ITP
that may be alternative therapies to TAVALISSE.
Currently, corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous
immunoglobulin (IVIg) or anti-Rh(D) to help further augment platelet count recovery, particularly in emergency situations. However, it has
been estimated that frontline agents lead to durable remissions in only a small percentage of newly-diagnosed adults with ITP. Moreover,
concerns with steroid-related side effects often restrict therapy to approximately four weeks. As such, many patients progress to persistent
or chronic ITP, requiring other forms of therapeutic intervention. In long-term treatment of chronic ITP, patients are often cycled through
several therapies over time in order to maintain a sufficient response to the disease.
Other approaches to treat ITP are varied in their mechanism of action, and there is no consensus about the sequence of their use.
Options include splenectomy, thrombopoietin receptor agonists (TPO-RAs) and various immunosuppressants (such as rituximab). The
response rate criteria of the above-mentioned options vary, precluding a comparison of response rates for individual therapies.
Even with the above treatment options, a significant number of patients remain severely thrombocytopenic for long durations and
are subject to risk of spontaneous or trauma-induced hemorrhage. The addition of fostamatinib to the currently available treatment options
could be beneficial because it has a different mechanism of action than any of the therapies that are currently available. Fostamatinib is a
potent and relatively selective SYK inhibitor, and its inhibition of Fc receptors and B-cell receptors of signaling pathways make it a
potentially broad immunomodulatory agent.
Other products in the US that are approved by the FDA to increase platelet production through binding to TPO receptors on
megakaryocyte precursors include PROMACTA® (Novartis International AG (Novartis)), Nplate® (Amgen, Inc.) and DOPTELET®
(Swedish Orphan Biovitrum AB). In the longer term, we may eventually face competition from potential manufacturers of generic versions
of our marketed products, including the proposed generic version of TAVALISSE that is the subject of an ANDA submitted to the FDA by
Annora, which, if approved and allowed to enter
10
Table of Contents
the market, it could result in significant decreases in the revenue derived from sale of TAVALISSE and thereby materially harm our
business and financial condition.
Fostamatinib in Global Markets
We have entered into various license agreements to commercialize fostamatinib globally. The following describes the
arrangements we have in place with Grifols, Kissei, Medison Pharma Trading AG (Medison Canada) and Medison Pharma Ltd. (Medison
Israel, and together with Medison Canada, Medison), and Knight Therapeutics International SA (Knight). We retain the global rights to
fostamatinib outside of the Grifols, Kissei, Medison and Knight territories.
Fostamatinib in Europe/Turkey
In January 2019, we entered into a commercialization license agreement with Grifols with exclusive rights to commercialize
fostamatinib for human diseases, including chronic ITP and AIHA, and non-exclusive rights to develop, fostamatinib in their territory.
Grifols territory includes Europe, the UK, Turkey, the Middle East, North Africa and Russia (including Commonwealth of Independent
States).
We are responsible for performing and funding certain development activities for fostamatinib for ITP and AIHA and Grifols is
responsible for all other development activities for fostamatinib in such territories. We remain responsible for the manufacturing and supply
of fostamatinib for all development and commercialization activities under the agreement. Under the terms of the agreement, we received
an upfront cash payment of $30.0 million and will be eligible to receive regulatory and commercial milestones of up to $297.5 million. In
January 2020, the EC granted a MA for fostamatinib for the treatment of chronic ITP in adult patients who are refractory to other
treatments. With this approval, we received a $20.0 million non-refundable milestone payment, consisted of a $17.5 million payment due
upon MAA approval by the EMA of fostamatinib for the first indication and a $2.5 million creditable advance royalty payment due upon
EMA approval of fostamatinib in the first indication. We will also receive tiered royalty payments ranging from the mid-teens to 30% of net
sales of fostamatinib in the Grifols Territory.
Fostamatinib in Japan/Asia
In October 2018, we entered into an exclusive license and supply agreement with Kissei to develop and commercialize
fostamatinib in all current and potential indications in Japan, China, Taiwan and the Republic of Korea. Kissei is a Japan-based
pharmaceutical company addressing patients’ unmet medical needs through its research, development and commercialization efforts, as
well as through collaborations with partners.
Under the terms of the agreement, we received an upfront cash payment of $33.0 million, with the potential for an
additional $147.0 million in development and commercial milestone payments, and will receive product transfer price payments in the mid
to upper twenty percent range based on tiered net sales for the exclusive supply of fostamatinib. Kissei receives exclusive rights to
fostamatinib in ITP and all future indications in Japan, China, Taiwan, and the Republic of Korea.
In September 2019, Kissei initiated a Phase 3 trial in Japan of fostamatinib in adult patients with chronic ITP. The efficacy and
safety of orally administered fostamatinib was assessed by comparing it with placebo in a randomized, double-blind study. Japan has the
third highest prevalence of chronic ITP in the world behind the US and Europe. In February 2020, Kissei was granted orphan drug
designation from the Japanese Ministry of Health, Labor and Welfare for R788 (fostamatinib) in chronic ITP. In December 2021, Kissei
reported positive top-line results for a Phase 3 clinical trial of fostamatinib in adult Japanese patients with chronic ITP, meeting its primary
endpoint. The Phase 3 clinical trial showed that patients receiving fostamatinib achieved a stable platelet response significantly higher
than patients receiving a placebo control. A stable platelet response was defined as achieving greater than or equal to 50,000 platelets per
microliter of blood on at least four of the last six scheduled visits between weeks 14 and 24 of treatment. Based on the positive Phase 3
results, in April 2022, Kissei submitted an NDA to Japan’s PMDA for fostamatinib in chronic ITP. With this milestone event, during the
second quarter of 2022, we received $5.0 million non-refundable and non-creditable payment from Kissei based on the terms of our
collaboration agreement, and such amount was recognized as revenue in the second quarter of 2022. In December 2022, Japan’s PMDA
approved TAVALISSE for the treatment of chronic ITP. With this milestone event, we are entitled to receive $20.0 million non-refundable
and non-creditable
11
Table of Contents
payment from Kissei based on the terms of our collaboration agreement, and such amount was recognized as revenue in the fourth quarter
of 2022. The amount was subsequently collected in January 2023.
Fostamatinib in Canada/Israel
In October 2019, we entered into exclusive commercial and license agreements with Medison to commercialize fostamatinib in all
potential indications in Canada and Israel. Under the terms of the agreements, we received an upfront payment of $5.0 million with the
potential for approximately $35.0 million in regulatory and commercial milestones. In addition, we will receive royalty payments beginning
at 30% of net sales. Under our agreement with Medison for the Canada territory, we have the option to buy back all rights to the product
upon regulatory approval in Canada for the indication of AIHA. The buyback provision, if exercised, would require both parties to mutually
agree on commercially reasonable terms for us to purchase back the rights, taking into account Medison’s investment and the value of the
rights, among others. Pursuant to this exclusive commercialization license agreement, in August 2020, we entered into a commercial supply
agreement with Medison.
In November 2020, Health Canada approved the New Drug Submission for TAVALISSE for the treatment of thrombocytopenia in
adult patients with chronic ITP who have had an insufficient response to other treatments. In August 2021, Medison Israel received the
licenses for registrational approval from the Ministry of Health, which triggered the first milestone that is the regulatory approval of the
product in Israel for the first indication, for a non-refundable payment of $0.1 million. In November 2022, Medison Israel made its first
commercial sale of TAVALISSE.
Fostamatinib in Latin America
In May 2022, we entered into commercial license agreement with Knight for the commercialization of fostamatinib for approved
indications in Latin America, consisting of Mexico, Central and South America, and the Caribbean (Knight territory). Pursuant to such
commercial license agreement, we received a $2.0 million one-time, non-refundable, and non-creditable upfront payment, with potential for
up to an additional $20.0 million in regulatory and sales-based commercial milestone payments, and will receive twenty- to mid-thirty
percent, tiered, escalated net-sales based royalty payments for products sold in the Knight territory. We are also responsible for the
exclusive manufacture and supply of fostamatinib for all future development and commercialization activities under a Commercial and
Supply Agreement.
REZLIDHIA in R/R AML with mIDH1
Disease background. mIDH1 alterations are seen in AML, glioma, chondrosarcoma, and intrahepatic cholangiocarcinoma. It is
estimated that there are approximately 1,000 adult patients, a well-identified patient population, with mIDH1 R/R AML, part of an AML
market estimated to have an incidence of 20,000 cases in the US and estimated 120,000 cases globally. Despite having approved treatment
options for R/R AML patients who are mIDH1 positive, an unmet need remains. Olutasidenib may represent a treatment option with
durable remissions, reduced QTc potential, and a stable pharmacokinetics profile that enables a consistent drug exposure over time.
In July 2022, we entered into a license and transition agreement with Forma for an exclusive license to develop, manufacture and
commercialize olutasidenib, Forma’s proprietary inhibitor of mIDH1, for any uses worldwide, including for the treatment of R/R AML and
other malignancies. Olutasidenib is an oral, small molecule drug designed to selectively bind to and inhibit mIDH1. This targeted agent has
the potential to provide therapeutic benefit by reducing 2-hydroxyglutarate levels and restoring normal cellular differentiation. IDH1 is a
natural enzyme that is part of the normal metabolism of all cells. When mutated, IDH1 activity can promote blood malignancies and solid
tumors.
Orally-available olutasidenib program. REZLIDHIA (olutasidenib) is an oral, small molecule, inhibitor of mIDH1 designed to
bind to and inhibit mIDH1 to reduce 2-hydroxyglutarate levels and restore normal cellular differentiation of myeloid cells. REZLIDHIA is
a novel, non-intensive monotherapy treatment in the R/R AML setting demonstrating a CR+CRh rate of 35% in patients with over 90% of
those responders in complete remission. The safety of REZLIDHIA 150 mg administered twice daily was evaluated in 153 adults with
relapsed or refractory AML with an IDH1 mutation.
12
Table of Contents
On December 1, 2022, the FDA has approved REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R
AML with IDH1 mutation as detected by an FDA approved test. On December 22, 2022, we began the commercialization of REZLIDHIA
and made it available to patients. The recommended dosage of REZLIDHIA is 150 mg taken orally twice daily until disease progression or
unacceptable toxicity. The FDA approval was based on the NDA for olutasidenib for the treatment of m1DH1 R/R AML submitted by
Forma, that had a PDUFA action date for the application of February 15, 2023. The NDA application was supported with Forma’s Phase 2
registrational trial for olutasidenib in mIDH1 R/R AML. Interim results from Forma’s Phase 2 registrational trial were reported at the
American Society of Clinical Oncology (ASCO) annual meeting in June 2021. The interim results of this trial of 153 patients showed that
olutasidenib demonstrated a favorable tolerability profile as a monotherapy in patients with R/R AML who have a susceptible mIDH1, and
achieved a composite complete remission (CR), or CR plus CR with partial hematologic recovery (CRh) rate of 33.3% (30% CR and 3%
CRh), the primary efficacy endpoint. While a median duration of CR/CRh was not yet reached, a sensitivity analysis (with a hematopoietic
stem cell transplant, or HCST, as the end of a response) indicated the median duration of CR/CRh was 13.8 months. The overall response
rate, comprised CR, CRh, CRi, partial response, and morphologic leukemia-free state (MLFS), was 46% and the median duration of ORR
was 11.7 months. The median overall survival (OS) was 10.5 months. For patients with CR/CRh, the median OS was not reached, but the
estimated 18-month survival was 87%. The most frequently reported treatment emergent adverse events were nausea, constipation,
increased white blood cell count , decreased RBC count, pyrexia, febrile neutropenia, and fatigue. Subsequently, Forma presented the first
Phase 2 results of olutasidenib used in combination with azacitidine, including safety/tolerability data, at the American Society of
Hematology (ASH) Annual Meeting in December 2021. Olutasidenib was designated by the FDA as an orphan drug for the treatment of
acute myeloid leukemia in April 2017.
On November 3, 2022, we announced the presentation of five posters highlighting data from our commercial and clinical
hematology-oncology portfolio at the 64th ASH Annual Meeting and Exposition which was held in December 2022. An updated interim
analysis from the Phase 2 registrational trial of olutasidenib in patients with R/R AML demonstrated robust efficacy and safety results. The
registrational cohort of the Phase 2 trial enrolled 153 patients with mIDH1 R/R AML who received olutasidenib monotherapy 150 mg twice
daily. The efficacy evaluable population was 147 patients who received their first dose at least six months prior to the interim analysis
cutoff date of June 18, 2021. The primary endpoint was a CR/CRh defined as less than 5% blasts in the bone marrow, no evidence of
disease, and partial recovery of peripheral blood counts (platelets >50,000/microliter and absolute neutrophil count >500/microliter).
Overall response rate comprises CR, CRh, CR with incomplete blood count recovery, partial response and MLFS. The results from the
updated interim analysis of patients with mIDH1 R/R AML demonstrated a 35% CR+CRh rate with a median duration of 25.9 months.
Olutasidenib was effective in a broad range of patients including those with prior high-intensity chemotherapy and/or post-venetoclax. The
abstract concluded that the observed activity is clinically meaningful and represents a therapeutic advance in the treatment of this patient
population. In this pivotal cohort, olutasidenib was well tolerated with an adverse event profile largely characteristic of symptoms or
conditions experienced by patients undergoing treatment for AML or of the underlying disease itself.
On November 10, 2022, we announced the publication of data in The Lancet Haematology, which summarizes the Phase 1 results
of the Phase 1/2 trial of olutasidenib. The objectives of the first phase of the multi-center, open-label Phase 1/2 trial were to assess the
safety, pharmacokinetic and pharmacodynamic profile, and clinical activity of olutasidenib, both as monotherapy and in combination with
azacitidine, in patients with treatment-naïve or R/R AML or myelodysplastic syndrome (MDS) harboring IDH1 mutations. The published
data suggest that olutasidenib, with or without azacitidine, was well-tolerated and was associated with improvements in clinical efficacy
endpoints in patients with mIDH1 AML. This trial showed that olutasidenib has the potential to provide an additional treatment option for
mIDH1 AML.
In January 2023, we announced that REZLIDHIA (olutasidenib) has been added by the National Comprehensive Cancer Network
(NCCN) to the latest NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AML. REZLIDHIA is now included as a
recommended targeted therapy for adult patients with R/R AML with IDH1 mutation.
13
Table of Contents
In February 2023, we announced peer-reviewed publication data in Blood Advances, which summarize clinical results from the
Phase 2 registrational trial of REZLIDHIA (olutasidenib) in patients with mIDH1 R/R AML. The published data demonstrate that
REZLIDHIA induced durable remissions and transfusion independence with a well-characterized safety profile. The observed efficacy is
clinically meaningful and represents a therapeutic advance in this poor prognosis patient population with limited treatment
options. REZLIDHIA demonstrated both a high rate of response and an extended median duration of complete response of 28.1 months,
which is more than a year longer than what is reported with the SoC.
We plan to pursue strategic actions to further develop olutasidenib for the treatment of other malignancies and expansion of
commercialization.
Commercial activities, including sales and marketing
REZLIDHIA is highly synergistic with our existing hematology-oncology focused commercial and medical affairs infrastructure.
Our commercial efforts will focus on targeting hematologists and hematologist-oncologists who manage patients with R/R AML with
mIDH1. We plan to enter collaborations with third parties to commercialize REZLIDHIA outside of US.
Competitive landscape for REZLIDHIA
There is currently one other product approved in the US for patients with IDH1 mutation. The FDA granted approval to
TIBSOVO® (ivosidenib), an oral targeted IDH1 mutation inhibitor, (i) in July 2018, for adult patients with R/R AML with a susceptible
IDH1 mutation, (ii) in May 2019, for newly diagnosed AML with a susceptible IDH1 mutation who are at least 75 years old or who have
comorbidities that preclude use of intensive induction chemotherapy, (iii) in August 2021, for adult patients with previously treated, locally
advanced or metastatic cholangiocarcinoma with an IDH1 mutation as detected by an FDA-approved test, and (iv) in May 2022, in
combination with azacitidine (azacitidine for injection) for newly diagnosed AML with a susceptible IDH1 mutation, as detected by an
FDA-approved test in adults 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. In
addition, some clinicians may utilize non-targeted treatments for patients with mIDH1 R/R AML, including use of venetoclax
combinations, hypomethylating agents, other chemotherapy regimens, or investigational agents that may be available to them.
Clinical Stage Programs
R289, an Oral IRAK1/4 Inhibitor for Autoimmune, Inflammatory and Hematology-Oncology Diseases
Orally Available IRAK 1/4 Inhibitor Program. During the second quarter of 2018, we selected R835, the active metabolite of
R289, a proprietary molecule from our IRAK 1/4 preclinical development program, for human clinical trials. This investigational candidate
is an orally administered, potent and selective inhibitor of IRAK1 and IRAK4 that blocks inflammatory cytokine production in response to
toll-like receptor (TLR) and the interleukin-1 receptor (IL-1R) family signaling. TLRs and IL-1Rs play a critical role in the innate immune
response and dysregulation of these pathways can lead to a variety of inflammatory conditions including psoriasis, rheumatoid arthritis,
inflammatory bowel disease and gout (among others). R835 prevents cytokine release in response to TLR and IL-1R activation in vitro.
R835 is active in multiple rodent models of inflammatory disease including psoriasis, arthritis, lupus, multiple sclerosis and gout.
Preclinical studies show that R835 inhibits both the IRAK1 and IRAK4 signaling pathways, which play a key role in inflammation and
immune responses to tissue damage. Dual inhibition of IRAK1 and IRAK4 allows for more complete suppression of pro-inflammatory
cytokine release than inhibition of either one individually.
In October 2019, we announced results from a Phase 1 clinical trial of R835 in healthy subjects to assess safety, tolerability,
pharmacokinetics (PK) and pharmacodynamics. The Phase 1 trial was a randomized, placebo-controlled, double-blind trial in 91 healthy
subjects, ages 18 to 55. The Phase 1 trial showed positive tolerability and PK data as well as established proof-of-mechanism by
demonstrating the inhibition of inflammatory cytokine production in response to a lipopolysaccharide (LPS) challenge.
14
Table of Contents
We continue to advance the development of our IRAK1/4 program, completing the evaluation of a new pro-drug formulation of
R835, R289, in single-ascending and multiple ascending dose studies with positive safety results in 2021. In January 2022, we received
clearance from the FDA on our clinical trial design to explore R289 in low-risk MDS. The open-label, Phase 1b trial will determine the
tolerability and preliminary efficacy of R289 in patients with low-risk MDS who are refractory or resistant to prior therapies. In December
2022, we announced that we dosed the first patient in our Phase 1b trial of R289. The Phase 1b trial of R289 is expected to enroll
approximately 22 patients. The primary objective of the trial is safety, with secondary and exploratory objectives to assess preliminary
efficacy and characterize the pharmacokinetic and pharmacodynamic profile of R289. The safety and efficacy data from this Phase 1b trial,
along with the safety and pharmacokinetic/pharmacodynamic data from the completed first-in-human study in heathy volunteers, are
intended to be used to determine the recommended Phase 2 dose for future clinical development of R289 targeting lower-risk MDS.
Fostamatinib in Hospitalized COVID-19 Patients
Disease background. COVID-19 is the infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-
CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS).
Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock resulting in endothelial
dysfunction and subsequently micro and macrovascular thrombosis. Much of the underlying pathology of SARS-CoV-2 is thought to be
secondary to a hyperinflammatory immune response associated with increased risk of thrombosis. SYK is involved in the intracellular
signaling pathways of many different immune cells. Therefore, SYK inhibition may improve outcomes in patients with COVID-19 via
inhibition of key Fc gamma receptor and c-type lectin receptor mediated drivers of pathology, such as inflammatory cytokine release by
monocytes and macrophages, production of NETs by neutrophils, and platelet aggregation. Furthermore, SYK inhibition in neutrophils and
platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19.
Rigel-led Phase 3 Trial. In November 2020, we launched our FOCUS Phase 3 clinical trial to evaluate the safety and efficacy of
fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors. In January 2021,
we were awarded $16.5 million from the US Department of Defense’s Joint Program Executive Office for Chemical, Biological,
Radiological and Nuclear Defense (JPEO-CBRND) to support this Phase 3 clinical trial. This multi-center, double-blind, placebo-
controlled, adaptive design study randomly assigns either fostamatinib plus SoC or matched placebo plus SoC (1:1) to targeted evaluable
patients. Treatment is administered orally twice daily for 14 days with follow up to day 60. In December 2021, we expanded the inclusion
criteria to include patients with more severe disease (NIAID Ordinal Scale 6) to more accurately reflect the clinically predominant patient
population hospitalized with COVID-19 and help speed enrollment. In collaboration with the FDA and Department of Defense, we also
updated the primary endpoint for the trial from progression to severe disease within 29 days, to the number of days on oxygen through day
29. This endpoint allows for closer comparison of the results with earlier results from the NIH/NHLBI Phase 2 clinical trial with
fostamatinib and various other NIH-sponsored trials, such as the ACTIV-4 Host Tissue Trial, which uses a similar outcome measure as a
primary endpoint. In July 2022, we completed enrollment with 280 patients. The trial had originally targeted a total of 308 patients;
however, we determined the trial would be sufficiently powered with 280 patients to potentially provide a clinically meaningful result and
determine the efficacy and safety of fostamatinib in hospitalized COVID-19 patients. On November 1, 2022, we announced the top-line
results of the FOCUS trial. The trial approached but did not meet statistical significance (p=0.0603) in the primary efficacy endpoint of the
number of days on oxygen through Day 29. All prespecified secondary endpoints in the trial numerically favored fostamatinib over placebo,
including mortality, time to sustained recovery, change in ordinal scale assessment, and number of days in the ICU. We are evaluating the
opportunity and discussing next steps with the FDA and in collaboration with our partner, the US Department of Defense.
NIH/NHLBI-sponsored Phase 2 Trial. In September 2020, we announced a Phase 2 clinical trial sponsored by the NIH/NHLBI to
evaluate the safety of fostamatinib for the treatment of hospitalized COVID-19 patients. This multi-center, double-blind, placebo-controlled
trial randomly assigned fostamatinib or matched placebo (1:1) to 59 evaluable patients. Treatment was administered orally twice daily for
14 days, and a follow-up period to day 60. The primary endpoint of this trial was cumulative incidence of Serious Adverse Events (SAEs)
through day 29. The trial also included multiple secondary endpoints designed to assess the early efficacy and clinically relevant endpoints
of disease course.
15
Table of Contents
The trial completed the enrollment in March 2021. In April 2021, we announced that the Phase 2 clinical trial met its primary endpoint of
safety. Fostamatinib reduced the incidence of SAEs by half. By day 29, there were three SAEs in the fostamatinib plus SoC group of thirty
patients compared to six SAEs in the placebo plus SoC group of twenty-nine patients (p=0.23). Of these, there was a reduction for the
disease related SAE of hypoxia in the fostamatinib group compared to placebo (1 vs 3, respectively; p=0.29). The data from the
NIH/NHLBI-Sponsored Phase 2 trial was published in Clinical Infectious Diseases, an official publication of the Infectious Disease Society
of America in September 2021.
In May 2021, the NIH/NHLBI Phase 2 clinical data were submitted as part of a request for an EUA from the FDA for fostamatinib
as a treatment for hospitalized patients with COVID-19. In August 2021, the FDA informed us that the clinical data submitted from the
NIH/NHLBI-sponsored Phase 2 trial of fostamatinib to treat hospitalized patients suffering from COVID-19 was insufficient for an EUA.
ACTIV-4 Host Tissue Phase 2/3 Trial. In June 2021, we announced that fostamatinib had been selected for the NIH ACTIV-4 Host
Tissue Trial in hospitalized patients with COVID-19. The ACTIV-4 Host Tissue Trial, initiated and funded by NHLBI, is a randomized,
placebo-controlled trial of therapies, including fostamatinib, targeting the host response to COVID-19 in hospitalized patients. The master
protocol for this trial was designed to be flexible in the number of study arms, the use of a single placebo group, and the stopping and
adding of new therapies. Eligible participants include patients hospitalized for COVID-19 with laboratory-confirmed SARS-CoV-2
infection and a new need for oxygen therapy. The primary outcome is oxygen-free days through day 28. Secondary outcomes include 28-
day hospital mortality, use of mechanical ventilation, and severity of disease as measured by World Health Organization (WHO) scale
scores. The ACTIV-4 Host Tissue Trial is evaluating fostamatinib in a targeted population of approximately 600 hospitalized patients with
COVID-19, 300 fostamatinib versus 300 placebo. An interim analysis of the trial was completed by the Data and Safety Monitoring Board
with a recommendation for the trial to continue.
Imperial College of London Phase 2 Trial. In July 2020, we announced a Phase 2 clinical trial sponsored by Imperial College of
London to evaluate the efficacy of fostamatinib for the treatment of COVID-19 pneumonia. This is a two-stage, open label, controlled
clinical trial with patients randomized (1:1:1) to fostamatinib plus SoC, ruxolitinib plus SoC, or SoC alone. Treatment was administered
twice daily for 14 days and patients receive a follow-up assessment at day 14 and day 28 after the first dose. The primary endpoint of this
trial is progression from mild to severe COVID-19 pneumonia within 14 days in hospitalized patients (WHO COVID-19 Severity Scale 3-
4). In April 2022, Imperial College of London completed a pre-planned interim analysis of the primary endpoint, patients progressing from
mild or moderate (modified WHO COVID-19 scale 3-4) to severe disease (modified WHO COVID-19 scale ≥5) within 14 days, in the
Phase 2 MATIS trial. The independent data monitoring committee determined that the fostamatinib plus SoC arm did not meet the
prespecified criteria for continuation to the next stage of the trial. No safety concerns were identified. The trial remains blinded and
Imperial College of London plans to share results with us and scientific community once the trial is complete.
Other Publications. Researchers at MIT and Harvard led a screen to identify FDA-approved compounds that reduce MUC1
protein abundance. MUC1 is a biomarker used to predict the development of ALI and ARDS and correlates with poor clinical outcomes. In
June 2020, the results were presented, and of the 3,713 compounds that were screened, fostamatinib was the only compound identified
which both decreased expression of MUC1 and is FDA approved. Fostamatinib demonstrated preferential depletion of MUC1 from
epithelial cells without affecting cell viability. The research was focused on drug repurposing for the much lower risk of toxicity and the
ability of FDA-approved treatments to be delivered on a shortened timescale, which is critical for patients afflicted with lung disease
resulting from COVID-19.
In addition, the in vitro studies led by the Amsterdam University Medical Center at the University of Amsterdam, showed that
R406, the active metabolite of fostamatinib, blocked macrophage hyperinflammatory responses to a combination of immune complexes
formed by anti-Spike IgG in serum from severe COVID-19 patients. Anti-Spike IgG levels are known to correlate with the severity of
COVID-19. These results, presented in July 2020, suggest that by inhibiting anti-Spike IgG-mediated hyperinflammation, R406 could
potentially play a role in the prevention of cytokine storms as well as pulmonary edema and thrombosis associated with severe COVID-19.
16
Table of Contents
In December 2020, the Journal of Infectious Diseases published research from NIH which demonstrated that R406, the active
metabolite of fostamatinib, was able to inhibit NETosis ex vivo in donor plasma from patients with COVID-19. NETosis is a unique type of
cell death resulting in the release of NETs. NETs contribute to thromboinflammation and have been associated with mortality in COVID-
19. These data provide insights for how fostamatinib may mitigate neutrophil-associated mechanisms contributing to COVID-19
immunopathogenesis.
Fostamatinib in wAIHA
Disease background. Autoimmune hemolytic anemia is a rare, serious blood disorder where the immune system produces
antibodies that result in the destruction of the body’s own red blood cells. Symptoms can include fatigue, shortness of breath, rapid
heartbeat, jaundice or enlarged spleen. While no medical treatments are currently approved for AIHA, physicians generally treat acute and
chronic cases of the disorder with corticosteroids, other immuno-suppressants, or splenectomy. Research has shown that inhibiting SYK
with fostamatinib may reduce the destruction of red blood cells. AIHA affects an estimated 45,000 Americans, and approximately 36,000 of
those patients have wAIHA, where no approved treatment options currently exist.
Orally-available fostamatinib program. We completed our Phase 2 clinical trial, also known as the SOAR study, in patients with
wAIHA. This trial was an open-label, multi-center, two-stage study that evaluated the efficacy and safety of fostamatinib in patients with
wAIHA who had previously received treatment for the disorder but have relapsed. The primary efficacy endpoint of this study was to
achieve increased hemoglobin levels by week 12 of greater than 10 g/dL, and greater than or equal to 2 g/dL higher than baseline. In
November 2019, we announced updated data that in a Phase 2 open-label study of fostamatinib in patients with wAIHA, data showed that
44% (11/25) of evaluable patients met the primary efficacy endpoint of a Hgb level >10 g/dL with an increase of ≥2 g/dL from baseline by
week 24. Including one late responder at week 30, the overall response rate was 48% (12/25). Adverse events were manageable and
consistent with those previously reported with fostamatinib. In February 2022, the American Journal of Hematology published the data
from our Phase 2 clinical trial of fostamatinib in adults with wAIHA who have failed at least one prior treatment. The published data
demonstrate that fostamatinib rapidly and durably increased hemoglobin (Hgb) levels, with clinically meaningful Hgb responses observed
in nearly half of the patients, and a safety and tolerability profile consistent with the existing fostamatinib safety database of patients across
multiple disease programs studied.
In January 2021, we announced that the FDA had granted Fast Track designation to fostamatinib for the treatment of wAIHA. The
FDA previously granted fostamatinib Orphan Drug designation for the treatment of wAIHA in January 2018.
In March 2019, we initiated our wAIHA pivotal Phase 3 clinical trial of fostamatinib, known as the FORWARD study. The clinical
trial protocol calls for a placebo-controlled study of 90 patients with primary or secondary wAIHA who have failed at least one prior
treatment. The primary endpoint is a durable Hgb response, defined as Hgb >10 g/dL and >2 g/dL increase from baseline and durability
measure, with the response not being attributed to rescue therapy. In November 2020, we reached an agreement with the FDA on the
durable response measure for the primary efficacy endpoint of the trial as well as the inclusion of additional secondary endpoints. In
November 2021, we completed the enrollment of this study. In April 2022, we completed the treatment period for the last patient under the
trial. In June 2022, we announced top-line efficacy and safety data from the FORWARD study with 90 patients. Patients were randomized
1:1 to receive fostamatinib or matching placebo twice daily for 24 weeks. The primary efficacy endpoint of Hgb response was defined as
achieving a Hgb ≥10 g/dL with an increase from baseline ≥2 g/dL on three consecutive available visits during the 24-week treatment
period. The trial did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin response in the overall
study population. The trial also included key secondary endpoints, including hemoglobin response on at least one visit, change in Hgb from
baseline of ≥2 g/dL, use of permitted rescue therapy after week 4, change in Hgb from baseline to end of treatment and change from
baseline to week 24 in FACIT-F scale. Across the trial’s overall patient population, fostamatinib was generally well-tolerated. The safety
profile of the product was consistent with prior clinical experience and no new safety issues were discovered. The most common adverse
events (≥10%) with fostamatinib and placebo were diarrhea, hypertension, fatigue, pyrexia, nausea, and dyspnea. Treatment-related SAEs
were 6.7% (3/45) for fostamatinib and 4.4% (2/45) for placebo. There were five deaths on the trial (2 with fostamatinib and 3 with
placebo), all of which were determined to be unrelated to study drug. The safety results were consistent with the overall safety profile data
collected to date, which includes more than 5,000 patients
17
Table of Contents
across multiple diseases. We conducted an in-depth analysis of these data to better understand differences in patient characteristics and
outcomes and submitted these findings to the FDA. In October 2022, we announced that we received guidance from the FDA’s review of
these findings. Based on the result of the trial and the guidance from the FDA, we did not file an sNDA for this indication.
Of the 90 patients that completed the FORWARD study, 71 (79%) enrolled in the open-label extension study. We plan on closing
this study in 2023.
Partnered Clinical Programs
BGB324 – BerGenBio
We have an exclusive, worldwide research, development and commercialization agreement with BerGenBio for our investigational
AXL receptor tyrosine kinase inhibitor, BGB324/R428 (now referred to as bemcentinib). In October 2022, BerGenBio announced the
initiation of a Phase 1b/2a trial evaluating bemcentinib in combination with the current SoC, checkpoint inhibitor pembrolizumab and
doublet chemotheraphy, for the treatment of first line non-small cell lung cancer patients harboring serine/threonine kinase 11 mutations. In
February 2023, BerGenBio also announced positive data from Phase 2 trial of bemcentinib in combination with pembrolizumab in patients
with 2L+ non-small cell lung cancer (NSCLC). The treatment with bemcentinib in combination with pembrolizumab demonstrated long
survival benefit and sustained disease control, particularly in patients with AXL TPS > 5, substantiating the relevance of AXL as a target
and bemcentinib’s selective inhibition capabilities in NSCLC. The product is also being investigated in Phase 2 clinical trials in patients
with AML and COVID-19. Bemcentinib is being studied in over 600 patients, demonstrating its safety as a monotherapy and in
combination with chemotheraphy and immune checkpoint inhibition.
DS-3032 - Daiichi
DS-3032 is an investigational oral selective inhibitor of the murine double minute 2 (MDM2) protein investigated by Daiichi in
three Phase 1 clinical trials for solid and hematological malignancies including AML, acute lymphocytic leukemia, chronic myeloid
leukemia in blast phase, lymphoma and MDS. Preliminary safety and efficacy data from a Phase 1 trial of DS-3032 suggests that DS-3032
may be a promising treatment for hematological malignancies including R/R AML and high-risk MDS.
In September 2020, worldwide rights to DS-3032 (milademetan) were out-licensed from Daiichi to Rain Oncology Inc., formerly
Rain Therapeutics Inc. (Rain). In July 2021, Rain announced that it initiated a Phase 3 trial to evaluate the efficacy and safety of
milademetan (RAIN-32) for the treatment of well-differentiated/dedifferentiated liposarcoma, a rare cancer originating from fat cells
located in the soft tissues of the body and in August 2022, Rain announced the completion of enrollment of its Phase 3 trial for milademetan
in liposarcoma. In late 2021, Rain commenced its second clinical trial for RAIN-32 in patients with MDM2-amplified advance solid
tumors, and in November 2022, Rain provided an interim analysis of the trial which showed that the drug safety profile of milademetan is
preliminary consistent with its prior Phase 1 trial.
Research, Preclinical and Clinical Development Programs
We have retained a selected team of experts in drug discovery and preclinical development to leverage our existing proprietary
collection of inhibitors, small-molecule compound libraries and large database of associated phenotypic and biochemical assay results of
therapeutic interest. We maintain leading expertise on specific areas of operation such as inhibition of SYK, IRAK1/4 , RIPK1 and mIDH1
kinases to assist clinical development and commercial affairs, as well as to expand and explore additional opportunities for such inhibitors
in the clinical space. Our preclinical operations involve collaborations with clinical research organizations, leading investigators from
universities and research organizations around the world, and strategic collaborations with other pharmaceutical companies.
We have assembled a team of experts in drug development to design and implement clinical trials and to analyze the data derived
from these trials. The clinical development group possesses expertise in project management
18
Table of Contents
and regulatory affairs. We work with external clinical research organizations with expertise in managing clinical trials, drug formulation,
and the manufacture of clinical trial supplies to support our drug development efforts.
Commercialization and Sponsored Research and License Agreements
For a discussion of our Commercialization and Sponsored Research and License, see “Note 4 - Sponsored Research and License
Agreements and Government Contract” to our “Notes to Financial Statements” contained in “Part II, Item 8, Financial Statements and
Supplementary Data” of this Annual Report on Form 10-K.
Intellectual Property
We are able to protect our technology from unauthorized use by third parties only to the extent that it is covered by valid and
enforceable patents or is effectively maintained as a trade secret. Accordingly, patents and other proprietary rights are an essential element
of our business. As of December 31, 2022, we owned or had exclusive license to 48 pending patent applications and 376 issued and active
patents in the US, as well as corresponding pending foreign patent applications and issued foreign patents. Our policy is to file patent
applications to protect technology, inventions and improvements to inventions that are commercially important to the development of our
business. We seek US and international patent protection for a variety of technologies, including new screening methodologies and other
research tools, target molecules that are associated with disease states identified in our screens, and lead compounds that can affect disease
pathways. We also intend to seek patent protection or rely upon trade secret rights to protect other technologies that may be used to discover
and validate targets and that may be used to identify and develop novel drugs. We seek protection, in part, through confidentiality and
proprietary information agreements. We are a party to various license agreements that give us rights to use technologies in our research and
development.
We currently hold a number of issued patents in the US, as well as corresponding applications that allow us to pursue patents in
other countries, some of which have been allowed and/or granted and others of which we expect to be granted. Specifically, in most cases
where we hold a US issued patent, the subject matter is covered at least by an application filed under the Patent Cooperation Treaty (PCT),
which is then used or has been used to pursue protection in certain countries that are members of the treaty. Our patents extend for varying
periods according to the date of patent filing or grant and the legal term of patents in the various countries where patent protection is
obtained. Some of these patents may be eligible for patent term extensions, depending on their subject matter and length of time required to
conduct clinical trials. Our material patents relate to fostamatinib, an oral SYK inhibitor, that is the active pharmaceutical ingredient in
TAVALISSE, and olutasidenib, an oral mIDH1 inhibitor that is the active pharmaceutical ingredient in REZLIDHIA. These patents will
expire at various dates from 2026 to 2032 for fostamatinib and from 2035 to 2039 for olutasidenib.
Fostamatinib. Fostamatinib is covered as a composition of matter in a US issued patent that has an expected expiration date of
September 2031, after taking into account a patent term adjustment and extension rules. Additional patents covering fostamatinib
composition of matter, methods for use, formulations, methods for making and intermediates expire at various dates from 2023 to 2041.
Corresponding applications have been filed in foreign jurisdictions under the PCT, and are at various stages of prosecution. Of note, a
patent covering fostamatinib as a composition of matter and in compositions for use treating various diseases has been granted by the
European Patent Office.
Olutasidenib. Olutasidenib is covered as a composition of matter in a US issued patent that has an expected expiration date of
December 2036, after taking into account patent term extension rules. Additional patents covering olutasidenib compositions of matter,
methods for use, solid forms, methods for making and intermediates expire at various dates from 2035 to 2042. Several corresponding
applications have been filed in foreign jurisdictions under the PCT and are at various stages of prosecution.
19
Table of Contents
Competition
The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological
change. Many of the drugs that we are attempting to discover will be competing with existing therapies. In addition, a number of companies
are pursuing the development of pharmaceuticals that target the same diseases and conditions that we are targeting.
We face, and will continue to face, intense competition from pharmaceutical and biotechnology companies, as well as from
academic and research institutions and government agencies, both in the US and abroad. Some of these competitors are pursuing the
development of pharmaceuticals that target the same diseases and conditions as our research programs. Our major competitors include fully
integrated pharmaceutical companies that have extensive drug discovery efforts and are developing novel small molecule and biologics
pharmaceuticals. We also face significant competition from organizations that are pursuing the same or similar technologies, including the
discovery of targets that are useful in compound screening, as the technologies used by us in our drug discovery efforts.
Competition may also arise from:
● new or better methods of target identification or validation;
● generic version of our products or of products with which we compete;
● other drug development technologies and methods of preventing or reducing the incidence of disease;
● new small molecules; or
● other classes of therapeutic agents.
Our competitors or their collaborative partners may utilize discovery technologies and techniques or partner with collaborators in
order to develop products more rapidly or successfully than we or our collaborators are able to do. Many of our competitors, particularly
large pharmaceutical companies, have substantially greater financial, technical and human resources and larger research and development
staffs than we do. In addition, academic institutions, government agencies and other public and private organizations conducting research
may seek patent protection with respect to potentially competitive products or technologies and may establish exclusive collaborative or
licensing relationships with our competitors.
We believe that our ability to compete is dependent, in part, upon our ability to create, maintain and license scientifically advanced
technology and upon our and our collaborators’ ability to develop and commercialize pharmaceutical products based on this technology, as
well as our ability to attract and retain qualified personnel, obtain patent protection or otherwise develop proprietary technology or
processes and secure sufficient capital resources for the expected substantial time period between technological conception and commercial
sales of products based upon our technology. The failure by any of our collaborators or us, including our commercial team, in any of those
areas may prevent the successful commercialization of our potential drug targets.
Many of our competitors, either alone or together with their collaborative partners, have significantly greater experience than we
do in:
● identifying and validating targets;
● screening compounds against targets; and
● undertaking preclinical testing and clinical trials.
Accordingly, our competitors may succeed in obtaining patent protection, identifying or validating new targets or discovering new
drug compounds before we do.
20
Table of Contents
Our competitors might develop technologies and drugs that are more effective or less costly than any that are being developed by
us or that would render our technology and product candidates obsolete and noncompetitive. In addition, our competitors may succeed in
obtaining the approval of the FDA or other regulatory agencies for product candidates more rapidly. Companies that complete clinical trials,
obtain required regulatory agency approvals and commence commercial sale of their drugs before us may achieve a significant competitive
advantage, including certain patent and FDA marketing exclusivity rights that would delay or prevent our ability to market certain products.
Any drugs resulting from our research and development efforts, or from our joint efforts with our existing or future collaborative partners,
might not be able to compete successfully with competitors’ existing or future products or obtain regulatory approval in the US or
elsewhere.
We face and will continue to face intense competition from other companies for commercial and collaborative arrangements with
pharmaceutical and biotechnology companies, for establishing relationships with academic and research institutions and for licenses to
additional technologies. These competitors, either alone or with their collaborative partners, may succeed in developing technologies or
products that are more effective than ours.
Our ability to compete successfully will depend, in part, on our ability to:
● identify and validate targets;
● discover candidate drug compounds that interact with the targets we identify;
● attract and retain scientific and product development personnel;
● obtain patent or other proprietary protection for our new drug compounds and technologies;
● enter commercialization agreements for our new drug compounds; and
● to obtain and maintain an appropriate reimbursement price and positive recommendations by HTA bodies.
ITP
There are existing therapies and drug candidates in development for the treatment of ITP that may be alternative therapies to
TAVALISSE. Currently, corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous
immuglobulin (IVIg) or anti-Rh(D) as added agents to help further augment platelet count recovery, particularly in emergency situations.
However, it has been estimated that frontline agents lead to durable remissions in only a small percentage of newly-diagnosed adults with
ITP. Moreover, concerns with steroid-related side effects often restrict therapy to approximately four weeks. As such, many patients
progress to persistent or chronic ITP, requiring other forms of therapeutic intervention.
The FDA can approve an ANDA for a generic version of a branded drug without the ANDA applicant undertaking the clinical
testing necessary to obtain approval to market a new drug. In September 2019, the FDA published product-specific bioequivalence
guidance on fostamatinib disodium to let potential ANDA applicants understand the data the FDA would expect to see for approval of a
generic version of TAVALISSE. The earliest an ANDA may be filed by a generic company was April 17, 2022. The ANDA process can
result in generic competition if the patents at issue are not upheld or if the generic competitor is found not to infringe our patents.
Other approaches to treat ITP are varied in their mechanism of action, and there is no consensus about the sequence of their use.
Options include splenectomy, TPO-Ras, and various immunosuppressants (such as rituximab). The response rate criteria of the above-
mentioned options vary, precluding a comparison of response rates for individual therapies. According to the most recent ITP guideline
from the ASH, there was a lack of evidence to support strong recommendations for various management approaches. In general, strategies
that avoided medication side effects were favored. A large focus was placed on shared decision-making especially with regard to second-
line therapy.
Even with the above treatment options, a significant number of patients remain severely thrombocytopenic for long durations and
are subject to risk of spontaneous or trauma-induced hemorrhage. The addition of fostamatinib to the treatment options could be beneficial
since it has a different mechanism of action than the TPO agonists. Fostamatinib is
21
Table of Contents
a potent and relatively selective SYK inhibitor, and its inhibition of Fc receptors and B-cell receptors signaling pathways make it a
potentially broad immunomodulatory agent.
Other products in the US that are approved by the FDA to increase platelet production through binding and TPO receptors on
megakaryocyte precursors include PROMACTA (Novartis), Nplate (Amgen, Inc.) and DOPTELET (Dova Pharmaceuticals).
AML with IDH1 Mutation
There is currently one other product approved in the US for patients with IDH1 mutation. TIBSOVO (ivosidenib), an oral targeted
IDH1 mutation inhibitor, is an FDA approved drug for (i) adult patients with R/R AML with a susceptible IDH1 mutation, (ii) newly
diagnosed AML with a susceptible IDH1 mutation who are at least 75 years old or who have comorbidities that preclude use of intensive
induction chemotherapy, (iii) for adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1
mutation as detected by an FDA-approved test, and (iv) in combination with azacitidine (azacitidine for injection), for newly diagnosed
AML with a susceptible IDH1 mutation, as detected by an FDA-approved test in adults 75 years or older, or who have comorbidities that
preclude use of intensive induction chemotherapy. TIBSOVO is a registered trademark of Servier Pharmaceuticals LLC, a wholly owned,
indirect subsidiary of Les Laboratoires Servier. In addition, some clinicians may utilize non-targeted treatments for patients with mIDH1
R/R AML, including use of venetoclax combinations, hypomethylating agents, other chemotherapy regimens, or investigational agents that
may be available to them.
Government Regulation
Government authorities in the US, at the federal, state and local level, and in other countries and jurisdictions, extensively
regulate, among other things, the research, development, testing, manufacture, quality control, approval, packaging, storage, recordkeeping,
labeling, advertising, promotion, distribution, marketing, sampling, tracking and tracing, sales, post-approval monitoring and reporting, and
import and export of pharmaceutical products. The processes for obtaining regulatory approvals in the US and in foreign countries and
jurisdictions, along with subsequent compliance with applicable statutes and regulations, such as those governing personal information and
information security, require the expenditure of substantial time and financial resources.
Review and Approval of Drugs in the US
In the US, the FDA approves and regulates drugs under the Federal Food, Drug, and Cosmetic Act (FDCA) and implementing
regulations. The failure to comply with requirements under the FDCA and other applicable laws 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 the FDA to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance
of warning letters and other types of letters, 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.
A drug product candidate must be approved by the FDA through the new drug application (NDA). An applicant seeking approval
to market and distribute a new drug product in the US must typically undertake the following:
● completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s good
laboratory practice regulations;
● submission to the FDA of an IND, which must take effect before human clinical trials may begin;
● approval by an independent institutional review board (IRB) for each clinical site before each clinical trial may be initiated;
● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices (GCP) to
establish the safety and efficacy of the proposed drug product for each indication;
22
Table of Contents
● preparation and submission to the FDA of an NDA requesting marketing for one or more proposed indications;
● review by an FDA advisory committee, if requested by the FDA;
● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or
components thereof, are produced to assess compliance with current Good Manufacturing Practices (cGMP), requirements
and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and
purity;
● satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical
data;
● payment of user fees and securing FDA approval of the NDA; and
● compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and
Mitigation Strategy, or REMS, and potentially post-market requirement, or PMR, and commitment, or PMC, studies.
Before an applicant begins testing a compound with potential therapeutic value in humans, the drug candidate enters the
preclinical testing stage. Preclinical studies include laboratory evaluation as well as in vitro and animal studies to assess product chemistry,
formulation, and toxicity, as well as the safety and activity of the drug for initial testing in humans and to establish a rationale for
therapeutic use. The results of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or
literature and plans for clinical studies, among other things, are submitted to the FDA as part of an IND. Some long-term preclinical testing,
such as animal tests of reproductive adverse events and carcinogenicity, and long-term toxicity studies, may continue after the IND is
submitted.
An IND is an exemption from the FDCA that allows an unapproved new drug to be shipped in interstate commerce for use in an
investigational clinical trial and a request for FDA authorization to administer an investigational drug to humans. In support of the IND,
applicants must submit a protocol for each clinical trial and any subsequent protocol amendments. In addition, the results of the preclinical
tests, together with manufacturing information, analytical data, any available clinical data or literature, among other things, are submitted to
the FDA as part of an IND. The FDA requires a 30-day waiting period after the submission of each IND before clinical trials may begin. At
any time during this 30-day period, or thereafter, the FDA may raise concerns or questions about the conduct of the trials as outlined in the
IND and impose a clinical hold or partial clinical hold. In this case, the IND sponsor and the FDA must resolve any outstanding concerns
before clinical trials can begin or resume. An IRB representing each institution participating in the clinical trial must review and approve
the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the study
at least annually. An IRB can suspend or terminate approval of a clinical trial.
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified
investigators in accordance with GCP requirements, which include, among other things, the requirement that all research subjects provide
their informed consent in writing before their participation in any clinical trial. Human clinical trials are typically conducted in sequential
phases, which may overlap or be combined:
● Phase 1. The drug is initially introduced into a small number of healthy human subjects or, in certain indications such as
cancer, patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism,
distribution, excretion and, if possible, to gain an early indication of its effectiveness and to determine optimal dosage.
● Phase 2. The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to
preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal
dosage.
● Phase 3. These clinical trials are commonly referred to as “pivotal” studies, which denote a study that presents the data that
the FDA or other relevant regulatory agency will use to determine whether or not to
23
Table of Contents
approve a drug. The drug is administered to an expanded patient population, generally at geographically dispersed clinical
trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the
product for approval, identify adverse effects, establish the overall risk-benefit profile of the product and to provide adequate
information for the labeling of the product.
● Phase 4. Post-approval studies may be conducted after initial marketing approval. These studies are used to gain additional
experience from the treatment of patients in the intended therapeutic indication.
In most cases the FDA requires at least two adequate and well-controlled Phase 3 clinical trials to demonstrate the efficacy of the
drug. A single Phase 3 trial with other confirmatory evidence may be sufficient in rare instances, such as where the study is a large
multicenter trial demonstrating internal consistency and a statistically very persuasive finding of a clinically meaningful effect on mortality,
irreversible morbidity or prevention of a disease with a potentially serious outcome and confirmation of the result in a second trial would be
practically or ethically impossible.
Concurrent with clinical trials, companies often 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 product in commercial
quantities in accordance with current good manufacturing practices (cGMP) requirements. The manufacturing process must be capable of
consistently producing quality batches of the drug candidate and, among other things, must develop methods for testing the identity,
strength, quality and purity of the final drug. 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.
The FDA or the sponsor or the data monitoring committee may suspend or terminate a clinical trial at any time on various grounds,
including a finding that the research subjects are being exposed to an unacceptable health risk.
Review and Approval of Drugs in the EU and the UK
Similar rules governing clinical trials to those in place in the US apply in the European Union (EU) and the UK, with a clinical
trial application (CTA) required to be submitted for each clinical trial to each EU Member State’s national competent authority (NCA) and
an independent Ethics Committee. Following the UK’s exit from the EU, commonly referred to as Brexit, and the end of the transition
period that was in place until the end of 2020, clinical trials that take place in the UK will be seen by the EMA as trials that have taken
place in a “third country” and will only be considered during the course of a marketing authorization application if they are carried out on a
basis that is in line with the regulations governing clinical trials in the EU. As of January 31, 2022, clinical trials in the EU must be
conducted in accordance with the requirements of the EU Clinical Trials Regulation (EU) No 536/2014 (CTR) that has amended the system
of approval for clinical trials in the EU. Under the CTR as of January 31, 2023, sponsors must apply for authorizations through the Clinical
Trials Information System (CTIS), the new clinical trials portal and database that allows a coordinated and streamlined application and
authorization process for clinical trials and ethical approvals throughout the EU. The UK has not applied the CTR, and is currently revising
its own clinical trials framework, and therefore its regulatory framework on clinical trials is not aligned with the EU CTR. This may result
in trials that take place in the UK potentially carrying less weight when applying for a marketing authorization in the EU.
Review of an NDA by the FDA
If clinical trials are successful, the next step in the drug development process is the preparation and submission to the FDA of an
NDA. The NDA is the vehicle through which drug applicants formally propose that the FDA approve a new drug for marketing and sale in
the US for one or more indications. The NDA must contain a description of the manufacturing process and quality control methods, as well
as results of preclinical tests, toxicology studies, clinical trials and proposed labeling, among other things. The submission of most NDAs is
subject to an application user fee and the sponsor of an approved NDA is also subject to annual program user fees. These fees are typically
increased annually.
Following submission of an NDA, the FDA conducts a preliminary review of an NDA to determine whether the application is
sufficiently complete to permit substantive review. The FDA has 60 days from its receipt of an NDA to determine whether the application
will be accepted for filing based on the agency’s threshold determination that it is
24
Table of Contents
sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In
this event, the application must be resubmitted with the additional information. The resubmitted application is also subject to review before
the FDA accepts it for filing. Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA has
agreed to goals to review and act within ten months from filing for standard review NDAs and within six months for NDAs that have been
designated for “priority review”.
Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is or will be manufactured.
The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP
requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving an
NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. In addition, as a condition of approval, the
FDA may require an applicant to develop a REMS. REMS use risk minimization strategies beyond the professional labeling to ensure that
the benefits of the product outweigh the potential risks. To determine whether a REMS is needed, the FDA will consider the size of the
population likely to use the product, seriousness of the disease or condition to be treated by the drug, expected benefit of the product,
expected duration of treatment, seriousness of known or potential adverse events, and whether the product is a new molecular entity.
The FDA is required to refer an application for a novel drug to an advisory committee or explain why such referral was not made.
Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates
and provides 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.
On the basis of the FDA’s evaluation of the NDA and accompanying information, including the results of the inspection of the
manufacturing facilities, the FDA may issue an approval letter or a complete response letter. An approval letter authorizes commercial
marketing of the product with specific prescribing information for specific indications. A complete response letter generally outlines the
deficiencies in the submission and may require substantial additional testing or information in order for the FDA to reconsider the
application. If and when those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue
an approval letter. The FDA intends to review such resubmissions in two or six months depending on the type of information included.
Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory
criteria for approval.
If the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications,
warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be
conducted to further assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after
commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS,
which can materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a
product based on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved
product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements
and submission to FDA of an sNDA, which may require FDA review and approval prior to implementation. An NDA supplement for a new
indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in
reviewing NDA supplements as it does in reviewing NDAs.
Expedited approval pathways
The FDA is authorized to designate certain products for expedited review if they are intended to address an unmet medical need in
the treatment of a serious or life-threatening disease or condition. These programs are referred to as Fast Track designation, Breakthrough
Therapy designation and Priority Review designation. In addition, accelerated approval offers the potential for approval based on a
surrogate or intermediate clinical endpoint. In May 2014, the FDA published a final Guidance for Industry titled “Expedited Programs for
Serious Conditions Drugs and Biologics,” which provides guidance on the FDA programs that are intended to facilitate and expedite
development and review of new drug candidates as well as threshold criteria generally applicable to concluding that a drug candidate is a
candidate for these
25
Table of Contents
expedited development and review programs.
The FDA may designate a product for Fast Track review if it is intended, whether alone or in combination with one or more other
products, for the treatment of a serious or life-threatening disease or condition, and nonclinical or clinical data demonstrate the potential to
address unmet medical needs for such a disease or condition. For Fast Track products, sponsors may have greater interactions with the FDA
and the FDA may initiate review of sections of a Fast Track product’s application before the application is complete. This rolling review
may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a Fast Track product
may be effective. The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining information
and the sponsor must pay applicable user fees. However, the FDA’s review clock for a Fast Track application does not begin until the last
section of the application is submitted. In addition, the Fast Track designation may be withdrawn by the FDA if the FDA believes that the
designation is no longer supported by data emerging in the clinical trial process.
A product may be designated as a Breakthrough Therapy if it is intended, either alone or in combination with one or more other
products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may
demonstrate substantial improvement over existing available therapies on one or more clinically significant endpoints, such as substantial
treatment effects observed early in clinical development. The FDA may take certain actions with respect to Breakthrough Therapies,
including holding meetings with the sponsor throughout the development process; providing timely advice to the product sponsor regarding
development and approval; involving more senior staff in the review process; assigning a cross disciplinary project lead for the review
team; rolling review; and, taking other steps to design the clinical trials in an efficient manner.
FDA intends to review applications for standard review drug products within ten months of the 60-day filing date; and, applications
for priority review drugs within six months. Priority review can be applied to drugs that the FDA determines treat a serious condition, and if
approved, would offer a significant improvement in safety or effectiveness. The FDA determines, on a case-by-case basis, whether the
proposed product represents a significant improvement when compared with other available therapies. Significant improvement may be
illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment limiting
product reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of
safety and effectiveness in a new subpopulation.
Accelerated approval pathway
The FDA may grant accelerated approval to a drug for a serious or life-threatening condition that provides a meaningful therapeutic
advantage to patients over available treatments based upon a determination that the drug has an effect on a surrogate endpoint that is
reasonably likely to predict clinical benefit. The FDA may also grant accelerated approval for such drug for such a condition when the
product has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality
(IMM) and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity or
prevalence of the condition and the availability or lack of alternative treatments. Drugs granted accelerated approval must meet the same
statutory standards for safety and effectiveness as those granted traditional approval.
For the purposes of accelerated approval, a surrogate endpoint is a marker, such as a laboratory measurement, radiographic image,
physical sign or other measure that is thought to predict clinical benefit but is not itself a measure of clinical benefit. Surrogate endpoints
can often be measured more easily or more rapidly than clinical endpoints. An intermediate clinical endpoint is a measurement of a
therapeutic effect that is considered reasonably likely to predict the clinical benefit of a drug, such as an effect on IMM. The FDA has
limited experience with accelerated approvals based on intermediate clinical endpoints but has indicated that such endpoints generally may
support accelerated approval where the therapeutic effect measured by the endpoint is not itself a clinical benefit and basis for traditional
approval, if there is a basis for concluding that the therapeutic effect is reasonably likely to predict the ultimate clinical benefit of a drug.
The accelerated approval pathway is most often used in settings in which the course of a disease is long, and an extended period of time is
required to measure the intended clinical benefit of a drug, even if the effect on the surrogate or intermediate clinical endpoint occurs
rapidly. Thus, accelerated approval has been used extensively in the
26
Table of Contents
development and approval of drugs for treatment of a variety of cancers in which the goal of therapy is generally to improve survival or
decrease morbidity and the duration of the typical disease course requires lengthy and sometimes large trials to demonstrate a clinical or
survival benefit.
The accelerated approval pathway is contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-
approval confirmatory studies to verify and describe the drug’s clinical benefit. As a result, a drug candidate approved on this basis is
subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or post-approval clinical trials to confirm
the effect on the clinical endpoint. Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing
studies, would allow the FDA to withdraw the drug from the market on an expedited basis. In addition, all promotional materials for drugs
approved under accelerated regulations are subject to prior review by the FDA.
Post-Approval Requirements
Drugs manufactured or distributed pursuant to FDA, EMA and MHRA approvals are subject to pervasive and continuing
regulation by the FDA, EMA and MHRA and other national competent authorities in the EU including, among other things, requirements
relating to recordkeeping, periodic reporting, product sampling and distribution, tracking and tracing, advertising and promotion and
reporting of adverse experiences with the product. After approval, most changes to the approved product, such as adding new indications or
other labeling claims, are subject to prior FDA review and approval. In addition, drug manufacturers and other entities involved in the
manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies, and are
subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the
manufacturing process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also require
investigation and correction of any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and any
third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must continue to expend time, money, and effort
in the area of production and quality control to maintain cGMP compliance.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and standards is not
maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product,
including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory
requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical
trials to assess new safety risks; or imposition of distribution or other restrictions under a REMS program.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be
promoted only for the approved indications and consistent with the provisions of the approved label. The FDA and other agencies actively
enforce the laws and regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-
label uses may be subject to significant liability. However, physicians may, in their independent medical judgment, prescribe legally
available products for off-label uses. The FDA does not regulate the behavior of physicians in their choice of treatments but the FDA does
restrict manufacturer’s communications on the subject of off-label use of their products.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA,
and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCSA, which regulate the distribution and tracing of
prescription drugs and prescription drug samples at the federal level, and set minimum standards for the regulation of drug distributors by
the states. The PDMA, its implementing regulations and state laws limit the distribution of prescription pharmaceutical product samples,
and the DSCA imposes requirements to track and trace drug products, ensure accountability in distribution and to identify and remove
counterfeit and other illegitimate products from the market.
Many jurisdictions, including the EU and the UK, require each marketing authorization holder, national competent authority and
the EMA to operate a pharmacovigilance system to ensure that the safety of all medicines is monitored throughout their use. The overall EU
pharmacovigilance system operates through cooperation between the EU Member States, EMA and the EC.
27
Table of Contents
Orphan Drug Designation and Exclusivity
Under the Orphan Drug Act, the 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 US, or more in cases in which there is no reasonable
expectation that the cost of developing and making a drug product available in the US for treatment of the disease or condition will be
recovered from sales of the product. A company must request orphan drug designation before submitting an NDA for the drug and rare
disease or condition. Orphan drug designation does not shorten the goal dates for the regulatory review and approval process, although it
does convey certain advantages such as tax benefits and exemption from the application fee. After the FDA grants Orphan Drug
Designation, the name of the drug and its potential orphan-designated use are disclosed publicly by the FDA.
If a product with orphan designation receives the first FDA approval for the disease or condition for which it has such designation,
the product generally will receive orphan drug exclusivity. Orphan drug exclusivity means that the FDA may not approve another sponsor’s
marketing application for the same drug for the same indication for seven years, except in certain limited circumstances. Orphan exclusivity
does not block the approval of a different drug for the same rare disease or condition, nor does it block the approval of the same drug for
different indications. If a drug designated as an orphan drug ultimately receives marketing approval for an indication broader than what was
designated in its orphan drug application, it may not be entitled to exclusivity. Orphan exclusivity will not bar approval of another product
under certain circumstances, including if a subsequent product with the same drug for the same indication is shown to be clinically superior
to the approved product on the basis of greater efficacy or safety, or providing a major contribution to patient care, or if the company with
orphan drug exclusivity is not able to meet market demand.
In the EU and UK, under Regulation (EC)141/2000 and the UK Human Medicines Regulation 2012 (as amended), respectively,
medicinal products may be granted an orphan drug designation if they are used to treat or prevent life-threatening or chronically debilitating
conditions that affect no more than five in 10,000 people in the EU/ UK and for which there is no satisfactory method of diagnosis,
prevention or treatment when the application is made, or when the medicinal product is of significant benefit to those affected by the
condition. In addition, orphan drug designation can be granted to drugs used to treat or prevent life-threatening or chronically debilitating
conditions which, for economic reasons, would be unlikely to be developed without incentives.
The application for orphan designation must be submitted to and approved by the EMA in respect of the EU or to the MHRA for
Great Britain before an application is made for marketing authorization for the product. Medicinal products which benefit from orphan
status, which they successfully maintain post-grant of the marketing authorization, can benefit from up to ten years of market exclusivity in
respect of the approved indication. This prevents regulatory authorities in the EU or Great Britain, as the case may be, from granting
marketing authorizations for similar medicinal products for the same therapeutic indication, unless another applicant can show that the
similar medicinal product in question is safer, more effective or clinically superior to the orphan-designated product or if the marketing
authorization holder consents to the second orphan medicinal product application, or where the marketing authorization holder cannot
supply the needs of the market.
The ten-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established that the product no
longer meets the criteria for orphan designation, for example, if the product is sufficiently profitable not to justify the maintenance of
market exclusivity. Conversely, the 10-year exclusivity period can be further extended by 2 years, when pediatric studies are conducted in
accordance with an agreed pediatric investigation plan (PIP) and in completion of all the legal requirements.
However, the general pharmaceutical legislative framework, as well as the framework applicable to orphan and pediatric medicinal
products in the EU, is under review. The EC expects to publish its position on this in March 2023. Although the final proposals are not yet
formally known, it is expected that there will be a reduction in applicable regulatory exclusivities which will significantly affect all
medicinal products that will be authorized after the legislative changes have taken effect, including a reduction in the 10-year orphan
market exclusivity, which will be modulated according to certain parameters.
28
Table of Contents
Pediatric studies and exclusivity
Under the Pediatric Research Equity Act of 2003, 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 enactment of the Food and Drug
Administration Safety and Innovation Act of 2012 (the FDASIA), sponsors must also submit pediatric study plans prior to the assessment
data.
Those plans must contain an outline of the proposed pediatric study or studies the applicant plans to conduct, including study
objectives and design, any deferral or waiver requests, and other information required by regulation. The applicant, the FDA and the FDA’s
internal review committee must then review the information submitted, consult with each other and agree upon a final plan. The FDA or the
applicant may request an amendment to the plan at any time.
The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until
after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. Additional requirements and
procedures relating to deferral requests and requests for extension of deferrals are contained in FDASIA. Unless otherwise required by
regulation, the pediatric data requirements do not apply to products with orphan designation.
Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the
attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, including the non-
patent and orphan exclusivity. This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a
written request from the FDA for such data. The data do not need to show the product to be effective in the pediatric population studied;
rather, if the clinical trial is deemed to fairly respond to the FDA’s request, the additional protection is granted. If reports of requested
pediatric studies are submitted to and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of
exclusivity or patent protection cover the product are extended by six months. This is not a patent term extension, but it effectively extends
the regulatory period during which the FDA cannot approve another application.
In the EU and the UK, a six-month extension to a supplementary protection certificate may be granted, subject to certain
circumstances, upon the completion of an agreed pediatric investigation plan (PIP). However, within the EU, regulatory protections
afforded to medicinal products such as data exclusivity, marketing protection, market exclusivity for orphan indications and pediatric
extensions are currently under review and could be curtailed in future years.
Abbreviated New Drug Applications for generic drugs
In 1984, with passage of the Hatch-Waxman Amendments to the FDCA, Congress established an abbreviated regulatory scheme
allowing the FDA to approve generic drugs that are shown to contain the same active ingredients as, and to be bioequivalent to, drugs
previously approved by the FDA pursuant to NDAs. To obtain approval of a generic drug, an applicant must submit an ANDA to the
agency. An ANDA is a comprehensive submission that contains, among other things, data and information pertaining to the active
pharmaceutical ingredient, bioequivalence, drug product formulation, specifications and stability of the generic drug, as well as analytical
methods, manufacturing process validation data and quality control procedures. ANDAs are “abbreviated” because they generally do not
include preclinical and clinical data to demonstrate safety and effectiveness. Instead, in support of such applications, a generic manufacturer
may rely on the preclinical and clinical testing previously conducted for a drug product previously approved under an NDA, known as the
reference listed drug (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. An applicant may submit an ANDA
suitability petition to request the FDA’s prior permission to submit an abbreviated application for a drug that differs from the RLD in route
of administration, dosage form, or strength, or for a drug that has one different active ingredient in a fixed combination drug product (i.e., a
drug product with multiple active ingredients). 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
29
Table of Contents
show a significant difference from the rate and extent of absorption of the listed drug.” Upon approval of an ANDA, the FDA indicates
whether the generic product is “therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic
Equivalence Evaluations,” also referred to as the “Orange Book.” Physicians and pharmacists may consider a therapeutic equivalent generic
drug to be fully substitutable for the RLD. In addition, by operation of certain state laws and numerous health insurance programs, the
FDA’s designation of therapeutic equivalence often results in substitution of the generic drug without the knowledge or consent of either the
prescribing physician or patient.
505(b)(2) New Drug Applications
As an alternative path to FDA approval for modifications to formulations or uses of products previously approved by the FDA
pursuant to an NDA, an applicant may submit an NDA under Section 505(b)(2) of the FDCA. Section 505(b)(2) was enacted as part of the
Hatch-Waxman Amendments and permits the filing of an NDA where at least some of the information required for approval comes from
studies not conducted by, or for, the applicant, and for which the applicant has not obtained a right of reference. If the 505(b)(2) applicant
can establish that reliance on the FDA’s previous findings of safety and effectiveness is scientifically and legally appropriate, it may
eliminate the need to conduct certain preclinical studies or clinical trials of the new product. The FDA may also require companies to
perform additional bridging studies or measurements, including clinical trials, to support the change from the previously approved reference
drug. The FDA may then approve the new drug candidate for all, or some, of the label indications for which the reference drug has been
approved, as well as for any new indication sought by the 505(b)(2) applicant.
Hatch-Waxman patent certification and the 30-month stay
In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent whose claims cover the
applicant’s product. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Orange
Book.
When an ANDA applicant files its application with the FDA, the applicant is required to certify to the FDA concerning any patents
listed for the reference product in the Orange Book, except for patents covering methods of use for which the ANDA applicant is not
seeking approval. To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the
applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same extent
that an ANDA applicant would. Specifically, the applicant must certify that (i) the required patent information has not been filed; (ii) the
listed patent has expired; (iii) the listed patent has not expired but will expire on a particular date and approval is sought after patent
expiration; or (iv) the listed patent is invalid or will not be infringed by the new product. The ANDA applicant may also elect to submit a
statement certifying that its proposed ANDA label does not contain (or carve out) any language regarding the patented method-of-use rather
than certify to a listed method-of-use patent, known as a Section VIII statement. If the applicant does not challenge the listed patents, the
ANDA application will not be approved until all the listed patents claiming the referenced product have expired. A certification that the new
product will not infringe the already approved product’s listed patents, or that such patents are invalid, is called a Paragraph IV
certification. 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 of the receipt of a Paragraph IV certification automatically prevents the FDA from approving the
ANDA until the earlier of 30 months, expiration of the patent, settlement of the lawsuit, or a decision in the infringement case that is
favorable to the ANDA applicant.
Patent term extension
After NDA approval, owners of relevant drug patents may apply for up to a five-year patent extension, which permits patent term
restoration as compensation for the patent term lost during the FDA regulatory process. The allowable patent term extension is typically
calculated as one-half the time between the effective date of an IND application and the submission date of a NDA, plus the time between
NDA submission date and the NDA approval date up to a maximum of five years. The time can be shortened if the FDA determines that the
applicant did not pursue approval with due diligence. The total patent term after the extension may not exceed 14 years from the date of
product
30
Table of Contents
approval. Only one patent applicable to an approved drug is eligible for extension and only those claims covering the approved drug, a
method for using it, or a method for manufacturing it may be extended and the application for the extension must be submitted prior to the
expiration of the patent in question. 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.
Exclusivity under the Hatch-Waxman Amendments
In addition, under the Hatch-Waxman Amendments, the FDA may not approve an ANDA or 505(b)(2) NDA referencing a
particular drug until any applicable period of non-patent exclusivity for the RLD has expired. The FDCA provides a period of five years
of non-patent data exclusivity for a new drug containing a new chemical entity (NCE). For the purposes of this provision, an NCE is a drug
that contains no active moiety that has previously been approved by the FDA in any other NDA. An active moiety is the molecule or ion
responsible for the physiological or pharmacological action of the drug substance. In cases where such NCE exclusivity has been granted,
an ANDA or 505(b)(2) NDA may not be submitted to the FDA until the expiration of five years from the date the NDA is approved, unless
the submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its application four years following
the original product approval.
The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new clinical
investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and are essential to the
approval of the application. This three-year exclusivity period often protects changes to a previously approved drug product, such as a new
dosage form, route of administration, combination or indication. Three-year exclusivity would be available for a drug product that contains
a previously approved active moiety, provided the statutory requirement for a new clinical investigation is satisfied. Unlike five-year NCE
exclusivity, an award of three-year exclusivity does not block the FDA from accepting ANDAs or 505(b)(2) NDAs seeking approval for
generic versions of the drug as of the date of approval of the original drug product; it does, however, block the FDA from approving
ANDAs or 505(b)(2) NDAs during the period of exclusivity. The FDA typically makes decisions about awards of data exclusivity shortly
before a product is approved.
FDA Emergency Use Authorization
Section 564 of the FDCA (21 U.S.C. § 360bbb-3) allows the FDA to authorize the shipment of drugs, biological products
(including vaccines), or medical devices that either lack required approval, licensure, or clearance (unapproved products), or are approved
but are to be used for unapproved ways to diagnose, treat, or prevent serious diseases or conditions in the event of an emergency declaration
by the HHS Secretary.
On February 4, 2020, then-HHS Secretary Alex M. Azar II determined that a public health emergency exists for COVID-19 and
declared that it justifies the authorization of emergency use of in vitro diagnostics for COVID-19, pursuant to Section 564 of the FDCA. On
March 2, 2020, March 24, 2020, and March 27, 2020, Secretary Azar issued corresponding declarations for personal respiratory protective devices;
for medical devices, including alternative products used as medical devices; and, for drugs and biological products. The determination and these
declarations were published in the Federal Register on February 7, 2020, March 10, 2020, March 27, 2020, and April 1, 2020, respectively.
While the emergency determination and declaration are effective, the FDA may authorize the use of an unapproved product or an
unapproved use of an approved product if it concludes that:
•
•
an agent referred to in the emergency declaration could cause a serious or life-threatening disease or condition;
it is reasonable to believe that the authorized product may be effective in diagnosing, treating, or preventing that disease or
condition or a serious or life-threatening disease or condition caused by an approved product or a product marketed under an
EUA;
31
Table of Contents
•
•
•
the known and potential benefits of the authorized product, when used for that disease or condition, outweigh known and
potential risks, taking into consideration the material threat of agents identified in the emergency declaration;
there is no adequate, approved, and available alternative to the authorized product for diagnosing, preventing, or treating the
relevant disease or condition;
any other criteria prescribed by the FDA is satisfied.
Medical products that are granted an EUA are only permitted to commercialize their products under the terms and conditions
provided in the authorization. The FDCA authorizes FDA to impose such conditions on an EUA as may be necessary to protect the public health.
Consequently, postmarketing requirements will vary across EUAs. In addition, FDA has, on occasion, waived requirements for drugs marketed
under an EUA.
Generally, EUAs for unapproved products or unapproved uses of approved products require that manufacturers distribute
factsheets for healthcare providers, addressing significant known and potential benefits and risk, and the extent to which benefits and risks
are unknown, and the fact that FDA has authorized emergency use; and, distribution of factsheets for recipients of the product, addressing
significant known and potential benefits and risk, and the extent to which benefits and risks are unknown, the option to accept or refuse the
product, the consequences of refusing, available alternatives, and the fact that FDA has authorized emergency use.
Generally, EUAs for unapproved products and, per FDA’s discretion, EUAs for unapproved uses of approved products, include
requirements for adverse event monitoring and reporting, and other recordkeeping and reporting requirements. Note, however, that
approved products are already subject to equivalent requirements.
In addition, FDA may include various requirements in an EUA as a matter of discretion as deemed necessary to protect the public
health, including restrictions on which entities may distribute the product, and how to perform distribution (including requiring that
distribution be limited to government entities), restrictions on who may administer the product, requirements for collection and analysis of
safety and effectiveness data, waivers of cGMP, and restrictions applicable to prescription drugs or restricted devices (including advertising
and promotion restrictions).
The FDA may revoke an EUA where it is determined that the underlying health emergency no longer exists or warrants such
authorization, if the conditions for the issuance of the EUA are no longer met, or if other circumstances make revocation appropriate to
protect the public health or safety.
It is difficult to predict when the determination and declaration will be revoked or ended, which will impact the marketing of
products under existing EUAs and the availability of new EUAs based on the determination and declaration. For example, in January 2023,
Congress proposed legislation that would end other COVID-19-related emergency declarations, if passed, and the White House has issued a
statement that those declarations will end on May 11, 2023. FDA officials have stated that this will not impact FDA’s ability to authorize
treatments for emergency use, such that existing EUAs will remain in effect and the agency may continue to issue new EUAs going
forward when criteria for issuance are met. This is nonetheless subject to change.
Pharmaceutical Coverage, Pricing and Reimbursement
In the US and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the
prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs. Third-party payors
include federal and state government health programs such as Medicare and Medicaid, commercial health insurers, managed care
organizations, and other organizations. Significant uncertainty exists as to the coverage and reimbursement status of products approved by
the FDA and other government authorities. For example, in the US, there have been several recent US Congressional inquiries and
proposed federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between
pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program reimbursement
methodologies for drugs. This includes the Consolidated Appropriations Act of 2021, which addressed
32
Table of Contents
several drug price reporting and transparency measures, such as a new requirement for prescription drug plan sponsors and Medicare
Advantage organizations to develop tools to display Medicare Part D prescription drug benefit information in real time and for insurance
companies and employer-based health plans to report information on pharmacy benefit and drug costs to the Secretaries of the Departments
of Health and Human Services, Labor and the Treasury. Additionally, on March 11, 2021, Congress enacted the American Rescue Plan Act
of 2021, which included among its provisions a sunset of the provision in the Patient Protection and Affordable Care Act and the Health
Care and Education Reconciliation Act (the Affordable Care Act) that capped pharmaceutical manufacturers’ rebate liability under the
Medicaid Drug Rebate Program (MDRP). Under the Affordable Care Act, manufacturers’ rebate liability was capped at 100% of the
average manufacturer price for a covered outpatient drug. Effective January 1, 2024, manufacturers’ MDRP rebate liability will no longer
be capped, potentially resulting in a manufacturer paying more in MDRP rebates than it receives on the sale of certain covered outpatient
drugs. In August 2022, President Biden signed into law the Inflation Reduction Act of 2022 (IRA), which implements substantial changes
to the Medicare program, including drug pricing reforms and changes to the Medicare Part D benefit design. Among other reforms, the IRA
imposes inflation rebates on drug manufacturers for products reimbursed under Medicare Parts B and D if the prices of those products
increase faster than inflation; implements changes to the Medicare Part D benefit that, beginning in 2025, will cap beneficiary annual out-
of-pocket spending at $2,000, while imposing new discount obligations for pharmaceutical manufacturers; and, beginning in 2026,
establishes a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D
following a price negotiation process with the Centers for Medicare and Medicaid Services (CMS). On February 9, 2023, CMS issued
guidance that further clarified the scope of the Medicare Part B and Part D inflationary rebates, including a detailed discussion of which
Part B and Part D products are eligible for such rebates and how the rebates are calculated. At the state level, legislatures have increasingly
passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including limitations on
reimbursement, discounts, restrictions on certain product access and marketing, cost disclosure, including disclosures for certain price
increases or launches of costly drugs, and transparency measures, and, in some cases, to encourage importation from other countries and
bulk purchasing. Thus, even if a product candidate is approved, sales of the product will depend, in part, on the extent to which third-party
payors provide coverage and establish adequate reimbursement levels for the product. It is likely that additional 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 a pharmaceutical manufacturer’s products or additional pricing
pressure.
In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct
expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the
costs required to obtain FDA or other comparable marketing approvals. Nonetheless, product candidates may not be considered medically
necessary or cost effective. A decision by a third-party payor not to cover a product candidate could reduce physician utilization once the
product is approved and have an adverse effect on sales, results of operations and financial condition. Additionally, a payor’s decision to
provide coverage for a product does not imply that adequate reimbursement will be approved at a rate that covers our costs, including
research, development, manufacture, sale and distribution. Further, one payor’s determination to provide coverage for a drug product does
not assure that other payors will also provide coverage and reimbursement for the product, and the level of coverage and reimbursement
can differ significantly from payor to payor.
The containment of healthcare costs also has become a priority of federal, state and foreign governments and the prices of drugs
have been a focus in this effort. Governments and third-party payors have shown significant interest in implementing cost-containment
programs, including price controls, restrictions on reimbursement and requirements for substitution of generic products. Increasingly, the
third-party payors who reimburse patients or healthcare providers, such as government and private insurance plans, are requiring that drug
companies provide them with predetermined discounts from list prices, and are seeking to reduce the prices charged or the amounts
reimbursed for medical products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in
jurisdictions with existing controls and measures, could further limit a company’s revenue generated from the sale of any approved
products. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement
status is attained for one or more products for which a company or its collaborators receive marketing approval, less favorable coverage
policies and reimbursement rates may be implemented in the future.
33
Table of Contents
In the EU, pricing and reimbursement methods can differ in each Member State. Some Member States and the UK may require
that health technology assessments (HTA) be completed to obtain reimbursement or pricing approval. The outcome of HTA assessments is
decided on a national basis and some Member States may decide not to reimburse the use of medicines or may reduce the rate of
reimbursement. In December 2021, the EU adopted a new Regulation on Health Technology Assessment which allows Member States to
carry out joint clinical assessments and operate joint clinical consultations. It is expected that the new Regulation will come into effect in
2025.
Healthcare and Privacy Law and Regulation
Healthcare providers and third-party payors play a primary role in the recommendation and prescription of drug products that are
granted marketing approval. Arrangements with providers, consultants, third-party payors and customers are subject to broadly applicable
federal and state fraud and abuse laws, anti-kickback laws, false claims laws, laws requiring reporting of payments to physicians and
teaching physicians and other healthcare providers, patient privacy laws and regulations and other healthcare laws and regulations that may
constrain business and/or financial arrangements. Restrictions under applicable healthcare laws and regulations, include the following:
● the federal Anti-Kickback Statute, which is a criminal law that prohibits, among other things, persons and entities from
knowingly and willfully soliciting, offering, paying, receiving or providing remuneration, directly or indirectly, in cash or in
kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or
service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and
Medicaid. The term “remuneration” has been broadly interpreted to include anything of value. The intent standard under the
federal Anti-Kickback Statute was amended by the Affordable Care Act to a stricter standard such that a person or entity no
longer needs to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. The
federal Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the
one hand and prescribers, purchasers, and formulary managers on the other, including, for example, consulting/speaking
arrangements, discount and rebate offers, grants, charitable contributions, and patient support offerings, among others. A
conviction for violation of the federal Anti-Kickback Statute can result in criminal fines and/or imprisonment and requires
mandatory exclusion from participation in federal health care programs. Exclusion may also be imposed if the government
determines that an entity has committed acts that are prohibited by the federal Anti-Kickback Statute. Although there are a
number of statutory exceptions and regulatory safe harbors to the federal Anti-Kickback Statute protecting certain common
business arrangements and activities from prosecution or regulatory sanctions, the exceptions and safe harbors are drawn
narrowly, and practices that involve remuneration to those who prescribe, purchase, or recommend pharmaceutical and
biological products, including certain discounts, or engaging such individuals as speakers or consultants, may be subject to
scrutiny if they do not fit squarely within an exception or safe harbor. Moreover, 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 civil
False Claims Act;
● the federal civil and criminal false claims laws and civil monetary penalty laws, including the civil False Claims Act, which
prohibits, among other things, (i) knowingly presenting, or causing to be presented, claims for payment of government funds
that are false or fraudulent; (ii) knowingly making, or using or causing to be made or used, a false record or statement
material to a false or fraudulent claim; (iii) knowingly making, using or causing to made or used a false record or statement
material to an obligation to pay money to the government; or (iv) knowingly concealing or knowingly and improperly
avoiding, decreasing, or concealing an obligation to pay money to the federal government. Private individuals, commonly
known as “whistleblowers,” can bring FCA qui tam actions, on behalf of the government and may share in amounts paid by
the entity to the government in recovery or settlement. Pharmaceutical companies have been investigated and/or subject to
government enforcement actions asserting liability under the FCA in connection with their alleged off-label promotion of
drugs, purportedly concealing price concessions in the pricing information submitted to the government for government price
reporting purposes, and allegedly providing free product to customers with the expectation that the customers would bill
federal healthcare programs for the product. In addition, a claim including items or services resulting
34
Table of Contents
from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the FCA.
Moreover, manufacturers can be held liable under the FCA even when they do not submit claims directly to government
payors if they are deemed to “cause” the submission of false or fraudulent claims. FCA liability is potentially significant in
the healthcare industry because the statute provides for treble damages and significant mandatory penalties per false or
fraudulent claim or statement for violations. Such per-claim penalties are currently set at $13,508 to $27,018 per false claim
or statement for penalties assessed after January 30, 2023, with respect to violations occurring after November 2, 2015.
Criminal penalties, including imprisonment and criminal fines, are also possible for making or presenting a false, fictitious or
fraudulent claim to the federal government;
● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability
for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program, including
any 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 statements or representations, or making false
statements relating to 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 to have committed a violation;
● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their respective
implementing regulations, which impose HIPAA-covered entities and their business associates obligations, including
mandatory contractual terms, with respect to safeguarding the privacy, security, accesibility and transmission of individually
identifiable health information, including protected health information (PHI). While the vast majority of HIPAA obligations
do not apply to pharmaceutical companies, the requirements inform privacy and security practices across the industry and
may impact interactions with health care providers. Moerver, HITECH created new tiers of civil monetary penalties, amended
HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new
authority to file civil actions for damages or injunctions in federal courts to enforce HIPAA laws and seek attorneys’ fees and
costs associated with pursuing federal civil actions;
● the federal payment transparency tracking and reporting requirements known as the federal Physician Payments Sunshine
Act, implemented as the Open Payments Program, which requires certain manufacturers of drugs, devices, biologics and
medical supplies, among others, to report annually to CMS, within the US Department of Health and Human Services (HHS),
information related to payments and other transfers of value made by that entity to US-licensed physicians (defined to include
doctors, dentists, optometrists, podiatrists and chiropractors), physician assistants, nurse practitioners, clinical nurse
specialists, anesthesiologist assistants, certified registered nurse anesthetists, certified nurse midwives, and teaching hospitals,
as well as ownership and investment interests held by physicians and their immediate family members; and
● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may be broader in
scope than analogous federal laws and may apply to sales or marketing arrangements and claims involving healthcare items
or services regardless of payor.
Some state, local and foreign laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary
compliance guidelines and the relevant compliance guidance promulgated by the federal government, restrict payments that may be made
to healthcare providers and other potential referral sources, and/or require drug manufacturers to report information related to payments and
transfers of value made to physicians and other health care providers or entities or marketing expenditures. In addition, there are state and
local laws that require registration of sales representatives; state laws that require drug manufacturers to report information related to drug
pricing; data privacy and security laws and regulations in foreign jurisdictions that may be more stringent than those in the US (such as the
EU’s General Data Protection Regulation (EU GDPR), which became effective in May 2018); federal and state laws governing the privacy
and security of personal information (including health information) many of
35
Table of Contents
which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and state laws
related to insurance fraud in the case of claims involving private insurers.
Efforts to ensure that our business arrangements will comply with applicable healthcare laws and regulations will involve
substantial costs. It is possible that governmental and enforcement authorities will conclude that our business practices may not comply
with current or future statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations. If
any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have
a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, disgorgement,
monetary fines, individual imprisonment, additional reporting obligations and oversight if we become subject to a corporate integrity
agreement or other agreement to resolve allegations of non-compliance with these laws, possible exclusion from participation in federal
healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment or restructuring of our
operations, any of which could adversely affect our ability to operate our business and our results of operations.
Healthcare Reform
The US and state governments continue to propose and pass legislation designed to reduce the cost of healthcare. In March 2010,
the US Congress enacted the Affordable Care Act, which included changes to the coverage and payment for drug products under
government health care programs. This law was designed to expand access to health insurance coverage for uninsured and underinsured
individuals while containing overall healthcare costs. There have been numerous judicial and Congressional challenges to certain aspects of
the Affordable Care Act, as well as efforts to repeal or replace certain aspects of the Affordable Care Act. For example, Congress has
considered legislation that would repeal, or repeal and replace, all or part of the Affordable Care Act. While Congress has not passed
comprehensive repeal legislation, several bills affecting the implementation of certain taxes under the Affordable Care Act have been
enacted. The Tax Cuts and Jobs Act of 2017 includes a provision that repealed the tax-based shared responsibility payment imposed by the
Affordable Care Act on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly
referred to as the “individual mandate”. Further, the Consolidated Appropriations Act of 2020 fully repealed the Affordable Care Act’s
mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and also eliminated the health insurer
tax. The Bipartisan Budget Act of 2018 (BBA) amended the Affordable Care Act to increase from 50% to 70% the point-of-sale discount
that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug
plans, commonly referred to as the “donut hole.” Under the IRA, this coverage gap will be eliminated beginning January 1, 2025. The IRA
also requires pharmaceutical manufacturers to pay 10% of the negotiated price of brands, biologics, and biosimilar products, when
Medicare Part D beneficiaries are in the initial coverage phase, and 20% of the negotiated price during the catastrophic phase of Medicare
Part D coverage. In December 2018, CMS published a new final rule permitting further collections and payments to and from certain
Affordable Care Act qualified health plans and health insurance issuers under the Affordable Care Act risk adjustment program in response
to the outcome of federal district court litigation regarding the method CMS uses to determine this risk adjustment. On June 17, 2021, the
US Supreme Court dismissed the most recent judicial challenge to the Affordable Care Act brought by several states without specifically
ruling on the constitutionality of the law. It is unclear how future actions before the Supreme Court, other such litigation, and the healthcare
reform measures of the Biden administration will impact the Affordable Care Act.
Other legislative changes have been proposed and adopted in the US since the Affordable Care Act was enacted. In August 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 of Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013, and, due to subsequent
legislative amendments, will remain in effect into 2031, unless additional Congressional action is taken (with the exception of a temporary
suspension instituted during the COVID-19 pandemic that expired on July 1, 2022). To offset the temporary suspension during the COVID-
19 pandemic, in 2030, reductions in Medicare payments will be 2.25% for the first half of the year, and 3% in the second half of the year.
The sequestration was temporarily halted from May 1, 2020 to March 31, 2022 as a result of various legislation, and later reduced to 1%
from April 2022 to until July 1, 2022. In January
36
Table of Contents
2013, former President Obama signed into law the American Taxpayer Relief Act of 2012 (ATRA), which, among other things, further
reduced Medicare payments to several providers, including hospitals and cancer treatment centers, and increased the statute of limitations
period for the government to recover overpayments to providers from three to five years.
In addition, there has been heightened governmental scrutiny in the US of pharmaceutical pricing practices in light of the rising
cost of prescription drugs and biologics. Such scrutiny has resulted in several congressional inquiries and proposed and enacted federal and
state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and
manufacturer patient programs, and reform government program reimbursement methodologies for products. For example, on March 11,
2021, President Biden signed the American Rescue Plan Act of 2021 into law, which among other changes, eliminates the statutory
Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacture price, for single source and innovator multiple source
drugs, beginning January 1, 2024. The American Rescue Plan Act also temporarily increased premium tax credit assistance for individuals
eligible for subsidies under the ACA for 2021 and 2022 and removed the 400% federal poverty level limit that otherwise applies for
purposes of eligibility to receive premium tax credits. The IRA extended this increased tax credit assistance and removal of the 400%
federal poverty limit through 2025. The Biden administration has also taken executive actions to address drug pricing and other healthcare
policy changes. For example, in response to a July 9, 2021 Executive Order from President Biden that included several prescription drug
initiatives, on September 9, 2021, the Department of Health and Human Services issued a Comprehensive Plan for Addressing High Drug
Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make drug
prices more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific
innovation. Additionally, on September 12, 2022, President Biden issued an Executive Order to promote biotechnology and
biomanufacturing innovation. The Order noted several methods through which the Biden Administration would support the advancement of
biotechnology and biomanufacturing in healthcare, and instructed the Department of Health and Human Service to submit, within 180 days
of the Order, a report assessing how to use biotechnology and biomanufacturing to achieve medical breakthroughs, reduce the overall
burden of disease, and improve health outcomes. In August 2022, President Biden signed into law the IRA, which implements substantial
changes to the Medicare program, including drug pricing reforms and changes to the Medicare Part D benefit design. Among other
reforms, the IRA imposes inflation rebates on drug manufacturers for products reimbursed under Medicare Parts B and D if the prices of
those products increase faster than inflation; implements changes to the Medicare Part D benefit that, beginning in 2025, will cap benefit
annual out-of-pocket spending at $2,000, while imposing new discount obligations for pharmaceutical manufacturers; and, beginning in
2026, establishes a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B
and D following a price negotiation process with CMS. On October 14, 2022 President Biden issued an Executive Order on Lowering
Prescription Drug Costs for Americans, which instructed the Secretary of the Department of Health and Human Services to consider
whether to select for testing by the CMS Innovation Center new health care payment and delivery models that would lower drug costs and
promote access to innovative drug therapies for beneficiaries enrolled in the Medicare and Medicaid programs. The Executive Order further
directed the Secretary of the Department of Health and Human Services to submit, within 90 days after the date of the Executive Order, a
report regarding any models that may lead to lower cost-sharing for commonly used drugs and support value-based payment that promotes
high-quality care. On February 14, 2023, the Department of Health and Human Services issued a report in response to the October 14,
2022, Executive Order, which, among other things, selects three potential drug affordability and accessibility models to be tested by the
CMS Innovation Center. Specifically, the report addresses: (1) a model that would allow Part D Sponsors to establish a “high-value drug
list” setting the maximum co-payment amount for certain common generic drugs at $2; (2) a Medicaid-focused model that would establish
a partnership between CMS, manufacturers, and state Medicaid agencies that would result in multi-state outcomes-based agreements for
certain cell and gene therapy drugs; and (3) a model that would adjust Medicare Part B payment amounts for Accelerated Approval
Program drugs to advance the developments of novel treatments. It remains to be seen how these drug pricing initiatives will affect the
broader pharmaceutical industry. At the state level, legislatures have increasingly passed legislation and implemented regulations designed
to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on
certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation
from other countries and bulk purchasing. Policy changes, including potential modification or repeal of all or parts of the ACA or the
implementation of new health care legislation, could result in significant changes to the health care system, which may prevent us from
being able to generate revenue, attain profitability or commercialize our drugs. We expect that additional state and federal healthcare reform
measures will be
37
Table of Contents
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 or lower pricing for our product candidates, or additional pricing pressures.
Outside the US, ensuring adequate coverage and payment for our products will face challenges. Pricing of prescription
pharmaceuticals is subject to governmental control in many countries. Pricing negotiations with governmental authorities can extend well
beyond the receipt of regulatory approval for a product and may require us to conduct a clinical trial that compares the cost effectiveness of
our product candidates or products to other available therapies. The conduct of such a clinical trial could be expensive and result in delays
in our commercialization efforts. Third-party payors are challenging the prices charged for medical products and services, and many third-
party payors limit reimbursement for newly approved health care products. Recent budgetary pressures in many EU countries are also
causing governments to consider or implement various cost-containment measures, such as price freezes, increased price cuts and rebates.
If budget pressures continue, governments may implement additional cost-containment measures. Cost-control initiatives could decrease
the price we might establish for products that we may develop or sell, which would result in lower product revenues or royalties payable to
us. There can be no assurance that any country that has price controls or reimbursement limitations for pharmaceutical products will allow
favorable reimbursement and pricing arrangements for any of our products. Further, it is possible that additional governmental action is
taken in response to the COVID-19 pandemic.
Manufacturing and Raw Materials
We currently do not have the manufacturing capabilities or experience necessary to produce our products or any product
candidates for clinical trials. We currently use one active pharmaceutical ingredient manufacturer and one finished goods manufacturer for
each of our products. We do not own or operate manufacturing or distribution facilities or resources for clinical or commercial production
and distribution of our product for commercial use or for preclinical and clinical trials. We assign internal personnel to manage and oversee
third parties working on our behalf under contract. These third parties manufacture raw materials, the active pharmaceutical ingredients and
finished drug product for commercial distribution and for use in clinical studies. We currently rely on and will continue to rely on these
third-party contract manufacturers to produce sufficient quantities of our products.
Human Capital Resources
As of December 31, 2022, we have 155 full-time employees. Of these employees, 84 were engaged in commercial activities, 40
were engaged in research and development activities, and 31 were engaged in general and administrative activities. We also engage
temporary employees and consultants. In November 2021, we announced our plan to exit early-stage research and focus resources on our
mid to late-stage development programs and commercial efforts which resulted in elimination of positions primarily in research
organization. In October 2022, we announced a reduction in our workforce primarily in our development and administration groups.
None of our employees are represented by a collective bargaining arrangement, and we believe our relationship with our
employees is good. We aim to provide a stimulating and rewarding work environment, with recognition for accomplishments and the
opportunity to advance our employees’ careers while sharing in the excitement of our growth and success. We know that our success
depends on the experience, intellect, and talent of our highly motivated team, and we truly value the people who make our organization
great. We provide a collaborative work environment that is both personally fulfilling and enables our employees to work together to achieve
the purpose and goals of the organization. Our human capital efforts focus on maintaining a sufficient number of skilled employees in each
respective department. Recruiting and retaining experienced and qualified sales and marketing personnel to successfully commercialize our
product and scientific personnel to continue to perform research and development work in the future will be critical to our business success.
Our ability to recruit, develop and retain highly skilled talent is a significant determinant of our success. To facilitate talent attraction,
retention, and development, we strive to be an inclusive, diverse, and safe workplace with opportunities for our employees to grow and
develop in their careers, supported by competitive compensation, opportunities for equity ownership, development opportunities that enable
continued learning and growth and employment packages that promote well-being across all aspects of our employees’ lives, including
health care, retirement planning and paid time off.
38
Table of Contents
The health, safety, and wellness of our employees is a priority in which we have always invested and intend to continue to do. We
provide our employees with access to a variety of innovative, flexible, and convenient health and wellness programs. Additionally, we offer
programs to help support employees physical and mental health by providing tools and resources to help them improve or maintain their
health status, encourage engagement in healthy behaviors, and offer choices where possible so they are customized to meet their needs. In
light of the COVID-19 pandemic, we have undertaken and plan to continue to undertake, safety measures to keep our employees’ health,
safety, and wellness a priority. We implemented significant changes that we determined were in the best interest of our employees, as well
as the communities in which we operate, in compliance with government regulations. We endeavor to provide the safest and most effective
work environment under the circumstances, but we cannot guarantee that employees who come to the office will not be exposed to
COVID-19 while at the office. It will be the responsibility of all employees to participate and cooperate in safety and cleaning protocols.
We expect all employees, contractors, and visitors to our facility to comply with our COVID-19 guidelines plan.
We provide compensation and benefits programs to help meet the needs of our employees. In addition to base compensation,
these programs include annual bonuses, Stock Award Plans, Employee Stock Purchase Plans, 401(k), healthcare and insurance benefits,
paid time off, health and fitness benefits and various additional employee programs. We have robust annual performance review processes
for reviewing employees’ performance and pay.
Scientific and Medical Advisors
We utilize scientists, key opinion leaders and physicians to advise us on scientific and medical matters as part of our ongoing
commercialization activities and research and product development efforts, including experts in clinical trial design, preclinical
development work, chemistry, biology, immunology, oncology and immuno-oncology. Certain of our consultants receive non-employee
options to purchase our common stock and certain of our scientific and medical advisors receive honorarium for time spent assisting us.
Corporate Information
Our principal executive office is currently located at 611 Gateway Boulevard, Suite 900, South San Francisco, CA 94080. Prior to
expiration of our previous lease agreement in January 2023, our principal executive office was in 1180 Veterans Boulevard, South San
Francisco, California 94080. Our telephone number is (650) 624-1100.
Available Information
We electronically file with the Securities and Exchange Commission (SEC) our Annual Report on Form 10-K, Quarterly Reports
on Form 10-Q, Current Reports on Form 8-K, proxy and information statements and amendments to such reports and statements filed or
furnished pursuant to Section 13(a) or 15(d) of the Exchange Act. We make copies of these reports available free of charge on or through
our website at www.rigel.com, as soon as reasonably practicable after we electronically file these reports with, or furnish them to, the SEC.
The information found on our website is not part of or incorporated by reference into this Annual Report on Form 10-K.
The SEC also maintains an internet site that contains reports, proxy and information statements and other information regarding
issuers that file electronically with the SEC at www.sec.gov.
39
Table of Contents
Item 1A. Risk Factors
In evaluating our business, you should carefully consider the following risks, as well as the other information contained in this
Annual Report on Form 10-K. These risk factors could cause our actual results to differ materially from those contained in forward-looking
statements we have made in this Annual Report on Form 10-K and those we may make from time to time. If any of the following risks
actually occurs, our business, financial condition and operating results could be harmed. The risks and uncertainties described below are
not the only ones facing us. Additional risks and uncertainties not presently known to us, or that we currently see as immaterial, may also
harm our business.
Risks Related to Our Business and Our Industry
If the market opportunities for our products and product candidates are smaller than we believe they are, our revenues may be adversely
affected, and our business may suffer.
Certain of the diseases that our products and our other product candidates being developed to address are in underserved and
underdiagnosed populations. Our projections of both the number of people who have these diseases, as well as the subset of people with
these diseases who will seek treatment utilizing our products or product candidates, may not be accurate. If our estimates of the prevalence
or number of patients potentially on therapy prove to be inaccurate, the market opportunities for fostamatinib and our other product
candidates may be smaller than what we believe they are, our prospects for generating expected revenue may be adversely affected and our
business may suffer.
We may need to continue to increase the size of our organization and we may encounter difficulties with managing our growth, which
could adversely affect our business and results of operations.
While we have substantially increased the size of our organization particularly in our sales force in the third quarter of 2021, we also
implemented two separate reductions in workforce in November 2021 and October 2022, and may need to add additional qualified
personnel and resources to support our commercial activities and expected growth. Our current infrastructure may be inadequate to support
our development and commercialization efforts and expected growth. Future growth will impose significant added responsibilities on
members of management, including the need to identify, recruit, maintain and integrate additional employees, and may take time away from
running other aspects of our business, including commercialization of our products and development of our other product candidates.
Our future financial performance and our ability to sustain successful commercialization of our products and our ability to
commercialize other product candidates that may receive regulatory approval will depend, in part, on our ability to manage any future
growth effectively. In particular, as we continue to commercialize our products, we will need to support the training and ongoing activities
of our sales force and will likely need to continue to expand the size of our employee base for managerial, operational, financial and other
resources. To that end, we must be able to successfully:
● manage our development efforts effectively;
● integrate additional management, administrative and manufacturing personnel;
● further develop our marketing and sales organization; and
● maintain sufficient administrative, accounting and management information systems and controls.
We may not be able to accomplish these tasks or successfully manage our operations and, accordingly, may not achieve our research,
development, and commercialization goals. Our failure to accomplish any of these goals, including as a result of business or other
interruptions resulting from the potential future impacts of the COVID-19 pandemic, if any, could adversely affect our business and
operations.
There is a high risk that drug discovery and development efforts might not generate successful product candidates.
At the present time, a significant portion of our operations are focused on various stages of drug identification and development.
We currently have various product candidates in the clinical testing stage. In our industry, it is statistically unlikely that the limited number
of compounds that we have identified as potential product candidates will actually lead to successful product development efforts. We have
invested a significant portion of our efforts and
40
Table of Contents
financial resources into the development of fostamatinib. Our ability to generate product revenue, which will not occur until after regulatory
approval, if ever, will depend on the successful development, regulatory approval and eventual commercialization of one of our product
candidates.
Our compounds in clinical trials and our future leads for potential drug compounds are subject to the risks and failures inherent in
the development of pharmaceutical products. These risks include, but are not limited to, the inherent difficulty in selecting the right drug
and drug target and avoiding unwanted side effects, as well as unanticipated problems relating to product development, testing, enrollment,
obtaining regulatory approvals, obtaining and maintaining reimbursement in national markets and positive recommendation from HTA
bodies, maintaining regulatory compliance, manufacturing, competition and costs and expenses that may exceed current estimates. In future
clinical trials, we or our partners may discover additional side effects and/or a higher frequency of side effects than those observed in
previously completed clinical trials. The results of preliminary and mid-stage clinical trials do not necessarily predict clinical or commercial
success, and larger later-stage clinical trials may fail to confirm the results observed in the previous clinical trials. Similarly, a clinical trial
may show that a product candidate is safe and effective for certain patient populations in a particular indication, but other clinical trials may
fail to confirm those results in a subset of that population or in a different patient population, which may limit the potential market for that
product candidate. With respect to our own compounds in development, we have established anticipated timelines with respect to the
initiation of clinical trials based on existing knowledge of the compounds. However, we cannot provide assurance that we will meet any of
these timelines for clinical development. Additionally, the initial results of a completed earlier clinical trial of a product candidate do not
necessarily predict final results and the results may not be repeated in later clinical trials.
Because of the uncertainty of whether the accumulated preclinical evidence (PK, pharmacodynamic, safety and/or other factors) or
early clinical results will be observed in later clinical trials, we can make no assurances regarding the likely results from our future clinical
trials or the impact of those results on our business. For example, we initiated our FORWARD study, a Phase 3 pivotal trial of fostamatinib
in patients with wAIHA in March 2019, completed the enrollment in November 2021 and completed the treatment period for the last
patient under the trial in April 2022. In June 2022, we announced top-line efficacy and safety data results of our FORWARD study, and the
results of the trial did not demonstrate statistical significance in the primary efficacy endpoint of durable hemoglobin response in the
overall study population. We conducted an in-depth analysis of these data to better understand differences in patient characteristics and
outcomes and submitted these findings to the FDA. In October 2022, we announced that we received guidance from the FDA’s review of
these findings. Based on the result of the trial and the guidance from the FDA, we did not file an sNDA for this indication. Further, we have
our Phase 3 clinical trial to evaluate safety and efficacy of fostamatinib in hospitalized COVID-19 patients which we launched in
November 2020. In July 2022, we completed the enrollment on this trial, and on November 1, 2022, we announced the top-line results of
the clinical trial. The trial approached but did not meet statistical significance in the primary efficacy endpoint. All prespecified secondary
endpoints in the trial numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale
assessment, and number of days in the ICU. We are evaluating the opportunity and discussing next steps with the FDA and in collaboration
with our partner, the US Department of Defense.
If the results of our clinical trials fail to meet the primary efficacy endpoints, or otherwise do not ultimately meet the requirements
for an NDA approval by the FDA, the commercial prospects of our business may be harmed, our ability to generate product revenues may
be delayed or eliminated or we may be forced to undertake other strategic alternatives that are in our shareholders’ best interests, including
cost reduction measures. If we are unable to obtain adequate financing or engage in a strategic transaction on commercially reasonable
terms or at all, we may be required to implement further cost reduction strategies which could significantly impact activities related to our
commercial efforts and/or research and development of our future product candidates, and could significantly harm our business, financial
condition and results of operations. In addition, these cost reduction strategies could cause us to further curtail our operations or take other
actions that would adversely impact our shareholders.
41
Table of Contents
We may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws, false claims laws and other federal and
state healthcare laws, and the failure to comply with such laws could result in substantial penalties. Our employees, independent
contractors, consultants, principal investigators, contract research organizations (CROs), commercial partners and vendors may engage
in misconduct or other improper activities, including noncompliance with regulatory standards and requirements.
Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party
payers and customers, may expose us to broadly applicable federal, state and foreign fraud and abuse and other healthcare laws and
regulations including anti-kickback and false claims laws, data privacy and security laws, and transparency reporting laws. These laws may
constrain the business or financial arrangements and relationships through which we conduct our operations, including how we research,
market, sell and distribute any product for which we have obtained regulatory approval, or for which we obtain regulatory approval in the
future. In particular, the promotion, sales and marketing of healthcare items and services, as well as certain business arrangements in the
healthcare industry, are subject to extensive laws and regulations intended to prevent fraud, misconduct, bribery kickbacks, self-dealing and
other abusive or inappropriate practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing
and promotion, including promoting off-label uses of our products, commission compensation, certain customer incentive programs, certain
patient support offerings, and other business arrangements generally. Activities subject to these laws also involve the improper use or
misrepresentation of information obtained in the course of patient recruitment for clinical trials, creating fraudulent data in our preclinical
studies or clinical trials or illegal misappropriation of drug product, which could result in regulatory sanctions and cause serious harm to
our reputation. See “Part I, Item 1, Business – Government Regulation – Healthcare and Privacy Law and Regulation and Healthcare
Reform” of this Annual Report on Form 10-K, for more information on the healthcare laws and regulations that may affect our ability to
operate.
We are also exposed to the risk of fraud, misconduct or other illegal activity by our employees, independent contractors,
consultants, principal investigators, CROs, commercial partners and vendors. Misconduct by these parties could include intentional,
reckless and/or negligent conduct that fails to: comply with the laws of the FDA and other similar foreign regulatory bodies; provide true,
complete and accurate information to the FDA and other similar foreign regulatory bodies; comply with manufacturing standards we have
established; comply with federal and state data privacy, security, fraud and abuse and other healthcare laws and regulations in the US and
similar foreign fraudulent misconduct laws; or report financial information or data accurately or to disclose unauthorized activities to us. It
is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent inappropriate conduct
may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other
actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.
We are also subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred.
Efforts to ensure that our business arrangements will comply with applicable healthcare laws and regulations will involve substantial costs.
It is possible that governmental and enforcement authorities will conclude that our business practices may not comply with current or future
statutes, regulations or case law interpreting applicable fraud and abuse or other healthcare laws and regulations. If any such actions are
instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact
on our business, including the imposition of significant civil, criminal and administrative penalties, damages, disgorgement, monetary fines,
imprisonment, additional reporting obligations and oversight if we become subject to a corporate integrity agreement or other agreement to
resolve allegations of non-compliance with these laws, possible exclusion from participation in Medicare, Medicaid and other federal
healthcare programs, contractual damages, reputational harm, diminished profits and future earnings, and curtailment or restructuring of our
operations, any of which could adversely affect our ability to operate our business and our results of operations.
42
Table of Contents
We are subject to stringent and evolving privacy and information security laws, regulations, rules, policies, and contractual obligations,
and changes in such laws, regulations, rules, policies, contractual obligations and our actual or perceived failure to comply with such
requirements could subject us to significant investigations, fines, penalties and claims, any of which may have a material adverse effect
on our business, financial condition, results of operations or prospects.
We are subject to, or affected by, various federal, state and foreign laws, rules, directives, and regulations, as well as regulatory
guidance, policies and contractual obligations relating to privacy and information security, governing the acquisition, collection, access,
use, disclosure, processing, modification, retention, storage, transfer, destruction, protection, and security (collectively, “processing”) of
personal information and other sensitive information about individuals. The global privacy and information security landscape is evolving
rapidly, and implementation standards and enforcement practices are likely to continue to develop for the foreseeable future and may result
in conflicting or inconsistent compliance obligations. Legislators and regulators are increasingly adopting or amending privacy and
information security laws, rules, directives, and regulations that may create uncertainty in our business, affect our or our collaborators’,
service providers’ and contractors’ ability to operate in certain jurisdictions or to process personal information, transfer data internationally,
necessitate the acceptance of more onerous obligations in our contracts, result in enforcement actions, litigation or other liability or impose
additional costs on us. The cost of compliance with these laws, regulations and standards is high and is likely to increase in the future. Any
failure or perceived failure by us or our collaborators, service providers and contractors to comply with federal, state or foreign laws or
regulations, our internal policies and procedures or our contracts governing the processing of personal information could result in negative
publicity, diversion of management time and effort and proceedings against us by governmental entities or others. In many jurisdictions,
enforcement actions, litigation, and other consequences for noncompliance with privacy and information security laws and regulations are
rising. Compliance with applicable privacy and information security laws and regulations, as well as regulatory guidance, policies and
contractual obligations, is a rigorous and time-intensive process, and we may be required to put in place additional mechanisms to ensure
compliance with the new privacy and information security requirements. If we fail to comply with any such obligations, we may face
significant investigations, fines, penalties and claims that could materially and adversely affect our business, financial condition, results of
operations, ability to process personal information and income from certain business initiatives.
In the US, these obligations include various federal, state, and local statutes, rules, and regulations relating to privacy and data
security. The Federal Trade Commission (FTC) has authority under Section 5 of the FTC Act to regulate unfair or deceptive or practices,
and has used this authority to initiate enforcement actions against companies that implement inadequate controls around privacy and
information security in violation of their externally facing policies. The US federal government has also enacted statutes to address privacy
and information security issues impacting particular industries or activities, including the following laws and regulations: the Electronic
Communications Privacy Act, the Computer Fraud and Abuse Act, the Health Insurance Portability and Accountability Act, the Health
Information Technology for Economic and Clinical Health Act, the Telephone Consumer Protection Act, the CAN-SPAM Act, and other
laws and regulations. In addition, state legislatures have enacted statutes to address privacy and information security issues, including the
California Consumer Privacy Act of 2018(the CCPA), and similar state laws such as Virginia’s Consumer Data Protection Act and the
Colorado Privacy Act. For example, the CCPA establishes a privacy framework applicable to for-profit entities that are doing business in
California, including an expansive definition of personal information and data privacy rights for California residents, and authorizes
potentially severe statutory damages and creates a private right of action for certain data security breaches. The CCPA also requires
businesses subject to the law to provide new disclosures to California residents and to provide them with expanded rights with respect to
their personal information, including the right to opt out of the sale of such information. Although there are limited exemptions for clinical
trial and other research-related data under the CCPA, the CCPA and other similar laws could impact our business depending on how it will
be interpreted by the new California Privacy Protection Agency. As we expand our operations, the CCPA may increase our compliance
costs and potential liability. In addition, California voters approved the California Privacy Rights Act of 2020 (CPRA), which goes into
effect on January 1, 2023. The CPRA will, among other things, give California residents the ability to limit the use of their sensitive
information, opt out of certain types of profiling and automated processing activities, provide for penalties for CPRA violations concerning
California residents under the age of 16, and establish a new California Privacy Protection Agency to implement and enforce the law.
Additionally, Colorado and Virginia both signed privacy legislation, each of which go into effect in 2023, and multiple other states and the
federal government are considering enacting similar legislation. Many states also have in place data security laws requiring companies to
maintain certain safeguards with respect to the
43
Table of Contents
processing of personal information, and all states require companies to notify individuals or government regulators in the event of a data
breach impacting such information. New privacy laws add additional complexity, requirements, restrictions and potential legal risk.
Accordingly, compliance programs may require additional investment in resources, and could impact availability of previously useful data.
Internationally, our operations abroad may also be subject to increased scrutiny or attention from foreign data protection
authorities. For example, our clinical trial programs and research collaborations outside the US may implicate foreign data protection laws,
including in the European Economic Area, Switzerland, and/or the UK (collectively, Europe). Many jurisdictions have established or are in
the process of establishing privacy and data security legal frameworks with which we, our collaborators, service providers, including our
CROs, and contractors must comply. For example, European data protection laws, including, without limitation, the General Data
Protection Regulation (the EU GDPR), impose strict requirements for processing personal information (i.e., data which identifies an
individual or from which an individual is identifiable), including clinical trial data and grant individuals’ various data protection rights (e.g.,
the right to erasure of personal information). In turn, the EU GDPR and similar laws increase our obligations with respect to clinical trials
conducted in Europe by expanding the definition of personal information to also include coded data and requiring (i) changes to informed
consent practices and more detailed notices for clinical trial participants and investigators; (ii) consideration of data protection as any new
products or services are developed, including to limit the amount of personal information processed; and (iii) implementation of appropriate
technical and organizational measures to safeguard personal information and to report certain personal data breaches to the relevant
supervisory authority without undue delay (for the EU GDPR no later than 72 hours where feasible). In the event of non-compliance, the
EU GDPR provides for robust regulatory enforcement and fines of up to €20 million or 4% of the annual global revenue, whichever is
greater. In addition, the EU GDPR confers a private right of action on data subjects and consumer associations to lodge complaints with
supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the EU GDPR.
European data protection laws, including the EU GDPR, generally also restrict the transfer of personal information from Europe to
the US and most other countries that are not recognized as having “adequate” data protection laws unless the parties to the transfer have
implemented specific safeguards to protect the transferred personal information. One of the primary safeguards allowing US companies to
import personal information from Europe has been certification to the EU-US Privacy Shield and Swiss-US Privacy Shield frameworks
administered by the US Department of Commerce. However, the Court of Justice of the European Union (CJEU) issued a decision in July
2020 invalidating the EU-US Privacy Shield framework as a data transfer mechanism (Schrems II) and imposing further restrictions on the
use of standard contractual clauses (SCCs), including a requirement for companies to carry out a transfer privacy impact assessment, which,
among other things, assesses laws governing access to personal information in the recipient country and considers whether supplementary
measures that provide privacy protections additional to those provided under the SCCs will need to be implemented to ensure an essentially
equivalent level of data protection to that afforded in Europe. Following that decision, the Swiss Federal Data Protection and Information
Commissioner (FDPIC) took a similar view and considered that data transfers based on the Swiss-US Privacy Shield framework are no
longer lawful (despite the fact that Schrems II is not directly applicable in Switzerland (unless the Swiss based company is subject to the
EU GDPR) and the Swiss-US Privacy Shield has not been officially invalidated). Further, the EC published new EU SCCs in June 2022,
which place onerous obligations on the contracting parties. At present, there are few, if any, viable alternatives to the SCCs. However, on
October 7, 2022, the US President introduced an Executive Order to facilitate a new Trans-Atlantic Data Privacy Framework which will act
as a successor to the invalidated Privacy Shield. On December 13, 2022, the EC also published its draft adequacy decision to reflect its
view that the new executive order and Trans-Atlantic Data Privacy Framework, is able to meet the concerns raised in Schrems II. If the
draft adequacy decision is approved and implemented, the agreement will facilitate the transatlantic flow of personal data and provide
additional safeguards to data transfer mechanisms (including EU SCCs and Binding Corporate Rules) for companies transferring personal
data from the EU to the US. However, before parties rely on the new framework, there are still legislative and regulatory steps that must be
undertaken both in the US and in the EU. As such, any transfers by us or our third-party vendors, collaborators or others of personal
information from Europe to the US or elsewhere may not comply with European data protection laws, may increase our exposure to
European data protection laws’ heightened sanctions for cross-border data transfer restrictions may restrict our clinical trial activities in
Europe and may limit our ability to collaborate with CROs, service providers, contractors and other companies subject to European data
protection laws. Loss of our ability to transfer personal information from Europe may also require us to increase our data processing
capabilities in those jurisdictions at significant expense.
44
Table of Contents
Following the UK’s departure from the EU (Brexit), the EU GDPR’s data protection obligations continue to apply to the UK in
substantially unvaried form under the so-called “UK GDPR” (i.e., the EU GDPR as it continues to form part of law in the UK by virtue of
section 3 of the European Union (Withdrawal) Act 2018, as amended (including by the various Data Protection, Privacy and Electronic
Communications (Amendments etc.) (EU Exit) Regulations)). The UK GDPR exists alongside the UK Data Protection Act 2018 that
implements certain derogations in the UK GDPR into UK law. Under the UK GDPR, companies not established in the UK but that process
personal information either in relation to the offering of goods or services to individuals in the UK, or to monitor their behavior will be
subject to the UK GDPR, the requirements of which are (at this time) largely aligned with those under the EU GDPR, and as such, may
lead to similar compliance and operational costs with potential fines of up to £17.5 million or 4% of global turnover. As a result, we are
potentially exposed to two parallel data protection regimes, each of which authorizes fines and the potential for divergent enforcement
actions. It should also be noted that the UK Government published its own form of EU SCCs, known as the International Data Transfer
Agreement (IDTA) and International Data Transfer Addendum (UK Addendum) to the new EU SCCs. The UK Information
Commissioner’s Office (ICO) has also published its version of the transfer impact assessment and revised guidance on international
transfers, although entities may choose to adopt either the EU or UK style transfer impact assessment. In terms of international data
transfers between the UK and US, it is understood that the UK and the US are negotiating an adequacy agreement.
Additionally, other countries outside of Europe have enacted or are considering enacting similar cross-border data transfer
restrictions and laws requiring local data residency, with strict requirements and limitations for processing personal information, which
could increase the cost and complexity of delivering our services and operating our business. For example, Brazil enacted the General Data
Protection Law, New Zealand enacted the New Zealand Privacy Act, China released its Personal Information Protection Law, which went
into effect November 1, 2021, and Canada introduced the Digital Charter Implementation Act. As with the EU GDPR, these laws are broad
and may increase our compliance burdens, including by mandating potentially burdensome documentation requirements and granting
certain rights to individuals to control how we collect, use, disclose, retain, and process personal information about them.
We publish privacy policies and other documentation regarding our collection, processing, use and disclosure of personal
information and/or other confidential information. Although we endeavor to comply with our published policies and other documentation,
we may at times fail to do so or may be perceived to have failed to do so. Moreover, despite our efforts, we may not be successful in
achieving compliance if our employees, collaborators, contractors, service providers or vendors fail to act in accordance with our published
policies and documentation. Such failures can subject us to potential foreign, local, state and federal action if they are found to be
deceptive, unfair, or misrepresentative of our actual practices. Moreover, trial participants or research subjects about whom we or our
partners obtain information, as well as the providers who share this information with us, may contractually limit our ability to use and
disclose the information or exercise their right to do so under applicable privacy legislation. Claims that we have violated individuals’
privacy rights or failed to comply with data protection laws or applicable privacy policies and documentation, even if we are not found
liable, could be expensive and time-consuming to defend and could result in adverse publicity that could harm our business.
In addition to data privacy requirements, many jurisdictions impose mandatory clinical trial information obligations on sponsors.
In the EU, such obligations arise under the Transparency Regulation No 1049/ 2001, EMA Policy 0043, EMA Policy 0070 and the Clinical
Trials Regulation No 536/2014, all of which impose on sponsors the obligation to make publicly available certain information stemming
from clinical studies. In the EU, the transparency framework provides EU-based parties the right to submit an access to documents request
to the EMA for information included in the marketing authorization application dossier for approved medicinal products. Only very limited
information is exempted from disclosure, i.e. commercially confidential information (which is construed increasingly narrowly) and
protected personal data. It is possible for competitors to access and use this data in their own research and development programs anywhere
in the world, once this data is in the public domain.
On May 3, 2022, the EC published a proposal for a regulation on the European Health Data Space (EHDS), which aims to further
enable exchange of electronic health data both for primary use (among national EU healthcare systems for patient care) and secondary use
(among private companies and regulators to enable scientific research). Whilst the regulation is currently under discussions among the EU
legislators, the text is expected to be finalized by the end of 2023 and for the EHDS to become applicable in 2025. This will impose new
obligations, but also create opportunities, for entities engaged in health-related research to share and access health data on a scale much
larger than
45
Table of Contents
what is foreseen under current applicable transparency provisions.
Our business could be materially and adversely affected by pandemics as a result of their potential impacts on our sales force and
commercialization efforts, supply chain, regulatory, clinical development and corporate development activities and other business
operations, in addition to the impact of a global economic slowdown.
Pandemics may result in extended travel and other restrictions in order to reduce the spread of diseases. Government measures
taken in response to pandemics could have a significant impact, both direct and indirect, on our business and commerce, as significant
reductions in business related activities may occur, supply chains may be disrupted, and manufacturing and clinical development activities
may be curtailed or suspended.
For example, since the COVID-19 pandemic was declared, we have observed reduced patient-doctor interactions and our
representatives have had fewer visits with health care providers, which has negatively affected our product sales and may continue to
negatively affect our product sales in the future. Physicians with practices severely impacted by the COVID-19 pandemic, and who
currently prescribe our products, may eventually decide to close their independent practices and join a larger medical organization with a
practice that does not prescribe our products. Additionally, commercial-related activities, such as our marketing programs, speaker bureaus,
and market access initiatives were conducted virtually, delayed or cancelled as a result of the COVID-19 pandemic. We had to deploy
resources to enable our field-based employees to continue to engage with health care providers in hybrid virtual and in-person interactions.
With respect to clinical development, in response to the COVID-19 pandemic, we have taken, and may continue to take, measures
to implement remote and virtual approaches, including remote patient monitoring where possible and working with our investigators for
appropriate care of these patients in a safe manner. We have a number of ongoing clinical trials, including our clinical studies in COVID
and IRAK 1/4 inhibitor program. A number of our clinical trial investigators have paused, postponed or delayed new patient enrollment and
restricted site visits of existing patients enrolled. Although some sites have resumed patient screening, the progress is slow, and we continue
to experience delays in new patient enrollment. We are continuing to make decisions country-by-country to minimize risk to the patients
and clinical trial sites. We also rely heavily on our clinical trial investigators to inform us of the best course of action with respect to
resuming enrollment/screening, considering the ability of sites to ensure patient safety or data integrity. Patients already enrolled in our
studies continue to receive study drugs, and we remain focused on supporting our sites in providing care for these patients and providing
continued investigational drug supply. We experienced slower than anticipated enrollment in some of our clinical trials, and in the future,
we may experience adverse impact that the COVID-19 pandemic may have on our clinical trials, including the timing thereof, or our ability
to continue to treat patients enrolled in our trials, enroll and assess new patients, supply study drugs and obtain complete data points in
accordance with study protocol.
Pandemics may cause significant disruption in the supply chain for our commercial products. We currently rely on third parties to,
among other things, manufacture and ship our commercial product, raw materials and product supply for our clinical trials, perform quality
testing and supply other goods and services to help manage our commercial activities, our clinical trials and our operations in the ordinary
course of business. While we have engaged actively with various elements of our supply chain and distribution channel, including our
customers, contract manufacturers, and logistics and transportation provider to meet demand for our products and to remain informed of
any challenges within our supply chain, we may face disruptions to our supply chain and operations, and associated delays in the
manufacturing and supply of our products. Such supply disruptions would adversely impact our ability to generate sales of and revenues
from our products and our business, financial condition, results of operations and growth prospects could be adversely affected.
Pandemics may affect our collaboration and licensing partners for the commercialization of fostamatinib globally, as well as our
ability to advance our various clinical stage programs. We cannot predict the impact of such disruptions on our partners’ ability to advance
commercialization of fostamatinib in the market and the timing of enrollment and completion of various clinical trials being conducted by
our collaboration partners.
46
Table of Contents
Health regulatory agencies globally may experience prolonged disruptions in their operations as a result of pandemics. For
example, in response to the COVID-19 pandemic, the FDA delayed inspections and evaluations of certain drug manufacturing facilities and
clinical research sites We cannot predict whether, and when, health regulatory agencies will decide to pause or resume inspections due to
pandemics. Any de-prioritization of our clinical trials or delay in regulatory review resulting from such disruptions could materially affect
the completion of our clinical trials.
In addition, as seen in the COVID-19 pandemic, pandemics could result in a significant disruption of global financial markets. We
could experience an inability to access additional capital or an impact on liquidity, which could in the future negatively affect our capacity
for certain corporate development transactions or our ability to make other important, opportunistic investments, or we may not be able to
meet the requirements under our Credit and Security Agreement (Credit Agreement) with MidCap Financial Trust (MidCap) in order for us
to access the funds remaining under such Credit Agreement. While we expect pandemics to adversely affect our business, financial
condition, results of operations and growth prospects in the future periods, the extent of the impact on our ability to generate sales of and
revenues from our approved products, our ability to continue to secure new collaborations and support existing collaboration efforts with
our partners, our clinical development and regulatory efforts, our corporate development objectives and the value of and market for our
common stock, will depend on future circumstances that are highly uncertain and cannot be predicted with confidence at this time, such as
the ultimate duration and severity of pandemics, travel restrictions, quarantines, social distancing and business closure requirements in the
US and other countries, and the effectiveness of actions taken globally to contain and treat diseases. To the extent pandemics adversely
affect our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties described
elsewhere in this “Risk Factors” section.
Enhanced governmental and public scrutiny over, or investigations or litigation involving, pharmaceutical manufacturer donations to
patient assistance programs may require us to modify our programs and could negatively impact our business practices, harm our
reputation, divert the attention of management and increase our expenses.
To help patients afford our products, we have a manufacturer-sponsored patient assistance program that helps financially needy
patients. This type of program has become the subject of enforcement scrutiny in recent years. For example, some pharmaceutical
manufacturers have been named in class action lawsuits challenging the legality of their patient assistance programs under a variety of
federal and state laws. In addition, certain state and federal enforcement authorities have pursued investigations and settlements and
members of Congress have initiated inquiries about manufacturer-sponsored patient support programs, including, for example,
manufacturer-sponsored patient assistance programs, co-payment assistance programs, and manufacturer contributions to independent
charitable patient assistance programs. Moreover, the Department of Health and Human Services, Office of the Inspector General recently
published an advisory opinion (OIG Ad Op. No. 22-19) that, while binding only on the requestor of the opinion, reflects the government’s
continued scrutiny of manufacturer financial contributions to patient assistance programs conducted through third parties, including
charitable organizations. Numerous organizations, including pharmaceutical manufacturers, have been subject to ongoing litigation,
enforcement activities and settlements related to their patient support programs and certain of these organizations have entered into, or have
otherwise agreed to, significant civil settlements with applicable enforcement authorities. It is possible that future legislation may be
proposed that would establish requirements or restrictions with respect to these programs and/or support that would affect pharmaceutical
manufacturers.
Our patient assistance program could become the target of similar inquiries, litigation, enforcement, and/or legislative proposals. If
we are deemed not to have complied with laws or regulations in the operation of, or our interactions with, these programs, we could be
subject to damages, fines, penalties or other criminal, civil or administrative sanctions or enforcement actions. We cannot ensure that our
compliance controls, policies and procedures will be sufficient to protect against acts of our employees, business partners or vendors that
may violate the laws or regulations of the jurisdictions in which we operate. A government investigation could negatively impact our
business practices, harm our reputation, divert the attention of management and increase our expenses.
47
Table of Contents
If manufacturers obtain approval for generic versions of our products, or of products with which we compete, our business may be
harmed.
Under the FDCA, the FDA can approve an ANDA for a generic version of a branded drug without the ANDA applicant
undertaking the clinical testing necessary to obtain approval to market a new drug. Generally, in place of such clinical studies, an ANDA
applicant usually needs only to submit data demonstrating that its product has the same active ingredient(s), strength, dosage form and route
of administration and that it is bioequivalent to the branded product. In September 2019, the FDA published product-specific
bioequivalence guidance on fostamatinib disodium to let potential ANDA applicants understand the data FDA would expect to see for
approval of a generic version of our products.
The FDCA requires that an applicant for approval of a generic form of a branded drug certify either that its generic product does
not infringe any of the patents listed by the owner of the branded drug in the Orange Book or that those patents are not enforceable. This
process is known as a paragraph IV challenge. Upon notice of a paragraph IV challenge, a patent owner has 45 days to bring a patent
infringement suit in federal district court against the company seeking ANDA approval of a product covered by one of the owner’s patents.
If this type of suit is commenced, the FDCA provides a 30-month stay on the FDA’s approval of the competitor’s application. If the
litigation is resolved in favor of the ANDA applicant or the challenged patent expires during the 30-month stay period, the stay is lifted, and
the FDA may thereafter approve the application based on the standards for approval of ANDAs. Once an ANDA is approved by the FDA,
the generic manufacturer may market and sell the generic form of the branded drug in competition with the branded medicine.
The ANDA process can result in generic competition if the patents at issue are not upheld or if the generic competitor is found not
to infringe the owner’s patents. If this were to occur with respect to our products or products with which it competes, our business would be
harmed. We have a number of patents listed in the Orange Book, the last of which is expected to expire in July 2032.
In June 2022, we received a notice letter regarding an ANDA submitted to the FDA by Annora, requesting approval to market a
generic version of TAVALISSE. The notice letter included a Paragraph IV certification with respect to our US Patent Nos. 7,449,458;
8,263,122; 8,652,492; 8,771,648 and 8,951,504, which are listed in the Orange Book. The notice letter asserts that these patents will not be
infringed by Annora’s proposed product, are invalid and/or are unenforceable. Annora’s notice letter does not provide a Paragraph IV
certification against our other patents listed in the Orange Book. On July 25, 2022, we filed a lawsuit in the US District Court for the
District of New Jersey against Annora and its affiliates, Hetero Labs Ltd., and Hetero USA, Inc., for infringement of our US patents
identified in Annora’s Paragraph IV certification. On September 21, 2022, Annora and its affiliates answered and counterclaimed for
declaratory judgment of non-infringement and invalidity of the ’458, ’122, ’492, ’648, and ’504 patents. We filed an answer to Annora’s
counterclaims on October 12, 2022. We intend to vigorously enforce and defend our intellectual property related to TAVALISSE. We cannot
be assured that such lawsuit will prevent the introduction of a generic version of TAVALISSE for any particular length of time, or at all. If
an ANDA from Annora or any other generic manufacturer is approved, and a generic version of TAVALISSE is introduced, whether
following the expiration of our patents, the invalidation of our patents as a result of any litigation, or the determination that the proposed
generic product does not infringe on our patents, our sales of TAVALISSE would be adversely affected. In addition, we cannot predict what
additional ANDAs could be filed by Annora or other potential generic competitors requesting approval to market generic forms of
fostamatinib, which would require us to incur significant additional expense and result in distraction for our management team, and if
approved, result in significant decreases in the revenue derived from sales of our marketed products and thereby materially harm our
business and financial condition.
Unforeseen safety issues could emerge with our products that could require us to change the prescribing information to add warnings,
limit use of the product, and/or result in litigation. Any of these events could have a negative impact on our business.
Discovery of unforeseen safety problems or increased focus on a known problem could impact our ability to commercialize our
products and could result in restrictions on its permissible uses, including withdrawal of the medicine from the market.
48
Table of Contents
If we or others identify additional undesirable side effects caused by our products after approval:
● regulatory authorities may require the addition of labeling statements, specific warnings, contraindications, or field alerts to
physicians and pharmacies;
● regulatory authorities may withdraw their approval of the product and require us to take our approved drugs off the market;
● we may be required to change the way the product is administered, conduct additional clinical trials, change the labeling of
the product, or implement a Risk Evaluation and Mitigation Strategy, or REMS;
● we may have limitations on how we promote our drugs;
● third-party payers may limit coverage or reimbursement for our products;
● sales of our products may decrease significantly;
● we may be subject to litigation or product liability claims; and
● our reputation may suffer.
Any of these events could prevent us from achieving or maintaining market acceptance of our products and could substantially
increase our operating costs and expenses, which in turn could delay or prevent us from generating significant revenue from sale of our
products.
Side effects and toxicities associated with our products, as well as the warnings, precautions and requirements listed in the
prescribing information for our products, could affect the willingness of physicians to prescribe, and patients to utilize, our products and
thus harm commercial sales of our products. The FDA approved label for REZLIDHIA contains a boxed warning describing the risk of
differentiation syndrome, which can be fatal, in patients receiving REZLIDHIA. This and other restrictions could limit the commercial
success of REZLIDHIA.
If a safety issue emerges post-approval, we may become subject to costly product liability litigation by our customers, their
patients or payers. Product liability claims could divert management’s attention from our core business, be expensive to defend, and result
in sizable damage awards against us that may not be covered by insurance. If we cannot successfully defend ourselves against claims that
our products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
● decreased demand for any product candidates or products that we may develop;
● the inability to commercialize any products that we may develop;
● injury to our reputation and significant negative media attention;
● withdrawal of patients from clinical studies or cancellation of studies;
● significant costs to defend the related litigation;
● substantial monetary awards to patients; and
● loss of revenue.
We currently hold $10.0 million in product liability insurance coverage, which may not be adequate to cover all liabilities that we
may incur. Insurance coverage is increasingly expensive. We may not be able to obtain insurance coverage at a reasonable cost or in
amounts adequate to satisfy any liability or associated costs that may arise in the future. These events could harm our business and results
of operations and cause our stock price to decline.
49
Table of Contents
If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental
pricing programs in the US, we could be subject to additional rebate or discount requirements, fines, sanctions and exposure under
other laws which could have an adverse effect on our business, results of operations and financial condition.
We participate in the Medicaid Drug Rebate Program, as administered by the CMS, the 340B Drug Pricing Program, and other
federal and state government drug pricing programs in the US, and we may participate in additional government pricing programs in the
future. These programs generally require us to pay rebates or otherwise provide discounts to government payers in connection with drugs
that are dispensed to beneficiaries/recipients of these programs. In some cases, such as with the Medicaid Drug Rebate Program, the rebates
are based on pricing metrics that we report on a monthly and quarterly basis to the government agencies that administer the programs.
Pricing requirements and rebate/discount calculations are complex, vary among products and programs, and are often subject to
interpretation by governmental or regulatory agencies and the courts. The requirements of these programs, including, by way of example,
their respective terms and scope, change frequently. Responding to current and future changes may increase our costs, and the complexity
of compliance will be time consuming. Invoicing for rebates is provided in arrears, and there is frequently a time lag of up to several
months between the sales to which rebate notices relate and our receipt of those notices, which further complicates our ability to accurately
estimate and accrue for rebates related to the Medicaid program as implemented by individual states. Thus, there can be no assurance that
we will be able to identify all factors that may cause our discount and rebate payment obligations to vary from period to period, and our
actual results may differ significantly from our estimated allowances for discounts and rebates. Changes in estimates and assumptions may
have an adverse effect on our business, results of operations and financial condition.
In addition, the Office of Inspector General of HHS and other Congressional enforcement and administrative bodies have recently
increased their focus on pricing requirements for products, including, but not limited to the methodologies used by manufacturers to
calculate average manufacturer price (AMP) and best price (BP) for compliance with reporting requirements under the Medicaid Drug
Rebate Program. We are liable for errors associated with our submission of pricing data and for any overcharging of government payers.
Failure to make necessary disclosures and/or to identify overpayments could result in allegations against us under the federal False Claims
Act and other laws and regulations. Any required refunds to the US government or response to a government investigation or enforcement
action would be expensive and time consuming and could have an adverse effect on our business, results of operations and financial
condition. In addition, in the event that CMS were to terminate our rebate agreement, no federal payments would be available under
Medicaid for our covered outpatient drugs or under Medicare Part B for any of our products that may be reimbursed under Part B.
Even for those product candidates that have or may receive regulatory approval, they may fail to achieve the degree of market
acceptance by physicians, patients, healthcare payors and others in the medical community necessary for commercial success, in which
case we may not generate significant revenues or become profitable.
For our product candidates that have or may receive regulatory approval, they may nonetheless fail to gain sufficient market
acceptance by physicians, hospital administrators, patients, healthcare payors and others in the medical community. The degree of market
acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including the following:
● relative convenience and ease of administration;
● the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;
● the willingness of physicians to change their current treatment practices;
● the willingness of hospitals and hospital systems to include our product candidates as treatment options;
● demonstration of efficacy and safety in clinical trials;
● the prevalence and severity of any side effects;
50
Table of Contents
● the ability to offer product candidates for sale at competitive prices;
● the price we charge for our product candidates;
● the strength of marketing and distribution support; and
● the availability of third-party coverage and adequate reimbursement and the willingness of patients to pay out-of-pocket in the
absence of such coverage and adequate reimbursement.
Efforts to educate the physicians, patients, healthcare payors and others in the medical community on the benefits of our product
candidates may require significant resources and may not be successful. If any of our product candidates are approved, if at all, but do not
achieve an adequate level of acceptance, we may not generate significant product revenue and we may not become profitable on a sustained
basis.
We will need additional capital in the future to sufficiently fund our operations and research.
We have consumed substantial amounts of capital to date as we continue our research and development activities, including
preclinical studies and clinical trials and for the commercialization of our products. We may seek another collaborator or licensee in the
future for further clinical development and commercialization of fostamatinib, as well as our other clinical programs, which we may not be
able to obtain on commercially reasonable terms or at all. We believe that our existing capital resources will be sufficient to support our
current and projected funding requirements, including the continued commercialization of our products through at least the next 12 months.
We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than
we currently expect. Because of the numerous risks and uncertainties associated with commercial launch, the development of our product
candidates and other research and development activities, we are unable to estimate with certainty our future product revenues, our
revenues from our current and future collaborative partners, the amounts of increased capital outlays and operating expenditures associated
with our current and anticipated clinical trials and other research and development activities.
We will continue to need additional capital and the amount of future capital needed will depend largely on the success of our
commercialization of our products, and the success of our internally developed programs as they proceed in later and more expensive
clinical trials, including any additional clinical trials that we may decide to conduct with respect to fostamatinib. While we intend to
opportunistically seek access to additional funds through public or private equity offerings or debt financings, we do not know whether
additional financing will be available when needed, or that, if available, we will obtain financing on reasonable terms. Our ability to raise
additional capital, including our ability to secure new collaborations and continue to support existing collaboration efforts with our partners,
may also be adversely impacted by potential worsening global economic conditions and the recent disruptions to, and volatility in, the
credit and financial markets in the US and worldwide resulting from the COVID-19 pandemic and the conflict in the Ukraine. Unless and
until we are able to generate a sufficient amount of product, royalty or milestone revenue, which may never occur, we expect to finance
future cash needs through public and/or private offerings of equity securities, debt financings or collaboration and licensing arrangements,
as well as through proceeds from the exercise of stock options and interest income earned on the investment of our cash balances and short-
term investments. To the extent we raise additional capital by issuing equity securities in the future, our stockholders could at that time
experience substantial dilution. In addition, we have a significant number of stock options outstanding. To the extent that outstanding stock
options have been or may be exercised or other shares issued, our stockholders may experience further dilution. Further, we may choose to
raise additional capital due to market conditions or strategic considerations even if we believe we have sufficient funds for our current or
future operating plans. Our credit facility with MidCap includes certain covenants that may restrict our business, and any other debt
financing that we are able to obtain in the future may involve operating covenants that restrict our business. To the extent that we raise
additional funds through any new collaboration and licensing arrangements, we may be required to refund certain payments made to us,
relinquish some rights to our technologies or product candidates or grant licenses on terms that are not favorable to us.
51
Table of Contents
We have indebtedness in the form of a term loan pursuant to the Credit Agreement (as defined below) with MidCap, which
could adversely affect our financial condition and our ability to respond to changes in our business. Further, if we are unable to satisfy
certain conditions of the Credit Agreement, we will be unable to draw down the remainder of the facility.
We entered into the Credit Agreement with MidCap on September 27, 2019, amended on March 29, 2021, February 11, 2022, and
July 27, 2022. Under the Credit Agreement, we are required to repay amounts due when there is an event of default for the term loans that
results in the principal, premium, if any, and interest, if any, becoming due prior to the maturity date for the term loans. The Credit
Agreement also contains a number of other affirmative and restrictive covenants. See “Note 9 – Debt” to our “Notes to Financial
Statements” contained in “Part II, Item 8, Financial Statements and Supplementary Data” of this Annual Report on Form 10-K for
additional details of the Credit Agreement. These and other terms in the Credit Agreement have to be monitored closely for compliance and
could restrict our ability to grow our business or enter into transactions that we believe would be beneficial to our business. Our business
may not generate cash flow from operations in the future sufficient to service our debt and support our growth strategies. If we are unable to
generate such cash flow, we may be required to adopt one or more alternatives, such as restructuring our debt or obtaining additional equity
capital on terms that may be onerous or highly dilutive. Our ability to refinance our indebtedness will depend on the capital markets and our
financial condition at such time. We may not be able to engage in any of these activities or engage in these activities on desirable terms,
which could result in a default on our current debt obligations. In addition, we cannot be sure that additional financing will be available
when required or, if available, will be on terms satisfactory to us. Further, even if we are able to obtain additional financing, we may be
required to use such proceeds to repay a portion of our debt.
Our indebtedness may have other adverse effects, such as:
● our vulnerability to adverse general economic conditions and heightened competitive pressures;
● dedication of a portion of our cash flow from operations to interest payments, limiting the availability of cash for other
operational purposes;
● limited flexibility in planning for, or reacting to, changes in our business and industry; and
● our inability to obtain additional financing in the future.
Our Credit Agreement with MidCap contains a mandatory prepayment provision that gives MidCap and/or its agent the right to
demand payment of the outstanding principal and additional interest and fees in the event of default. We may not have enough available
cash or be able to obtain financing at the time we are required to repay the term loan with additional interest and fees prior to maturity.
The Credit Agreement provides for a $60.0 million term loan credit facility. As of December 31, 2022, the outstanding principal
balance of the loan was $40.0 million, and the facility gives us the ability to access an additional $20.0 million aggregate principal amount
of term loan at our option through March 31, 2023, subject to the satisfaction of applicable funding conditions which include minimum net
revenue and compliance with financial covenants set forth in the Credit Agreement. If we are unable to satisfy these or other required
conditions, we would not be able to draw down the remaining tranches of financing and may not be able to obtain alternative financing on
commercially reasonable terms or at all, which could adversely impact our business.
We rely and may continue to rely on two distribution facilities for the sale of our products and potential sale of any of our product
candidates.
Our distribution operations for the sale of our products are currently concentrated in two distribution centers owned by a third-
party logistics provider. Additionally, our distribution operations, if and when we launch any of our product candidates in the future, may
also be concentrated in such distribution centers owned by a third-party logistics provider. Any errors in inventory level management and
unforeseen inventory shortage could adversely affect our business. In addition, any significant disruption in the operation of the facility due
to natural disaster or severe weather, or events such as fire, accidents, power outages, system failures, or other unforeseen causes, could
devalue or damage a significant portion of our inventories and could adversely affect our product distribution and sales until such time as
we
52
Table of Contents
could secure an alternative facility. Further, climate change may increase both the frequency and severity of extreme weather conditions and
natural disasters, which may affect our business operations. If we encounter difficulties with any of our distribution facilities, whether due
to the potential future impacts of the COVID-19 pandemic (including as a result of disruptions of global shipping and the transport of
products) or otherwise, or other problems or disasters arise, we cannot ensure that critical systems and operations will be restored in a
timely manner or at all, and this would have an adverse effect on our business. In addition, growth could require us to further expand our
current facility, which could affect us adversely in ways that we cannot predict.
Forecasting potential sales for any of our product candidates will be difficult, and if our projections are inaccurate, our business may be
harmed, and our stock price may be adversely affected.
Our business planning requires us to forecast or make assumptions regarding product demand and revenues for any of our product
candidates if they are approved despite numerous uncertainties. These uncertainties may be increased if we rely on our collaborators or
other third parties to conduct commercial activities in certain geographies and provide us with accurate and timely information. Actual
results may differ materially from projected results for various reasons, including the following, as well as risks identified in other risk
factors:
● the efficacy and safety of any of our product candidates, including as relative to marketed products and product candidates in
development by third parties;
● pricing (including discounting or other promotions), reimbursement, product returns or recalls, competition, labeling, adverse
events and other items that impact commercialization;
● the rate of adoption in the particular market, including fluctuations in demand for various reasons;
● potential future impacts, if any, due to the COVID-19 pandemic;
● lack of patient and physician familiarity with the drug;
● lack of patient use and physician prescribing history;
● lack of commercialization experience with the drug;
● actual sales to patients may significantly differ from expectations based on sales to wholesalers; and
● uncertainty relating to when the drug may become commercially available to patients and rate of adoption in other territories.
We expect that our revenues from sales of any of our product candidates will continue to be based in part on estimates, judgment
and accounting policies. Any incorrect estimates or disagreements with regulators or others regarding such estimates or accounting policies
may result in changes to our guidance, projections or previously reported results. Expected and actual product sales and quarterly and other
results may greatly fluctuate, including in the near-term, and such fluctuations can adversely affect the price of our common stock,
perceptions of our ability to forecast demand and revenues, and our ability to maintain and fund our operations.
We do not and will not have access to all information regarding fostamatinib and product candidates we licensed to Lilly, Kissei, Grifols,
Medison and Knight.
We do not and will not have access to all information regarding fostamatinib and other product candidates, including potentially
material information about commercialization plans, medical information strategies, clinical trial design and execution, safety reports from
clinical trials, safety reports, regulatory affairs, process development, manufacturing and other areas known by Lilly, Kissei, Grifols,
Medison and Knight. In addition, we have confidentiality obligations under our respective agreements with Lilly, Kissei, Grifols, Medison
and Knight. Thus, our ability to keep our shareholders informed about the status of fostamatinib and other product candidates will be
limited by the degree to which Lilly, Kissei, Grifols, Medison and/or Knight keep us informed and allows us to disclose such information to
the public. If Lilly, Kissei, Grifols, Medison and/or Knight fail to keep us informed about commercialization efforts related to fostamatinib,
or the status of the clinical development or regulatory approval pathway of other product candidates
53
Table of Contents
licensed to them, we may make operational and/or investment decisions that we would not have made had we been fully informed, which
may adversely affect our business and operations.
Our future funding requirements will depend on many uncertain factors.
Our future funding requirements will depend upon many factors, many of which are beyond our control, including, but not limited
to:
● the costs to commercialize our products in the US, or any other future product candidates, if any such candidate receives
regulatory approval for commercial sale;
● the progress and success of our clinical trials and preclinical activities (including studies and manufacture of materials) of our
product candidates conducted by us;
● potential future impacts, if any, of the evolving COVID-19 pandemic;
● the costs and timing of regulatory filings and approvals by us and our collaborators;
● the progress of research and development programs carried out by us and our collaborative partners;
● any changes in the breadth of our research and development programs;
● the ability to achieve the events identified in our collaborative agreements that may trigger payments to us from our
collaboration partners;
● our ability to acquire or license other technologies or compounds that we may seek to pursue;
● our ability to manage our growth;
● competing technological and market developments;
● the costs and timing of obtaining, enforcing and defending our patent and other intellectual property rights; and
● expenses associated with any unforeseen litigation, including any arbitration and securities class action lawsuits.
Insufficient funds may require us to delay, scale back or eliminate some or all of our commercial efforts and/or research and
development programs, to reduce personnel and operating expenses, to lose rights under existing licenses or to relinquish greater or all
rights to product candidates at an earlier stage of development or on less favorable terms than we would otherwise choose or may adversely
affect our ability to operate as a going concern.
Our success as a company is uncertain due to our history of operating losses and the uncertainty of any future profitability.
For the year ended December 31, 2022, we recognized loss from operations of $55.6 million primarily due to higher operating and
non-operating expenses, partly offset by our net product sales and collaboration revenues. We have historically incurred losses from
operations each year since we were incorporated in June 1996 other than in fiscal year 2010, due in large part to the significant research and
development expenditures required to identify and validate new product candidates and pursue our development efforts, and the costs of
our ongoing commercial efforts for our products. We expect to continue to incur losses from operations, at least in the next 12 months, and
there can be no assurance that we will generate annual operating income in the foreseeable future. Currently, our potential sources of
revenues are our sales of our products, upfront payments, research and development contingent payments and royalty payments pursuant to
our collaboration arrangements, which may never materialize if our collaborators do not achieve certain events or generate net sales to
which these contingent payments are dependent on. If our future drug candidates fail or do not gain regulatory approval, or if our drugs do
not achieve sustainable market acceptance, we may not be profitable. As of December 31, 2022, we had an accumulated deficit of
approximately $1.4 billion. The extent of our
54
Table of Contents
future losses or profitability, if any, especially due to the COVID-19 pandemic, is highly uncertain.
If our corporate collaborations or license agreements are unsuccessful, or if we fail to form new corporate collaborations or license
agreements, our research and development efforts could be delayed.
Our strategy depends upon the formation and sustainability of multiple collaborative arrangements and license agreements with
third parties now and in the future. We rely on these arrangements for not only financial resources, but also for expertise we need now and
in the future relating to clinical trials, manufacturing, sales and marketing, and for licenses to technology rights. To date, we have entered
into several such arrangements with corporate collaborators; however, we do not know if these collaborations or additional collaborations
with third parties, if any, will dedicate sufficient resources or if any development or commercialization efforts by third parties will be
successful. In addition, our corporate collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a
clinical trial or abandon a drug candidate or development program. Should a collaborative partner fail to develop or commercialize a
compound or product to which it has rights from us for any reason, including corporate restructuring, such failure might delay our ongoing
research and development efforts, because we might not receive any future payments, and we would not receive any royalties associated
with such compound or product. We may seek another collaborator or licensee in the future for clinical development and commercialization
of fostamatinib, as well as our other clinical programs, which we may not be able to obtain on commercially reasonable terms or at all. If
we are unable to form new collaborations or enter into new license agreements, our research and development efforts could be delayed. In
addition, the continuation of some of our partnered drug discovery and development programs may be dependent on the periodic renewal of
our corporate collaborations.
Each of our collaborations could be terminated by the other party at any time, and we may not be able to renew these
collaborations on acceptable terms, if at all, or negotiate additional corporate collaborations on acceptable terms, if at all. If these
collaborations terminate or are not renewed, any resultant loss of revenues from these collaborations or loss of the resources and expertise
of our collaborative partners could adversely affect our business.
Conflicts also might arise with collaborative partners concerning proprietary rights to particular compounds. While our existing
collaborative agreements typically provide that we retain milestone payments, royalty rights and/or revenue sharing with respect to drugs
developed from certain compounds or derivative compounds, any such payments or royalty rights may be at reduced rates, and disputes
may arise over the application of payment provisions or derivative payment provisions to such drugs, and we may not be successful in such
disputes. For example, in September 2018, BerGenBio served us with a notice of arbitration seeking declaratory relief related to the
interpretation of provisions under our June 2011 license agreement, particularly as they relate to the rights and obligations of the parties in
the event of the license or sale of a product in the program by BerGenBio and/or the sale of BerGenBio to a third party. The arbitration
panel dismissed four of the six declarations sought by BerGenBio, and we thereafter consented to one of the remaining declarations
requested by BerGenBio. On February 27, 2019, the arbitration panel issued a determination granting the declaration sought by BerGenBio
on the remaining issue, and held that in the event of a sale of shares by BerGenBio’s shareholders where there is no monetary benefit to
BerGenBio, we would not be entitled to a portion of the proceeds from such a sale. In this circumstance where the revenue share provision
is not triggered, the milestone and royalty payment provisions remain in effect. While we do not believe that the determination will have an
adverse effect on our operations, cash flows or financial condition, we can make no assurance regarding any such impact. Additionally, the
management teams of our collaborators may change for various reasons including due to being acquired. Different management teams or an
acquiring company of our collaborators may have different priorities which may have adverse results on the collaboration with us.
We are also a party to various license agreements that give us rights to use specified technologies in our research and development
processes. The agreements pursuant to which we have in-licensed technology permit our licensors to terminate the agreements under certain
circumstances. If we are not able to continue to license these and future technologies on commercially reasonable terms, our product
development and research may be delayed or otherwise adversely affected.
55
Table of Contents
If conflicts arise between our collaborators or advisors and us, any of them may act in their self-interest, which may be adverse to our
stockholders’ interests.
If conflicts arise between us and our corporate collaborators or scientific advisors, the other party may act in its self-interest and
not in the interest of our stockholders. Some of our corporate collaborators are conducting multiple product development efforts within
each disease area that is the subject of the collaboration with us or may be acquired or merged with a company having a competing
program. In some of our collaborations, we have agreed not to conduct, independently or with any third party, any research that is
competitive with the research conducted under our collaborations. Our collaborators, however, may develop, either alone or with others,
products in related fields that are competitive with the products or potential products that are the subject of these collaborations. Competing
products, either developed by our collaborators or to which our collaborators have rights, may result in their withdrawal of support for our
product candidates.
If any of our corporate collaborators were to breach or terminate its agreement with us or otherwise fail to conduct the
collaborative activities successfully and in a timely manner, the preclinical or clinical development or commercialization of the affected
product candidates or research programs could be delayed or terminated. We generally do not control the amount and timing of resources
that our corporate collaborators devote to our programs or potential products. We do not know whether current or future collaborative
partners, if any, might pursue alternative technologies or develop alternative products either on their own or in collaboration with others,
including our competitors, as a means for developing treatments for the diseases targeted by collaborative arrangements with us.
Our success is dependent on intellectual property rights held by us and third parties, and our interest in such rights is complex and
uncertain.
Our success will depend to a large part on our own, our licensees’ and our licensors’ ability to obtain and defend patents for each
party’s respective technologies and the compounds and other products, if any, resulting from the application of such technologies. For
example, fostamatinib is covered as a composition of matter in a US issued patent that has an expected expiration date of September 2031,
after taking into account patent term adjustment and extension rules.
In the future, our patent position might be highly uncertain and involve complex legal and factual questions. For example, we may
be involved in post-grant proceedings before the US Patent and Trademark Office. Post-grant proceedings are complex and expensive legal
proceedings and there is no assurance we will be successful in any such proceedings. A post-grant proceeding could result in our losing our
patent rights and/or our freedom to operate and/or require us to pay significant royalties. Additionally, third parties may challenge the
validity, enforceability or scope of our issued patents, which may result in such patents being narrowed, invalidated or held unenforceable
through interference, opposition or invalidity proceedings before the US Patent and Trademark Office or non-US patent offices. Any
successful opposition to our patents could deprive us of exclusive rights necessary for the successful commercialization of fostamatinib or
our other product candidates. Oppositions could also be filed to complementary patents, such as formulations, methods of manufacture and
methods of use, that are intended to extend the patent life of the overall portfolio beyond the patent life covering the composition of matter.
A successful opposition to any such complementary patent could impact our ability to extend the life of the overall portfolio beyond that of
the related composition of matter patent.
An adverse outcome may allow third parties to use our intellectual property without a license and/or allow third parties to
introduce generic and other competing products, any of which would negatively impact our business. For example, in June 2022, we
received a notice letter from Annora advising that it has filed an ANDA with the FDA for a generic version of TAVALISSE and asserting
that certain patents related to TAVALISSE that are listed in the Orange Book will not be infringed by Annora’s proposed product, are
invalid and/or are unenforceable. In July 2022, we filed a lawsuit in the US District Court for the District of New Jersey against Annora and
its subsidiaries for infringement of those US patents. In September 2022, Annora and its subsidiaries answered and counterclaimed for
declaratory judgment of non-infringement and invalidity of those patents. We filed an answer to Annora’s counterclaims on October 12,
2022. We intend to vigorously enforce and defend our intellectual property rights related to TAVALISSE. Should Annora or any other third
parties receive FDA approval of an ANDA for a generic version of fostamatinib or a 505(b)(2) NDA with respect to fostamatinib, and if our
patents covering fostamatinib were held to be invalid (or if such competing generic versions of fostamatinib were found to not infringe our
patents), then they could introduce generic versions of
56
Table of Contents
fostamatinib or other such 505(b)(2) products before our patents expire, and the resulting competition would negatively affect our business,
financial condition and results of operations. Please also see the risk factor entitled, “If manufacturers obtain approval for generic versions
of our products, or of products with which we compete, our business may be harmed.”
Additional uncertainty may result because no consistent policy regarding the breadth of legal claims allowed in biotechnology
patents has emerged to date. Accordingly, we cannot predict the breadth of claims allowed in our or other companies’ patents.
Because the degree of future protection for our proprietary rights is uncertain, we cannot assure you that:
● we were the first to make the inventions covered by each of our pending patent applications;
● we were the first to file patent applications for these inventions;
● others will not independently develop similar or alternative technologies or duplicate any of our technologies;
● any of our pending patent applications will result in issued patents;
● any patents issued to us or our collaborators will provide a basis for commercially viable products or will provide us with any
competitive advantages or will not be challenged by third parties;
● we will develop additional proprietary technologies that are patentable;
● we will obtain a supplemental protection certificate that will extend the protection afforded by the patent to the product with a
marketing authorization; or
● the patents of others will not have a negative effect on our ability to do business.
We rely on trade secrets to protect technology where we believe patent protection is not appropriate or obtainable; however, trade
secrets are difficult to protect. While we require employees, collaborators and consultants to enter into confidentiality agreements, we may
not be able to adequately protect our trade secrets or other proprietary information in the event of any unauthorized use or disclosure or the
lawful development by others of such information.
We are a party to certain in-license agreements that are important to our business, and we generally do not control the prosecution
of in-licensed technology. Accordingly, we are unable to exercise the same degree of control over this intellectual property as we exercise
over our internally developed technology. Moreover, some of our academic institution licensors, research collaborators and scientific
advisors have rights to publish data and information in which we have rights. If we cannot maintain the confidentiality of our technology
and other confidential information in connection with our collaborations, our ability to receive patent protection or protect our proprietary
information may otherwise be impaired. In addition, some of the technology we have licensed relies on patented inventions developed
using US government resources.
The US government retains certain rights, as defined by law, in such patents, and may choose to exercise such rights. Certain of
our in-licenses may be terminated if we fail to meet specified obligations. If we fail to meet such obligations and any of our licensors
exercise their termination rights, we could lose our rights under those agreements. If we lose any of our rights, it may adversely affect the
way we conduct our business. In addition, because certain of our licenses are sublicenses, the actions of our licensors may affect our rights
under those licenses.
If a dispute arises regarding the infringement or misappropriation of the proprietary rights of others, such dispute could be costly and
result in delays in our research and development activities, partnering and commercialization activities.
Our success will depend, in part, on our ability to operate without infringing or misappropriating the proprietary rights of others.
There are many issued patents and patent applications filed by third parties relating to products or processes that are similar or identical to
our licensors or ours, and others may be filed in the future. There may also be
57
Table of Contents
copyrights or trademarks that third parties hold. There can be no assurance that our activities, or those of our licensors, will not violate
intellectual property rights of others. We believe that there may be significant litigation in the industry regarding patent and other
intellectual property rights, and we do not know if our collaborators or we would be successful in any such litigation. Any legal action
against our collaborators or us claiming damages or seeking to enjoin commercial activities relating to the affected products, our methods
or processes could:
● require our collaborators or us to obtain a license to continue to use, manufacture or market the affected products, methods or
processes, which may not be available on commercially reasonable terms, if at all;
● prevent us from using the subject matter claimed in the patents held by others;
● subject us to potential liability for damages;
● consume a substantial portion of our managerial and financial resources; and
● result in litigation or administrative proceedings that may be costly, whether we win or lose.
Our effective tax rate may fluctuate, and we may incur obligations in tax jurisdictions in excess of accrued amounts.
We are subject to taxation in numerous US states and territories. As a result, our effective tax rate is derived from a combination of
applicable tax rates in the various places that we operate. In preparing our financial statements, we estimate the amount of tax that will
become payable in each of such places. Nevertheless, our effective tax rate may be different than experienced in the past due to numerous
factors, including passage of the newly enacted federal income tax law, changes in the mix of our profitability from state to state, the results
of examinations and audits of our tax filings, our inability to secure or sustain acceptable agreements with tax authorities, changes in
accounting for income taxes and changes in tax laws. Any of these factors could cause us to experience an effective tax rate significantly
different from previous periods or our current expectations and may result in tax obligations in excess of amounts accrued in our financial
statements.
Our ability to use net operating losses (NOLs) and certain other tax attributes is uncertain and may be limited.
Our ability to use our federal and state NOLs to offset potential future taxable income and related income taxes that would
otherwise be due is dependent upon our generation of future taxable income before the expiration dates of the NOLs, and we cannot predict
with certainty when, or whether, we will generate sufficient taxable income to use all of our NOLs. Federal NOLs generated prior to 2018
will continue to be governed by the NOL carryforward rules as they existed prior to the adoption of the Tax Cuts and Jobs Act (Tax Act),
which means that generally they will expire 20 years after they were generated if not used prior thereto. Many states have similar laws.
Accordingly, our federal and state NOLs could expire unused and be unavailable to offset future income tax liabilities. Under the Tax Act as
modified by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act), federal NOLs incurred in tax years beginning after
December 31, 2017 and before January 1, 2021 may be carried back to each of the five tax years preceding such loss, and NOLs arising in
tax years beginning after December 31, 2020 may not be carried back. Moreover, federal NOLs generated in tax years ending after
December 31, 2017 may be carried forward indefinitely, but the deductibility of such federal NOLs may be limited to 80% of current year
taxable income for tax years beginning after January 1, 2021. Under A.B. 85, our California NOL carryforwards are suspended for tax years
2020, 2021, and 2022, but the period to use these carryovers was extended. Further, the Tax Act requires the taxpayers to capitalize
Research and Experimental (R&E) expenditures under Section 174 of the Internal Revenue Code, as amended (Code), effective for taxable
years beginning after December 31, 2021, which will reduce our NOLs beginning in 2022. R&E expenditures attributable to US-based
research must be amortized over a period of 5 years and R&E expenditures attributable to research conducted outside of the US must be
amortized over a period of 15 years.
In addition, utilization of NOLs to offset potential future taxable income and related income taxes that would otherwise be due is
subject to annual limitations under the “ownership change” provisions of Sections 382 and 383 of the Code and similar state provisions,
which may result in the expiration of NOLs before future utilization. In general, under the Code, if a corporation undergoes an “ownership
change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s
ability to use its pre-change NOLs and other pre-
58
Table of Contents
change tax attributes (such as research and development credit carryforwards) to offset its post-change taxable income or taxes may be
limited. Our equity offerings and other changes in our stock ownership, some of which are outside of our control, may have resulted or
could in the future result in an ownership change. Although we have completed studies to provide reasonable assurance that an ownership
change limitation would not apply, we cannot be certain that a taxing authority would reach the same conclusion. If, after a review or audit,
an ownership change limitation were to apply, utilization of our domestic NOLs and tax credit carryforwards could be limited in future
periods and a portion of the carryforwards could expire before being available to reduce future income tax liabilities. Moreover, our ability
to utilize our NOLs is conditioned upon us achieving profitability and generating US federal taxable income.
Because we expect to be dependent upon collaborative and license agreements, we might not meet our strategic objectives.
Our ability to generate revenue in the near term depends on the timing of recognition of certain upfront payments, achievement of
certain payment triggering events with our existing collaboration agreements and our ability to enter into additional collaborative
agreements with third parties. Our ability to enter into new collaborations and the revenue, if any, that may be recognized under these
collaborations is highly uncertain. If we are unable to enter into one or more new collaborations, our business prospects could be harmed,
which could have an immediate adverse effect on our ability to continue to develop our compounds and on the trading price of our stock.
Our ability to enter into a collaboration may be dependent on many factors, such as the results of our clinical trials, competitive factors and
the fit of one of our programs with another company’s risk tolerance, including toward regulatory issues, patent portfolio, clinical pipeline,
the stage of the available data, particularly if it is early, overall corporate goals and financial position.
To date, a portion of our revenues have been related to the research or transition phase of each of our collaborative agreements.
Such revenues are for specified periods, and the impact of such revenues on our results of operations is at least partially offset by
corresponding research costs. Following the completion of the research or transition phase of each collaborative agreement, additional
revenues may come only from payments triggered by milestones and/or the achievement of other contingent events, and royalties, which
may not be paid, if at all, until certain conditions are met. This risk is heightened due to the fact that unsuccessful research efforts may
preclude us from receiving any contingent payments under these agreements. Our receipt of revenues from collaborative arrangements is
also significantly affected by the timing of efforts expended by us and our collaborators and the timing of lead compound identification. We
have received payments from our collaborations with Lilly, Grifols, Kissei, Medison, Aclaris, Celgene, BMS, AZ, BerGenBio, Janssen
Pharmaceutica N.V., a division of Johnson & Johnson, Novartis Pharma A.G., Daiichi, Merck & Co., Inc., Merck Serono and Pfizer. Under
many agreements, future payments may not be earned until the collaborator has advanced product candidates into clinical testing, which
may never occur or may not occur until sometime well into the future. If we are not able to generate revenue under our collaborations when
and in accordance with our expectations or the expectations of industry analysts, this failure could harm our business and have an
immediate adverse effect on the trading price of our common stock.
Our business requires us to generate meaningful revenue from royalties and licensing agreements. To date, we have not recognized
material amount of revenue from royalties for the commercial sale of drugs, and we do not know when we will be able to generate such
meaningful revenue in the future.
Securities class action lawsuits or other litigation could result in substantial damages and may divert management’s time and attention
from our business.
We have been subject to class action lawsuits in the past and we may be subject to lawsuits in the future, such as those that might
occur if there was to be a change in our corporate strategy. These and other lawsuits are subject to inherent uncertainties, and the actual
costs to be incurred relating to the lawsuit will depend upon many unknown factors. The outcome of litigation is necessarily uncertain, and
we could be forced to expend significant resources in the defense of such suits, and we may not prevail. Monitoring and defending against
legal actions is time-consuming for our management and detracts from our ability to fully focus our internal resources on our business
activities. In addition, we may incur substantial legal fees and costs in connection with any such litigation. We have not established any
reserves for any potential liability relating to any such potential lawsuits. It is possible that we could, in the future, incur judgments or enter
into settlements of claims for monetary damages. A decision adverse to our interests on any such
59
Table of Contents
actions could result in the payment of substantial damages, or possibly fines, and could have an adverse effect on our cash flow, results of
operations and financial position.
If our competitors develop technologies that are more effective than ours, our commercial opportunity will be reduced or eliminated.
The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological
change. Many of the drugs that we are attempting to discover will be competing with existing therapies. In addition, a number of companies
are pursuing the development of pharmaceuticals that target the same diseases and conditions that we are targeting. For example, the
commercialization of new pharmaceutical products is highly competitive, and we face substantial competition with respect to our products
in which there are existing therapies and drug candidates in development for the treatment of hematologic disorders and cancer that may be
alternative therapies to our products. Many of our competitors, including a number of large pharmaceutical companies that compete directly
with us, have significantly greater financial resources and expertise commercializing approved products than we do. Also, many of our
competitors are large pharmaceutical companies that will have a greater ability to reduce prices for their competing drugs in an effort to
gain market share and undermine the value proposition that we might otherwise be able to offer to payers. We face, and will continue to
face, intense competition from pharmaceutical and biotechnology companies, as well as from academic and research institutions and
government agencies, both in the US and abroad. Some of these competitors are pursuing the development of pharmaceuticals that target
the same diseases and conditions as our research programs. Our competitors including fully integrated pharmaceutical companies have
extensive drug discovery efforts and are developing novel small-molecule pharmaceuticals. We also face significant competition from
organizations that are pursuing the same or similar technologies, including the discovery of targets that are useful in compound screening,
as the technologies used by us in our drug discovery efforts.
Competition may also arise from:
● new or better methods of target identification or validation;
● generic versions of our products or of products with which we compete;
● other drug development technologies and methods of preventing or reducing the incidence of disease;
● new small molecules; or
● other classes of therapeutic agents.
Our competitors or their collaborative partners may utilize discovery technologies and techniques or partner with collaborators in
order to develop products more rapidly or successfully than we or our collaborators are able to do. Many of our competitors, particularly
large pharmaceutical companies, have substantially greater financial, technical and human resources and larger research and development
staffs than we do. In addition, academic institutions, government agencies and other public and private organizations conducting research
may seek patent protection with respect to potentially competitive products or technologies and may establish exclusive collaborative or
licensing relationships with our competitors.
We believe that our ability to compete is dependent, in part, upon our ability to create, maintain and license scientifically-advanced
technology and upon our and our collaborators’ ability to develop and commercialize pharmaceutical products based on this technology, as
well as our ability to attract and retain qualified personnel, obtain patent protection or otherwise develop proprietary technology or
processes, secure effective market access by ensuring competitive pricing and reimbursement in territories of interest, and secure sufficient
capital resources for the expected substantial time period between technological conception and commercial sales of products based upon
our technology. The failure by any of our collaborators or us in any of those areas may prevent the successful commercialization of our
potential drug targets.
Many of our competitors, either alone or together with their collaborative partners, have significantly greater experience than we
do in:
60
Table of Contents
● identifying and validating targets;
● screening compounds against targets; and
● undertaking preclinical testing and clinical trials.
Accordingly, our competitors may succeed in obtaining patent protection, identifying or validating new targets or discovering new
drug compounds before we do.
Our competitors might develop technologies and drugs that are more effective or less costly than any that are being developed by
us or that would render our technology and product candidates obsolete and noncompetitive. In addition, our competitors may succeed in
obtaining the approval of the FDA or other regulatory agencies for product candidates more rapidly. Companies that complete clinical trials,
obtain required regulatory agency approvals and commence commercial sale of their drugs before us may achieve a significant competitive
advantage, including certain patent and FDA marketing exclusivity rights that would delay or prevent our ability to market certain products.
Any drugs resulting from our research and development efforts, or from our joint efforts with our existing or future collaborative partners,
might not be able to compete successfully with competitors’ existing or future products or obtain regulatory approval in the US or
elsewhere.
We face and will continue to face intense competition from other companies for collaborative arrangements with pharmaceutical
and biotechnology companies, for establishing relationships with academic and research institutions and for licenses to additional
technologies. These competitors, either alone or with their collaborative partners, may succeed in developing technologies or products that
are more effective than ours.
Our ability to compete successfully will depend, in part, on our ability to:
● identify and validate targets;
● discover candidate drug compounds that interact with the targets we identify in a safe and efficacious way;
● attract and retain scientific and product development personnel;
● recruit subjects into our clinical trials;
● obtain and maintain required regulatory approvals;
● obtain patent or other proprietary protection for our new drug compounds and technologies;
● enter commercialization agreements for our new drug compounds; and
● obtain and maintain appropriate reimbursement price and positive recommendations by HTA bodies.
Our stock price may be volatile, and our stockholders’ investment in our common stock could decline in value.
The market prices for our common stock and the securities of other biotechnology companies have been highly volatile and may
continue to be highly volatile in the future. The following factors, in addition to other risk factors described in this section, may have a
significant impact on the market price of our common stock:
● the progress and success of our clinical trials and preclinical activities (including studies and manufacture of materials) of our
product candidates conducted by us;
● our ability to continue to sell our products in the US;
● our ability to enter into partnering opportunities across our pipeline;
● the receipt or failure to receive the additional funding necessary to conduct our business;
● selling of our common stock by large stockholders;
61
Table of Contents
● presentations of detailed clinical trial data at medical and scientific conferences and investor perception thereof;
● announcements of technological innovations or new commercial products by our competitors or us;
● the announcement of regulatory applications, such as Annora’s ANDA, seeking approval of generic versions of our marketed
products;
● developments concerning proprietary rights, including patents;
● developments concerning our collaborations;
● publicity regarding actual or potential medical results relating to products under development by our competitors or us;
● regulatory developments in the US and foreign countries;
● changes in the structure of healthcare payment systems;
● litigation or arbitration;
● economic and other external factors or other disaster or crisis; and
● period-to-period fluctuations in financial results.
If we fail to continue to meet the listing standards of Nasdaq, our common stock may be delisted, which could have a material adverse
effect on the liquidity of our common stock.
Our common stock is currently listed on the Nasdaq Global Market. The Nasdaq Stock Market LLC has requirements that a
company must meet in order to remain listed on Nasdaq. In particular, Nasdaq rules require us to maintain a minimum bid price of $1.00
per share of our common stock (the “Bid Price Requirement”). If the closing bid price of our common stock falls below $1.00 per share for
30 consecutive trading days or we do not meet other listing requirements, we would fail to be in compliance with Nasdaq listing standards.
There can be no assurance that we will continue to meet the minimum bid price requirement, or any other requirement in the future.
On November 22, 2022, we received a deficiency letter from the Listing Qualifications Department of the Nasdaq Stock Market
LLC notifying us that, for the last 30 consecutive business days, the bid price for our common stock closed below the Bid Price
Requirement.
We were provided a period of 180 calendar days, or until May 22, 2023 (the “Compliance Date”), to regain compliance with the
Bid Price Requirement. On January 5, 2023, we received notification from the Listing Qualifications Department of the Nasdaq Stock
Market LLC that we have regained compliance with the Bid Price Requirement because the closing bid price of our common stock closed
at $1.00 or more for over 10 consecutive business days from December 13, 2022 to January 4, 2023.
While we have regained compliance, the Nasdaq Stock Market LLC may in the future initiate the delisting process with a
notification letter if we were to again fall out of compliance. If we were to receive such a notification, we would be afforded a grace period
of 180 calendar days to regain compliance with the minimum bid price requirement. In order to regain compliance, shares of our common
stock would need to maintain a minimum closing bid price of at least $1.00 per share for a minimum of 10 consecutive trading days. In
addition, we may be unable to meet other applicable Nasdaq listing requirements, including maintaining minimum levels of stockholders’
equity or market values of our common stock in which case, our common stock could be delisted. If our common stock were to be delisted,
the liquidity of our common stock would be adversely affected and the market price of our common stock could decrease.
62
Table of Contents
The withdrawal of the UK from the EU may adversely impact our ability to obtain regulatory approvals of our product candidates in the
UK and the EU, result in restrictions or imposition of taxes and duties for importing our product candidates into the UK and the EU,
and may require us to incur additional expenses in order to develop, manufacture and commercialize our product candidates in the UK
and the EU.
Following the result of a referendum in 2016, the UK left the EU on January 31, 2020, commonly referred to as Brexit. Pursuant
to the formal withdrawal arrangements agreed between the UK and the EU, the UK was subject to a transition period until December 31,
2020, or the Transition Period, during which EU rules continued to apply. A trade and cooperation agreement (Trade Agreement) that
outlines the future trading relationship between the UK and the EU was agreed to in December 2020 and has been approved by each EU
member state and the UK.
Since a significant proportion of the regulatory framework in the UK applicable to our business and our product candidates is
derived from EU directives and regulations, Brexit has had, and will continue to have, a material impact upon the regulatory regime with
respect to the development, manufacture, importation, approval and commercialization of our product candidates in the UK or the EU.
Great Britain (made up of England, Scotland, and Wales) is no longer covered by the EEA’s procedures for the grant of marketing
authorizations (Northern Ireland will be covered by such procedures). A separate marketing authorization will be required to market drugs
in Great Britain. It is currently unclear whether the Medicines and Healthcare Products Regulatory Agency, or MHRA, in the UK is
sufficiently prepared to handle the increased volume of marketing authorization applications that it is likely to receive. Any delay in
obtaining, or an inability to obtain, any marketing approvals would delay or prevent us from commercializing our product candidates in the
UK or the EU and restrict our ability to generate revenue and achieve and sustain profitability.
While the Trade Agreement provides for the tariff-free trade of medicinal products between the UK and the EU, there may be
additional non-tariff costs to such trade which did not exist prior to the end of the Transition Period. Further, should the UK diverge from
the EU from a regulatory perspective in relation to medicinal products, tariffs could be put into place in the future. We could therefore,
both now and in the future, face significant additional expenses (when compared to the position prior to the end of the Transition Period) to
operate our business, which could significantly and materially harm or delay our ability to generate revenues or achieve profitability of our
business. Any further changes in international trade, tariff and import/export regulations as a result of Brexit or otherwise may impose
unexpected duty costs or other non-tariff barriers on us. These developments, or the perception that any of them could occur, may
significantly reduce global trade and, in particular, trade between the impacted nations and the UK. It is also possible that Brexit may
negatively affect our ability to attract and retain employees, particularly those from the EU.
Orphan designation in Great Britain following Brexit is granted on an essentially identical basis as in the EU but is based on the
prevalence of the condition in Great Britain. It is therefore possible that conditions that are currently designated as orphan conditions in
Great Britain will no longer be, and conditions that are not currently designated as orphan conditions in the EU will be designated as such
in Great Britain.
If product liability lawsuits are successfully brought against us, we may incur substantial liabilities and may be required to limit
commercialization of our products.
The testing and marketing of medical products and the sale of any products for which we obtain marketing approval exposes us to
the risk of product liability claims. Product liability claims might be brought against us by consumers, health care providers, pharmaceutical
companies or others selling or otherwise coming into contact with our products. If we cannot successfully defend ourselves against product
liability claims, we may incur substantial liabilities or be required to limit commercialization of our products. We carry product liability
insurance that is limited in scope and amount and may not be adequate to fully protect us against product liability claims. If and when we
obtain marketing approval for our product candidates, we intend to expand our insurance coverage to include the sale of commercial
products; however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts. Our
inability to obtain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could
prevent or inhibit the commercialization of pharmaceutical products we develop, alone or with corporate collaborators. We, or our
corporate collaborators, might not be able to obtain insurance at a reasonable cost, if at all. While under various circumstances we are
entitled to be indemnified against losses by our corporate collaborators, indemnification may not be available or adequate should any claim
arise.
63
Table of Contents
We depend on various scientific consultants and advisors for the success and continuation of our research and development efforts.
We work extensively with various scientific consultants and advisors. The potential success of our drug discovery and
development programs depends, in part, on continued collaborations with certain of these consultants and advisors. We, and various
members of our management and research staff, rely on certain of these consultants and advisors for expertise in our research, regulatory
and clinical efforts. Our scientific advisors are not our employees and may have commitments to, or consulting or advisory contracts with,
other entities that may limit their availability to us. We do not know if we will be able to maintain such consulting agreements or that such
scientific advisors will not enter into consulting arrangements with competing pharmaceutical or biotechnology companies, any of which
may have a detrimental impact on our research objectives and could have an adverse effect on our business, financial condition and results
of operations.
While we have a strong compliance process in place to ensure we are complying with all requirements of law, our consulting or
advisory contracts with our scientific consultants and advisors may be scrutinized under the Anti-Kickback Statute, the UK Bribery Act
2010, and other similar national and state-level legislation, which prohibit, among other things, companies from offering or paying anything
of value as remuneration for ordering, purchasing, or recommending the ordering or purchasing of pharmaceutical and biological products
that may be paid for, in whole or in part, by Medicare, Medicaid, or another federal healthcare program. Although there are several
statutory exceptions and regulatory safe harbors that may protect these arrangements from prosecution or regulatory sanctions, our
consulting and advising contracts may be subject to scrutiny if they do not fit squarely within an available exception or safe harbor.
If we use biological and hazardous materials in a manner that causes injury or violates laws, we may be liable for damages, penalties or
fines.
Our research and development activities involve the controlled use of potentially harmful biological materials as well as hazardous
materials, chemicals, animals, and various radioactive compounds. We cannot completely eliminate the risk of accidental contamination or
injury from the use, storage, handling or disposal of these animals and materials. In the event of contamination or injury, we could be held
liable for damages that result or for penalties or fines that may be imposed, and such liability could exceed our resources. We are also
subject to federal, state and local laws and regulations governing the use, storage, handling and disposal of these materials and specified
waste products. The cost of compliance with, or any potential violation of, these laws and regulations could be significant.
Our information technology systems, or those used by our CROs or other contractors or consultants, may fail or suffer other
breakdowns, cyber-attacks, or information security breaches.
We are increasingly dependent upon information technology systems, infrastructure, and data to operate our business, particularly
during the COVID-19 pandemic. We also rely on third party vendors and their information technology systems. Despite the implementation
of security measures, our recovery systems, security protocols, network protection mechanisms and other security measures and those of
our CROs and other contractors and consultants are vulnerable to compromise from natural disasters; terrorism; war; telecommunication
and electric failures; traditional computer hackers; malicious code (such as computer viruses or worms); employee error, theft or misuse;
denial-of-service attacks; cyber-attacks by sophisticated nation-state and nation-state supported actors including ransomware; or other
system disruptions. We receive, generate and store significant and increasing volumes of personal (including health), confidential and
proprietary information. There can be no assurance that we, or our collaborators, CROs, third-party vendors, contractors and consultants
will be successful in efforts to detect, prevent, protect against or fully recover systems or data from all break-downs, service interruptions,
attacks or breaches. Any breakdown, cyber-attack or information security breach could result in a disruption of our drug development
programs or other aspects of our business. For example, the loss of clinical trial data from completed or ongoing clinical trials for a product
candidate could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. 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 personal, confidential or proprietary information, we could incur liability, incur significant remediation or litigation costs, result in
product development delays, disrupt key business operations, cause loss of revenue and divert attention of management and key
information technology resources.
64
Table of Contents
Hackers and data thieves are increasingly sophisticated and operate large-scale and complex automated attacks, including on
companies within the healthcare industry. As the cyber-threat landscape evolves, these threats are likely growing in frequency,
sophistication and intensity and are increasingly difficult to detect. The costs of maintaining or upgrading our cyber-security systems at the
level necessary to keep up with our expanding operations and prevent against potential attacks are increasing. Cyber threats may be generic,
or they may be targeted against our information systems. Our network and storage applications and those of our contract manufacturing
organizations, collaborators, contractors, CROs or vendors may be subject to unauthorized access or processing by hackers or breached due
to operator or other human error, theft, malfeasance or other system disruptions. We may be unable to anticipate or immediately detect
information security incidents and the damage caused by such incidents. These data breaches and any unauthorized access, processing or
disclosure of our information or intellectual property could compromise our intellectual property and expose our sensitive business
information. Such attacks, such as in the case of a ransomware attack, also may interfere with our ability to continue to operate and may
result in delays and shortcomings due to an attack that may encrypt our or our service providers’ or partners’ systems unusable.
Additionally, because our services involve the processing of personal information and other sensitive information about individuals we are
subject to various laws, regulations, industry standards, and contractual requirements related to such processing. Any event that leads to
unauthorized access, processing or disclosure of personal information, including personal information regarding our clinical trial
participants or employees, could harm our reputation and business, compel us to comply with federal and/or state breach notification laws
and foreign law equivalents, subject us to investigations and mandatory corrective action, and otherwise subject us to liability under laws,
regulations or contracts that protect the privacy and security of personal information, which could disrupt our business, damage our
reputation with our stakeholders, result in increased costs or loss of revenue, lead to negative publicity or result in significant financial
exposure. The CCPA, in particular, includes a private right of action for California consumers whose personal information is impacted by a
data security incident resulting from a company’s failure to maintain reasonable security procedures, and hence may result in civil litigation
in the event of a security breach impacting such information. In addition, legislators and regulators in the US have enacted and are
proposing new and more robust privacy and cybersecurity laws and regulations in response to increasing broad-based cyberattacks,
including the CCPA and New York SHIELD Act. New data security laws add additional complexity, requirements, restrictions and potential
legal risk, and compliance programs may require additional investment in resources, and could impact strategies and availability of
previously useful data.
The costs to respond to a security breach and/or to mitigate any identified security vulnerabilities could be significant, our efforts
to address these issues may not be successful, and these issues could result in interruptions, delays, negative publicity, loss of customer
trust, and other harms to our business and competitive position. Remediation of any potential security breach may involve significant time,
resources, and expenses. We could be required to fundamentally change our business activities and practices in response to a security
breach and our systems or networks may be perceived as less desirable, which could negatively affect our business and damage our
reputation.
A security breach may cause us to breach our contracts with third parties. Our agreements with relevant stakeholders such as
collaborators may require us to use legally required, industry-standard or reasonable measures to safeguard personal information. A security
breach could lead to claims by relevant stakeholders that we have failed to comply with such contractual obligations, or require us to
cooperate with these stakeholders in their own compliance efforts related to the security breach. In addition, any non-compliance with our
data privacy obligations in our contracts or our inability to flow down such obligations from relevant stakeholders to our vendors may cause
us to breach our contracts. As a result, we could be subject to legal action or the relevant stakeholders could end their relationships with us.
There can be no assurance that the limitations of liability in our contracts would be enforceable or adequate or would otherwise protect us
from liabilities or damages.
We may not have adequate insurance coverage for security incidents or breaches. The successful assertion of one or more large
claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium
increases or the imposition of large deductible or co-insurance requirements), could have an adverse effect on our business. In addition, we
cannot be sure that our existing insurance coverage will continue to be available on acceptable terms or that our insurers will not deny
coverage as to any future claim.
65
Table of Contents
Future equity issuances or a sale of a substantial number of shares of our common stock may cause the price of our common stock to
decline.
Because we will continue to need additional capital in the future to continue to expand our business and our research and
development activities, among other things, we may conduct additional equity offerings. For example, on August 3, 2021, a new automatic
shelf registration statement was filed by us, as a well-known seasoned issuer (WKSI). The automatic shelf registration statement was filed
to register, among other securities, the sale of up to a maximum aggregate offering price of $100.0 million of shares of our common stock
that may be issued and sold from time to time under our Open Market Sale Agreement with Jefferies LLC. (Jefferies), and a base
prospectus which covers the offering, issuance, and sale by us of the securities identified above from time to time in one or more
offerings. On March 1, 2022, we filed a post-effective amendment to the automatic shelf registration statement immediately after filing our
Annual Report Form 10-K for the year ended December 31, 2021 because we no longer qualified as a WKSI upon filing of such Annual
Report. The post-effective amendment was declared effective on May 3, 2022. The post-effective amendment registers, among other
securities, a base prospectus which covers the offering, issuance, and sale by us of up to $250.0 million in the aggregate of the securities
identified from time to time in one or more offerings, which include the $100.0 million of shares of our common stock that may be offered,
issued and sold under the Open Market Sale Agreement.
We may also in the future enter into underwriting or sales agreements with financial institutions for the offer and sale of any
combination of common stock, preferred stock, debt securities and warrants in one or more offerings. If we or our stockholders sell, or if it
is perceived that we or they will sell, substantial amounts of our common stock in the public market, the market price of our common stock
could fall. A decline in the market price of our common stock could make it more difficult for us to sell equity or equity-related securities in
the future at a time and price that we deem appropriate. In addition, future sales by us of our common stock may be dilutive to existing
stockholders. Furthermore, if we obtain funds through a credit facility or through the issuance of debt or preferred securities, these
securities would likely have rights senior to the rights of our common stockholders, which could impair the value of our common stock.
Risks Related to Clinical Development and Regulatory Approval
Enacted or future legislation, and/or potentially unfavorable pricing regulations or other healthcare reform initiatives, may increase the
difficulty and cost for us to obtain regulatory approval of our product candidates and/or commercialize fostamatinib or our product
candidates, once approved, and affect the prices we may set or obtain.
The regulations that govern, among other things, regulatory approvals, coverage, pricing and reimbursement for new drug
products vary widely from country to country. In the US and some foreign jurisdictions, there have been a number of legislative and
regulatory changes and proposed changes regarding the healthcare system that could prevent or delay regulatory approval of our product
candidates, restrict or regulate post-approval activities and affect our ability to successfully sell fostamatinib or any product candidates for
which we obtain regulatory approval in the future. In particular, in March 2010, the Affordable Care Act was enacted, which substantially
changed the way health care is financed by both governmental and private insurers, and continues to significantly impact the US
pharmaceutical industry. On June 17, 2021, the US Supreme Court dismissed the most recent judicial challenge to the Affordable Care Act
brought by several states without specifically ruling on the constitutionality of the law. Prior to the Supreme Court’s decision, President
Biden issued an executive order that instructed certain governmental agencies to review and reconsider their existing policies and rules that
limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work
requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the
Affordable Care Act. It is unclear how future actions before the Supreme Court, other such litigation, and the healthcare reform measures of
the Biden administration will impact the Affordable Care Act and our business.
There have been, and likely will continue to be, legislative and regulatory proposals at the foreign, federal and state levels directed
at broadening the availability of healthcare and containing or lowering the cost of healthcare. We cannot predict the initiatives that may be
adopted in the future. The continuing efforts of the government, insurance companies, managed care organizations and other payors of
healthcare services to contain or reduce the costs of healthcare and/or impose price controls may adversely affect, for example:
66
Table of Contents
● the demand for fostamatinib or our product candidates, if we obtain regulatory approval;
● our ability to set a price that we believe is fair for our products;
● our ability to generate revenue and achieve or maintain profitability;
● the level of taxes that we are required to pay; and
● the availability of capital.
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from
private payors, which may adversely affect our future profitability.
In the US, the EU and other potentially significant markets for our current and future products, government authorities and third-
party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative
products and therapies, which has resulted in lower average selling prices. In the US, there have been several recent Congressional inquiries
and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing
and manufacturer-sponsored patient assistance programs, and reform government program reimbursement methodologies for drugs.
On March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which, among other changes,
eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacture price, for single source and
innovator multiple source drugs, beginning January 1, 2024. The American Rescue Plan Act also temporarily increased premium tax credit
assistance for individuals eligible for subsidies under the ACA for 2021 and 2022 and removed the 400% federal poverty level limit that
otherwise applies for purposes of eligibility to receive premium tax credits. The IRA extended this increased tax credit assistance and
removal of the 400% federal poverty limit through 2025. Additionally, the temporary suspension of the 2% reduction in Medicare payments
to providers that was instituted in the wake of the COVID-19 pandemic expired on July 1, 2022, with the 2% reduction set to remain in
effect until 2031 unless additional Congressional action is taken. Moreover, on June 16, 2022, the Federal Trade Commission issued a
policy statement stating its intension to increase enforcement scrutiny of “exclusionary rebates” to PBMs and other intermediaries that
“foreclose competition.” On August 16, 2022, President Biden signed into law the IRA, which, among other reforms, allows Medicare to:
beginning in 2026, establish a “maximum fair price” for certain pharmaceutical and biological products covered under Medicare Parts B
and D; beginning in 2023, penalize drug companies that raise prices for products covered under Medicare Parts B and D faster than
inflation; and beginning in 2025 impose new discounts obligations on pharmaceutical and biological manufacturers for products covered
under Medicare Part D.
The Biden administration has also taken executive action to address drug pricing and other healthcare policy changes. For
example, in response to a July 9, 2021 Executive Order from President Biden that included several prescription drug initiatives, on
September 9, 2021, the Department of Health and Human Services issued a Comprehensive Plan for Addressing High Drug Prices that
identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make drug prices more
affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation.
Additionally, on September 12, 2022, President Biden issued an Executive Order to promote biotechnology and biomanufacturing
innovation. The Order noted several methods through which the Biden Administration would support the advancement of biotechnology
and biomanufacturing in healthcare, and instructed the Department of Health and Human Service to submit, within 180 days of the Order, a
report assessing how to use biotechnology and biomanufacturing to achieve medical breakthroughs, reduce the overall burden of disease,
and improve health outcomes. On October 14, 2022, President Biden issued an Executive Order on Lowering Prescription Drug Costs for
Americans which instructed the Secretary of the Department of Health and Human Services to consider whether to select for testing by the
CMS Innovation Center new health care payment and delivery models that would lower drug costs and promote access to innovative drug
therapies for beneficiaries enrolled in the Medicare and Medicaid programs. The Executive Order further directed the Secretary of the
Department of Health and Human Services to submit, within 90 days after the date of the Executive Order, a report regarding any models
that may lead to lower cost-sharing for commonly used drugs and support value-based payment that promotes high-quality care. On
February 14, 2023, the Department of Health and Human Services issued a report in response to the October 14, 2022, Executive Order,
67
Table of Contents
which, among other things, selects three potential drug affordability and accessibility models to be tested by the CMS Innovation Center.
Specifically, the report addresses: (1) a model that would allow Part D Sponsors to establish a “high-value drug list” setting the maximum
co-payment amount for certain common generic drugs at $2; (2) a Medicaid-focused model that would establish a partnership between
CMS, manufacturers, and state Medicaid agencies that would result in multi-state outcomes-based agreements for certain cell and gene
therapy drugs; and (3) a model that would adjust Medicare Part B payment amounts for Accelerated Approval Program drugs to advance
the developments of novel treatments. It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical
industry.
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to
control pharmaceutical and biological product pricing. Specifically, several U.S. states and localities have enacted legislation requiring
pharmaceutical companies to establish marketing compliance programs, file periodic reports, and/or make periodic public disclosures on
sales, marketing, pricing, clinical trials, and other activities. Other state laws prohibit certain marketing-related activities including the
provision of gifts, meals or other items to certain healthcare providers, and restrict the ability of manufacturers to offer co-pay support to
patients for certain prescription drugs. In addition, several recently passed state laws require disclosures related to state agencies and/or
commercial purchasers with respect to certain price increases that exceed a certain level as identified in the relevant statutes. Some of these
laws and regulations contain ambiguous requirements that government officials have not yet clarified. Given the lack of clarity in the laws
and their implementation, our reporting actions could be subject to the penalty provisions of the pertinent federal and state laws and
regulations.
Furthermore, the increased emphasis on managed healthcare in the US and on country and regional pricing and reimbursement
controls in the EU and the UK will put additional pressure on product pricing, reimbursement and usage, which may adversely affect our
sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial decisions and
governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and
pricing in general. Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and
promotional activities for pharmaceutical products.
We cannot predict the likelihood, nature, or extent of health reform initiatives that may arise from future legislation or
administrative action. However, we expect these initiatives to increase pressure on drug pricing. Further, certain broader legislation that is
not targeted to the health care industry may nonetheless adversely affect our profitability. If we or any third parties we may engage are
slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we or such third parties
are not able to maintain regulatory compliance, our product candidates may lose any regulatory approval that may have been obtained and
we may not achieve or sustain profitability.
See “Part I, Item 1 – Business – Government Regulation – Healthcare Reform” of this Annual Report on Form 10-K for the year
ended December 31, 2022.
Regulatory approval for any approved product is limited by the FDA, the EC and other regulators to those specific indications and
conditions for which clinical safety and efficacy have been demonstrated, and we may incur significant liability if it is determined that
we are promoting the “off-label” use of our products or any of our future product candidates if approved.
Any regulatory approval is limited to those specific diseases, indications and patient populations for which a product is deemed to
be safe and effective by the FDA, the EC and other regulators. For example, the FDA-approved label for TAVALISSE is only approved for
use in adults with ITP who have had an insufficient response to other treatments and for REZLIDHIA is only approved for use in adult
patients with R/R AML with a susceptible IDH1 mutation as detected by an FDA-approved test. In addition to the FDA approval required
for new formulations, any new indication for an approved product also requires FDA approval. If we are not able to obtain FDA approval
for any desired future indications for our products and product candidates, our ability to effectively market and sell our products may be
reduced and our business may be adversely affected.
68
Table of Contents
While physicians may choose to prescribe drugs for uses that are not described in the product’s labeling and for uses that differ
from those tested in clinical studies and approved by the regulatory authorities, our ability to promote the products is limited to those
indications and patient populations that are specifically approved by the FDA. These “off-label” uses are common across medical
specialties and may constitute an appropriate treatment for some patients in varied circumstances. We have implemented compliance and
monitoring policies and procedures, including a process for internal review of promotional materials, to deter the promotion of our products
for off-label uses. We cannot guarantee that these compliance activities will prevent or timely detect off-label promotion by sales
representatives or other personnel in their communications with health care professionals, patients and others, particularly if these activities
are concealed from us. Regulatory authorities in the US generally do not regulate the behavior of physicians in their choice of treatments.
Regulatory authorities do, however, restrict communications by pharmaceutical companies on the subject of off-label use. If our
promotional activities fail to comply with the FDA’s or other competent national authority’s regulations or guidelines, we may be subject to
warnings from, or enforcement action by, these regulatory authorities. In addition, our failure to follow FDA rules and guidelines relating to
promotion and advertising may cause the FDA to issue warning letters or untitled letters, suspend or withdraw an approved product from
the market, require a recall or institute fines, which could result in the disgorgement of money, operating restrictions, injunctions or civil or
criminal enforcement, and other consequences, any of which could harm our business.
Notwithstanding the regulatory restrictions on off-label promotion, the FDA and other regulatory authorities allow companies to
engage in truthful, non-misleading and non-promotional scientific exchange concerning their products. We engage in medical education
activities and communicate with investigators and potential investigators regarding our clinical trials. If the FDA or other regulatory or
enforcement authorities determine that our communications regarding our marketed product are not in compliance with the relevant
regulatory requirements and that we have improperly promoted off-label uses, or that our communications regarding our investigational
products are not in compliance with the relevant regulatory requirements and that we have improperly engaged in pre-approval promotion,
we may be subject to significant liability, including civil and administrative remedies as well as criminal sanctions.
Delays in clinical testing could result in increased costs to us.
We may not be able to initiate or continue clinical studies or trials for our product candidates if we are unable to locate and enroll a
sufficient number of eligible patients to participate in these clinical trials as required by the FDA or other regulatory authorities, whether
due to the impacts of the COVID-19 pandemic, the Russian-Ukrainian conflict or otherwise. Even if we are able to enroll a sufficient
number of patients in our clinical trials, if the pace of enrollment is slower than we expect, the development costs for our product
candidates may increase and the completion of our clinical trials may be delayed, or our clinical trials could become too expensive to
complete. Significant delays in clinical testing could negatively impact our product development costs and timing. Our estimates regarding
timing are based on a number of assumptions, including assumptions based on past experience with our other clinical programs. If we are
unable to enroll the patients in these trials at the projected rate, the completion of the clinical program could be delayed and the costs of
conducting the program could increase, either of which could harm our business.
Clinical trials can be delayed for a variety of reasons, including delays in obtaining regulatory approval to commence a study,
delays from scaling up of a study, delays in reaching agreement on acceptable clinical trial agreement terms with prospective clinical sites,
delays in obtaining institutional review board approval to conduct a study at a prospective clinical site or delays in recruiting subjects to
participate in a study. In addition, we typically rely on third-party clinical investigators to conduct our clinical trials and other third-party
organizations to oversee the operations of such trials and to perform data collection and analysis. The clinical investigators are not our
employees, and we cannot control the amount or timing of resources that they devote to our programs. Failure of the third-party
organizations to meet their obligations, whether due to the potential future impacts of the COVID-19 pandemic, the Russian-Ukrainian
conflict or otherwise, could adversely affect clinical development of our products. As a result, we may face additional delaying factors
outside our control if these parties do not perform their obligations in a timely fashion. For example, any number of those issues could arise
with our clinical trials causing a delay. Delays of this sort could occur for the reasons identified above or other reasons. If we have delays in
conducting the clinical trials or obtaining regulatory approvals, our product development costs will increase. For example, we may need to
make additional payments to third-party investigators and organizations to retain their services or we may need to pay recruitment
incentives. If the delays are significant, our financial results and the commercial prospects for our product candidates will be harmed, and
our ability
69
Table of Contents
to become profitable will be delayed. Moreover, these third-party investigators and organizations may also have relationships with other
commercial entities, some of which may compete with us. If these third-party investigators and organizations assist our competitors at our
expense, it could harm our competitive position.
Due to the evolving effects of the COVID-19 pandemic, for several of our development programs, we had experienced and may
continue to experience disruption or delay in our ability to enroll and assess patients, maintain patient enrollment, supply study drug, report
trial results, or interact with regulators, ethics committees or other important agencies due to limitations in employee resources or
otherwise. In addition, some patients may not be able or willing to comply with clinical trial protocols if quarantines impede patient
movement or interrupt healthcare services. Similarly, our ability to recruit and retain patients and principal investigators and site staff who,
as healthcare providers, may have heightened exposure to COVID-19 may adversely impact our clinical trial operations. In light of the
evolving effects of the COVID-19 pandemic, we had taken measures to implement remote and virtual approaches to clinical development,
including remote patient monitoring where possible, and if the COVID-19 pandemic continues and persists for an extended period of time,
we could experience significant disruptions to our clinical development timelines, which would adversely affect our business, financial
condition, results of operations and growth prospects.
We have conducted in the past and are currently conducting clinical trials in the US and outside US including Ukraine and Russia.
Recent actions taken by the Russian Federation in Ukraine and surrounding areas have destabilized the region and caused the adoption of
comprehensive sanctions by, among others, the EU, the US and the UK, which restrict a wide range of trade and financial dealings with
Russia and Russian persons, as well as certain regions in Ukraine. Further, some patients may not be able to comply with clinical trial
protocols if the conflict impedes patient movement or interrupts healthcare services. In addition, clinical trial site initiation and patient
enrollment may be delayed, and we may not be able to access sites for initiation and monitoring in regions affected by the Russian-
Ukrainian conflict including due to the prioritization of hospital resources away from clinical trials or as a result of government-imposed
curfews, warfare, violence or other governmental actions or events that restrict movement. We could also experience disruptions in our
supply chain or limits our ability to obtain sufficient materials for our drug products in certain regions.
We may not be able to obtain an EUA for fostamatinib for the treatment of hospitalized patients with COVID-19, and, even if we do,
absent sNDA approval for that indication, such EUA would be revoked when the COVID-19 emergency terminates.
Based on the results of the NIH/NHLBI-sponsored Phase 2 trial, in May 2021, we filed an EUA for the use of fostamatinib for the
treatment of hospitalized patients with COVID-19. In August 2021, the FDA informed us that the clinical data submitted from the
NIH/NHLBI-sponsored Phase 2 trial of fostamatinib to treat hospitalized patients suffering from COVID-19 was insufficient for EUA. In
July 2022, we completed enrollment with 280 patients in our pivotal FOCUS Phase 3 clinical trial evaluating fostamatinib in high-risk
patients hospitalized with COVID-19. The trial had originally targeted a total of 308 patients; however, we determined the trial would be
sufficiently powered with 280 patients to potentially provide a clinically meaningful result and determine the efficacy and safety of
fostamatinib in hospitalized COVID-19 patients. On November 1, 2022, we announced the top-line results of the clinical trial. The trial
approached but did not meet statistical significance in the primary efficacy endpoint. All prespecified secondary endpoints in the trial
numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment, and
number of days in the ICU. We are evaluating the opportunity and discussing next steps with the FDA and in collaboration with our partner,
the US Department of Defense.
Section 564 of the FDCA (21 U.S.C. § 360bbb-3) allows the FDA to authorize the shipment of drugs, biological products, or
medical devices that either lack required approval, licensure, or clearance (unapproved products), or are approved but are to be used for
unapproved ways to diagnose, treat, or prevent serious diseases or conditions in the event of an emergency declaration by the HHS
Secretary.
On February 4, 2020, then-HHS Secretary Alex M. Azar II determined that a public health emergency exists for COVID-19 and
declared that it justifies the authorization of emergency use of in vitro diagnostics for COVID-19, pursuant to Section 564 of the FDCA. On
March 2, 2020, March 24, 2020, and March 27, 2020, Secretary Azar issued corresponding declarations for personal respiratory protective devices;
for medical devices, including alternative products used as medical devices; and, for drugs and biological products. The determination and these
declarations were published in the Federal
70
Table of Contents
Register on February 7, 2020, March 10, 2020, March 27, 2020, and April 1, 2020, respectively.
While the emergency determination and declarations are effective, the FDA may authorize the use of an unapproved product or an
unapproved use of an approved product if it concludes that:
•
•
•
•
•
an agent referred to in the emergency declaration could cause a serious or life-threatening disease or condition;
it is reasonable to believe that the authorized product may be effective in diagnosing, treating, or preventing that disease or
condition or a serious or life-threatening disease or condition caused by an approved product or a product marketed under an
EUA;
the known and potential benefits of the authorized product, when used for that disease or condition, outweigh known and
potential risks, taking into consideration the material threat of agents identified in the emergency declaration;
there is no adequate, approved, and available alternative to the authorized product for diagnosing, preventing, or treating the
relevant disease or condition;
any other criteria prescribed by the FDA is satisfied.
Medical products that are granted an EUA are only permitted to commercialize their products under the terms and conditions
provided in the authorization. The FDCA authorizes FDA to impose such conditions on an EUA as may be necessary to protect the public health.
Consequently, postmarketing requirements will vary across EUAs. In addition, FDA has, on occasion, waived requirements for drugs marketed
under an EUA.
Generally, EUAs for unapproved products or unapproved uses of approved products require that manufacturers distribute
factsheets for healthcare providers, addressing significant known and potential benefits and risk, and the extent to which benefits and risks
are unknown, and the fact that FDA has authorized emergency use; and, distribution of factsheets for recipients of the product, addressing
significant known and potential benefits and risk, and the extent to which benefits and risks are unknown, the option to accept or refuse the
product, the consequences of refusing, available alternatives and the fact that FDA has authorized emergency use.
Generally, EUAs for unapproved products and, per FDA’s discretion, EUAs for unapproved uses of approved products, include
requirements for adverse event monitoring and reporting, and other recordkeeping and reporting requirements. Note, however, that
approved products are already subject to equivalent requirements.
In addition, the FDA may include various requirements in an EUA as a matter of discretion as deemed necessary to protect the
public health, including restrictions on which entities may distribute the product, and how to perform distribution (including requiring that
distribution be limited to government entities), restrictions on who may administer the product, requirements for collection and analysis of
safety and effectiveness data, waivers of cGMP, and restrictions applicable to prescription drugs or restricted devices (including advertising
and promotion restrictions).
The FDA may revoke an EUA when it is determined that the underlying health emergency no longer exists or warrants such
authorization, if the conditions for the issuance of the EUA are no longer met, or if other circumstances make revocation appropriate to
protect the public health or safety. We cannot predict how long, if ever, an EUA would remain in place.
It is difficult to predict when the determination and declaration will be revoked or ended, which will impact the marketing of
products under existing EUAs and the availability of new EUAs based on the determination and declaration. For example, in January 2023,
Congress proposed legislation that would end other COVID-19-related emergency declarations, if passed, and the White House has issued a
statement that those declarations will end on May 11, 2023. FDA officials have stated that this will not impact FDA’s ability to authorize
treatments for emergency use, such that existing EUAs will remain in effect and the agency may continue to issue new EUAs going
forward when criteria for issuance are met. This is nonetheless subject to change.
71
Table of Contents
We cannot predict with certainty whether the result of our trial will be sufficient for submission of a second application for an
EUA for fostamatinib, and we cannot predict whether FDA will grant an EUA for fostamatinib based on the trial data. We also cannot
predict how long, if ever, an EUA would remain in place.
Our COVID-19 product candidate may not successfully protect against variants of the SARS-CoV-2 virus.
As the SARS-CoV-2 virus continues to evolve, new strains of the virus or those that are already in circulation may prove more
transmissible or cause more severe forms of COVID-19 disease than the predominant strains to date. There is a risk that any product
candidates we develop will not be as effective against variant strains of the SARS-CoV-2 virus expressing variants of the spike protein,
particularly strains with mutations in the receptor binding domain and N-terminal domain. Such failure could lead to significant
reputational harm, in addition to adversely affecting our financial results.
Public perception of the risk-benefit balance for our COVID-19 product candidates may be affected by adverse events in clinical trials
involving our product candidate or other COVID-19 treatments.
Negative perception of the efficacy, safety, or tolerability of any investigational medicines that we develop, or of other products
similar to products we are developing, such as fostamatinib for the treatment of COVID-19, could adversely affect our ability to conduct
our business, advance our investigational medicines, or obtain regulatory approvals.
Adverse events in clinical trials of our investigational medicines or in clinical trials of others developing similar products,
including other COVID-19 treatments, could result in a decrease in the perceived benefit of one or more of our programs, increased
regulatory scrutiny, decreased confidence by patients and clinical trial collaborators in our investigational medicines, and less demand for
any product that we may develop. If and when they are used in clinical trials, our developmental candidates and investigational medicines
could result in a greater quantity of reportable adverse events, including suspected unexpected serious adverse reactions, other reportable
negative clinical outcomes, manufacturing reportable events or material clinical events that could lead to clinical delay or hold by the FDA
or applicable regulatory authority or other clinical delays, any of which could negatively impact the perception of one or more of our
programs, as well as our business as a whole. In addition, responses by US, state, or foreign governments to negative public perception may
result in new legislation or regulations that could limit our ability to develop any investigational medicines or commercialize any approved
products, obtain or maintain regulatory approval, or otherwise achieve profitability. More restrictive statutory regimes, government
regulations, or negative public opinion would have an adverse effect on our business, financial condition, results of operations, and
prospects and may delay or impair the development of our investigational medicines and commercialization of any approved products or
demand for any products we may develop.
We lack the capability to manufacture compounds for clinical development, and we rely on and intend to continue relying on third
parties for commercial supply, manufacturing and distribution if any of our product candidates which receive regulatory approval and
we may be unable to obtain required material or product in a timely manner, at an acceptable cost or at a quality level required to
receive regulatory approval.
We currently do not have the manufacturing capabilities or experience necessary to produce our products or any product
candidates for clinical trials, including fostamatinib in our ongoing clinical trials for certain indications. We currently use one active
pharmaceutical ingredient manufacturer and one finished goods manufacturer for each of our products. We do not currently have, nor do we
plan to acquire the infrastructure or capability to supply, manufacture or distribute preclinical, clinical or commercial quantities of drug
substances or products. For each clinical trial of our unpartnered product candidates, we rely on third-party manufacturers for the active
pharmaceutical ingredients, as well as various manufacturers to manufacture starting components, excipients and formulated drug products.
Our ability to develop our product candidates, and our ability to commercially supply our products will depend, in part, on our ability to
successfully obtain the active pharmaceutical ingredients and other substances and materials used in our product candidates from third
parties and to have finished products manufactured by third parties in accordance with regulatory requirements and in sufficient quantities
for preclinical and clinical testing and commercialization. If we fail to develop and maintain supply relationships with these third parties,
we may be unable to continue to develop or commercialize our product candidates.
72
Table of Contents
We rely and will continue to rely on certain third parties, including those located outside the US, as our limited source of the
materials they supply or the finished products they manufacture. The drug substances and other materials used in our product candidates are
currently available only from one or a limited number of suppliers or manufacturers and certain of our finished product candidates are
manufactured by one or a limited number of contract manufacturers. Any of these existing suppliers or manufacturers may:
● fail to supply us with product on a timely basis or in the requested amount due to unexpected damage to or destruction of
facilities or equipment or otherwise;
● fail to increase manufacturing capacity and produce drug product and components in larger quantities and at higher yields in a
timely or cost-effective manner, or at all, to sufficiently meet our commercial needs;
● be unable to meet our production demands due to issues related to their reliance on sole-source suppliers and manufacturers;
● supply us with product that fails to meet regulatory requirements;
● become unavailable through business interruption or financial insolvency;
● lose regulatory status as an approved source;
● be unable or unwilling to renew current supply agreements when such agreements expire on a timely basis, on acceptable
terms or at all; or
● discontinue production or manufacturing of necessary drug substances or products.
Our current and anticipated future dependence upon these third-party manufacturers may adversely affect our ability to develop
and commercialize product candidates on a timely and competitive basis, which could have an adverse effect on sales, results of operations
and financial condition. If we were required to transfer manufacturing processes to other third-party manufacturers and we were able to
identify an alternative manufacturer, we would still need to satisfy various regulatory requirements. Satisfaction of these requirements
could cause us to experience significant delays in receiving an adequate supply of our products and products in development and could be
costly. Moreover, we may not be able to transfer processes that are proprietary to the manufacturer, if any. These manufacturers may not be
able to produce material on a timely basis or manufacture material at the quality level or in the quantity required to meet our development
timelines and applicable regulatory requirements and may also experience a shortage in qualified personnel, including due to the impacts of
the COVID-19 pandemic. Our third-party manufacturers import certain materials from China to produce our products. The tensions
between the US and China have led to a series of tariffs and sanctions being imposed by the US on imports from China mainland, as well as
other business restrictions. Such tensions could adversely impact us and our third-party manufacturers. We may not be able to maintain or
renew our existing third-party manufacturing arrangements, or enter into new arrangements, on acceptable terms, or at all. Our third-party
manufacturers could terminate or decline to renew our manufacturing arrangements based on their own business priorities, at a time that is
costly or inconvenient for us. If we are unable to contract for the production of materials in sufficient quantity and of sufficient quality on
acceptable terms, our planned clinical trials may be significantly delayed. Manufacturing delays could postpone the filing of our IND
applications and/or the initiation or completion of clinical trials that we have currently planned or may plan in the future.
Drug manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the Drug Enforcement Administration,
the European Medicines Agency, national competent authorities in the EU and UK and other federal and state government and regulatory
agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards. We do not have
control over third-party manufacturers’ compliance with these regulations and standards and they may not be able to comply. Switching
manufacturers may be difficult because the number of potential manufacturers is limited. It may be difficult or impossible for us to find a
replacement manufacturer quickly on acceptable terms, or at all. Additionally, if we are required to enter into new supply arrangements, we
may not be able to obtain approval from the FDA of any alternate supplier in a timely manner, or at all, which could delay or prevent the
clinical development and commercialization of any related product candidates. Failure of our third-party manufacturers or us to comply
with applicable regulations, whether due to the impacts of the
73
Table of Contents
COVID-19 pandemic or otherwise, could result in sanctions being imposed on us, including fines, civil penalties, delays in or failure to
grant marketing approval of our product candidates, injunctions, delays, suspension or withdrawal of approvals, license revocation, seizures
or recalls of products and compounds, operating restrictions and criminal prosecutions, warning or similar letters or civil, criminal or
administrative sanctions against us, any of which could adversely affect our business.
Any product for which we have obtained regulatory approval, or for which we obtain approval in the future, is subject to, or will be
subject to, extensive ongoing regulatory requirements by the FDA, EMA and other comparable regulatory authorities, and if we fail to
comply with regulatory requirements or if we experience unanticipated problems with our products, we may be subject to penalties, we
may be unable to generate revenue from the sale of such products, our potential for generating positive cash flow will be diminished,
and the capital necessary to fund our operations will be increased.
In April 2018, the FDA approved TAVALISSE for the treatment of adult patients with chronic ITP who have had insufficient
response to previous treatment. In December 2022, the FDA approved REZLIDHIA for the treatment of adult patients with R/R AML with
a susceptible IDH1 mutation as detected by an FDA-approved test. We commercialize TAVALISSE and REZLIDHIA in the US and we
have entered into commercialization agreements with third parties to commercialize fostamatinib outside the US. Any product for which we
have obtained regulatory approval, or for which we obtain regulatory approval in the future, along with the manufacturing processes and
practices, post-approval clinical research, product labeling, advertising and promotional activities for such product, are subject to continual
requirements of, and review by, the FDA, the EMA and other comparable international regulatory authorities. These requirements include
submissions of safety and other post-marketing information and reports, registration and listing requirements, current good manufacturing
practices (cGMP) requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and
documents, requirements regarding the distribution of samples to physicians, import and export requirements and recordkeeping. If we or
our suppliers encounter manufacturing, quality or compliance difficulties with respect to our products or any of our product candidates,
when and if approved, whether due to the impacts of the COVID-19 pandemic (including as a result of disruptions of global shipping and
the transport of products) or otherwise, we may be unable to obtain or maintain regulatory approval or meet commercial demand for such
products, which could adversely affect our business, financial conditions, results of operations and growth prospects.
Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and
must be consistent with the information in the product’s approved labeling. Thus, we will not be able to promote any products we develop
for indications or uses for which they are not approved.
In addition, the FDA often requires post-marketing testing and surveillance to monitor the effects of products. The FDA, the EMA
and other comparable international regulatory agencies may condition approval of our product candidates on the completion of such post-
marketing clinical studies. These post-marketing studies may suggest that a product causes undesirable side effects or may present a risk to
the patient. Additionally, the FDA may require Risk Evaluation and Mitigation Strategies (REMS) to help ensure that the benefits of the
drug outweigh its risks. A REMS may be required to include various elements, such as a medication guide or patient package insert, a
communication plan to educate healthcare providers of the drug’s risks, limitations on who may prescribe or dispense the drug,
requirements that patients enroll in a registry or undergo certain health evaluations or other measures that the FDA deems necessary to
ensure the safe use of the drug.
Discovery after approval of previously unknown problems with any of our products, manufacturers or manufacturing processes, or
failure to comply with regulatory requirements, may result in actions such as:
● restrictions on our ability to conduct clinical trials, including full or partial clinical holds on ongoing or planned trials;
● restrictions on product manufacturing processes;
● restrictions on the marketing of a product;
● restrictions on product distribution;
74
Table of Contents
● requirements to conduct post-marketing clinical trials;
● untitled or warning letters or other adverse publicity;
● withdrawal of products from the market;
● refusal to approve pending applications or supplements to approved applications that we submit;
● recall of products;
● refusal to permit the import or export of our products;
● product seizure;
● fines, restitution or disgorgement of profits or revenue;
● refusal to allow us to enter into supply contracts, including government contracts;
● injunctions; or
● imposition of civil or criminal penalties.
If such regulatory actions are taken, the value of our company and our operating results will be adversely affected. Additionally, if
the FDA, the EMA or any other comparable international regulatory agency withdraws its approval of a product that is or may be approved,
we will be unable to generate revenue from the sale of that product in the relevant jurisdiction, our potential for generating positive cash
flow will be diminished and the capital necessary to fund our operations will be increased. Accordingly, we continue to expend significant
time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance, post-marketing
studies and quality control.
If any of our third-party contractors fail to perform their responsibilities to comply with FDA rules and regulations, the marketing and
sales of our products could be delayed and we may be subject to enforcement action, which could decrease our revenues.
Conducting our business requires us to manage relationships with third-party contractors. As a result, our success depends partially
on the success of these third parties in performing their responsibilities to comply with FDA rules and regulations. Although we pre-qualify
our contractors and we believe that they are fully capable of performing their contractual obligations, we cannot directly control the
adequacy and timeliness of the resources and expertise that they apply to these activities.
If any of our partners or contractors fail to perform their obligations in an adequate and timely manner, or fail to comply with the
FDA’s rules and regulations, then the marketing and sales of our products could be delayed. The FDA may also take enforcement actions
against us based on compliance issues identified with our contractors. If any of these events occur, we may incur significant liabilities,
which could decrease our revenues. For example, sales and medical science liaison or MSL personnel, including contractors, must comply
with FDA requirements for the advertisement and promotion of products.
Fast track designation by the FDA may not actually lead to a faster development or regulatory review or approval process and does not
assure FDA approval of our product candidates.
If a product candidate is intended for the treatment of a serious or life-threatening condition and the product candidate
demonstrates the potential to address unmet medical need for this condition, the sponsor may apply for FDA fast track designation. Fast
track designation applies to the combination of the product and the specific indication for which it is being studied. The sponsor of a fast
track product has opportunities for more frequent interactions with the review team during product development, and the FDA may
consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule
for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is
acceptable, and the sponsor
75
Table of Contents
pays any required user fees upon submission of the first section of the NDA.
However, fast track designation does not change the standards for approval and does not ensure that the product candidate will
receive marketing approval or that approval will be granted within any particular timeframe. As a result, while the FDA has granted fast
track designation to fostamatinib for the treatment of wAIHA and/or we may seek and receive fast track designation for our future product
candidates, we may not experience a faster development process, review or approval compared to conventional FDA procedures. In
addition, the FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical
development program. Fast track designation alone does not guarantee qualification for the FDA’s priority review procedures.
If we are unable to obtain regulatory approval to market products in the US and foreign jurisdictions, we will not be permitted to
commercialize products we or our collaborative partners may develop.
We cannot predict whether regulatory clearance will be obtained for any product that we, or our collaborative partners, hope to
develop. Satisfaction of regulatory requirements typically takes many years, is dependent upon the type, complexity and novelty of the
product and requires the expenditure of substantial resources. Of particular significance to us are the requirements relating to research and
development and testing.
Before commencing clinical trials in humans in the US, we, or our collaborative partners, will need to submit and receive approval
from the FDA of an IND application. Clinical trials are subject to oversight by institutional review boards and the FDA and:
● must be conducted in conformance with the FDA’s good clinical practices and other applicable regulations;
● must meet requirements for institutional review board oversight;
● must meet requirements for informed consent;
● are subject to continuing FDA and regulatory oversight;
● may require large numbers of test subjects; and
● may be suspended by us, our collaborators or the FDA at any time if it is believed that the subjects participating in these trials
are being exposed to unacceptable health risks or if the FDA finds deficiencies in the IND or the conduct of these trials.
While we have stated that we intend to file additional INDs for future product candidates, this is only a statement of intent, and we
may not be able to do so because we may not be able to identify potential product candidates. In addition, the FDA may not approve any
IND we or our collaborative partners may submit in a timely manner, or at all.
Before receiving FDA approval to market a product, we must demonstrate with substantial clinical evidence that the product is
safe and effective in the patient population and the indication that will be treated. Data obtained from preclinical and clinical activities are
susceptible to varying interpretations that could delay, limit or prevent regulatory approvals. In addition, delays or rejections may be
encountered based upon additional government regulation from future legislation or administrative action or changes in FDA policy during
the period of product development, clinical trials and FDA regulatory review. Failure to comply with applicable FDA or other applicable
regulatory requirements may result in criminal prosecution, civil penalties, recall or seizure of products, total or partial suspension of
production or injunction, adverse publicity, as well as other regulatory action against our potential products or us. Additionally, we have
limited experience in conducting and managing the clinical trials necessary to obtain regulatory approval.
If regulatory approval of a product is granted, this approval will be limited to those indications or disease states and conditions for
which the product is demonstrated through clinical trials to be safe and efficacious. We cannot assure you that any compound developed by
us, alone or with others, will prove to be safe and efficacious in clinical trials and will meet all of the applicable regulatory requirements
needed to receive marketing approval.
Outside the US, our ability, or that of our collaborative partners, to market a product is contingent upon receiving a marketing
authorization from the appropriate regulatory authorities. This foreign regulatory approval process typically
76
Table of Contents
includes all of the risks and costs associated with FDA approval described above and may also include additional risks and costs, such as
the risk that such foreign regulatory authorities, which often have different regulatory and clinical trial requirements, interpretations and
guidance from the FDA, may require additional clinical trials or results for approval of a product candidate, any of which could result in
delays, significant additional costs or failure to obtain such regulatory approval. There can be no assurance, however, that we or our
collaborative partners will not have to provide additional information or analysis, or conduct additional clinical trials, before receiving
approval to market product candidates.
We may be unable to expand our product pipeline, which could limit our growth and revenue potential.
Our business is focused on the development and commercialization of novel therapies that significantly improve the lives of
patients with hematologic disorders and cancer. In this regard, we are pursuing internal drug discovery efforts with the goal of identifying
new product candidates to advance into clinical trials. Internal discovery efforts to identify new product candidates require substantial
technical, financial and human resources. These internal discovery efforts may initially show promise in identifying potential product
candidates, yet ultimately fail to yield product candidates for clinical development for a number of reasons. For example, potential product
candidates may, on later stage clinical trial, be shown to have inadequate efficacy, harmful side effects, suboptimal pharmaceutical profiles
or other characteristics suggesting that they are unlikely to be commercially viable products.
Apart from our internal discovery efforts, our strategy to expand our development pipeline is also dependent on our ability to
successfully identify and acquire or in-license relevant product candidates. In July 2022, we entered into a license and transition services
agreement with Forma for an exclusive license to develop, manufacture and commercialize olutasidenib, Forma’s proprietary inhibitor of
mIDH1, for any uses worldwide, including for the treatment of AML and other malignancies. Forma submitted an NDA for olutasidenib to
the FDA with PDUFA action date for the application of February 15, 2023. On December 1, 2022, the FDA approved REZLIDHIA
(olutasidenib) capsules for the treatment of adult patients with R/R AML with a susceptible IDH1 mutations as detected by and FDA-
approved test. REZLIDHIA is our second commercial product and is highly synergistic with our existing hematology-oncology focused
commercial and medical affairs infrastructure. The in-licensing and acquisition of product candidates is a highly competitive area, and
many other companies are pursuing the same or similar product candidates to those that we may consider attractive. In particular, larger
companies with more well-established and diverse revenue streams may have a competitive advantage over us due to their size, financial
resources and more extensive clinical development and commercialization capabilities. Furthermore, companies that perceive us to be a
competitor may be unwilling to assign or license rights to us. We may also be unable to in-license or acquire additional relevant product
candidates on acceptable terms that would allow us to realize an appropriate return on our investment. If we are unable to develop suitable
product candidates through internal discovery efforts, whether due to the impacts of the COVID-19 pandemic or otherwise, or if we are
unable to successfully obtain rights to additional suitable product candidates, our business and prospects for growth could suffer. Even if we
succeed in our efforts to obtain rights to suitable product candidates, the competitive business environment may result in higher acquisition
or licensing costs, and our investment in these potential products will remain subject to the inherent risks associated with the development
and commercialization of new medicines. In certain circumstances, we may also be reliant on the licensor for the continued development of
the in-licensed technology and their efforts to safeguard their underlying intellectual property.
With respect to acquisitions, we may not be able to integrate the target company successfully into our existing business, maintain
the key business relationships of the target, or retain key personnel of an acquired business. Furthermore, we could assume unknown or
contingent liabilities or incur unanticipated expenses. Any acquisitions or investments made by us also could result in our spending
significant amounts, issuing dilutive securities, assuming or incurring significant debt obligations and contingent liabilities, incurring large
one-time expenses and acquiring intangible assets that could result in significant future amortization expense and significant write-offs, any
of which could harm our operating results.
77
Table of Contents
We have obtained orphan drug designation from the FDA for fostamatinib for the treatment of ITP and wAIHA, but we may not be able
to obtain or maintain orphan drug designation or exclusivity for fostamatinib for the treatment of ITP, wAIHA or our other product
candidates, or we may be unable to maintain the benefits associated with orphan drug designation, including the potential for market
exclusivity.
We have obtained orphan drug designation in the US for fostamatinib for the treatment of ITP and wAIHA. We may seek orphan
drug designation for other product candidates in the future. Under the Orphan Drug Act, the FDA may grant orphan drug designation to a
drug or biologic intended to treat a rare disease or condition, which is defined as one occurring in a patient population of fewer than
200,000 in the US, or a patient population greater than 200,000 in the US where there is no reasonable expectation that the cost of
developing the drug will be recovered from sales in the US. In the US, orphan drug designation entitles a party to financial incentives such
as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. In addition, if a product that has orphan
drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to
orphan drug exclusivity, which means that the FDA may not approve any other applications, including a full NDA, to market the same drug
for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with
orphan drug exclusivity or where the manufacturer is unable to assure sufficient product quantity. At this time, we do not have nor will we
seek to apply for orphan drug designation in the EU or the UK in the foreseeable future.
We cannot assure you that any future application for orphan drug designation with respect to any other product candidate will be
granted. If we are unable to obtain orphan drug designation with respect to other product candidates in the US, we will not be eligible to
obtain the period of market exclusivity that could result from orphan drug designation or be afforded the financial incentives associated
with orphan drug designation. Even though we have received orphan drug designation for fostamatinib for the treatment of ITP and wAIHA
in the US, we may not be the first to obtain marketing approval for the orphan-designated indication due to the uncertainties associated with
developing pharmaceutical products or we might not maintain our orphan drug designation. In addition, exclusive marketing rights in the
US for fostamatinib for the treatment of ITP, wAIHA or any future product candidate may be limited if we seek approval for an indication
broader than the orphan-designated indication or may be lost if the FDA later determines that the request for designation was materially
defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or
condition. Further, even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from
competition because different drugs with different active moieties can be approved for the same condition. Even after an orphan product is
approved, the FDA can subsequently approve the same drug with the same active moiety for the same condition if the FDA concludes that
the later drug is safer, more effective, or makes a major contribution to patient care. Orphan drug designation neither shortens the
development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.
In addition, Congress is considering updates to the orphan drug provisions of the FDCA in response to a recent 11th Circuit
decision. Any changes to the orphan drug provisions could change our opportunities for, or likelihood of success in obtaining, orphan drug
exclusivity and would materially adversely affect our business, financial condition, results of operations, cash flows and prospects.
Risks Related to Commercialization
Our prospects are highly dependent on our commercial products. To the extent that the commercial success of our products in the US is
diminished or is not commercially successful, our business, financial condition and results of operations may be adversely affected, and
the price of our common stock may decline.
TAVALISSE is our first drug that has been approved for sale in the US and Europe for patients with chronic ITP. REZLIDHIA is
our second drug product which was recently approved by the FDA for the treatment of adult patients with R/R AML with susceptible IDH1
mutations as detected by an FDA-approved test, and began its commercialization in December 2022. We are focusing a significant portion
of our activities and resources on our products, and we believe our prospects are highly dependent on, and a significant portion of the value
of our company relates to, our ability to sustain successful commercialization of our products in the US. We have also entered into
exclusive commercialization agreements with third parties to commercialize fostamatinib outside the US, and we plan to further enter
partnership with existing or other third parties to commercialize fostamatinib and olutasidenib outside the
78
Table of Contents
US in the future.
Sustained successful commercialization of our products is subject to many risks and uncertainties, including the impact of the
COVID-19 pandemic on the successful commercialization in the US, as well as the successful commercialization efforts for our products
through our collaborative partners. There are numerous examples of unsuccessful product launches and failures to meet high expectations
of market potential, including by pharmaceutical companies with more experience and resources than us.
As we continue to build out our commercial team, there are many factors that could cause the commercialization of our products to
be unsuccessful, including a number of factors that are outside our control. The commercial success of our products depends on the extent
to which patients and physicians accept and adopt our products to treat the related diseases. We also do not know how physicians, patients
and payors will respond to our future price increases of our products. Physicians may not prescribe our products and patients may be
unwilling to use our products if coverage is not provided or reimbursement is inadequate to cover a significant portion of the cost. Our
products compete, and may in the future compete, with currently existing therapies, including generic drugs, and products currently under
development. Our competitors, particularly large pharmaceutical companies, may deploy more resources to market, sell and distribute their
products. If our efforts are not appropriately resourced to adequately promote our products, the commercial potential of our sales may be
diminished. Additionally, any negative development for fostamatinib in clinical development in additional indications, such as in the
clinical trials of fostamatinib in COVID-19 patients, may adversely impact the commercial results and potential of fostamatinib. Thus,
significant uncertainty remains regarding the commercial potential of fostamatinib.
Market acceptance of fostamatinib will depend on a number of factors, including:
● the timing of market introduction of the product as well as competitive products;
● the clinical indications for which the product is approved;
● acceptance by physicians, the medical community and patients of the product as a safe and effective treatment;
● potential future impacts, if any, due to the evolving effects of the COVID-19 pandemic and the Russian-Ukrainian conflict;
● the ability to distinguish safety and efficacy from existing, less expensive generic alternative therapies, if any;
● the convenience of prescribing, administrating and initiating patients on the product and the length of time the patient is on
the product;
● the potential and perceived value and advantages of the product over alternative treatments;
● the cost of treatment in relation to alternative treatments, including any similar generic treatments;
● pricing and the availability of coverage and adequate reimbursement by third-party payors and government authorities;
● a positive HTA assessment concluding that the product is cost-effective and the HTA bodies issuing a positive
recommendation for the use of the product as a first or second line of treatment for the granted therapeutic indication;
● the prevalence and severity of adverse side effects; and
● the effectiveness of sales and marketing efforts.
79
Table of Contents
If we are unable to sustain anticipated level of sales growth from our products, or if we fail to achieve anticipated product royalties
and collaboration milestones, we may need to reduce our operating expenses, access other sources of cash or otherwise modify our business
plans, which could have a negative impact on our business, financial condition and results of operations. For example, during 2021, we
experienced lower than anticipated sales of our products due to continuing impacts of physician and patient access issues created by the
COVID-19 pandemic. From time to time, our net product sales are negatively impacted by the decrease in level of inventories remaining at
our distribution channels.
We also may not be successful entering into arrangements with third parties to sell and market one or more of our product
candidates or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, including
Kissei’s development and commercialization of fostamatinib in all indications in Japan, China, Taiwan, and the Republic of Korea, Grifols’
commercialization of fostamatinib in Europe and Turkey, Medison for future commercialization of fostamatinib in Canada and Israel, and
Knight for commercialization of fostamatinib in Latin America. As a consequence of our license agreements with Kissei, Grifols, Medison
and Knight, we rely heavily upon their regulatory, commercial, medical affairs, market access and other expertise and resources for
commercialization of fostamatinib in their respective territories outside of the US. We cannot control the amount of resources that our
partners dedicate to the commercialization of fostamatinib, and our ability to generate revenues from the commercialization of fostamatinib
by our partners depends on their ability to achieve market acceptance of fostamatinib in its approved indications in their respective
territories.
Furthermore, foreign sales of fostamatinib by our partners could be adversely affected by the imposition of governmental controls,
political and economic instability, outbreaks of pandemic diseases, such as the COVID-19 pandemic, trade restrictions or barriers and
changes in tariffs and escalating global trade and political tensions. For example, the COVID-19 pandemic has resulted in increased travel
restrictions and extended shutdowns of certain businesses in the US and around the world. If our collaborators are unable to successfully
complete clinical trials, delay commercialization of fostamatinib or do not invest the resources necessary to successfully commercialize
fostamatinib in international territories where it has been approved, this could reduce the amount of revenue we are due to receive under
these license agreements, resulting in harm to our business and operations. If we do not establish and maintain sales and marketing
capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product
candidates.
Even if we, or any of our collaborative partners, are able to continue to commercialize our products or any product candidate that we,
or they, develop, the product may become subject to unfavorable pricing regulations, third-party payor reimbursement practices or
labeling restrictions, all of which may vary from country to country and any of which could harm our business.
The commercial success of any product for which we have obtained regulatory approval, or for which we obtain regulatory
approval in the future will depend substantially on the extent to which the costs of our product or product candidates are or will be paid by
third-party payors, including government health care programs and private health insurers. There is a significant trend in the health care
industry by public and private payers to contain or reduce their costs, including by taking the following steps, among others: decreasing the
portion of costs payers will cover, ceasing to provide full payment for certain products depending on outcomes, and/or not covering certain
products at all. If payers implement any of the foregoing with respect to our products, it would have an adverse impact on our revenue and
results of operations. If coverage is not available, or reimbursement is limited, we, or any of our collaborative partners, may not be able to
successfully commercialize our products or any of our product candidates in some jurisdictions. Even if coverage is provided, the approved
reimbursement amount may not be at a rate that covers our costs, including research, development, manufacture, sale and distribution. In
the US, no uniform policy of coverage and reimbursement for products exists among third-party payors; therefore, coverage and
reimbursement levels for products can differ significantly from payor to payor. As a result, the coverage determination process is often a
time consuming and costly process that may require us to provide scientific, clinical or other support for the use of our products to each
payor separately, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance.
There is significant uncertainty related to third-party payor coverage and reimbursement of newly approved drugs. Marketing
approvals, pricing and reimbursement for new drug products vary widely from country to country.
80
Table of Contents
Some countries require approval of the sale price of a drug before it can be marketed, which could delay market entry (or, if pricing is not
approved, we may be unable to sell at all in a country where we have received regulatory approval for a product. In many countries, the
pricing review period begins after marketing or product licensing approval is granted. In some countries, the proposed pricing for a drug
must be approved before it may be lawfully marketed). In addition, authorities in some countries impose additional obligations, such as
HTAs, which assess the performance of a drug in comparison with its cost. The outcome of HTA assessments is judged on a national basis
and some payers may not reimburse the use of our products or may reduce the rate of reimbursement for our products and as a result,
revenue from such products may decrease.
In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control even after initial
approval is granted. As a result, we, or any of our collaborative partners, might obtain marketing approval for a product in a particular
country, but then be subject to price regulations that delay commercial launch of the product, possibly for lengthy time periods, which may
negatively impact the revenues we are able to generate from the sale of the product in that country. In particular, we cannot predict to what
extent the evolving effects of the COVID-19 pandemic, depending on its scale and duration, may continue to disrupt global healthcare
systems and access to our products or result in a widespread loss of individual health insurance coverage due to unemployment, a shift from
commercial payor coverage to government payor coverage, or an increase in demand for patient assistance and/or free drug programs, any
of which would adversely affect access to and demand for our products and our net sales. Adverse pricing limitations may also hinder our
ability or the ability of any future collaborators to recoup our or their investment in one or more product candidates, even if our product
candidates obtain marketing approval. Further, even if favorable coverage and reimbursement status is attained for one or more products for
which we or our collaborative partners receive regulatory approval, less favorable coverage policies and reimbursement rates may be
implemented in the future.
Patients who are provided medical treatment for their conditions generally rely on third-party payors to reimburse all or part of the
costs associated with their treatment. Therefore, our ability, and the ability of any of our collaborative partners, to successfully
commercialize our products or any of our product candidates will depend in part on the extent to which coverage and adequate
reimbursement for these products and related treatments will be available from third-party payors.
Additionally, the labeling ultimately approved for any of our product candidates for which we have or may obtain regulatory
approval may include restrictions on their uses and may be subject to ongoing FDA or international regulatory authority requirements
governing the labeling, packaging, storage, distribution, safety surveillance, advertising, promotion, record-keeping and reporting of safety
and other post-market information. If we or any of our collaborative partners do not timely obtain or comply with the labeling approval by
the FDA or international regulatory authorities on any of our product candidates, it may delay or inhibit our ability to successfully
commercialize our products and generate revenues.
If we are unable to successfully market and distribute our products and retain experienced commercial personnel, our business will be
substantially harmed.
We currently have limited experience in marketing and selling pharmaceutical products. As a result, we will be required to expend
significant time and resources to maintain a sales force that is credible and compliant with applicable laws in marketing our products. In
addition, we must continually train our sales force to ensure that an appropriate and compliant message about our products is being
delivered. If we are unable to effectively train our sales force and equip them with compliant and effective materials, including medical and
sales literature to help them appropriately inform and educate health care providers regarding the potential benefits and proper
administration of our products, our efforts to successfully commercialize our products could be put in jeopardy, which would negatively
impact our ability to generate product revenues.
We have established our distribution, sales, marketing and market access capabilities, all of which will be necessary to
successfully commercialize our products. As a result, we will be required to expend significant time and resources to market, sell, and
distribute our products to hematologists and hematologists-oncologists. There is no guarantee that the marketing strategies we have
developed, or the distribution, sales, marketing and market access capabilities that we have developed will be successful. Particularly, we
are dependent on third-party logistics, specialty pharmacies and distribution partners in the distribution of our products. If they are unable
to perform effectively or if they do not provide efficient distribution of the medicine to patients, our business may be harmed. In addition,
we
81
Table of Contents
actively participate in medical conferences and exhibits, such as the ASCO and ASH Annual Meeting & Exposition that are significant
opportunities for us to educate physicians and key opinion leaders about our products. ASCO was held in Chicago, Illinois as well as
virtually in June 2022, and ASH was held in New Orleans, Louisiana as well as virtually in December 2022. In the future, other key
conferences may be held live, virtually, postponed or cancelled. Such disruptions may prevent us from effectively educating the prescribing
physicians and key opinion leaders about our products which would negatively impact utilization of our products and our results of
operations and growth prospects could be adversely affected.
Maintaining our sales, marketing, market access and product distribution capabilities requires significant resources, and there are
numerous risks involved with managing our commercial team, including our potential inability to successfully train, retain and incentivize
adequate numbers of qualified and effective sales and marketing personnel. We are also competing for talent with numerous commercial
and pre-commercial-stage oncology-focused biotechnology companies seeking to build out their commercial organizations, as well as other
large pharmaceutical organizations that have extensive, well-funded and more experienced sales and marketing operations, and we may be
unable to maintain or adequately scale our commercial organization as a result of such competition. If we cannot maintain effective sales,
marketing, market access and product distribution capabilities, whether as a result of the COVID-19 pandemic or otherwise, we may be
unable to realize the commercial potential of our products. Also, to the extent that the commercial opportunities for our products grow over
time, we may not properly judge the requisite size and experience of our current commercialization teams or the level of distribution
necessary to market and sell our products, which could have an adverse impact on our business, financial condition and results of
operations.
We may not be able to successfully develop or commercialize our product candidates if problems arise in the clinical testing and
approval process.
The activities associated with the research, development and commercialization of fostamatinib and other product candidates in
our pipeline must undergo extensive clinical trials, which can take many years and require substantial expenditures, subject to extensive
regulation by the FDA and other regulatory agencies in the US and by comparable authorities in other countries. The process of obtaining
regulatory approvals in the US and other foreign jurisdictions is expensive, and lengthy, if approval is obtained at all.
Our clinical trials may fail to produce results satisfactory to the FDA or regulatory authorities in other jurisdictions. The regulatory
process also requires preclinical testing, and data obtained from preclinical and clinical activities are susceptible to varying interpretations.
The FDA has substantial discretion in the approval process and may refuse to approve any NDA or sNDA and decide that our data is
insufficient for approval and require additional preclinical, clinical or other studies. Varying interpretations of the data obtained from
preclinical and clinical testing could delay, limit or prevent regulatory approval of fostamatinib for any individual, additional indications.
For example, in June 2022, we announced that the top-line results from our Phase 3 trial in wAIHA did not demonstrate statistical
significance in the primary efficacy endpoint of durable hemoglobin response in the overall study population. While we conducted an in-
depth analysis of these data to better understand differences in patient characteristics and outcomes and submitted these findings to the
FDA, in October 2022, we announced that we received guidance from the FDA’s of these findings. Based on the result of the trial and the
guidance from the FDA, we did not file an sNDA for wAIHA.
Due to the evolving effects of COVID-19 pandemic, it is also possible that we could experience delays in the timing of our
interactions with regulatory authorities due to absenteeism by governmental employees or the diversion of regulatory authority efforts and
attention to approval of other therapeutics or other activities related to COVID-19 or other public health emergencies, which could delay or
limit our ability to make planned regulatory submissions or develop and commercialize our product candidates on anticipated timelines.
In addition, delays or rejections may be encountered based upon changes in regulatory policy for product approval during the
period of product development and regulatory agency review, which may cause delays in the approval or rejection of an application for
fostamatinib or for our other product candidates.
Commercialization of our product candidates depends upon successful completion of extensive preclinical studies and clinical
trials to demonstrate their safety and efficacy for humans. Preclinical testing and clinical development are long, expensive and uncertain
processes.
82
Table of Contents
In connection with clinical trials of our product candidates, we may face the following risks among others:
● the product candidate may not prove to be effective;
● the product candidate may cause harmful side effects;
● the clinical results may not replicate the results of earlier, smaller trials;
● we or third parties with whom we collaborate, may be significantly impacted by the evolving impacts of the COVID-19
pandemic;
● we, or the FDA or similar foreign regulatory authorities, may delay, terminate or suspend the trials;
● our results may not be statistically significant;
● patient recruitment and enrollment may be slower than expected;
● patients may drop out of the trials or otherwise not enroll; and
● regulatory and clinical trial requirements, interpretations or guidance may change.
We do not know whether we will be permitted to undertake clinical trials of potential products beyond the trials already concluded
and the trials currently in process. It will take us or our collaborative partners several years to complete any such testing, and failure can
occur at any stage of testing. Interim results of trials do not necessarily predict final results, and acceptable results in early trials may not be
repeated in later trials. A number of companies in the pharmaceutical industry, including biotechnology companies, have suffered
significant setbacks in advanced clinical trials, even after achieving promising results in earlier trials.
General Risk Factors
Shareholder activism could cause material disruption to our business.
Publicly traded companies have increasingly become subject to campaigns by our stakeholders, including investors, and more
recently regulatory organizations advocating corporate actions such as actions related to environment, social and governance (ESG)
matters, impacts of climate change, financial restructuring, increased borrowing, dividends, share repurchases and even sales of assets or
the entire company. Responding to proxy contests and other actions by such activist investors or others in the future could be costly and
time-consuming, disrupt our operations and divert the attention of our Board of Directors and senior management from the pursuit of our
business strategies, which could adversely affect our results of operations and financial condition.
Anti-takeover provisions in our charter documents and under Delaware law may make an acquisition of us, which may be beneficial to
our stockholders, more difficult.
Provisions of our amended and restated certificate of incorporation and bylaws, as well as provisions of Delaware law, could make
it more difficult for a third party to acquire us, even if doing so would benefit our stockholders. These provisions:
● establish that members of the board of directors may be removed only for cause upon the affirmative vote of stockholders
owning a majority of our capital stock;
● authorize the issuance of “blank check” preferred stock that could be issued by our board of directors to increase the number
of outstanding shares and thwart a takeover attempt;
● limit who may call a special meeting of stockholders;
● prohibit stockholder action by written consent, thereby requiring all stockholder actions to be taken at a meeting of our
stockholders;
83
Table of Contents
● establish advance notice requirements for nominations for election to the board of directors or for proposing matters that can
be acted upon at stockholder meetings;
● provide for a board of directors with staggered terms; and
● provide that the authorized number of directors may be changed only by a resolution of our board of directors.
In addition, Section 203 of the Delaware General Corporation Law (DGCL), which imposes certain restrictions relating to
transactions with major stockholders, may discourage, delay or prevent a third party from acquiring us.
Our bylaws designate a state or federal court located within the State of Delaware as the sole and exclusive forum for substantially all
disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes
with us or our current or former directors, officers, stockholders, or other employees.
Our bylaws provide that, unless we consent in writing to the selection of an alternative forum, the Court of Chancery of the State
of Delaware shall be the sole and exclusive forum for (i) any derivative action or proceeding brought on behalf of us under Delaware law,
(ii) any action asserting a claim of breach of a fiduciary duty owed by any current or former director, officer, or other employee of the
Company to us or our stockholders, (iii) any action asserting a claim against us or any of our directors, officers, or other employees arising
pursuant to any provision of the DGCL or our amended and restated certificate of incorporation and bylaws (as either may be amended
from time to time), (iv) any action asserting a claim against us governed by the internal affairs doctrine, or (v) any other action asserting an
“internal corporate claim,” as defined under Section 115 of the DGCL. The forgoing provisions do not apply to any claims arising under the
Securities Act and, unless we consent in writing to the selection of an alternative forum, the federal district courts of the United States will
be the sole and exclusive forum for resolving any action asserting a claim arising under the Securities Act.
These choice of forum provisions may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for
disputes with us or any of our current or former directors, officers, or other employees, which may discourage lawsuits with respect to such
claims. There is uncertainty as to whether a court would enforce such provisions, and the enforceability of similar choice of forum
provisions in other companies’ charter documents has been challenged in legal proceedings. It is possible that a court could find these types
of provisions to be inapplicable or unenforceable, and if a court were to find the choice of forum provision to be inapplicable or
unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could harm our
business, results of operations, and financial condition.
Increasing use of social media could give rise to liability and may harm our business.
We and our employees are increasingly utilizing social media tools and our website as a means of communication. Despite our
efforts to monitor evolving social media communication guidelines and comply with applicable laws, regulations and national and EU
codes of conduct, there is risk that the unauthorized use of social media by us or our employees to communicate about our products or
business, sharing of publications in unintended audiences in other jurisdictions, or any inadvertent promotional activity or disclosure of
material, nonpublic information through these means, may cause us to be found in violation of applicable laws and regulations, which may
give rise to liability and result in harm to our business. In addition, there is also risk of inappropriate disclosure of sensitive information,
which could result in significant legal and financial exposure and reputational damages that could potentially have an adverse impact on our
business, financial condition and results of operations. Furthermore, negative posts or comments about us or our products on social media
could seriously damage our reputation, brand image and goodwill.
Our research and development efforts will be seriously jeopardized if we are unable to attract and retain key employees and
relationships.
Our success depends on the continued contributions of our principal management and scientific personnel and on our ability to
develop and maintain important relationships with leading academic institutions, scientists and companies in the face of intense competition
for such personnel. In particular, our research programs depend on our
84
Table of Contents
ability to attract and retain highly skilled chemists, other scientists, and development, regulatory and clinical personnel. If we lose the
services of any of our key personnel, our research and development efforts could be seriously and adversely affected. Our employees can
terminate their employment with us at any time.
Global economic conditions could adversely impact our business.
The US government has indicated its intent to alter its approach to international trade policy and in some cases to renegotiate, or
potentially terminate, certain existing bilateral or multi-lateral trade agreements and treaties with foreign countries. In addition, the US
government has initiated or is considering imposing tariffs on certain foreign goods. Related to this action, certain foreign governments,
including China, have instituted or are considering imposing tariffs on certain US goods. It remains unclear what the US Administration or
foreign governments will or will not do with respect to tariffs or other international trade agreements and policies. A trade war or other
governmental action related to tariffs or international trade agreements or policies has the potential to disrupt our research activities, affect
our suppliers and/or the US economy or certain sectors thereof and, thus, could adversely impact our businesses.
The transition away from the London Interbank Offered Rate (LIBOR) could affect the value of certain short-term investments.
The UK’s Financial Conduct Authority (FCA), which regulates LIBOR, has announced plans to phase out the use of LIBOR
discontinued as a floating rate benchmark. The date of discontinuation will vary depending on the LIBOR currency and tenor. The FCA has
announced that, after specified dates, LIBOR settings will cease to be provided by any administrator or will no longer be representative.
Those dates are: (i) June 30, 2023, in the case of the principal US dollar LIBOR tenors (overnight and one, three, six and 12 month s); and
(ii) December 31, 2021, in all other cases (i.e., one-week and two-month US dollar LIBOR and all tenors of non-US dollar LIBOR).
LIBOR has been the principal floating rate benchmark in the financial markets, and its discontinuation has affected and will continue to
affect the financial markets generally and may also affect our operations specifically.
The FCA and certain US regulators have stated that, despite expected publication of US dollar LIBOR through June 30, 2023, no
new contracts using US dollar LIBOR should be entered into after December 31, 2021. Regulators have also stated that, for certain
purposes, market participants should transition away from US. dollar LIBOR sooner. Regulatory authorities and legislative bodies have
taken other actions related to the LIBOR discontinuation and are expected to continue to do so. There is no assurance as to the
consequences of any such statements and other actions.
Although the foregoing reflects the likely timing of the LIBOR discontinuation and certain consequences, there is no assurance
that LIBOR, of any particular currency or tenor, will continue to be published until any particular date or in any particular form, and there is
no assurance regarding the consequences of the LIBOR discontinuation.
We have certain short-term investments which include financial instruments subject to LIBOR. Our debt facility with MidCap was
subject to LIBOR prior to the Third Amendment to the Credit Agreement entered in July 2022, whereby the interest rate benchmark was
changed from LIBOR to Secured Overnight Financing Rate (SOFR) (as defined in the amended Credit Agreement). There remains
uncertainty regarding the future utilization of LIBOR and the nature of any replacement rate, and any potential effects of the transition
away from LIBOR on certain instruments into which we may enter in the future are not known. The transition process may involve, among
other things, increased volatility or illiquidity in markets for instruments that currently rely on LIBOR. The transition may also result in
reductions in the value of certain instruments or the effectiveness of related transactions such as hedges, increased borrowing costs,
uncertainty under applicable documentation, or difficult and costly consent processes. Any such effects of the transition away from LIBOR,
as well as other unforeseen effects, result in expenses, difficulties, complications or delays in connection with future financing efforts,
which could have an adverse impact on our business, financial condition and results of operations.
85
Table of Contents
Our facilities are located near known earthquake fault zones, and the occurrence of an earthquake or other catastrophic disaster could
cause damage to our facilities and equipment, which could require us to cease or curtail operations.
Our facilities are located in the San Francisco Bay Area near known earthquake fault zones and are vulnerable to significant
damage from earthquakes. We are also vulnerable to damage from other types of disasters, including fires, floods, power loss,
communications failures and similar events. If any disaster were to occur, our ability to operate our business at our facilities would be
seriously, or potentially completely, impaired, and our research could be lost or destroyed. In addition, the unique nature of our research
activities and of much of our equipment could make it difficult for us to recover from a disaster. The insurance we maintain may not be
adequate to cover our losses resulting from disasters or other business interruptions.
Item 1B. Unresolved Staff Comments
None.
Item 2. Properties
In October 2022, we entered into a sublease agreement with Atara Biotherapeutics, Inc. (Atara) to sublease approximately 13,670
rentable square feet of office space located at 611 Gateway Boulevard, Suite 900, South San Francisco, California, which lease commenced
in November 2022 and shall expire in May 2025. This new leased facility is currently held as our new Headquarters following the
expiration of our previous lease in January 2023. We believe that this new leased facility is in good operating condition and is adequate for
all our present and near term uses.
We previously leased a facility consisting of approximately 147,000 square feet of research and office space located at 1180
Veterans Boulevard, South San Francisco, California, which expired in January 2023. We subleased approximately 66,000 square feet of
this leased facility to an unrelated third party which also expired in January 2023.
Item 3. Legal Proceedings
In June 2022, we received a notice letter regarding an ANDA submitted to the FDA by Annora, requesting approval to market a
generic version of TAVALISSE. The notice letter included a Paragraph IV certification with respect to our US Patent Nos. 7,449,458;
8,263,122; 8,652,492; 8,771,648 and 8,951,504, which are listed in the FDA’s Approved Drug Products with Therapeutic Equivalence
Evaluations (referred to as the “Orange Book”). The notice letter asserts that these patents will not be infringed by Annora’s proposed
product, are invalid and/or are unenforceable. Annora’s notice letter does not provide a Paragraph IV certification against our other patents
listed in the Orange Book. On July 25, 2022, we filed a lawsuit in the US District Court for the District of New Jersey against Annora and
its affiliates, Hetero Labs Ltd., and Hetero USA, Inc., for infringement of our US patents identified in Annora’s Paragraph IV certification.
On September 21, 2022, Annora and its affiliates answered and counterclaimed for declaratory judgment of non-infringement and invalidity
of the ’458, ’122, ’492, ’648, and ’504 patents. We filed an answer to Annora’s counterclaims on October 12, 2022. Annora served
invalidity and non-infringment contentions on December 31, 2022.We intend to vigorously enforce and defend our intellectual property
related to TAVALISSE.
We may also from time to time become a party or subject to other legal proceedings and claims, either asserted or unasserted,
which arise in the ordinary course of business. Some of these proceedings that we may be involved in the future, are claims that are subject
to substantial uncertainties and unascertainable damages or other remedies.
Item 4. Mine Safety Disclosures
Not applicable.
86
Table of Contents
PART II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Market Information
Our common stock commenced trading publicly on the Nasdaq Global Market under the symbol “RIGL” on December 7, 2000.
Holders
As of February 28, 2023, there were approximately 90 holders of record of our common stock.
Dividends
We have not paid any cash dividends on our common stock and currently do not plan to pay any cash dividends in the foreseeable
future.
Performance Measurement Comparison
The graph below shows the cumulative total stockholder return of an investment of $100 (and the reinvestment of any dividends
thereafter) on December 31, 2017 in (i) our common stock, (ii) the Nasdaq Composite Index and (iii) the Nasdaq Biotechnology Index. The
Nasdaq Biotechnology Index is a modified-capitalization weighted index that includes securities of Nasdaq-listed companies classified
according to the Industry Classification Benchmark as either Biotechnology or Pharmaceuticals and which also meet other eligibility
criteria. Our stock price performance shown in the graph below is based upon historical data and is not indicative of future stock price
performance.
87
Table of Contents
The following graph and related information shall not be deemed “soliciting material” or be deemed to be “filed” with the SEC,
nor shall such information be incorporated by reference into any future filing, except to the extent that we specifically incorporate it by
reference into such filing.
COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN*
Among Rigel Pharmaceuticals, Inc., the Nasdaq Composite Index
and the Nasdaq Biotechnology Index
*
$100 invested on 12/31/17 in stock or index, including reinvestment of dividends. Fiscal year ending December 31.
Item 6. [Reserved]
88
Table of Contents
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion should be read in conjunction with our “Notes to Financial Statements” contained in Part II, Item 8 of
this Form 10-K. This section of this Form 10-K discusses 2022 and 2021 items and 2022 and 2021 year-to-year comparisons. This section
does not discuss 2020 items and 2021 to 2020 year-to-year comparisons. Discussions of 2020 items and 2021 to 2020 year-to-year
comparisons can be found in the “Part II, Item 7 Management’s Discussion and Analysis of Financial Condition and Result of Operations”
of our Annual Report on Form 10-K for the year ended December 31, 2021.
Overview
We are a biotechnology company dedicated to discovering, developing and providing novel therapies that significantly improve
the lives of patients with hematologic disorders and cancer. Our pioneering research focuses on signaling pathways that are critical to
disease mechanisms.
Our first product approved by the FDA is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only approved oral SYK
inhibitor, for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment. The product is
also commercially available in Europe and UK (as TAVLESSE), and in Canada and Israel (as TAVALISSE) for the treatment of chronic ITP
in adult patients.
Our second FDA approved product is REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R AML with
a susceptible IDH1 mutation as detected by an FDA-approved test. We began our commercialization of REZLIDHIA (olutasidenib) in
December 2022. We in-licensed olutasidenib from Forma with exclusive, worldwide rights for its development, manufacturing and
commercialization.
We conducted a Phase 3 clinical trial evaluating fostamatinib for the treatment of wAIHA and announced that we did not file an
sNDA for this indication considering the top-line data results and guidance received from the FDA. We announced the completion of the
FOCUS Phase 3 clinical trial of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19. Fostamatinib is currently
being studied in an NIH/NHLBI sponsored Phase 2/3 trial (ACTIV-4 Host Tissue Trial) for the treatment of COVID-19 in hospitalized
patients.
For discussions of recent business updates, please refer to “Part I, Item 1, Business – Business Updates” of this Annual Report on
Form 10-K.
Critical Accounting Estimates
The preparation of these financial statements requires us to make estimates and assumptions that affect the amounts reported in the
financial statements and accompanying notes. We base our estimates on historical experience and on various other assumptions that we
believe to be reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of
assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different
assumptions or conditions.
Our significant accounting policies are more fully described in “Note 1- Description of Business and Summary of Significant
Accounting Policies”, in the “Notes to Financial Statements” contained in “Part II, Item 8, Financial Statements and Supplementary Data”
of this Annual Report on Form 10-K. We believe our critical accounting estimates which require subjective and complex judgments include
estimates around our product sales allowances and discounts; estimates around accounting for collaboration arrangements; estimates around
the fair value of our stock option awards and the probability of achievement of corporate performance-based milestones for our
performance-based stock option awards; and estimates around research and development accruals.
89
Table of Contents
Product Sales Allowances and Discounts
Our revenues from product sales are recognized at net sales price when our customers, the specialty distributors, obtain control of
our product, which occurs at a point in time, upon delivery to such specialty distributors. Under the revenue recognition guidance, we are
required to estimate the transaction price, including variable consideration that is subject to a constraint, in our contracts with our
customers. Variable considerations are included in the transaction price to the extent that it is probable that a significant reversal in the
amount of cumulative revenue recognized will not occur. Revenue from product sales is recorded net of certain variable considerations
which includes estimated government-mandated rebates and chargebacks, PBM rebates, distribution fees, estimated product returns and
other deductions.
Provisions for sales discounts, returns and allowances are provided for in the period the related revenue is recorded. Our estimates
are based on available customer and payer data received from the specialty pharmacies and distributors, as well as third-party market
research data. Actual amounts of consideration ultimately received may differ from our estimates. If actual results in the future vary from
our estimates, we will adjust these estimates, which would affect net product revenue and earnings in the period such variances become
known.
Contract Revenues from Collaborations
In the normal course of business, we conduct research and development programs independently and in connection with our
corporate collaborators, pursuant to which we license certain rights to our intellectual property to third parties. The terms of these
arrangements typically include payment to us for a combination of one or more of the following: upfront license fees; development,
regulatory and commercial milestone payments; product supply services; and royalties on net sales of licensed products.
Upfront License Fees: If the license to our intellectual property is determined to be distinct from the other performance obligations
identified in the arrangement, we recognize revenues from upfront license fees allocated to the license when the license is transferred to the
licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other promises, we determine
whether the combined performance obligation is satisfied over time or at a point in time. If the combined performance obligation is
satisfied over time, we use judgment in determining the appropriate method of measuring progress for purposes of recognizing revenue
from the up-front license fees. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of
performance and related revenue recognition.
For arrangements that require us to share in the development costs but to which we do not participate in the co-development work,
the portion of the upfront fee attributed to our share in the future development costs is excluded from the transaction price. If such share in
the development costs is payable beyond 12 months from the delivery of the corresponding license, a significant financing component is
deemed to exist. If a significant financing component is identified, we adjust the transaction price by reducing the upfront fee by the net
present value of our share in future development costs over the expected commitment period. Such discounted amount will be reported as a
liability in the balance sheet, with a corresponding interest expense being accreted based on a discount rate applied over the expected
commitment period.
Development, Regulatory or Commercial Milestone Payments: At the inception of each arrangement that includes payments based
the achievement of certain development, regulatory and commercial or launch events, we evaluate whether the milestones are considered
probable of being achieved and estimate the amount to be included in the transaction price using the most likely amount method. If it is
probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone
payments that are not within our or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until
uncertainty associated with the approvals has been resolved. The transaction price is then allocated to each performance obligation, on a
relative standalone selling price basis, for which we recognize revenue as or when the performance obligations under the contract are
satisfied. At the end of each subsequent reporting period, we re-evaluate the probability of achieving such development and regulatory
milestones and any related constraint, and if necessary, adjust our estimate of the overall transaction price. Any such adjustments are
recorded on a cumulative catch-up basis, and are recorded as part of contract revenues from collaborations during the period of adjustment.
90
Table of Contents
Product Supply Services: Arrangements that include a promise for future supply of drug product for either clinical development or
commercial supply at the licensee’s discretion are generally considered as options. We assess if these options provide a material right to the
licensee and if so, they are accounted for as separate performance obligations.
Sales-based Milestone Payments and Royalties: For arrangements that include sales-based royalties, including milestone payments
based on the volume of sales, we determine whether the license is deemed to be the predominant item to which the royalties or sales-based
milestones relate to and if such is the case, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the
performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).
Stock-Based Compensation
The fair value of our stock option award is estimated on the date of grant using the Black-Scholes option pricing model which
considered our stock price, as well as assumptions regarding a number of complex and subjective variables. These variables include, but are
not limited to, volatility, expected term, risk-free interest rate and dividends. We estimate volatility over the expected term of the option
using historical share price performance. For expected term, we take into consideration our historical data of options exercised, cancelled
and expired. The risk-free rate is based on the US Treasury constant maturity rate. We have not paid and do not expect to pay dividends in
the foreseeable future. We use the straight-line attribution method over the requisite employee service period for the entire award in
recognizing stock-based compensation expense. We account for forfeitures as they occur.
We granted performance-based stock options to purchase shares of our common stock which will vest upon the achievement of
certain corporate performance-based milestones. We determined the fair values of these performance-based stock options using the Black-
Scholes option pricing model at the date of grant. For the portion of the performance-based stock options of which the performance
condition is considered probable of achievement, we recognize stock-based compensation expense on the related estimated grant date fair
values of such options on a straight-line basis from the date of grant up to the date when we expect the performance condition will be
achieved. For the performance conditions that are not considered probable of achievement at the grant date or upon quarterly re-evaluation,
prior to the event actually occurring, we recognize the related stock-based compensation expense when the event occurs or when we can
determine that the performance condition is probable of achievement. In those cases, we recognize the change in estimate at the time we
determine the condition is probable of achievement (by recognizing stock-based compensation expense as cumulative catch-up adjustment
as if we had estimated at the grant date that the performance condition would have been achieved) and recognize the remaining
compensation cost up to the date when we expect the performance condition will be achieved, if any.
Research and Development Accruals
We have various contracts with third parties related to our research and development activities. Costs that are incurred but not
billed to us as of the end of the period are accrued. We make estimates of the amounts incurred in each period based on the information
available to us and our knowledge of the nature of the contractual activities generating such costs. Clinical trial contract expenses are
accrued based on units of activity. Expenses related to other research and development contracts, such as research contracts, toxicology
study contracts and manufacturing contracts are estimated to be incurred generally on a straight-line basis over the duration of the contracts.
Raw materials and study materials not related to our approved drug, purchased for us by third parties are expensed at the time of purchase.
We make significant judgments and estimates in determining the accrual balance in each reporting period. As actual costs become
known, we adjust our accruals. Although we do not expect our estimates to be materially different from amounts actually incurred, such
estimates for the status and timing of services performed relative to the actual status and timing of services performed may vary and could
result in us reporting amounts that are too high or too low in any particular period. Variations in assumptions used to estimate accruals
including, but not limited to, the number of patients enrolled, the rate of patient enrollment and the actual services performed may result in
adjustments in research and development accruals in future periods. Changes in these estimates that result in material changes to our
accruals could materially affect our financial condition and results of operations.
91
Table of Contents
Recent Accounting Pronouncements
Recently issued accounting guidance is either not applicable or did not have, or is not expected to have, a material impact on us.
Results of Operations
Revenues
Year Ended December 31,
2021
2022
2020
Aggregate Change
2022 from 2021 2021 from 2020
Product sales, net
Contract revenues from collaborations
Government contract
Total revenues
$
76,718
39,024
4,500
$ 120,242
$
63,010
75,726
10,500
$ 149,236
$
(in thousands)
61,696
$
46,925
—
$ 108,621
$
$
13,708
(36,702)
(6,000)
(28,994) $
1,314
28,801
10,500
40,615
The following table summarizes revenues from each of our customers who individually accounted for 10% or more (wherein *
denotes less than 10%) of the total net product sales and revenues from collaborations:
McKesson Specialty Care Distribution Corporation
Kissei
Cardinal Healthcare
ASD Healthcare and Oncology Supply
Lilly
Grifols
2022
Year Ended December 31,
2021
2020
31%
24%
19%
17%
*
*
20%
*
*
17%
48%
*
23%
—
*
30%
—
41%
Net product sales pertained to sales of our products in the US, net of chargebacks, discounts and fees, government and other
rebates and returns. The increase in our net product sales in 2022 compared to 2021 was primarily driven by the increase in quantities sold
of TAVALISSE mainly due to the recent sales force expansion and increased in-person engagements, as well as the increase in price per
bottle. These increases were partially offset by the increase in revenue reserves mainly due to higher rebates on contracts we entered with
certain PBMs, and higher government program rebates. Following the approval by the FDA in December 2022, we commenced the
commercialization of REZLIDHIA in the US and recorded net product sales of $0.9 million in 2022.
Following table summarizes our revenues by collaborative partners for the periods presented:
Year Ended December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
Kissei
Medison
Grifols
Knight
Lilly
Daiichi
Other third party
Total revenues from collaborations
$ 27,569
5,726
2,989
2,000
740
—
—
$ 39,024
$
341
75
2,955
—
66,555
1,800
4,000
$ 75,726
92
$
(in thousands)
— $
—
44,825
—
—
2,100
—
$ 46,925
$
27,228
5,651
34
2,000
(65,815)
(1,800)
(4,000)
(36,702)
$
$
341
75
(41,870)
—
66,555
(300)
4,000
28,801
Table of Contents
In 2022, contract revenues from collaborations consisted of $27.6 million in revenue from Kissei primarily related to the $25.0
million regulatory milestones associated with the NDA application and approval of fostamatinib for the treatment of patients with chronic
ITP in Japan, and delivery of fostamatinib supplies, $5.7 million in revenue from Medison related to the release of outstanding financing
liability associated with the buy-back option, $3.0 million in revenue from Grifols related to the delivery of fostamatinib supplies, royalty
revenue and research and development services, $2.0 million in revenue related to our license agreement with Knight, and $0.7 million in
revenue related to our license agreement with Lilly. In 2021, contract revenues from collaborations consisted of $66.6 million revenue
related to our license agreement with Lilly, $4.0 million revenue related to grant of non-exclusive license of a certain patent to an unrelated
third-party company, $1.8 million in revenue related to the achievement of milestone under our collaboration agreement with Daiichi, $3.0
million related to our performance of research and development services and delivery of drug supply under our collaboration agreement
with Grifols, $0.3 million related delivery of drug supply to Kissei, and $0.1 million milestone payment under our commercial and license
agreement with Medison.
Government contract revenue was related to the income we recognized from the $16.5 million government award granted to us,
pursuant to the agreement we entered in January 2021 with the US Department of Defense to support our ongoing Phase 3 clinical trial to
evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients. Through December 31, 2022, we recognized $15.0
million of revenue from this award, and we expect to receive the remaining award of $1.5 million, subject to us meeting certain clinical trial
events or milestones and approval by the US Department of Defense as specified in the agreement.
Our potential future revenues may include product sales, payments from our collaboration partners and from new collaboration
partners with whom we enter into agreements in the future, if any, and from existing government grants and any future grants we may be
entitled to, if any, the timing and amount of which is unknown at this time. We cannot currently fully forecast the extent of the impacts that
the COVID-19 pandemic may have on our revenues. Our net product sales may be impacted by changes to the government program rebates
and new private payer rebate contracts we entered or may enter in the future. As of December 31, 2022, we had deferred revenues of $1.4
million, which we will recognize as revenue upon satisfaction of our remaining performance obligations under our respective collaboration
agreements.
Cost of Product Sales
Cost of product sales
December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
$ 1,749 $ 1,083 $
(in thousands)
895 $
666 $
188
The cost of product sales includes the cost of inventories sold to specialty distributors and to our collaborative partners.
Inventories sold for the periods presented include inventory quantities acquired or produced prior to the FDA approval of the product, and
do not reflect the full cost of the inventories sold, since such costs incurred prior to FDA approval were previously expensed and charged to
research and development expense. We expect to continue to have a lower cost of product sales as we sell inventory quantities that were
acquired or produced prior to the FDA approval of the product, until we sell inventory quantities reflecting the full cost. We expect that this
will be the case in the near term, and as a result, our cost of product sales will be less than we anticipate it will be in future periods. As we
acquire or produce more FDA approved inventory quantities in the future, our inventory cost in the balance sheet and cost of product sales
will increase, reflecting the full cost of acquiring or producing such products. Further, following the approval of REZLIDHIA, we
recognize the amortization expense of capitalized intangible asset and royalty on REZLIDHIA sales, within cost of sales.
The increase in cost of product sales in 2022 compared to 2021 was primarily due to increased inventory quantities sold to our
specialty distributors and delivery of drug supply pursuant to our supply agreements with our collaborative partners, Grifols and Kissei. In
addition, cost of product sales in 2022 increased due to the amortization of capitalized intangible asset and royalty expense associated with
REZLIDHIA amounting to $0.2 million.
93
Table of Contents
Research and Development Expenses
Research and development expense
Stock-based compensation expense included in research
and development expense
Year Ended December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
(in thousands)
$ 60,272 $ 65,237 $ 60,101 $
(4,965) $
5,136
$
2,168
$
1,700
$
2,072
$
468
$
(372)
The decrease in research and development expense in 2022 compared to 2021 was mainly due to the decrease in personnel-related
costs of $3.5 million and decrease in various research and development expenses including allocated facilities and laboratory costs of $3.9
million, primarily as a result of the restructuring of our early-stage research department in November 2021 and certain development
personnel in October 2022. Further, research and development costs decreased by $4.3 million on our COVID-19 study, and $3.5 million
on our AIHA study, primarily due to timing of activities related to such studies. These decreases were partially offset by the increase
of research and development of $5.8 million in our IRAK 1/4 inhibitor program, and the $4.5 million upfront and pre-regulatory approval
milestone payments to Forma recorded as research and development expense in 2022.
Our research and development expenditures include costs related to preclinical and clinical trials, scientific personnel, supplies,
equipment, consultants, sponsored research, stock-based compensation, allocated facility costs, and upfront payment related to our in-
licensed agreement with Forma. We expect to continue to incur significant research and development expense as we continue our activities
in our clinical studies including our IRAK 1/4 inhibitor program. In July 2022, we completed the enrollment of the FOCUS Phase 3 clinical
trial of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19 and on November 1, 2022, we announced the top-
line results did not meet statistical significance in the primary efficacy endpoint. We are evaluating the opportunity and discussing next
steps with the FDA and in collaboration with our partner, the US Department of Defense. Our Phase 3 clinical trial for hospitalized
COVID-19 patients is partially funded by the award granted to us by the US Department of Defense as discussed above. Our Phase 3
wAIHA study completed enrollment in November 2021 and in June 2022, we announced that the top-line results did not demonstrate
statistical significance in the primary efficacy endpoint. In October 2022, we announced that we received guidance from the FDA’s further
review of these findings. Based on the result of the trial and the guidance from FDA, we did not file an sNDA for this indication.
Following our agreement with Forma to acquire exclusive license to develop, manufacture and commercialize olutasidenib, we
recorded the upfront payment of $2.0 million as in-process research and development (IPR&D), and included such amount within research
and development expense in 2022. As specified in the agreement, Forma is entitled to receive future potential development and regulatory
milestones. Milestone payment obligations incurred at development stage or prior to a regulatory approval are recorded as research and
development expenses. In 2022, we also recorded $2.5 million development milestone incurred prior to regulatory approval of the product
as research and development expense. For further discussions, see “Note 4 - Sponsored Research and License Agreements and Government
Contract” to our “Notes to Financial Statements” contained in “Part II, Item 8, Financial Statements and Supplementary Data” of this
Annual Report on Form 10-K. Further, we may incur research and development costs as we continue to pursue strategic actions to further
develop olutasidenib for the treatment of other malignancies.
In November 2021, we exited our early-stage research to focus our resources on our mid to late-stage development programs and
our commercialization efforts. In October 2022, we announced further reduction in our workforce resulting to elimination of certain
positions primarily in development as well as administration group. We continue to expect cost savings on our research and development
costs because of this reduction in workforce. We believe that this strategy strengthens our ability to execute on near-term value drivers, such
as growing ITP sales, expanding the addressable market for fostamatinib and olutasidenib, and advancing our other clinical trials.
Currently, we cannot fully forecast the scope of the evolving effects that the COVID-19 pandemic may have on our ability to
continue to treat patients enrolled in our trials, enroll and assess new patients, supply study drug, obtain complete data points in accordance
with the study protocol, and overall impact on, and timing of, clinical trial results.
94
Table of Contents
We do not track fully burdened research and development costs separately for each of our drug candidates. We review our research
and development expenses by focusing on three categories: research, development, and other. Our research team is focused on identifying
and evaluating product candidates in our focused range of therapeutic indications that can be developed into small molecule therapeutics in
our own proprietary programs or with potential collaborative partners. “Research” expenses relate primarily to personnel expenses, lab
supplies, fees to third party research consultants and compounds. Our development group leads the implementation of our clinical and
regulatory strategies and prioritizes disease indications in which our compounds may be studied in clinical trials. “Development” expenses
relate primarily to clinical trials, personnel expenses, costs related to our regulatory filings, lab supplies and fees to third party research
consultants. “Other” expenses primarily consist of allocated facilities costs and allocated stock-based compensation expense relating to
personnel in research and development groups. “Other” expenses also include the upfront payment to Forma and pre-regulatory approval
milestone recorded as research and development expense in 2022.
In addition to reviewing the three categories of research and development expenses described in the preceding paragraph, we
principally consider qualitative factors in making decisions regarding our research and development programs, which include enrollment in
clinical trials and the results thereof, the clinical and commercial potential for our drug candidates and competitive dynamics. We also make
our research and development decisions in the context of our overall business strategy, which includes the evaluation of potential
collaborations for the development of our drug candidates.
We do not have reliable estimates regarding the timing of our clinical trials. Preclinical testing and clinical development are long,
expensive and uncertain processes. In general, biopharmaceutical development involves a series of steps, beginning with identification of a
potential target and including, among others, proof of concept in animals and Phase 1, 2 and 3 clinical trials in humans. Significant delays
in clinical testing could materially impact our product development costs and timing of completion of the clinical trials. We do not know
whether planned clinical trials will begin on time, will need to be halted or revamped or will be completed on schedule, or at all. Clinical
trials can be delayed for a variety of reasons, including delays in obtaining regulatory approval to commence a trial, delays from scale up,
delays in reaching agreement on acceptable clinical trial agreement terms with prospective clinical sites, delays in obtaining institutional
review board approval to conduct a clinical trial at a prospective clinical site or delays in recruiting subjects to participate in a clinical trial.
We currently do not have reliable estimates of total costs for a particular drug candidate to reach the market. Our potential products
are subject to a lengthy and uncertain regulatory process that may involve unanticipated additional clinical trials and may not result in
receipt of the necessary regulatory approvals. Failure to receive the necessary regulatory approvals would prevent us from commercializing
the product candidates affected. In addition, clinical trials of our potential products may fail to demonstrate safety and efficacy, which could
prevent or significantly delay regulatory approval.
The following table presents our total research and development expenses by category:
Categories:
Research
Development
Other
2022
Year Ended December 31,
2021
2020
From January 1, 2007*
to December 31, 2022
$
$
3,051
45,501
11,720
60,272
$
$
8,195
49,557
7,485
65,237
$
$
9,307
42,758
8,036
60,101
$
$
267,283
542,820
274,156
1,084,259
* We started tracking research and development expenses by category on January 1, 2007.
“Other” expenses in 2022, 2021 and 2020 consisted of allocated facilities costs of $5.0 million, $5.8 million and $6.0 million,
respectively, and allocated stock-based compensation expense of $2.2 million, $1.7 million and $2.1 million, respectively. “Other” expenses
in 2022 also included upfront payment and pre-regulatory approval milestone amounting to $4.5 million related to our in-license agreement
with Forma. In 2022 and 2021, a major portion of our total research and development expense was associated with our COVID-19, AIHA
and IRAK programs,
95
Table of Contents
personnel-related costs of our research and development personnel and allocated facilities costs.
Selling, General and Administrative Expense
Selling, general and administrative expense
Stock-based compensation expense included in selling,
general and administrative expense
Year Ended December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
(in thousands)
$ 112,451 $ 91,891 $ 76,598 $
20,560 $
15,293
$
10,217
$
7,337
$
5,223
$
2,880
$
2,114
Stock-based compensation expense recorded within selling, general and administrative expense in 2022 include incremental
charges of approximately $1.4 million due to stock option modifications related to the extension of exercise period of the of the outstanding
vested stock options of two former members of our Board of Directors whose terms expired in May 2022, and acceleration of vesting and
extension of exercise period of outstanding vested stock options of a former officer whose employment ended in October 2022.
The increase in selling, general and administrative expense in 2022 compared to 2021 was mainly due to the increase in personnel-
related costs of $8.0 million, increase in costs of commercial activities of $5.7 million, increase in trainings, conferences and travel related
costs of $3.4 million, and increase in other various sales, general and administrative costs of $0.6 million, primarily as a result of our
commercial expansion. In addition, stock-based compensation expense increased by $2.9 million primarily due to incremental charges from
stock option modifications as discussed above, and higher stock-based compensation expense due to timing of achievement of our
performance-based stock option awards.
We expect our selling, general and administrative expenses to increase as we continue to expand our commercial activities on
TAVALISSE, as well as commercialization of REZLIDHIA. As discussed above, in October 2022, we announced a reduction in our
workforce resulting to elimination of certain positions in our administrative group. We expect some cost savings on our general and
administrative costs in the future because of such reduction in workforce. In response to the limitations on in-person office visits due to
evolving effects of COVID-19 pandemic, we may continue to deploy resources to enable our field-based employees to continue to engage
virtually with healthcare providers as needed. The virtual engagements have enabled our field team to support existing prescribers as well
as partner with new prescribers to identify appropriate patients for our product. However, we are not currently able to fully forecast the
scope of impacts that the COVID-19 pandemic may have on our commercial activities and sales of our product.
Restructuring charges
Restructuring charges
Stock-based compensation expense included in restructuring
charges
Year Ended December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
$ 1,320 $ 3,521 $
(in thousands)
— $
(2,201) $
3,521
$
— $
449 $
— $
(449) $
449
In October 2022, we announced a reduction in our workforce primarily in our development and administration groups. We
recorded restructuring charges of $1.3 million in the statements of operations for the year ended December 31, 2022, comprised cash
severance, bonus and related employee benefits and taxes of affected employees.
In November 2021, we announced a reduction in our workforce resulting in the elimination of positions primarily in the research
organization. We recorded restructuring charges of $3.5 million in the statements of operations in 2021, comprised $2.9 million cash
severance, bonus and related taxes of affected employees, $0.4 million of stock-based compensation expense related to modification of
stock options and $0.1 million impairment of certain property and equipment which was recorded within depreciation expense14.
96
Table of Contents
Interest Income and Expense
Interest income
Interest expense
Year Ended December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
684 $
$
47 $
$ (3,707) $ (4,860) $
(in thousands)
582 $
(1,353) $
637 $
1,153 $
(535)
(3,507)
Interest income consists primarily of interest earned from our interest-bearing cash equivalents and short-term investments. The
increase in interest income in 2022 compared to 2021 was primarily due to increased interest rates on our investments.
Interest expense in 2022 and 2021 were consisted of interest on outstanding balance on our term loan from Midcap and interest on
the financing liability from our collaboration agreements. The decrease in interest expense in 2022 compared to 2021 was mainly due to
higher interest expense associated with the financing liability from our collaboration partners of $2.5 million in 2021, partially offset by the
increase in interest expense in 2022 on our term loan with MidCap of $1.3 million primarily due to the increase in the outstanding term loan
balance, as well as higher interest rate. In February 2022, we accessed additional $10.0 million term loan (Tranche 3), and in July 2022, we
accessed additional $10.0 million term loan (Tranche 4) from our credit facility with MidCap.
Provision for Income Taxes
Provision for income taxes
Year Ended December 31,
Aggregate Change
2022
2021
2020
2022 from 2021
2021 from 2020
$
— $
605 $
(in thousands)
— $
(605) $
605
The provision for income taxes in 2021 was related to the state tax liability primarily due to revenue recognized for the Lilly
agreement. We do not expect to owe federal income taxes due to the sufficient NOL carryforwards that were generated prior to the
enactment of the Tax Act, as well as significant research and development credit carryforwards. We continue to record a full valuation
allowance on our deferred tax assets considering our cumulative losses in prior years and forecasted losses in the future.
Liquidity and Capital Resources
Liquidity
As of December 31, 2022, we had $58.2 million in cash, cash equivalents and short-term investments, as compared to
$125.0 million as of December 31, 2021. We continue to maintain investment portfolios primarily in money market funds, US treasury
bills, government-sponsored enterprise securities, and corporate bonds and commercial paper. Cash in excess of immediate requirements is
invested with regard to liquidity and capital preservation. We view our investments portfolio as available-for-sale and are available for use
in current operations. Wherever possible, we seek to minimize the potential effects of concentration and degrees of risk. We continue to
monitor the impact of the changes in the conditions of the credit and financial markets to our investment portfolio and assess if future
changes in our investment strategy are necessary.
97
Table of Contents
Following summarizes our cash flow activity for the periods presented:
Net cash provided by (used in):
Operating activities
Investing activities
Financing activities
Net increase (decrease) in cash and cash equivalents
2022
Year Ended December 31,
2021
(in thousands)
2020
$
$
(73,758)
72,777
6,550
5,569
$
$
5,878
(80,036)
62,675
(11,483)
$
$
(52,185)
47,466
12,571
7,852
Net cash used in operating activities in 2022 was primarily related to payments for our research and development programs and
other operating expenses, partially offset by the proceeds from sales of our products, and the timing of cash receipt from our collaboration
partners and cash grant from the US Department of Defense. Net cash provided by operating activities in 2021 was primarily due to the
cash received from Lilly for the portion allocated as net transaction price of $67.1 million, proceeds from sales of our product, and timing
of cash receipt from our collaboration partners and cash grant from the US Department of Defense. These increases were partially offset by
payments of our research and development programs and other operating expenses.
Net cash provided by investing activities in 2022 comprises net maturities of short-term investments of $72.3 million and proceeds
from disposal of assets of $0.9 million, partially offset by capital expenditures of $0.5 million. Net cash used in investing activities in 2021
comprises net purchases of short-term investments of $79.4 million and capital expenditures of $0.6 million.
Net cash provided by financing activities in 2022 was primarily due to the net cash proceeds from term loan financing (Tranche 3
and 4) of $19.5 million and proceeds from exercises of stock options and participation in the Purchase Plan of $2.1 million, partially offset
by our cost share payments to Lilly of $15.1 million. Net cash provided by financing activities in 2021 was primarily due to the cash
received from Lilly for the portion allocated as financing component amounting to $57.9 million and proceeds from exercise of stock
options and participation in the Purchase Plan of $4.8 million.
We believe that our existing capital resources will be sufficient to support our current and projected funding requirements,
including the continued commercialization of our products, through at least the next 12 months from the date of issuance of this Annual
Report on Form 10-K. We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital
resources sooner than we currently expect. Because of the numerous risks and uncertainties associated with commercializing a product, the
development of our product candidates and other research and development activities, we are unable to estimate with certainty our future
product revenues, our revenues from our current and future collaborative partners, the amounts of increased capital outlays and operating
expenditures associated with our current and anticipated clinical trials and other research and development activities.
Capital Resources
Since inception, we have financed our operations primarily through sales of equity securities, debt financing, from sales of our
products, and contract payments under our collaboration agreements.
Under our existing collaboration agreements that we entered in the ordinary course of business, we received or may be entitled to
receive upfront cash payments, payments contingent upon specified events achieved by such partners and royalties on any net sales of
products sold by such partners under the agreements. As of December 31, 2022, total future contingent payments to us under our existing
agreements, excluding terminated agreements, could exceed $1.3 billion if all potential product candidates achieved all of the payment
triggering events under all of our current agreements. This estimated future contingent amount does not include any estimated royalties that
could be due to us if the partners successfully commercialize any of the licensed products. Future events that may trigger payments to us
under the agreements are based solely on our partners’ future efforts and achievements of specified development, regulatory and/or
commercial events. In December 2022, a regulatory milestone with Kissei was met which entitled us to receive a $20.0 million milestone
payment, and such amount was received in January 2023. See further discussion in
98
Table of Contents
“Note 4 - Sponsored Research and License Agreements and Government Contract” to our “Notes to Financial Statements” contained in
“Part II, Item 8, Financial Statements and Supplementary Data” of this Annual Report on Form 10-K.
In January 2021, we were awarded $16.5 million by the US Department of Defense to support our ongoing Phase 3 clinical trial to
evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients. Under the agreement with the US Department of
Defense, we are entitled to receive such award based on the agreed-upon payment schedule, subject to submission of proper documentation
as evidence of completion of certain clinical trial events or milestones as specified in the agreement, and approval by the US Department of
Defense that such events or milestones have been met. Through December 31, 2022, we recognized $15.0 million in revenue from this
award and expect to receive the remaining awards of $1.5 million, subject to us meeting certain clinical trial events or milestones and
approval by the US Department of Defense as specified in the agreement.
In August 2020, we entered into an Open Market Sale Agreement with Jefferies, as a sole agent, pursuant to which we may sell
from time to time, through Jefferies, shares of our common stock in sales deemed to be “at-the-market offerings” as defined in Rule 415
under the Securities Act, subject to conditions specified in the Open Market Sale Agreement, including maintaining an effective registration
statement covering the sale of shares under the Open Market Sale Agreement. In April 2021, the registration statement registering the sale
of shares under the Open Market Sale Agreement expired. From the time of implementation of the Open Market Sale Agreement through
expiration of the registration statement, no sales of shares occurred. On August 3, 2021, we filed a new automatic shelf registration
statement as a qualified WKSI, such term as defined in Rule 405 of the Securities Act. The automatic shelf registration statement was filed
to register, among other securities, the sale of up to a maximum aggregate offering price of $100.0 million of shares of our common stock
that may be issued and sold from time to time under the Open Market Sale Agreement; and a base prospectus which covers the offering,
issuance, and sale by us of the securities identified from time to time in one or more offerings. On March 1, 2022, we filed a post-
effective amendment to the automatic shelf registration statement immediately after filing our Annual Report on Form 10-K for the year
ended December 31, 2021, because we no longer qualified as a WKSI upon filing of such Annual Report. The post-effective amendment
was declared effective on May 3, 2022. The post-effective amendment registers, among other securities, a base prospectus which covers the
offering, issuance, and sale by us of up to $250.0 million in the aggregate of the securities identified from time to time in one or more
offerings, which include the $100.0 million of shares of our common stock that may be offered, issued and sold under the Open Market
Sale Agreement.
We have a Credit Agreement with MidCap entered in September 2019, and subsequently amended in March 2021, February 2022
and July 27, 2022. The Credit Agreement provides for $60.0 million term loan credit facility. As of December 31, 2022, the outstanding
principal balance of the loan was $40.0 million, and the facility gives us the ability to access an additional $20.0 million aggregate principal
amount of term loan at our option through March 31, 2023, subject to the achievement of certain customary conditions.
We had a sublease agreement originally entered in December 2014, and subsequently amended in February 2017 and July 2017,
with an unrelated third party to occupy a portion of our research and office space which expired in January 2023. As of December 31, 2022,
the remaining future sublease income (excluding our subtenant’s share of facility’s operating expenses) amounted to $0.4 million.
Our operations will require significant additional funding in the foreseeable future. Unless and until we can generate sufficient
cash from our operating activities, we may choose to raise additional funds through public and/or private offerings of equity securities, debt
financings, or from other sources. However, certain external factors such as COVID-19, conflicts in Russia and Ukraine, political and
economic legislations, and other factors may continue to rapidly evolve which could significantly disrupt the global financial markets. Our
ability to raise additional funds may be adversely impacted by potential worsening of global economic conditions and volatility in the credit
and financial markets in the US and worldwide. We could experience an inability to access additional funds, which could in the future
negatively affect our capacity for certain corporate development transactions or our ability to make important, opportunistic investments. To
the extent that we raise additional funds through the sale of equity, our shareholders’ ownership interest may experience substantial dilution.
Our current credit facility with MidCap and any debt financing that we can obtain in the future may involve operating covenants that may
restrict our business. To the extent that we
99
Table of Contents
raise additional funds through collaboration and licensing arrangements, we may be required to relinquish some of our rights to our
technologies or product candidates or grant licenses on terms that are not favorable to us.
Our future funding requirements will depend upon many factors, including, but not limited to:
● the ongoing costs to commercialize our products, or any other future product candidates, if any such candidate receives
regulatory approval for commercial sale;
● our ability to generate expected revenue from our commercialization efforts;
● the progress and success of our clinical trials and preclinical activities (including studies and manufacture of materials) of our
product candidates conducted by us;
● our ability to meet operating covenants under our current and future credit facilities, if any;
● our ability to enter into partnering opportunities across our pipeline within and outside the US;
● the costs and timing of regulatory filings and approvals by us and our collaborators;
● the progress of research and development programs carried out by us and our collaborative partners;
● any changes in the breadth of our research and development programs;
● the ability to achieve the events identified in our collaborative agreements that may trigger payments to us from our
collaboration partners;
● our ability to acquire or license other technologies or compounds that we may seek to pursue;
● our ability to manage our growth;
● competing technological and market developments;
● the costs and timing of obtaining, enforcing and defending our patent and other intellectual property rights; and
● expenses associated with any unforeseen litigation, including any arbitration and securities class action lawsuits.
Insufficient funds may require us to delay, scale back or eliminate some or all of our commercial efforts and/or research or
development programs, to lose rights under existing licenses or to relinquish greater or all rights to product candidates at an earlier stage of
development or on less favorable terms than we would otherwise choose or may adversely affect our ability to operate as a going concern.
Material Cash Requirements
We conduct our commercial activities and research and development programs internally and through third parties that include,
among others, arrangements with vendors, consultants, CROs and universities. We have contractual arrangements with these parties,
however our contracts with them are cancelable generally on reasonable notice within one year and our obligations under these contracts
are primarily based on services performed. We do not have any purchase commitments under any collaboration arrangements.
We have agreements with certain clinical research organizations to conduct our clinical trials and with third parties relative to our
commercialization of our products. The timing of payments for any amounts owed under the respective agreements will depend on various
factors including, but not limited to, patient enrollment and other progress of the clinical trial and various activities related to commercial
launch. We expect we will continue to enter into contracts in the normal course of business with various third parties who support our
clinical trials, support our preclinical research studies, and provide other services related to our operating purposes as well as our
commercialization of our products. We can terminate these agreements at any time, and if terminated, we would not be liable for the full
amount of the respective agreements. Instead, we will be liable for services provided through the termination date plus certain cancellation
charges, if any, as defined in each of the respective agreements. In addition, these agreements may, from time to time, be subjected to
amendments as a result of any change orders executed by the parties.
100
Table of Contents
As discussed in detail in “Note 4 – Sponsored Research and License Agreements and Government Contract” of our “Notes to
Financial Statements” contained in “Part II, Item 8, Financial Statements and Supplementary Data” of this Annual Report on Form 10-K,
pursuant to our global exclusive license agreement and strategic collaboration agreement with Lilly, we are responsible for funding the
development costs for R552 in the US, Europe, and Japan, up to $65.0 million through April 1, 2024. Through December 31, 2022, Lilly
billed us $15.1 million of the funding development costs and the amounts were fully paid as of December 31, 2022. We have the right to
opt-out of co-funding of development costs at two different specified times. If we decide not to exercise our opt-out rights, we will be
required to share in global development costs up to certain amounts at a specified cap, as set forth in the agreement.
Additionally, as discussed in detail in “Note 4 - Sponsored Research and License Agreements and Government Contract” to
our “Notes to Financial Statements” contained in “Part II, Item 8, Financial Statements and Supplementary Data” of this Annual Report on
Form 10-K, in July 2022, we entered into a license and transition services agreement with Forma. Pursuant to such agreement, we paid
Forma an upfront fee of $2.0 million, with potential for an additional development and regulatory milestone payments of up to $67.5
million, commercial milestone payments of up to $165.5 million, and tiered royalty payments. As of December 31, 2022, certain milestones
were met which entitled Forma to receive a $17.5 million milestone payment, of which, $15.0 million was outstanding and included within
accounts payable in our balance sheet.
As of December 31, 2022, we have a contractual commitment related to our facilities leased facilities of $2.6 million, with
approximately $1.5 million is payable within 12 months. See “Note 11 – Leases” to our “Notes to Financial Statements” contained in “Part
II, Item 8, Financial Statements and Supplementary Data” of this Annual Report on Form 10-K for further discussions of our leases.
As discussed above, we have a contractual commitment with respect to our credit facility with MidCap. Under the amended Credit
Agreement, the term loans mature on September 1, 2026, and the interest-only period is through October 1, 2024. The interest rate
applicable to the term loans under the amended Credit Agreement is the sum of one-month SOFR, plus an adjustment of 0.11448%, subject
to 1.50% applicable floor, plus applicable margin of 5.65%. A final payment fee of 2.5% of principal is due at maturity date of the term
loans. As of December 31, 2022, the outstanding principal amount of the loan was $40.0 million, and no principal payments are due within
12 months. We are also obligated to pay annual administrative fees. As of December 31, 2022, future interest calculated using the base
interest rate as per the Credit Agreement, and the final fee payments associated with the credit facility amounted to $8.9 million, with
approximately $3.0 million payable within 12 months.
We are also subject to claims related to the patent protection of certain of our technologies, as well as purported securities class
action lawsuit, other litigations, and other contractual agreements. We are required to assess the likelihood of any adverse judgments or
outcomes to these matters as well as potential ranges of probable losses. A determination of the amount of reserves required, if any, for
these contingencies is made after careful analysis of each individual matter. We do not have other material contractual commitments with
respect to matters discussed above.
Item 7A. Quantitative and Qualitative Disclosures about Market Risk
We are exposed to market risks in the ordinary course of our business. These risks primarily include interest rate sensitivities
related to our investments and borrowings. Our cash equivalents and short-term investments consists of money market funds, US treasury
bills, government-sponsored enterprise securities, and corporate bonds and commercial paper. Our cash equivalents and short-terms
investments are invested in high-grade securities, and as a result, we believe represent a minimal credit risk. The goals of our investment
policy are liquidity and capital preservation; we do not enter into investments for trading or speculative purposes and have not used any
derivative financial instruments to manage our interest rate exposure. If interest rates were to increase or decrease by 100 basis points, the
fair value of our cash equivalents and short-term investments would increase or decrease by an immaterial amount.
The outstanding principal balance of our loan from Midcap bears interest at an annual rate of one-month SOFR, plus an
adjustment of 0.11448%, subject to 1.50% applicable floor, plus applicable margin of 5.65%. Accordingly, our interest expense under the
MidCap Credit Agreement is subject to changes in SOFR. Fluctuations in SOFR above the contractual floor rate may have a material effect
on our interest payment obligations in the future.
101
Table of Contents
Item 8. Financial Statements and Supplementary Data
INDEX TO FINANCIAL STATEMENTS
Rigel Pharmaceuticals, Inc.
Report of Independent Registered Public Accounting Firm (PCAOB ID: 42)
Balance Sheets
Statements of Operations
Statements of Comprehensive Loss
Statements of Stockholders’ Equity (Deficit)
Statements of Cash Flows
Notes to Financial Statements
Supplementary Data
102
Page
103
105
106
107
108
109
110
138
Table of Contents
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Rigel Pharmaceuticals, Inc.
Opinion on the Financial Statements
We have audited the accompanying balance sheets of Rigel Pharmaceuticals, Inc. (the Company) as of December 31, 2022 and 2021, the
related statements of operations, comprehensive loss, stockholders’ equity (deficit) and cash flows for each of the three years in the period
ended December 31, 2022, and the related notes (collectively referred to as the “financial statements”). In our opinion, the financial
statements present fairly, in all material respects, the financial position of the Company at December 31, 2022 and 2021, and the results of
its operations and its cash flows for each of the three years in the period ended December 31, 2022, in conformity with U.S. generally
accepted accounting principles.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the
Company’s internal control over financial reporting as of December 31, 2022, based on criteria established in Internal Control—Integrated
Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission (2013 framework) and our report dated
March 7, 2023 expressed an unqualified opinion thereon.
Basis for Opinion
These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the
Company’s financial statements based on our audits. We are a public accounting firm registered with the 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 audit to
obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. Our
audits included performing procedures to assess the risks of material misstatement of the 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 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 financial statements. We believe that our audits
provide a reasonable basis for our opinion.
Critical Audit Matter
The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that was
communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that are material to the
financial statements and (2) involved our especially challenging, subjective or complex judgments. The communication of the critical audit
matter does not alter in any way our opinion on the 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.
Product Sales Allowances and Discounts
Description of the
Matter
As described in Note 1 to the financial statements, revenue from product sales is recorded net of adjustments for
estimated government-mandated and/or privately-negotiated rebates and chargebacks, distribution fees, estimated
product returns, and other deductions. Provisions for these adjustments are recorded in the period in which the
related revenue is recorded and are presented either as a reduction of accounts receivable or as an accrued liability
in the Company’s
103
Table of Contents
balance sheet. As of December 31, 2022, the Company has recorded net liabilities for product sales allowances
and discounts of $12.1 million.
Auditing product sales allowances and discounts involved evaluation of management’s subjective judgments
regarding the reasonableness of estimated payor and channel mix applied to product sales during the period. These
estimates are based on available customer and payor data received from specialty pharmacies and distributors and
reflect management’s judgments regarding adjustments to historical trends. The Company has a limited history
upon which to base such estimates, and changes in the estimated payor and channel mix can have a material effect
on the amount of variable consideration recognized.
How We Addressed
the Matter in Our
Audit
We tested the Company’s internal controls over the process for estimating and recording product sales allowances
and discounts. Our testing included controls over management’s review of significant assumptions, such as payor
mix and channel mix, and other inputs such as product sold, contractual terms, discount rates, historical data and
expected channel inventory levels, used in the estimates.
To test the Company’s provisions for allowances and discounts, our audit procedures included, among others,
evaluating the methodologies and assumptions used and the underlying data used by the Company. We evaluated
the assumptions used by management against historical trends, evaluated the change in estimated accruals from
prior periods, and assessed the historical accuracy of the Company’s estimates against actual results. We
performed substantive analytical procedures on material ending accrual balances by assessing whether the accrued
balance is reasonable relative to historical payment lag and sales activity.
/s/ Ernst & Young LLP
We have served as the Company’s auditor since 1998.
San Francisco, California
March 7, 2023
104
Table of Contents
RIGEL PHARMACEUTICALS, INC.
BALANCE SHEETS
(In thousands, except share and per share amounts)
Assets
Current assets:
Cash and cash equivalents
Short-term investments
Accounts receivable, net
Inventories
Prepaid and other current assets
Total current assets
Property and equipment, net
Intangible asset, net
Operating lease right-of-use assets
Other assets
Total assets
Liabilities and stockholders’ (deficit) equity
Current liabilities:
Accounts payable
Accrued compensation
Accrued research and development
Revenue reserves and refund liability
Other accrued liabilities
Lease liabilities, current portion
Deferred revenue
Other long-term liabilities, current portion
Total current liabilities
Long-term portion of lease liabilities
Loans payable, net of discount
Other long-term liabilities
Total liabilities
Commitments
Stockholders’ equity (deficit):
Preferred stock, $0.001 par value; 10,000,000 shares authorized; none issued and
outstanding as of December 31, 2022 and 2021
Common stock, $0.001 par value; 400,000,000 shares authorized; 173,398,645 and
171,602,226 shares issued and outstanding as of December 31, 2022 and 2021, respectively
Additional paid-in capital
Accumulated other comprehensive loss
Accumulated deficit
Total stockholders’ (deficit) equity
Total liabilities and stockholders’ (deficit) equity
See Accompanying Notes to Financial Statements.
105
As of December 31,
2022
2021
$
$
$
24,459
33,747
40,320
9,118
8,259
115,903
857
14,949
1,930
640
134,279
22,508
8,866
7,708
12,145
6,485
1,133
1,369
4,997
65,211
972
39,448
42,264
147,895
18,890
106,077
15,472
6,616
7,412
154,467
2,184
—
9,703
974
167,328
3,795
10,690
10,384
7,915
4,776
9,892
2,596
13,506
63,554
759
19,914
52,727
136,954
—
—
174
1,368,822
(153)
(1,382,459)
(13,616)
134,279
$
172
1,354,190
(102)
(1,323,886)
30,374
167,328
$
$
$
$
Table of Contents
Revenues:
Product sales, net
Contract revenues from collaborations
Government contract
Total revenues
Costs and expenses:
Cost of product sales
Research and development
Selling, general and administrative
Restructuring charges
Total costs and expenses
Loss from operations
Interest income
Interest expense
Loss before income taxes
Provision for income taxes
Net loss
Net loss per share, basic and diluted
RIGEL PHARMACEUTICALS, INC.
STATEMENTS OF OPERATIONS
(In thousands, except per share amounts)
Year Ended December 31,
2021
2022
2020
$
76,718
39,024
4,500
120,242
$
63,010
75,726
10,500
149,236
$
61,696
46,925
—
108,621
1,749
60,272
112,451
1,320
175,792
(55,550)
684
(3,707)
(58,573)
—
(58,573)
(0.34)
$
$
1,083
65,237
91,891
3,521
161,732
(12,496)
47
(4,860)
(17,309)
605
(17,914)
(0.11)
$
$
895
60,101
76,598
—
137,594
(28,973)
582
(1,353)
(29,744)
—
(29,744)
(0.18)
$
$
Weighted average shares used in computing net loss per share, basic and diluted
172,406
170,492
168,754
See Accompanying Notes to Financial Statements.
106
Table of Contents
RIGEL PHARMACEUTICALS, INC.
STATEMENTS OF COMPREHENSIVE LOSS
(In thousands)
Net loss
Other comprehensive loss:
Net unrealized loss on short-term investments
Comprehensive loss
$
$
See Accompanying Notes to Financial Statements.
107
Year Ended December 31,
2021
(17,914)
$
$
2022
(58,573)
2020
(29,744)
(51)
(58,624)
(98)
(18,012)
$
(27)
(29,771)
$
Table of Contents
RIGEL PHARMACEUTICALS, INC.
STATEMENTS OF STOCKHOLDERS’ EQUITY (DEFICIT)
(In thousands, except number of shares)
Balance as of January 1, 2020
Net loss
Net change in unrealized loss on short-term
investments
Issuance of common stock upon exercise of options
and participation in Purchase Plan
Stock-based compensation expense
Balance as of December 31, 2020
Net loss
Net change in unrealized loss on short-term
investments
Issuance of common stock upon exercise of options
and participation in Purchase Plan
Stock-based compensation expense
Balance as of December 31, 2021
Net loss
Net change in unrealized loss on short-term
investments
Issuance of common stock upon exercise of options
and participation in Purchase Plan
Issuance of common stock upon vesting of restricted
stock units (RSUs)
Stock-based compensation expense
Balance as of December 31, 2022
Common Stock
Shares
167,987,850
—
Amount
$
168
—
$
Additional
Paid-in
Capital
1,329,852
—
$
Accumulated Other
Comprehensive
Income (Loss)
$
23
—
Accumulated
Deficit
(1,276,228)
(29,744)
Total
Stockholders’
Equity (Deficit)
$
53,815
(29,744)
—
1,328,932
—
169,316,782
—
—
2,285,444
—
171,602,226
—
—
1,580,169
216,250
—
173,398,645
$
—
1
—
169
—
—
3
—
172
—
—
2
—
—
174
—
2,595
7,386
1,339,833
—
—
4,772
9,585
1,354,190
—
—
2,122
(27)
—
—
(4)
—
(98)
—
—
(102)
—
(51)
—
—
—
—
(1,305,972)
(17,914)
—
—
—
(1,323,886)
(58,573)
—
—
—
12,510
1,368,822
$
$
—
—
(153) $
—
—
$
(1,382,459)
(27)
2,596
7,386
34,026
(17,914)
(98)
4,775
9,585
30,374
(58,573)
(51)
2,124
—
12,510
(13,616)
See Accompanying Notes to Financial Statements.
108
Table of Contents
RIGEL PHARMACEUTICALS, INC.
STATEMENTS OF CASH FLOWS
(In thousands)
Operating activities
Net loss
Adjustments to reconcile net loss to net cash (used in) provided by operating activities:
Stock-based compensation expense
Net gain on sale and write-down of property and equipment
Depreciation and amortization
Non-cash interest expense
Net amortization and accretion of discount on short-term investments and term loan
Changes in assets and liabilities:
Accounts receivable, net
Inventories
Prepaid and other current assets
Other assets
Right-of-use assets
Accounts payable
Accrued compensation
Accrued research and development
Revenue reserves and refund liability
Other accrued liabilities
Lease liability
Deferred revenue
Other current and long-term liabilities
Net cash (used in) provided by operating activities
Investing activities
Purchases of short-term investments
Maturities of short-term investments
Proceeds from sale of property and equipment
Purchases of property and equipment
Net cash provided by (used in) investing activities
Financing activities
Cost share advance from a collaboration partner
Cost share payments to a collaboration partner
Net proceeds from issuances of common stock upon exercise of options and participation
in Purchase Plan
Net proceeds from term loan financing
Net cash provided by financing activities
Net increase (decrease) in cash and cash equivalents
Cash and cash equivalents at beginning of period
Cash and cash equivalents at end of period
Supplemental disclosure of cash flow information
Interest paid
Purchases of intangible asset included within accounts payable
Year Ended December 31,
2021
2020
2022
$ (58,573) $
(17,914) $
(29,744)
12,385
(138)
998
682
(63)
(24,848)
(2,377)
(847)
334
7,773
3,788
(1,824)
(2,676)
4,230
1,709
(8,546)
(1,227)
(4,538)
(73,758)
9,486
—
1,162
3,139
287
501
(4,875)
6,633
(150)
8,192
41
1,098
5,495
1,850
(24)
(8,621)
(422)
—
5,878
7,297
—
706
—
(122)
(5,862)
(126)
(4,583)
(128)
7,814
(331)
773
(1,071)
2,733
1,318
(7,230)
(23,629)
—
(52,185)
(28,894)
101,228
893
(450)
72,777
(141,459)
62,050
—
(627)
(80,036)
(81,706)
130,434
—
(1,262)
47,466
—
(15,116)
2,124
19,542
6,550
5,569
18,890
24,459
2,495
15,000
$
$
$
$
$
$
57,900
—
4,775
—
62,675
(11,483)
30,373
18,890
$
—
—
2,596
9,975
12,571
7,852
22,521
30,373
1,500
$
— $
1,180
—
See Accompanying Notes to Financial Statements.
109
Table of Contents
RIGEL PHARMACEUTICALS, INC.
NOTES TO FINANCIAL STATEMENTS
In this Annual Report on Form 10-K, “Rigel,” “we,” “us” and “our” refer to Rigel Pharmaceuticals, Inc. and “common stock” refers to
Rigel’s common stock, par value $0.001 per share.
1. DESCRIPTION OF BUSINESS AND SUMMARY OF SIGNIFICANT ACCOUNTING POLICIES
Description of Business
We are a biotechnology company dedicated to discovering, developing and providing novel theraphies that significantly improve
the lives of patients with hematologic disorders and cancer. Our pioneering research focuses on signaling pathways that are critical to
disease mechanisms.
Our first product approved by the FDA is TAVALISSE (fostamatinib disodium hexahydrate) tablets, the only approved oral SYK
inhibitor, for the treatment of adult patients with chronic ITP who have had an insufficient response to a previous treatment. The product is
also commercially available in Europe and UK (as TAVLESSE), and in Canada and Israel (as TAVALISSE) for the treatment of chronic ITP
in adult patients.
Our second FDA approved product is REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with R/R AML with
a susceptible IDH1 mutation as detected by an FDA-approved test. We began our commercialization of REZLIDHIA (olutasidenib) in
December 2022. We in-licensed olutasidenib from Forma with exclusive, worldwide rights for its development, manufacturing and
commercialization.
We conducted a Phase 3 clinical trial evaluating fostamatinib for the treatment of wAIHA and announced that we did not file an
sNDA for this indication considering the top-line data results and guidance received from the FDA. We announced the completion of the
FOCUS Phase 3 clinical trial of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19. Fostamatinib is currently
being studied in an NIH/NHLBI sponsored Phase 2/3 trial (ACTIV-4 Host Tissue Trial) for the treatment of COVID-19 in hospitalized
patients.
Basis of Presentation
The accompanying financial statements have been prepared in accordance with United States generally accepted accounting
principles (US GAAP). Any reference in these notes to applicable accounting guidance is meant to refer to the authoritative US GAAP
included in the Accounting Standards Codification (ASC), and Accounting Standards Update (ASU) issued by the Financial Accounting
Standards Board (FASB). We manage our operations as one business segment for purposes of assessing performance, making operating
decisions, and allocating resources.
Liquidity
As of December 31, 2022, we had approximately $58.2 million in cash, cash equivalents and short-term investments. Since
inception, we have financed our operations primarily through sales of equity securities, debt financing arrangement, contract payments
under our collaboration agreements and from product sales. Based on our current operating plan, we believe that our existing cash, cash
equivalents, and short-term investments will be sufficient to fund our expenses and capital expenditure requirements through at least the
next 12 months from the date of issuance of this Annual Report on Form 10-K.
Use of Estimates
The preparation of financial statements in conformity with US GAAP requires management to make estimates and assumptions
that affect the amounts reported in the financial statements and accompanying notes. Significant estimates and assumptions made by
management include those relating to revenue recognition on product sales and collaboration agreements, recoverability of our assets,
including accounts receivables and inventories, stock-based compensation and the probability of achievement of corporate performance-
based milestones for our performance-based
110
Table of Contents
stock option awards, impairment issues, the weighted average incremental borrowing rate for our lease, estimated interest rate for our
financing liability, the estimated useful life of assets, and estimated accruals, particularly research and development accruals, on an ongoing
basis. We base our estimates on historical experience and on various other assumptions that we believe to be reasonable under the
circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not
readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions. To the extent
there are material differences between these estimates and actual results, our financial statements will be affected.
Reclassifications
We presented revenue reserves and refund liability on the face of balance sheets, which was previously classified within other
accrued liabilities. The prior period financial information has been reclassified to conform with the current period presentation.
Revenue Recognition
We recognize revenue in accordance with ASC Topic 606, Revenue from Contracts with Customers (ASC 606), when a customer
obtains control of promised goods or services, in an amount that reflects the consideration which we expect to receive in exchange for those
goods or services. To determine whether arrangements are within the scope of ASC 606, we perform the following five steps: (i) identify
the contract(s) with a customer; (ii) identify the performance obligations in the contract; (iii) determine the transaction price; (iv) allocate
the transaction price to the performance obligations in the contract; and (v) recognize revenue when (or as) we satisfy our performance
obligation. We apply the five-step model to contracts when it is probable that we will collect the consideration we are entitled to in
exchange for the goods or services we transfer to the customer. At contract inception, once the contract is determined to be within the scope
of this new guidance, we assess the goods or services promised within each contract and identify, as a performance obligation, and assess
whether each promised good or service is distinct. We then recognize as revenue the amount of the transaction price that is allocated to the
respective performance obligation when (or as) the performance obligation is satisfied.
Product Sales
Revenues from product sales are recognized when the specialty distributors, who are our customers, obtain control of our product,
which occurs at a point in time, upon delivery to such specialty distributors. These specialty distributors subsequently resell our products to
specialty pharmacy providers, health care providers, hospitals and clinics. In addition to distribution agreements with our specialty
distributors, we also have arrangements with certain specialty pharmacy providers, in-office dispensing providers, group purchasing
organizations, and government entities that provide for government-mandated and/or privately-negotiated rebates, chargebacks and
discounts with respect to the purchase of our products.
Under ASC 606, we are required to estimate the transaction price, including variable consideration that is subject to a constraint, in
our contracts with our customers. Variable consideration is included in the transaction price to the extent that it is probable that a significant
reversal in the amount of cumulative revenue recognized will not occur. Revenue from product sales is recorded net of certain variable
consideration which includes estimated government-mandated rebates and chargebacks, distribution fees, estimated product returns and
other deductions.
Provisions for returns and other adjustments are provided for in the period the related revenue is recorded. Actual amounts of
consideration ultimately received may differ from our estimates. If actual results in the future vary from our estimates, we will adjust these
estimates, which would affect net product revenue and earnings in the period such variances become known.
The following are our significant categories of sales discounts and allowances:
Sales Discounts. We provide certain customer a prompt payment discount that is explicitly stated in our contract. The sales
discount is recorded as a reduction of revenue in the period the related product revenue is recognized.
111
Table of Contents
Product Returns. We offer our specialty distributors a right to return product purchased directly from us, which is principally based
upon the product’s expiration date. Product return allowances are estimated and recorded at the time of sale.
Government and Private Payor Rebates: We are subject to discount obligations under the state Medicaid programs and Medicare
prescription drug coverage gap program. We estimate our Medicaid and Medicare prescription drug coverage gap rebates based upon a
range of possible outcomes that are probability-weighted for the estimated payor mix. We also have rebate program agreements with certain
PBMs for certain product, pursuant to which rebates will be paid in accordance with the respective agreements. The rebate reserves are
recorded in the same period the related revenue is recognized, resulting in a reduction of product revenue and related liability is recorded as
revenue reserves within other accrued liabilities in the balance sheet. Our liability for these rebates consists primarily of estimates of claims
for the current quarter, and estimated future claims that will be made for product that has been recognized as revenue, but remains in the
distribution channel inventories at the end of each reporting period.
Chargebacks and Discounts: Chargebacks for fees and discounts represent the estimated obligations resulting from contractual
commitments to sell products to certain specialty pharmacy providers, in-office dispensing providers, group purchasing organizations, and
government entities at prices lower than the list prices charged to our specialty distributors who directly purchase the product from us.
These specialty distributors charge us for the difference between what they pay for the product and our contracted selling price to these
specialty pharmacy providers, in-office dispensing providers, group purchasing organizations, and government entities. These reserves are
established in the same period that the related revenue is recognized, resulting in a reduction of product revenue. Actual chargeback
amounts are generally determined at the time of resale to the specialty pharmacy providers, in-office dispensing providers, group
purchasing organizations, and government entities by our specialty distributors. The estimated obligations arising from these chargebacks
and discounts are recorded as revenue reserves within other accrued liabilities in the balance sheet.
Co-Payment Assistance: We offer co-payment assistance to commercially insured patients meeting certain eligibility requirements.
The calculation of the accrual for co-pay assistance is based on an estimate of claims and the cost per claim that we expect to receive
associated with product that has been recognized as revenue.
Contract Revenues from Collaborations
In the normal course of business, we conduct research and development programs independently and in connection with our
corporate collaborators, pursuant to which we license certain rights to our intellectual property to third parties. The terms of these
arrangements typically include payment to us for a combination of one or more of the following: upfront license fees; development,
regulatory and commercial milestone payments; product supply services; and royalties on net sales of licensed products.
Upfront License Fees: If the license to our intellectual property is determined to be distinct from the other performance obligations
identified in the arrangement, we recognize revenues from upfront license fees allocated to the license when the license is transferred to the
licensee and the licensee is able to use and benefit from the license. For licenses that are bundled with other promises, we determine
whether the combined performance obligation is satisfied over time or at a point in time. If the combined performance obligation is
satisfied over time, we use judgment in determining the appropriate method of measuring progress for purposes of recognizing revenue
from the up-front license fees. We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of
performance and related revenue recognition.
For arrangements that require us to share in the development costs but to which we do not participate in the co-development work,
the portion of the upfront fee attributed to our share in the future development costs is excluded from the transaction price. If such share in
the development costs is payable beyond 12 months from the delivery of the corresponding license, a significant financing component is
deemed to exist. If a significant financing component is identified, we adjust the transaction price by reducing the upfront fee by the net
present value of our share in future development costs over the expected commitment period. Such discounted amount will be reported as a
liability in the balance sheet, with a corresponding interest expense being accreted based on a discount rate applied over the expected
commitment period.
112
Table of Contents
Development, Regulatory or Commercial Milestone Payments: At the inception of each arrangement that includes payments based
on the achievement of certain development, regulatory and commercial or launch events, we evaluate whether the milestones are
considered probable of being achieved and estimate the amount to be included in the transaction price using the most likely amount
method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction
price. Milestone payments that are not within our or the licensee’s control, such as regulatory approvals, are not considered probable of
being achieved until uncertainty associated with the approvals has been resolved. The transaction price is then allocated to each
performance obligation, on a relative standalone selling price basis, for which we recognize revenue as or when the performance
obligations under the contract are satisfied. At the end of each subsequent reporting period, we re-evaluate the probability of achieving such
development and regulatory milestones and any related constraint, and if necessary, adjust our estimate of the overall transaction price. Any
such adjustments are recorded on a cumulative catch-up basis, and recorded as part of contract revenues from collaborations during the
period of adjustment.
Product Supply Services: Arrangements that include a promise for future supply of drug product for either clinical development or
commercial supply at the licensee’s discretion are generally considered as options. We assess if these options provide a material right to the
licensee and if so, they are accounted for as separate performance obligations.
Sales-based Milestone Payments and Royalties: For arrangements that include sales-based royalties, including milestone payments
based on the volume of sales, we determine whether the license is deemed to be the predominant item to which the royalties or sales-based
milestones relate to and if such is the case, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the
performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).
Government Contract
In January 2021, we were awarded up to $16.5 million by the US Department of Defense’s Joint Program Executive Office for
Chemical, Biological, Radiological and Nuclear Defense (referred to here as the US Department of Defense) to support our ongoing Phase
3 clinical trial to evaluate the safety and efficacy of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19. We
determined that the government award should be accounted for under IAS 20, Accounting for Government Grants and Disclosure of
Government Assistance, which is outside the scope of Topic 606, as the US Department of Defense is not receiving reciprocal value for
their contributions. Revenue is recognized when there is reasonable assurance that the conditions of the grant will be met, and the grant will
be received. For the US Department of Defense’s contract, this occurs when either each milestone has been accepted by the US Department
of Defense or management has concluded that the conditions of the grant have been substantially met. See “Note 4 – Sponsored Research
and License Agreements and Government Contract” for further discussion.
Stock-based Compensation
Share-based awards are valued at fair value on the date of grant and that fair value is recognized over the requisite service period,
which is generally the vesting period of the respective award. We use the straight-line attribution method over the requisite employee
service period for the entire award in recognizing stock-based compensation expense. We account for forfeitures as they occur.
The fair value of each option award is estimated on the date of grant using the Black-Scholes option pricing model. The model
requires management to make a number of assumptions including expected volatility, expected term, risk-free interest rate and expected
dividends. A number of these assumptions are subjective, and their determination generally require judgment. We segregate option awards
into the following three homogenous groups for the purposes of determining fair values of options: officers and directors, all other
employees, and consultants. We determine the weighted-average valuation assumptions separately for each of these groups as follows:
● Volatility – We estimate volatility using the historical share price performance over the expected life of the option up to the
point where we have historical market data. We also consider other factors, such as implied volatility, our current clinical
trials and other company activities that may affect the volatility of our stock
113
Table of Contents
in the future. We determined that at this time historical volatility is more indicative of our expected future stock performance
than implied volatility.
● Expected term – We analyze various historical data to determine the applicable expected term for each of the other option
groups. This data includes: (1) for exercised options, the term of the options from option grant date to exercise date; (2) for
cancelled options, the term of the options from option grant date to cancellation date, excluding non-vested option forfeitures;
and (3) for options that remained outstanding at the balance sheet date, the term of the options from option grant date to the
end of the reporting period and the estimated remaining term of the options. The consideration and calculation of the above
data gives us reasonable estimates of the expected term for each employee group. We also consider the vesting schedules of
the options granted and factors surrounding exercise behavior of the option groups, our current market price and company
activity that may affect our market price. In addition, we consider the optionee type (i.e., officers and directors or all other
employees) and other factors that may affect the expected term of the option. For options granted to consultants, we use the
contractual term of the option, which is generally 10 years, for the initial valuation of the option and the remaining
contractual term of the option for the succeeding periods.
● Risk-free interest rate – The risk-free interest rate is based on US Treasury constant maturity rates with similar terms to the
expected term of the options for each option group.
● Dividend yield – The expected dividend yield is 0% as we have not paid and do not expect to pay dividends in the future.
We grant performance-based stock options to purchase shares of our common stock which will vest upon the achievement of
certain corporate performance-based milestones. We determine the fair values of these performance-based stock options using the Black-
Scholes option pricing model at the date of grant. For the portion of the performance-based stock options of which the performance
condition is considered probable of achievement, we recognize stock-based compensation expense on the related estimated grant date fair
values of such options on a straight-line basis from the date of grant up to the date when we expect the performance condition will be
achieved. For the performance conditions that are not considered probable of achievement at the grant date or upon re-evaluation at each
reporting date, prior to the event actually occurring, we recognize the related stock-based compensation expense when the event occurs or
when we can determine that the performance condition is probable of achievement. In those cases, we recognize the change in estimate at
the time we determine the condition is probable of achievement (by recognizing stock-based compensation expense as cumulative catch-up
adjustment as if we had estimated at the grant date that the performance condition would have been achieved) and recognize the remaining
compensation cost up to the date when we expect the performance condition will be achieved, if any.
The fair value of the RSU grant is based on the market price of our common stock on the date of grant.
Accounts Receivable
Accounts receivable are recorded net of customer allowances for prompt payment discounts and any allowance for doubtful
accounts. We monitor the financial performance and creditworthiness of our customers so that we can properly assess and respond to
changes in their credit profile. We will reserve against our accounts receivable for estimated losses that may arise from a customer’s
inability to pay. We have historically not experienced significant credit losses and no amounts were reserved for estimated losses as of the
balance sheet dates presented.
114
Table of Contents
The following table summarizes the activity of our customer allowances for prompt payment discounts for the periods presented
(in thousands):
Balance at the beginning of the year
Provision for prompt payment discount
Reduction in prompt payment discount
Balance at end of the year
Concentration of Credit Risk
Year Ended December 31,
2022
2021
2020
$
$
106
557
(527)
136
$
$
171
609
(674)
106
$
$
109
807
(745)
171
Financial instruments that potentially subject us to a concentration of credit risk are primarily cash, investment in debt securities
and accounts receivable. All of our cash and investment in debt securities are maintained with financial institutions that management
believes are creditworthy. By policy, we limit the concentration of credit risk by diversifying our investments among a variety of high
credit-quality issuers. Due to the short-term nature of these investments, we believe we do not have a material exposure to credit risk
arising from our investments. We have not historically experienced any significant credit losses related to these financial instruments and do
not believe that we are exposed to any significant credit risk related to these instruments.
Concentration of credit risk with respect to our accounts receivable is limited due to our small number of customers. Our accounts
receivable consists mostly of outstanding invoices from our sale of our product to our specialty distributors. Accounts receivable may also
include outstanding invoice or invoices from our collaboration partners with respect to the related sponsored research and license
agreements, as well as outstanding invoice or invoices from the US Government with respect to the related government contract. Our
outstanding receivable as of December 31, 2022 includes $20.0 million of regulatory milestone due from Kissei which was collected in
January 2023. As of December 31, 2022, 49% of our accounts receivable are outstanding invoices from our specialty distributors, and the
remaining 51% are outstanding invoices from other collaboration partners, mainly Kissei and Grifols. As of December 31, 2021, 85% of
our accounts receivable consisted of outstanding invoices from our specialty distributors, and the remaining 15% are outstanding invoices
from the US Government and from other collaboration partners, mainly Grifols and Kissei.
See “Note 3 - Revenues” for summary of revenues from each of our customers who individually accounted for 10% or more of the
total net product sales and revenues from collaborations.
Cash, Cash Equivalents and Short-Term Investments
Our investment in debt securities consists of money market funds, US treasury bills, government- sponsored enterprise securities,
and corporate bonds and commercial paper. All of our investment in debt securities are available-for-sale and are classified based on their
maturities. We consider all highly liquid investments in debt securities with maturity of 90 days or less from the date of purchase to be cash
equivalents. All other investments with maturity greater than 90 days from the date of purchase are classified as short-term investments.
Unrealized gains (losses) are reported within the statements of stockholders’ equity (deficit) and comprehensive income (loss). The cost of
securities sold is based on the specific identification method.
We periodically evaluate our available-for-sale marketable debt securities for impairment. When the fair value of a marketable
debt security is below its amortized cost, the amortized cost is reduced to its fair value if it is more likely than not that we are required to
sell the impaired security before recovery of our amortized cost basis, or we have the intention to sell the security. If neither of these
conditions are met, we determine whether the impairment is due to credit losses by comparing the present value of the expected cash flows
of the security with its amortized cost basis. The amount of impairment recognized is limited to the excess of the amortized cost over the
fair value of the security. An allowance for credit losses for the excess of amortized cost over the expected cash flows is recorded in other
income (expense), net on the statements of operations. Impairment losses that are not credit-related are included in accumulated other
comprehensive income (loss) in stockholders’ equity (deficit).
115
Table of Contents
Fair Value of Financial Instruments
The carrying amounts of our financial instruments, including cash, accounts receivable, accounts payable and accrued liabilities,
approximate fair value due to their relatively short maturities. The carrying value of our loans payable and other long-term debt
approximates fair value based on management’s estimation that a current interest rate would not differ materially from the stated rate, or the
discount rate applied.
The fair value of our cash equivalents and short-term investments measured at fair value on a recurring basis and are categorized
based upon the lowest level of significant input to the valuations.
Assets and liabilities recorded at fair value in our financial statements are categorized based upon the level of judgment associated
with the inputs used to measure their fair value. Fair value is an exit price, representing the amount that would be received to sell an asset or
paid to transfer a liability in an orderly transaction between market participants. As such, fair value is a market-based measurement that
should be determined based on assumptions that market participants would use in pricing an asset or liability. Hierarchical levels directly
related to the amount of subjectivity associated with the inputs to fair valuation of these assets and liabilities, are as follows:
● Level 1 – Inputs are unadjusted, quoted prices in active markets for identical assets at the reporting date. Active markets are
those in which transactions for the asset or liability occur in sufficient frequency and volume to provide pricing information
on an ongoing basis.
The fair valued assets we hold that are generally included under this Level 1 are money market securities where fair value is
based on publicly quoted prices.
● Level 2 – Inputs, other than quoted prices included in Level 1, that are either directly or indirectly observable for the asset or
liability through correlation with market data at the reporting date and for the duration of the instrument’s anticipated life.
The fair valued assets we hold that are generally assessed under Level 2 included government-sponsored enterprise securities,
US treasury bills and corporate bonds and commercial paper. We utilize third party pricing services in developing fair value
measurements where fair value is based on valuation methodologies such as models using observable market inputs, including
benchmark yields, reported trades, broker/dealer quotes, bids, offers and other reference data. We use quotes from external
pricing service providers and other on-line quotation systems to verify the fair value of investments provided by our third-
party pricing service providers.
● Level 3 – Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the
assets or liabilities and which reflect management’s best estimate of what market participants would use in pricing the asset or
liability at the reporting date. Consideration is given to the risk inherent in the valuation technique and the risk inherent in the
inputs to the model. We do not have fair valued assets classified under Level 3.
Inventories and Cost of Product Sales
Inventories are stated at the lower-of-cost or estimated net realizable value. We determine the cost of inventories using the
standard cost method, which approximates actual cost, and is valued using the first-in, first-out method. Inventory costs primarily consist of
active pharmaceutical ingredients, third-party manufacturing costs and allocated internal overhead costs. We capitalize inventory costs
when the product is approved by the FDA, or when based on management’s judgment, future commercialization was considered probable,
and the future economic benefits are expected to be realized.
Prior to FDA approval of a product, costs to purchase active pharmaceutical ingredients including costs to manufacture a product
are charged to research and development expense when incurred. Our physical inventories as of balance sheet dates include inventory
quantities where costs have been previously charged to research and development
116
Table of Contents
expenses since such costs were incurred prior to FDA approval of the product.
We provide reserves for potential excess, dated or obsolete inventories based upon assumptions about future demand and market
conditions, as well as product shelf life.
Cost of product sales primarily includes cost of inventories sold, and product shipping and handling costs. Further, following the
approval of REZLIDHIA, we recognize the amortization expense of capitalized intangible asset and royalty expense incurred pursuant to
our license agreement with Forma, within cost of sales.
Property and Equipment
Property and equipment are stated at cost. Depreciation is calculated using the straight-line method over the estimated useful lives
of the assets, which range from three to seven years. Leasehold improvements are amortized over the shorter of the lease term or the
estimated useful lives of the assets. Maintenance and repairs are charged to expense as incurred. When assets are retired or otherwise
disposed of, the cost and accumulated depreciation are removed from the balance sheet and any resulting gain or loss is reflected in
statements of operations in the period realized.
Research and Development Expenses
Research and development expenses include costs for scientific personnel, supplies, equipment, consultants, research sponsored by
us, allocated facility costs, costs related to pre-clinical and clinical trials, including raw materials, and stock-based compensation expense.
All such costs are charged to research and development expenses as incurred and at the time raw materials are purchased.
We have various contracts with third parties related to our research and development activities. Costs that are incurred but not
billed to us as of the end of the period are accrued. We make estimates of the amounts incurred in each period based on the information
available to us and our knowledge of the nature of the contractual activities generating such costs. Clinical trial contract expenses are
accrued based on units of activity. Expenses related to other research and development contracts, such as research contracts, toxicology
study contracts and manufacturing contracts are estimated to be incurred generally on a straight-line basis over the duration of the contracts.
Raw materials and study materials not related to our approved drug are charged to research and development expenses at the time of
purchase.
Research and development expenses also include milestone payment obligations incurred prior to regulatory approval of the
product, which are accrued when the event requiring payment of the milestone occurs. See related discussions below.
Advertising Expense
Advertising costs are expensed as incurred and are included within selling general and administrative expenses in the statements of
operations. Advertising costs for the years ended December 31, 2022, 2021 and 2020 amounted to $2.7 million, $2.3 million, and $1.7
million, respectively.
IPR&D/Intangible Asset
In July 2022, we entered into a license and transition services agreement with Forma. The transaction was accounted for as an
acquisition of asset under ASC 730, Research and Development. In accordance with the guidance, in a transaction accounted for as an asset
acquisition, any acquired IPR&D that does not have alternative future use is charged to expense at the acquisition date. Further, we account
for milestone payment obligations incurred at development stage and prior to a regulatory approval of an indication associated with the
acquired licensed asset as research and development expenses when the event requiring payment of the milestone occurs. Milestone
payment obligations incurred upon and after a regulatory approval of an indication associated with the acquired licensed asset, and at the
commercial stage, will be recorded as intangible asset when the event requiring payment of the milestones occurs. The amount recorded as
an intangible asset is amortized over the estimated useful life of the acquired licensed asset. See “Note 4 – Sponsored Research and
License Agreements and Government Contract” for further discussion.
117
Table of Contents
Leases
We account for leases in accordance with ASU No. 2016-02, Leases (Topic 842). Topic 842 requires a lessee to determine if an
arrangement is a lease or contains a lease at contract inception. Right-of-use lease assets represent the right to use the underlying asset for
the lease term and the lease liability represents the obligation to make the lease payments arising from the lease. Right-of-use lease assets
and lease liability are recognized at the commencement date based on the present value of future minimum lease payments over the term of
the lease. The operating right-of-use lease asset may also include initial direct costs and prepaid lease payments less lease incentives. In
measuring the present value of the future minimum lease payments, we generally use our incremental borrowing rate as our lease
agreement do not provide an implicit borrowing rate and we deemed that our incremental borrowing rate would be the rate of interest that
we would have to pay to borrow on a collateralized basis over a similar term of the lease payments in a similar economic environment. If a
lease includes options to extend the lease term, we do not assume the option will be exercised in the initial lease term assessment unless
there is reasonable certainty that we will renew based on an assessment of economic factors present as of the lease commencement date.
Leases with an initial term of 12 months or less are not recorded on the balance sheet. Lease expense for our operating leases is recognized
on a straight-line basis over the lease term, subject to any changes in the lease or expectations regarding the terms. Variable lease costs such
as common area costs and property taxes are expensed as incurred.
For our sublease agreement wherein we were the lessor, we recognized sublease income on a straight-line basis over the term of
the related sublease agreement.
Restructuring
Restructuring costs comprised severance, other termination benefit costs, stock-based compensation expense for stock award and
stock option modifications related to workforce reductions and accelerated depreciation. We recognize restructuring charges when the
liability is probable, and the amount is estimable. Employee termination benefits are accrued at the date management has committed to a
plan of termination and affected employees have been notified of their termination date and expected severance benefits.
Income Taxes
We use the asset and liability method to account for income taxes. Deferred tax assets and liabilities are recognized for the future
tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their
respective tax bases and operating loss and tax credit carryforwards. Deferred tax assets and liabilities are measured using enacted tax rates
expected to apply to taxable income in the years in which those temporary differences are expected to be recovered or settled. The effect on
deferred tax assets and liabilities from a change in tax rates is recognized in income in the period the change is enacted. A valuation
allowance is established to reduce deferred tax assets to an amount whose realization is more likely than not.
Recent Accounting Pronouncements
Recently issued accounting guidance is either not applicable or did not have, or is not expected to have, a material impact on us.
118
Table of Contents
2. NET LOSS PER SHARE
Basic net loss per share is computed by dividing net loss by the weighted-average number of shares of common stock outstanding
during the period. Diluted net loss per share is computed by dividing net loss by the weighted-average number of shares of common stock
outstanding during the period and the number of additional shares of common stock that would have been outstanding if potentially dilutive
securities had been issued. Potentially dilutive securities include stock options, RSUs and shares issuable under our Purchase Plan. The
dilutive effect of these potentially dilutive securities is reflected in diluted earnings per share using the treasury stock method. Under the
treasury stock method, an increase in the fair market value of our common stock can result in a greater dilutive effect from potentially
dilutive securities.
The potential shares of common stock that were excluded from the computation of diluted net loss per share for the periods
presented because including them would have been antidilutive are as follows (in thousands):
Outstanding stock options
RSUs
Total
3. REVENUES
Revenues disaggregated by category were as follows (in thousands):
2022
34,696
1,104
35,800
Year Ended December 31,
2021
30,009
226
30,235
2020
27,260
—
27,260
Product sales:
Gross product sales
Discounts and allowances
Total product sales, net
Revenues from collaborations:
License revenues
Development milestones
Research and development services and others
Total revenues from collaborations
Government contract
Total revenues
2022
Year Ended December 31,
2021
2020
$
$
108,523
(31,805)
76,718
7,932
25,000
6,092
39,024
4,500
120,242
$
$
81,186
(18,176)
63,010
70,553
1,875
3,298
75,726
10,500
149,236
$
$
76,470
(14,774)
61,696
40,358
2,100
4,467
46,925
—
108,621
Revenue from product sales is primarily related to sales of our first commercial product, TAVALISSE. In December 2022,
following the FDA approval of our second commercial product, REZLIDHIA, we delivered product quantities to our customers and
recognized $0.9 million of net revenue included within net product sales for the year ended December 31, 2022. Our net product sales
include sale of products to our specialty distributors, net of chargebacks, discounts and fees, government and other rebates and returns. The
following tables summarize the activities in chargebacks, discounts and fees, government and other rebates and returns that were accounted
for within other accrued liabilities, for each of the periods presented (in thousands):
Balance as of January 1, 2022
Provision related to current period sales
Credit or payments made during the period
Balance as of December 31, 2022
Chargebacks,
Discounts and
Fees
Government
and Other
Rebates
$
$
3,404
23,488
(20,679)
6,213
$
$
2,494
5,901
(5,759)
2,636
$
$
Returns
Total
2,017
1,514
(235)
3,296
$
$
7,915
30,903
(26,673)
12,145
119
Table of Contents
Balance as of January 1, 2021
Provision related to current period sales
Credit or payments made during the period
Balance as of December 31, 2021
Chargebacks,
Discounts and
Fees
Government
and Other
Rebates
$
$
2,461 $
10,731
(9,788)
3,404
$
2,115
5,036
(4,657)
2,494
$
$
Returns
Total
1,489
1,021
(493)
2,017
$
$
6,065
16,788
(14,938)
7,915
Of the $31.8 million discounts and allowances from gross product sales for the year ended December 31, 2022, $30.9 million was
accounted for as additions to revenue reserves and refund liability and $0.9 million as reductions in accounts receivable (as it relates to
allowance for prompt pay discount) and prepaid and other current assets (as it relates to certain chargebacks and other fees that were
prepaid) in the balance sheet.
Of the $18.2 million discounts and allowances from gross product sales for the year ended December 31, 2021, $16.8 million was
accounted for as additions to revenue reserves and refund liability and $1.4 million as reductions in accounts receivable (as it relates to
allowance for prompt pay discount) and prepaid and other current assets (as it relates to certain chargebacks and other fees that were
prepaid) in the balance sheet.
For detailed discussions of our revenues from collaboration and government contract, see “Note 4 – Sponsored Research and
License Agreements and Government Contract” below.
The following table summarizes revenues from each of our customers who individually accounted for 10% or more (wherein *
denotes less than 10%) of the total net product sales and revenues from collaborations:
McKesson Specialty Care Distribution Corporation
Kissei
Cardinal Healthcare
ASD Healthcare and Oncology Supply
Lilly
Grifols
2022
Year Ended December 31,
2021
2020
31%
24%
19%
17%
*
*
20%
*
*
17%
48%
*
23%
—
*
30%
—
41%
4. SPONSORED RESEARCH AND LICENSE AGREEMENTS AND GOVERNMENT CONTRACT
Sponsored Research and License Agreements
We conduct research and development programs independently and in connection with our corporate collaborators. As of
December 31, 2022, we are a party to collaboration agreements with Lilly to develop and commercialize R552, a RIPK1 inhibitor, for the
treatment of non-CNS diseases and collaboration aimed at developing additional RIPK1 inhibitors for the treatment of CNS diseases; with
Grifols to commercialize fostamatinib for human diseases in all indications, including chronic ITP and AIHA, in Grifols territory which
includes Europe, the UK, Turkey, the Middle East, North Africa and Russia (including Commonwealth of Independent States); with Kissei
to develop and commercialize fostamatinib in Kissei territory which includes Japan, China, Taiwan and the Republic of Korea; with
Medison to commercialize fostamatinib in all indications, including chronic ITP and AIHA, in Medison territory which includes Canada
and Israel; and with Knight to commercialize fostamatinib in all indications, including chronic ITP and AIHA, in Knight territory which
includes Latin America, consisting of Mexico, Central and South America, and the Caribbean.
Further, we are also a party to collaboration agreements, but do not have ongoing performance obligations with BerGenBio for the
development and commercialization of AXL inhibitors in oncology, and with Daiichi to pursue research related to MDM2 inhibitors, a
novel class of drug targets called ligases.
120
Table of Contents
Under the above existing agreements that we entered into in the ordinary course of business, we received or may be entitled to
receive upfront cash payments, payments contingent upon specified events achieved by such partners and royalties on any net sales of
products sold by such partners under the agreements. As of December 31, 2022, total future contingent payments to us under all of above
existing agreements, excluding terminated agreements, could exceed $1.3 billion if all potential product candidates achieved all of the
payment triggering events under all of our current agreements. Of this amount, $279.5 million relates to the achievement of development
events, $263.1 million relates to the achievement of regulatory events and $796.0 million relates to the achievement of certain commercial
or launch events. This estimated future contingent amount does not include any estimated royalties that could be due to us if the partners
successfully commercialize any of the licensed products. Future events that may trigger payments to us under the agreements are based
solely on our partners’ future efforts and achievements of specified development, regulatory and/or commercial events.
Global Exclusive License Agreement with Lilly
On February 18, 2021, we entered into a global exclusive license and collaboration agreement with Lilly (Lilly Agreement), which
became effective on March 27, 2021, upon clearance under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, to develop and
commercialize R552 for the treatment of non-CNS diseases. In addition, the collaboration is aimed at developing additional RIPK1
inhibitors for the treatment of CNS diseases. Pursuant to the terms of the license agreement, we granted to Lilly exclusive rights to develop
and commercialize R552 and related RIPK1 inhibitors in all indications worldwide. The parties’ collaboration is governed through a joint
governance committee and appropriate subcommittees.
We are responsible for 20% of development costs for R552 in the US, Europe, and Japan, up to a specified cap. Lilly is responsible
for funding the remainder of all development activities for R552 and other non-CNS disease development candidates. We have the right to
opt- out of co-funding the R552 development activities in the US, Europe and Japan at two different specified times. If we exercise our first
opt-out right (no later than September 30, 2023), under the Lilly Agreement, we are required to fund our share of the R552 development
activities in the US, Europe, and Japan up to a maximum funding commitment of $65.0 million through April 1, 2024. If we decide not to
exercise our opt-out rights, we will be required to share in global development costs of up to certain amounts at a specified cap, as provided
for in the Lilly Agreement.
We are responsible for performing and funding initial discovery and identification of CNS disease development candidates.
Following candidate selection, Lilly will be responsible for performing and funding all future development and commercialization of the
CNS disease development candidates.
Under the terms of the license agreement, we were entitled to receive a non-refundable and non-creditable upfront cash payment
amounting to $125.0 million, which we received in April 2021. We are also entitled to additional milestone payments for non-CNS disease
products consisting of up to $330.0 million milestone payments upon the achievement of specified development and regulatory milestones,
and up to $100.0 million in sales milestone payments on a product-by-product basis. In addition, depending on the extent of our co-funding
of R552 development activities, we would be entitled to receive tiered royalty payments on net sales of non-CNS disease products at
percentages ranging from the mid-single digits to high-teens, subject to certain standard reductions and offsets. We are also eligible to
receive milestone payments for CNS disease products consisting of up to $255.0 million in milestone payments upon the achievement of
specified development, regulatory and commercial milestones, and up to $150.0 million in sales milestone payments on a product-by-
product basis. We would be entitled to receive tiered royalty payments on net sales of CNS disease products up to low-double digits, subject
to certain standard reductions and offsets.
We accounted for this agreement under ASC 606 and identified the following distinct performance obligations at inception of the
agreement: (a) granting of the license rights over the non-CNS penetrant intellectual property (IP), and (b) granting of the license rights
over the CNS penetrant IP which will be delivered to Lilly upon completion of the additional research and development efforts specified in
the agreement. We concluded each of these performance obligations is distinct. We based our assessment on the assumption that Lilly can
benefit from each of the licenses on its own by developing and commercializing the underlying product using its own resources.
121
Table of Contents
Under the Lilly Agreement, we are required to share 20% of the development costs for R552 in the US, Europe and Japan up to a
specified cap. Given our rights to opt- out from the development of R552, we believe at the minimum, we have a commitment to fund the
development costs up to $65.0 million as discussed above. We considered this commitment to fund the development costs as a significant
financing component of the contract, which we accounted for as a reduction of the upfront fee to derive the transaction price. This financing
component was recorded as a liability at its net present value of approximately $57.9 million using a 6.4% discount rate. Interest expense is
being accreted on such liability over the expected commitment period and adjusted for timing of expected cost share payments. Interest
expense accreted during the year ended December 31, 2022 and 2021 was $0.7 million and $2.8 million, respectively. Through December
31, 2022, Lilly billed us $15.1 million for our share of development costs under this agreement, the amount was fully paid as of December
31, 2022. As of December 31, 2022 and 2021, the outstanding financing liability to Lilly was $46.2 million and $60.7 million, respectively,
and included within other long-term liabilities, current portion, and other long-term liabilities in the balance sheet.
We allocated the net transaction price of $67.1 million to each performance obligation based on our best estimate of its relative
standalone selling price using the adjusted market assessment approach. We concluded that the license rights over the non-CNS penetrant
IP represents functional IP that is not expected to change over time, and we have no ongoing or undelivered obligations relative to such IP
that Lilly will benefit from the use of such IP on the delivery date. As such, the transaction price allocated to the non-CNS penetrant IP of
$60.4 million was recognized as revenue in the year ended December 31, 2021 upon delivery of the non-CNS penetrant IP to Lilly in
March 2021. For the delivery of license rights over the CNS penetrant IP, we are obligated to perform additional research and development
efforts before Lilly can accept the license. The allocated transaction price to the CNS penetrant IP of $6.7 million is being recognized as
revenue from the effective date of the Lilly Agreement through the eventual acceptance by Lilly using the input method. In June 2022, Lilly
provided notice of continuance pursuant to the terms of the Lilly Agreement, whereby Lilly elected its option to lead the identification and
selection of CNS penetrant lead candidate, and as such, we recognized the remaining outstanding deferred revenue related to delivery of the
CNS penetrant IP. For the year ended December 31, 2022 and 2021, we recognized revenue of $0.5 million and $6.2 million, respectively,
relative to the delivery of CNS penetrant IP. Further, we recognized $0.2 million of revenue related to the delivery of CNS compound to
Lilly during the year ended December 31, 2022.
The remaining future variable consideration related to future milestone payments as discussed above were fully constrained
because we cannot conclude that it is probable that a significant reversal of the amount of cumulative revenue recognized will not occur,
given the inherent uncertainty of success with these future milestones. For sales-based milestones and royalties, we determined that the
license is the predominant item to which the royalties or sales-based milestones relate. Accordingly, we will recognize revenue at the later
of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been
satisfied (or partially satisfied). We will re-evaluate the transaction price in each reporting period and as uncertain events are resolved or
other changes in circumstances occur.
Grifols License Agreement
In January 2019, we entered into a commercialization license agreement with Grifols with exclusive rights to commercialize
fostamatinib for human diseases, including chronic ITP and AIHA, and non-exclusive rights to develop, fostamatinib in Grifols territory.
Under the agreement, we received an upfront payment of $30.0 million, with the potential for $297.5 million in total regulatory and
commercial milestones. We are also entitled to receive stepped double-digit royalty payments based on tiered net sales which may reach
30% of net sales. The agreement also required us to continue to conduct our long-term open-label extension study on patients with ITP
through EMA approval of ITP in Europe or until the study ends as well as conduct the Phase 3 trial of fostamatinib in AIHA.
In January 2020, the EC granted a centralized Marketing Authorization for fostamatinib valid throughout the EU and in the UK
after the departure of the UK from the EU for the treatment of chronic ITP in adult patients who are refractory to other treatments. With this
approval, in February 2020, we received $20.0 million non-refundable payment, consisted of a $17.5 million payment due upon MAA
approval by the EMA of fostamatinib for the first indication and a $2.5 million creditable advance royalty payment, based on the terms of
our collaboration agreement with Grifols. The above milestone payment was allocated to the distinct performance obligations in the
collaboration agreement with
122
Table of Contents
Grifols.
We accounted for this agreement under ASC 606 and identified the following distinct performance obligations at inception of the
agreement: (a) granting of the license, (b) performance of research and regulatory services related to our ongoing long-term open-label
extension study on patients with ITP, and (c) performance of research services related to our Phase 3 trial in AIHA. In October 2020, we
entered into a commercial supply agreement for the licensed territories. We concluded each of these performance obligations is distinct. We
based our assessment on the following: (i) our assessment that Grifols can benefit from the license on its own by developing and
commercializing the underlying product using its own resources, and (ii) the fact that the manufacturing services are not highly specialized
in nature and can be performed by other vendors. Upon execution of our agreement with Grifols, we determined that the upfront fee of
$5.0 million, which is the non-refundable portion of the $30.0 million upfront fee, represented the transaction price. In the first quarter of
2020, we revised the transaction price to include the $25.0 million of the upfront payment that is no longer refundable under our agreement
and the $20.0 million payment received that is no longer constrained. We allocated the updated transaction price to the distinct performance
obligations in our collaboration agreement based on our best estimate of the relative standalone selling price as follows: (a) for the license,
we estimated the standalone selling price using the adjusted market assessment approach to estimate its standalone selling price in the
licensed territories; and (b) for the research and regulatory services, we estimated the standalone selling price using the cost plus expected
margin approach. As a result of the adjusted transaction price, adjustments are recorded on a cumulative catch-up basis, and recorded as
part of contract revenues from collaborations in 2020.
For the years ended December 31, 2022, 2021 and 2020, we recognized revenue associated with the research and development
services of $0.7 million, $0.9 million and $3.8 million, respectively. For the year ended December 31, 2020, we also recognized revenue of
$39.9 million related to licensed rights and $0.5 million related to the exercise of options to include additional territories.
For the year ended December 31, 2022, we recognized $0.7 million of royalty revenue from Grifols, and such amount was
included within contract revenues from collaboration. No such revenue was recognized for the years ended December 31, 2021 and 2020.
The remaining future variable consideration of $277.5 million related to future regulatory and commercial milestones were fully
constrained due to the fact that it was probable that a significant reversal of cumulative revenue would occur, given the inherent uncertainty
of success with these future milestones. We are recognizing revenues related the research and regulatory services throughout the term of the
respective clinical programs using the input method. For sales-based milestones and royalties, we determined that the license is the
predominant item to which the royalties or sales-based milestones relate. Accordingly, we will recognize revenue at the later of (i) when the
related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or
partially satisfied). We will re-evaluate the transaction price in each reporting period and as uncertain events are resolved or other changes
in circumstances occur.
We entered into a Commercial Supply Agreement with Grifols in October 2020 to supply and sell our drug product priced at a
certain markup specified in the agreement, in quantities Grifols shall order from us pursuant to and in accordance with the agreement. Prior
to the Commercial Supply Agreement, we had a Drug Product Purchase Agreement with Grifols entered in December 2019. For the years
ended December 31, 2022, 2021, and 2020, we recognized revenue of $1.6 million, $2.0 million and $0.7 million, respectively, related to
delivery of drug supply to Grifols for its commercialization.
123
Table of Contents
Kissei License Agreement
In October 2018, we entered into an exclusive license and supply agreement with Kissei to develop and commercialize
fostamatinib in all current and potential indications in Kissei territory. Kissei is responsible for performing and funding all development
activities for fostamatinib in the above-mentioned territories. We received an upfront cash payment of $33.0 million, with the potential for
up to an additional $147.0 million in development, regulatory and commercial milestone payments, and will receive mid- to upper twenty
percent, tiered, escalated net sales-based payments for the supply of fostamatinib. Under the agreement, we granted Kissei the license rights
to fostamatinib in Kissei territory and are obligated to supply Kissei with drug product for use in clinical trials and pre-commercialization
activities. We are also responsible for the manufacture and supply of fostamatinib for all future development and commercialization
activities under the agreement.
We accounted for this agreement under ASC 606 and identified the following distinct performance obligations at inception of the
agreement: (a) granting of the license, (b) supply of fostamatinib for clinical use and (c) material right associated with discounted
fostamatinib that are supplied for use other than clinical or commercial. In addition, we will provide commercial product supply if the
product is approved in the licensed territory. We concluded that each of these performance obligations is distinct. We based our assessment
on the following: (i) our assessment that Kissei can benefit from the license on its own by developing and commercializing the underlying
product using its own resources and (ii) the fact that the manufacturing services are not highly specialized in nature and can be performed
by other vendors. Moreover, we determined that the upfront fee of $33.0 million represented the transaction price and was allocated to the
performance obligations based on our best estimate of the relative standalone selling price as follows: (a) for the license, we estimated the
standalone selling price using the adjusted market assessment approach to estimate its standalone selling price in the licensed territories; (b)
for the supply of fostamatinib and the material right associated with discounted fostamatinib, we estimated the standalone selling price
using the cost plus expected margin approach. Variable consideration of $147.0 million related to future development and regulatory
milestones was fully constrained because we cannot conclude that it is probable that a significant reversal in the amount of cumulative
revenue recognized will not occur, given the inherent uncertainty of success with these future milestones. We recognize revenues related to
the supply of fostamatinib and material right upon delivery of fostamatinib to Kissei. For sales-based milestones and royalties, we
determined that the license is the predominant item to which the royalties or sales-based milestones relate to. Accordingly, we recognize
revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been
allocated has been satisfied (or partially satisfied). We re-evaluate the transaction price in each reporting period and as uncertain events are
resolved or other changes in circumstances occur.
In April 2022, Kissei announced that an NDA was submitted to Japan’s PMDA for fostamatinib in chronic ITP. With this milestone
event, we received $5.0 million non-refundable and non-creditable payment from Kissei pursuant to the terms of our collaboration
agreement, and such amount was recognized as revenue for the year ended December 31, 2022. In December 2022, Kissei announced that
Japan’s PMDA approved the NDA for fostamatinib in chronic ITP. With this milestone event, we were entitled to receive $20.0 million
non-refundable and non-creditable payment from Kissei pursuant to the terms of our collaboration agreement, which we recognized as
revenue for the year ended December 31, 2022. The amount was subsequently collected in January 2023.
As of December 31, 2022 and 2021, the remaining deferred revenue was $1.4 million related to the material right associated with
discounted fostamatinib supply. For the years ended December 31, 2022, 2021 and 2020, there were no material revenues recognized
associated with such outstanding deferred revenue.
For the years ended December 31, 2022, 2021, and 2020, we recognized revenue of $2.6 million, $0.3 million and no revenue,
respectively, related to delivery of drug products to Kissei.
Medison Commercial and License Agreements
In October 2019, we entered into two exclusive commercial and license agreements with Medison for the commercialization of
fostamatinib for chronic ITP in Medison territory, pursuant to which we received a $5.0 million upfront payment with respect to the
agreement in Canada. We accounted for the agreement made with an upfront
124
Table of Contents
payment under ASC 606 and identified the following combined performance obligations at inception of the agreement: (a) granting of the
license and (b) obtaining regulatory approval in Canada of fostamatinib in ITP. We determined that the non-refundable upfront fee of
$5.0 million represented the transaction price. However, under the agreement, we have the option to buy back all rights to the product in
Canada within six months from obtaining regulatory approval for the treatment of AIHA in Canada. The buyback option precludes us from
transferring control of the license to Medison under ASC 606. We believe that the buyback provision, if exercised, will require us to
repurchase the license at an amount equal to or more than the upfront $5.0 million. As such this arrangement is accounted for as a financing
arrangement. Interest expense was accreted on such liability over the expected buyback period. No interest was accreted during the year
ended December 31, 2022 and 2020. During the year ended December 31, 2021, we accreted $0.4 million of interest related to this
financing arrangement. We also billed Medison for the delivery of fostamatinib supplies for clinical use which we deferred and included
within the outstanding financing liability considering the buy-back provision.
The decision to exercise the buyback option is dependent of many factors including management’s cost and benefit assessments
and the success of obtaining regulatory approval for the treatment of AIHA in Canada. In June 2022, we reported the top-line results from
our Phase 3 trial of fostamatinib in wAIHA which showed that the trial did not demonstrate statistical significance in the primary efficacy
endpoint in the overall study population. We also announced in early October 2022 that we do not expect to file an sNDA for wAIHA
indication considering the top-line data results and the guidance received from the FDA. With these recent developments, we assessed our
options path forward, including our buyback option right with regards to the Medison license agreement. Based on management’s
assessment, it is highly remote that we will exercise our buyback option right. As such, we relieved the outstanding financing liability to
Medison amounting to $5.7 million in the fourth quarter of 2022 and recognized such amount as collaboration revenue in accordance with
ASC 606 in the year ended December 31, 2022. As of December 31, 2022, no outstanding financing liability to Medison. The outstanding
financing liability to Medison as of December 31, 2021 amounting to $5.6 million was included within other long-term liabilities in the
balance sheet.
In August 2021, Medison Israel received the licenses for registrational approval from the Ministry of Health. Pursuant to the
exclusive commercial and license agreement, this event triggered the first milestone that is the regulatory approval of the product in Israel
for the first indication, for a non-refundable payment of $0.1 million. We recognized this amount as revenue during the year ended
December 31, 2021.
Knight Commercial License and Supply Agreement
In May 2022, we entered into commercial license and supply agreements with Knight for the commercialization of fostamatinib
for approved indications in Knight territory. Pursuant to such commercial license agreement, we received a $2.0 million one-time, non-
refundable, and non-creditable upfront payment, with potential for up to an additional $20.0 million in regulatory and sales-based
commercial milestone payments, and will receive twenty- to mid-thirty percent, tiered, escalated net-sales based royalty payments for
products sold in the Knight territory. We accounted for this agreement under ASC 606 and identified that the upfront payment was a
consideration for granting Knight the license to commercialize fostamatinib for approved indication in the Knight territory, and no further
material deliverables associated to such upfront payment. As such, we recognized the upfront payment as revenue during the second quarter
of 2022. Variable consideration related to future regulatory milestones was fully constrained because we cannot conclude that it is probable
that a significant reversal in the amount of cumulative revenue recognized will not occur, given the inherent uncertainty of success with
these future milestones. For sales-based milestones and royalties, we determined that the license is the predominant item to which the
royalties or sales-based milestones relate to. Accordingly, we will recognize revenue at the later of (i) when the related sales occur, or (ii)
when the performance obligation to which some or all the royalty has been allocated has been satisfied (or partially satisfied). We will re-
evaluate the transaction price in each reporting period and as uncertain events are resolved or other changes in circumstances occur. We are
also responsible for the exclusive manufacture and supply of fostamatinib for all future development and commercialization activities under
agreement.
125
Table of Contents
Daiichi Collaboration Agreement
Pursuant to the Amended Collaboration Agreement dated April 20, 2005 with Daiichi, during the years ended December 31, 2021
and 2020, we recognized $1.8 million and $2.1 million, respectively, of revenue related to the achievement of certain milestones. All
deliverables under the agreement had been previously delivered, and as such the above had been recognized as revenue in the
corresponding periods such milestones were achieved.
Other license agreements
In February 2021, we entered into a non-exclusive license agreement with an unrelated third party whereby we granted such
unrelated third-party rights to a certain patent. In consideration for the license rights granted, we received a one-time fee of $4.0 million. All
the deliverables under the agreement had been delivered and the one-time fee was recognized as revenue during the year ended December
31, 2021.
Government Contract - US Department of Defense’s JPEO-CBRND
In January 2021, we were awarded up to $16.5 million by the US Department of Defense to support our ongoing Phase 3 clinical
trial to evaluate the safety and efficacy of fostamatinib for the treatment of hospitalized high-risk patients with COVID-19. The amount of
award we will receive from the US Department of Defense is subject to submission of proper documentation as evidence of completion of
certain clinical trial events or milestones as specified in the agreement, and approval by the US Department of Defense that such events or
milestones have been met. We determined that this government award should be accounted for under IAS 2, Accounting for Government
Grants and Disclosure of Government Assistance, which is outside of the scope of Topic 606, as the US Department of Defense is not
receiving reciprocal value for their contributions. We record government contract revenue in the statement of operations in the period when
it is probable that we will receive the award, which is when we comply with the conditions associated with the award and obtain approval
from the US Department of Defense that such conditions have been met. For the years ended December 31, 2022 and 2021, we recognized
$4.5 million and $10.5 million, respectively, related to this grant. Through December 31, 2022, we recognized $15.0 million revenue, and
we expect to receive the remaining award of $1.5 million, subject to us meeting certain clinical trial events or milestones and approval by
the US Department of Defense as specified in the agreement.
License and Transition Services Agreement with Forma
On July 27, 2022, we entered into a license and transition services agreement with Forma for an exclusive license to develop,
manufacture and commercialize olutasidenib, Forma’s proprietary inhibitor of mIDH1, for any uses worldwide, including for the treatment
of AML and other malignancies. Pursuant to the terms of the license and transition services agreement, we paid Forma an upfront fee of
$2.0 million, with the potential to pay up to $67.5 million of additional payments upon achievement of specified development and
regulatory milestones and up to $165.5 million of additional payments upon achievement of certain commercial milestones. The potential
development and regulatory milestone payments of $67.5 million include a $2.5 million payment upon achievement of a certain near-term
regulatory milestone, a $5.0 million payment upon the first regulatory approval of the licensed product, and $10.0 million payment upon
the licensed product’s first commercial sale subject to certain other conditions. In addition, subject to the terms and conditions of the license
and transition services agreement, Forma would be entitled to tiered royalty payments on net sales of licensed products at percentages
ranging from low-teens to mid-thirties, as well as certain portion of our sublicensing revenue, subject to certain standard reductions and
offsets.
The transaction was accounted for as an acquisition of asset under ASC 730, Research and Development. In accordance with the
guidance, in a transaction accounted for as an asset acquisition, any acquired IPR&D that does not have alternative future use is charged to
expense at the acquisition date. At the acquisition date, the acquired license asset was accounted for as IPR&D, and we do not anticipate
any economic benefit to be derived from such acquired licensed asset other than the primary indications. As such, we accounted for the
upfront fee of $2.0 million paid to Forma as IPR&D and recorded such cost within research and development expenses in the statements of
operations for the year ended December 31, 2022.
126
Table of Contents
Under the accounting guidance, contingent cash payments will be accrued when it is probable that a liability has been incurred and
the amount can be reasonably estimated. We will account for milestone payment obligations incurred at development stage and prior to a
regulatory approval of an indication associated with the acquired licensed asset as research and development expenses when the event
requiring payment of the milestone occurs. Milestone payment obligations incurred upon and after a regulatory approval of an indication
associated with the acquired licensed asset, and at the commercial stage, will be recorded as intangible asset when the event requiring
payment of the milestones occurs. The amount recorded as intangible asset will be amortized over the estimated useful life of the acquired
licensed asset. Royalty payments related to the acquired licensed asset will be recorded as cost of sales when incurred. During the fourth
quarter of 2022 prior to the approval of FDA on December 1, 2022, a near-term regulatory milestone was met which entitled Forma to
receive a $2.5 million milestone payment. Since such milestone payment obligation was incurred prior to a regulatory approval of an
indication associated with the acquired licensed asset, we recorded such amount as research and development expense in the year ended
December 31, 2022. On December 1, 2022, the FDA approved REZLIDHIA (olutasidenib) capsules for the treatment of adult patients with
R/R AML with susceptible IDH1 mutations as detected by an FDA-approved test. Following the FDA approval, we launched REZLIDHIA
and made first shipments of the product to our customers. With this FDA approval and first commercial sale of the product, Forma was
entitled to receive a total of $15.0 million milestone payments. Since such milestone payment obligations were incurred upon and after
regulatory approval of the product, we recorded such amount as intangible asset on the balance sheet. As of December 31, 2022,
outstanding milestone payable to Forma of $15.0 million was recorded within accounts payable in our balance sheet.
5. STOCK-BASED COMPENSATION
Total stock-based compensation expense related to all of our stock-based awards was as follows (in thousands):
Selling, general and administrative
Research and development
Restructuring charges
Total stock-based compensation expense
$
$
Year Ended December 31,
2021
$
$
7,337
1,700
449
9,486
$
$
2022
10,217
2,168
—
12,385
2020
5,223
2,072
—
7,295
Stock-based compensation expense for the years ended December 31, 2022 and 2021 include incremental charges of $1.4 million
and $0.4 million, respectively, related to stock option modifications. In November 2021, we announced a reduction of workforce, primarily
in the research organization and entered in severance agreements with certain affected employees, which provided, among others, extension
of the date through which certain affected employees can exercise their vested options. In March 2022, our Board of Directors approved to
extend the exercise period of stock option grants made to our two former Board of Directors whose terms expired in May 2022. In October
2022, our Board of Directors approved to accelerate the vesting and extend the exercise period of certain stock option grants made to a
former officer who retired in October 2022. The incremental compensation expenses were computed based on the fair values of the
modified awards on the modification date. As a result of these stock option modifications, we recorded the incremental stock-based
compensation expense for each of the respective periods. The incremental stock-based compensation expense related to the modification of
stock options of our two former Board of Directors and former officer were recorded within sales, general and administrative expense, and
the modification of stock options of certain affected employees due to workforce reduction were recorded within restructuring charges.
Equity Incentive Plans
On May 16, 2018, our stockholders approved the adoption of our 2018 Equity Incentive Plan (2018 Plan). The 2018 Plan is the
successor plan to the 2011 Equity Incentive Plan, the 2000 Equity Incentive Plan, and the 2000 Non-Employee Directors’ Stock Option
Plan. We have two active equity plans, our 2018 Plan and the Rigel’s Inducement Plan, as amended (Inducement Plan, and together with
2018 Plan, the Equity Incentive Plans). The 2018 Plan provides for granting of stock awards to our officers, directors, all other employees
and consultants. The Inducement Plan, which is a non-stockholder approved stock plan, is intended mainly to provide an inducement
material by granting awards for certain individuals to enter into employment with us. Awards granted under our Equity Incentive Plans
expire no later than 10 years from the date of grant. Awards may be granted with different vesting terms from time to time. To date, we
127
Table of Contents
granted stock options and RSUs under our Equity Incentive Plans.
In March 2022 and August 2022, we filed Registration Statements to register additional 1,709,000 shares and 626,000 shares,
respectively, of common stock reserved for issuance under our Inducement Plan. In May 2022, our stockholders approved to amend our
2018 Plan, among other items, added an additional 5,000,000 shares to the number of shares of common stock authorized for issuance
under our 2018 Plan, and such shares were registered in the Registration Statement filed in August 2022. Further, in December 2022, our
Board of Directors approved to increase the number of common stock reserved for issuance under our Inducement Plan by 375,000 shares.
Stock Options and RSUs
The following table summarizes stock options and RSUs activity, and shares available for grant under our Equity Incentive Plans
for the periods presented:
Outstanding as of December 31, 2021
Authorized for grant
Granted
Exercised/Released
Cancelled and forfeited
Outstanding as of December 31, 2022
Vested and Expected to Vest as of December 31,
2022
Exercisable as of December 31, 2022
Shares Available
For Grant
Number of
Shares
Stock Options
Weighted
Average
Exercise Price
Weighted
Intrinsic Value
(in thousands)
10,715,312
7,080,000
(9,880,277)
—
2,697,583
10,612,618
30,008,665 $
3.13 $
6,812
8,179,113 $
(433,318) $
(3,058,187) $
34,696,273 $
32,473,773 $
22,669,120 $
1.96
2.23
4.54
2.74 $
2.73 $
2.91 $
1,605
1,493
2
RSUs
Weighted Average
Number of
Shares
226,250 $
1,181,362 $
(216,250) $
(87,709) $
1,103,653 $
Grant Date
Fair Value
3.67
2.36
3.59
2.42
2.39
Of the total stock options outstanding as of December 31, 2022, 2,222,500 shares outstanding are performance-based stock options
wherein the achievements of the corresponding corporate-based milestones were not probable. Accordingly, the related grant date fair value
for these performance-based stock options of $4.3 million has not been recognized as stock-based compensation expense as of December
31, 2022.
For the years ended December 31, 2022, 2021 and 2020, stock options vested were 5,280,235 shares, 4,765,814 shares
and 4,386,910 shares, respectively, with weighted-average exercise price of $2.60 per share, $2.67 per share, and $2.41 per share,
respectively.
The aggregate intrinsic values of stock options outstanding, vested and expected to vest, and exercisable represents the difference
between the exercise price of the underlying awards and the quoted price of our common stock for the options that were in-the-money as of
December 31, 2022. For the years ended December 31, 2022, 2021 and 2020, the aggregate intrinsic values of stock option exercises were
approximately $0.2 million, $2.1 million and $0.5 million, respectively, representing the difference between the fair value of our common
stock at the date of exercise and the exercise price paid.
For the years ended December 31, 2022, 2021 and 2020, we granted options to purchase 8,179,113 shares, 6,997,981
shares and 8,462,090 shares, respectively, of common stock, with weighted-average grant date fair value of $1.29 per share, $2.34 per share
and $1.42 per share, respectively.
The following table summarizes the weighted-average assumptions relating to stock options granted during the periods presented:
Risk-free interest rate
Expected term (in years)
Dividend yield
Expected volatility
2022
Year Ended December 31,
2021
2020
2.6 %
6.3
0.0 %
74.8 %
1.0 %
6.4
0.0 %
70.5 %
1.2 %
6.5
0.0 %
66.1 %
128
Table of Contents
As of December 31, 2022, there was approximately $14.1 million of unrecognized stock-based compensation cost which is
expected to be recognized over the remaining weighted-average period of 2.55 years, related to time-based stock options, performance-
based stock options wherein achievement of the corresponding corporate-based milestones was considered as probable, and RSUs.
Details of our stock options by exercise price are as follows as of December 31, 2022:
Exercise Price
$0.90 - $2.00
$2.01 - $2.34
$2.37 - $2.40
$2.42 - $2.42
$2.44 - $3.52
$3.54 - $3.68
$3.71 - $6.51
$0.90 - $6.51
Employee Stock Purchase Plan
Number of
Shares
7,143,200
5,979,493
495,000
6,189,723
4,982,149
5,864,451
4,042,257
34,696,273
Options Outstanding
Weighted-Average
Remaining Contractual
Life (in years)
Weighted-Average
Exercise Price
7.54
4.78
4.90
8.14
5.56
6.28
4.09
6.24
$
$
$
$
$
$
$
$
1.55
2.20
2.39
2.42
2.94
3.60
4.69
2.74
Options Exercisable
Number of
Shares
4,222,496
5,143,388
457,500
2,502,752
3,339,194
3,108,284
3,895,506
22,669,120
$
$
$
$
$
$
$
$
Weighted-Average
Exercise Price
1.95
2.18
2.39
2.42
2.92
3.62
4.70
2.91
Our Purchase Plan permits eligible employees to purchase common stock at a discount through payroll deductions during defined
offering periods. Our Purchase Plan provides for a 24-month offering period comprised four six-month purchase periods with a look-back
option. A look-back option is a provision in our Purchase Plan under which eligible employees can purchase shares of our common stock at
a price per share equal to the lesser of 85% of the fair market value on the first day of the offering period or 85% of the fair market value on
the purchase date. Our Purchase Plan also includes a feature that provides for a new offering period to begin when the fair market value of
our common stock on any purchase date during an offering period falls below the fair market value of our common stock on the first day of
such offering period. This feature is called a “reset.” Participants are automatically enrolled in the new offering period.
Our previous 24-month offering period under our Purchase Plan ended on June 30, 2022, and a new 24-month offering period
started on July 1, 2022. The fair value of awards under our Purchase Plan is estimated on the date of our new offering period using the
Black-Scholes option pricing model, which is being amortized over the requisite service periods.
The table below summarizes the weighted-average assumptions related to our Purchase Plan for periods presented. Expected
volatilities for our Purchase Plan are based on the two-year historical volatility of our stock. Expected term represents the weighted-
average of the purchase periods within the offering period. The risk-free interest rate for periods within the expected term is based on US
Treasury constant maturity rates.
Risk-free interest rate
Expected term (in years)
Dividend yield
Expected volatility
Year Ended December 31,
2022
3.1 %
1.3
0.0 %
121.0 %
2021
*
*
*
*
2020
1.0 %
1.6
0.0 %
62.3 %
*
Not a measurement period since the last two-year offering period started on January 1, 2020, and there was no reset in 2021.
The weighted average fair value of awards under our Purchase Plan at the measurement period during the year ended December
31, 2022 and 2020 was $0.78 per share and $0.87 per share, respectively. As of December 31, 2022, unrecognized stock-based
compensation cost related to our Purchase Plan amounted to $0.9 million, which is expected to be recognized over the remaining weighted
average period of 0.99 years.
129
Table of Contents
For the years ended December 31, 2022, 2021 and 2020, there were 1,146,851 shares, 932,018 shares and 567,391 shares,
respectively, of common stock purchased under the Purchase Plan, at an average price of $1.01 per share, $1.51 per share and $1.54 per
share, respectively. As of December 31, 2022, there were 3,437,633 shares reserved for future issuance under the Purchase Plan.
6. INVENTORIES
The following table summarizes inventories, net (in thousands):
Raw materials
Work in process
Finished goods
Total
As of December 31,
2022
2021
$
$
4,555
2,659
1,904
9,118
$
$
5,142
162
1,312
6,616
As of December 31, 2022, finished goods inventories include inventory quantities acquired from Forma, pursuant to the terms of
the license and transition agreement. As of December 31, 2022, we have $0.8 million in advance payments to the manufacturer of our raw
materials, which was included within prepaid and other current assets in the balance sheet.
7. CASH, CASH EQUIVALENTS AND SHORT-TERM INVESTMENTS
Cash, cash equivalents and short-term investments consisted of the following (in thousands):
Cash
Money market funds
US treasury bills
Government-sponsored enterprise securities
Corporate bonds and commercial paper
Reported as:
Cash and cash equivalents
Short-term investments
As of December 31,
2022
6,264
4,155
5,225
15,796
26,766
58,206
24,459
33,747
58,206
$
$
$
$
2021
6,249
6,842
35,366
14,678
61,832
124,967
18,890
106,077
124,967
$
$
$
$
Cash equivalents and short-term investments include the following securities with gross unrealized gains and losses (in
thousands):
Gross
Gross
As of December 31, 2022
US treasury bills
Government-sponsored enterprise securities
Corporate bonds and commercial paper
Total
$
Amortized
Cost
5,251
15,882
26,807
$ 47,940
130
Unrealized
Gains
Unrealized
Losses
$
$
— $
1
—
$
1
(26) $
(87)
(41)
Fair Value
5,225
15,796
26,766
(154) $ 47,787
Table of Contents
As of December 31, 2021
US treasury bills
Government-sponsored enterprise securities
Corporate bonds and commercial paper
Total
$
Amortized
Cost
35,416
14,705
61,857
$ 111,978
Gross
Gross
Unrealized
Gains
Unrealized
Losses
$
$
— $
—
2
2
$
(50) $
(27)
(27)
Fair Value
35,366
14,678
61,832
(104) $ 111,876
As of December 31, 2022 and 2021, our cash equivalents and short-term investments had a weighted-average time to maturity of
approximately 89 days and 96 days, respectively. Our short-term investments are classified as available-for-sale securities. Accordingly, we
have classified certain securities as short-term investments on our balance sheets as they are available for use in the current operations. As
of December 31, 2022, we had no investments that had been in a continuous unrealized loss position for more than 12 months. As of
December 31, 2022, a total of 36 individual securities had been in an unrealized loss position for 12 months or less, and the losses were
determined to be temporary. The gross unrealized losses above were caused by interest rate increases. No significant facts or circumstances
have arisen to indicate that there has been any significant deterioration in the creditworthiness of the issuers of the securities held by us.
Based on our review of these securities, including the assessment of the duration and severity of the unrealized losses, we have not
recognized any credit losses on these securities as of December 31, 2022 and 2021.
The following table shows the fair value and gross unrealized losses of our investments in individual securities that are in an
unrealized loss position, aggregated by investment category (in thousands):
As of December 31, 2022
US treasury bills
Government-sponsored enterprise securities
Corporate bonds and commercial paper
Total
8. FAIR VALUE
$
Fair Value Unrealized Losses
(26)
$
(87)
(41)
(154)
5,225
14,322
26,766
$ 46,313
$
The table below summarizes the fair value of our cash equivalents and short-term investments measured at fair value on a
recurring basis, and are categorized based upon the lowest level of significant input to the valuations (in thousands):
Assets at Fair Value as of December 31, 2022
Level 1
Level 2
Level 3
Total
Money market funds
US treasury bills
Government-sponsored enterprise securities
Corporate bonds and commercial paper
Total
Money market funds
US treasury bills
Government-sponsored enterprise securities
Corporate bonds and commercial paper
Total
$
$
$
$
131
$
4,155
—
—
—
$
4,155
— $
5,225
15,796
26,766
47,787
$
— $
—
—
—
— $
4,155
5,225
15,796
26,766
51,942
Assets at Fair Value as of December 31, 2021
Level 1
Level 2
Level 3
$
6,842
—
—
—
$
6,842
— $
35,366
14,678
61,832
111,876
$
— $
—
—
—
— $
Total
6,842
35,366
14,678
61,832
118,718
Table of Contents
9. OTHER BALANCE SHEET COMPONENTS
Property and equipment
Property and equipment consist of the following (in thousands):
Laboratory equipment
Computer and software
Furniture and equipment
Fixed assets in progress
Total property and equipment
Less accumulated depreciation and amortization
Property and equipment, net
As of December 31,
2022
7,435
2,048
2,107
74
11,664
(10,807)
857
2021
12,154
1,783
2,107
691
16,735
(14,551)
2,184
$
$
$
$
Total depreciation and amortization expense was $0.9 million, $1.2 million and $0.7 million for the years ended December 31,
2022, 2021 and 2020, respectively. During the year ended December 31, 2022, we wrote down certain property and equipment amounting
to $0.7 million associated with our leased facility which expired in January 2023, and recognized such amount within selling, general and
administrative expense.
Intangible asset
Intangible asset pertain to amortized cost of capitalized milestone payment obligations to Forma, incurred upon and after
regulatory approval of an acquired product. See “Note 4 - Sponsored Research and License Agreements and Government Contract” for
related discussions. Such costs are being amortized on a straight-line basis over the estimated useful life of approximately 14 years. For the
year ended December 31, 2022, we recorded amortization expense of approximately $0.1 million, which was included within cost of sales
in the statements of operations.
The following table presents the estimated future amortization expense of intangible asset (in thousands):
For the year ending December 31,
2023
2024
2025
2026
2027
Thereafter
Other accrued liabilities
Other accrued liabilities consist of the following (in thousands):
Accrued commercial expenses
Accrued other expenses
Total other accrued liabilities
132
$
1,071
1,071
1,071
1,071
1,071
9,594
$ 14,949
As of December 31,
2022
2021
3,144
3,341
6,485
$
$
1,949
2,827
4,776
$
$
Table of Contents
10. DEBT
We have a Credit Agreement with MidCap entered on September 27, 2019 (Closing Date) and amended on March 29, 2021 (First
Amendment), February 11, 2022 (Second Amendment) and July 27, 2022 (Third Amendment). The Credit Agreement provides for a
$60.0 million term loan credit facility. At the Closing Date, $10.0 million was funded (Tranche 1), in May 2020, an additional $10.0 million
term funded (Tranche 2), at the Second Amendment, an additional $10.0 million was funded (Tranche 3), and at the Third Amendment, an
additional $10.0 million was funded (Tranche 4). As of December 31, 2022, the outstanding principal balance of the loan was $40.0
million, and the facility gives us the ability to access an additional $20.0 million aggregate principal amount of term loan at our option
through March 31, 2023 (Tranche 5).
The First Amendment to the Credit Agreement entered in March 2021 extended the period through which Tranche 3 was available
to us. The Second Amendment to the Credit Agreement entered in February 2022, among other things, amended the applicable funding
conditions, applicable commitments and certain other terms relating to available credit facilities (Tranches 3 and 4), added additional term
loan credit facility (Tranche 5), and revised certain terms related to the financial covenants.
Prior to the Third Amendment, the outstanding principal balance of the loan bore interest at an annual rate of one-month LIBOR,
or a comparable applicable index rate determined pursuant to the Credit Agreement if the LIBOR is no longer available, plus applicable
margin of 5.65%, subject to a LIBOR floor of 1.50% and is payable monthly in arrears. Further, the Credit Agreement provided for an
interest-only payment period of 24 months from October 1, 2019, followed by 36 months of amortization payments. The interest-only
period can be extended to 36 months (first interest-only extension) and again to 48 months (second interest-only extension) upon the
satisfaction of certain conditions set forth in the Credit Agreement. In June 2021 and June 2022, we satisfied the first and second interest-
only extension conditions, respectively, which effectively extended the interest-only period through October 1, 2023. All unpaid principal
and accrued interest are due and payable no later than September 1, 2024. A final payment fee of 2.5% of principal is due on the final
payment of the term loan.
Following the Third Amendment, the maturity date for the term loans was extended to September 1, 2026, and the interest-only
period was extended to October 1, 2024. Further, the interest rate benchmark was changed from LIBOR to SOFR. The interest rate
applicable to the term loans under the amended Credit Agreement is the sum of one-month SOFR, plus an adjustment of 0.11448%, subject
to 1.50% applicable floor, plus applicable margin of 5.65%. A final payment fee of 2.5% of principal is due at maturity date of the term
loans.
Under the amended Credit Agreement, the prepayment fee applicable to the term loans was reset at the Third Amendment date. We
may make voluntary prepayments, in whole or in part, subject to certain prepayment premiums and additional interest payments. The Credit
Agreement also contains certain provisions, such as event of default and change in control provisions, which, if triggered, would require us
to make mandatory prepayments on the term loan, which are subject to certain prepayment premiums and additional interest payments. The
obligations under the amended Credit Agreement are secured by a perfected security interest in all of our assets including our intellectual
property.
The amendment to the Credit Agreement was accounted for as debt modification. As such, fees paid to Midcap of $0.4 million
were recorded as additional debt discount and added to the unamortized debt discount that are being amortized as interest expense through
maturity using the effective interest rate method. Debt issuance costs are recorded as a direct deduction from the outstanding principal
balance of the term loan. As December 31, 2022 and 2021, the unamortized issuance costs and debt discounts amounted to $0.6 million and
$0.1 million, respectively. As of December 31, 2022 and 2021, the outstanding balance of the loan, net of unamortized debt discount was
classified as long-term liability in the accompanying balance sheet.
Interest expense, including amortization of the debt discount and accretion of the final fees related to the Credit Agreement for the
years ended December 31, 2022, 2021 and 2020 were $3.0 million, $1.7 million and $1.4 million, respectively. Accrued interest of $0.8
million was included within other accrued liabilities in the balance sheet as of December 31, 2022.
133
Table of Contents
The following table presents the future minimum principal payments of the outstanding loan as of December 31, 2022 (in
thousands):
For the year ending December 31,
2023
2024
2025
2026
Principal amount (Tranches 1, 2, 3 and 4)
$
$
—
5,000
20,000
15,000
40,000
The amended Credit Agreement contains certain covenants which, among others, require us to deliver financial reports at
designated times of the year and maintain minimum unrestricted cash and trailing net revenues. As of December 31, 2022, we were not in
violation of any covenants.
11. LEASES
We had a lease agreement with a landlord, Healthpeak Properties, Inc. (formerly known as HCP BTC, LLC), to occupy
approximately 147,000 square feet of research and office space located in South San Francisco, California, wherein the lease expired in
January 2023. We also had a sublease agreement with an unrelated third-party to sublet a portion of the leased facility of approximately
66,000 square feet, wherein the sublease expired in January 2023.
On October 28, 2022, we entered into a sublease agreement with Atara to sublease approximately 13,670 rentable square feet of
office space located in South San Francisco, California. Subject to the terms of the sublease agreement, the lease term commenced in
November 2022 and shall expire in May 2025. This new leased facility is currently held as our new Headquarters following the expiration
of our previous leased facility. In accordance with ASC 842, Leases, at lease measurement date, we recognized the operating lease right-of-
use asset and lease liability of approximately $1.3 million. The amount recognized as operating right-of-use lease asset and lease liability
represents the present value of the future minimum lease payments over the term of the lease, measured using our incremental borrowing
rate.
As of December 31, 2022, we recorded $0.7 million of lease incentives from our previous leased facility and $0.2 million from our
sublease with Atara, which we recorded as reductions to the operating lease right-of-use assets. The weighted average remaining term of
our leases as of December 31, 2022 was 2.50 years.
The components of our operating lease expense were as follows (in thousands):
Fixed operating lease expense
Variable operating lease expense
Total operating lease expense
2022
Year Ended December 31,
2021
2020
$
$
5,470 $
818
6,288 $
5,360 $
910
6,270 $
5,360
926
6,286
Supplemental information related to our operating lease expense was as follows (in thousands):
Cash payments included in the measurement of operating lease
liabilities
$
10,485
$
10,082
$
9,694
Year Ended December 31,
2022
2021
2020
134
Table of Contents
Supplemental information related to our operating sublease was as follows (in thousands):
Fixed sublease expense
Variable sublease expense
Sublease income
Net
2022
Year Ended December 31,
2021
2020
$
$
4,381 $
911
(5,292)
— $
4,381 $
917
(5,298)
— $
4,381
962
(5,343)
—
The following table presents the future minimum lease payments of our operating lease liabilities as of December 31, 2022 (in
thousands):
For year ending December 31,
2023
2024
2025
Total minimum payments required
12. STOCKHOLDERS’ EQUITY
Preferred Stock
Operating Lease
Sublease Receipts
Net
$
$
1,534
739
301
2,574
$
$
(394) $
—
—
(394) $
1,140
739
301
2,180
We are authorized to issue 10,000,000 shares of preferred stock. As of December 31, 2022 and 2021, there were no issued and
outstanding shares of preferred stock. Our board of directors is authorized to fix or alter the designation, powers, preferences and rights of
the shares of each series of preferred shares, and the qualifications, limitations or restrictions of any wholly unissued shares, to establish
from time to time the number of shares constituting any such series, and to increase or decrease the number of shares, if any.
Common Stock
Our Certificate of Incorporation as amended and restate in May 2018, authorizes us to issue 400,000,000 shares of common stock.
Open Market Sale Agreement
In August 2020, we entered into an Open Market Sale Agreement with Jefferies, as our sole sales agent pursuant to which we may
sell from time to time, through Jefferies, shares of our common stock in sales deemed to be “at-the-market offerings” as defined in Rule
415 under the Securities Act, subject to conditions specified in the Open Market Sale Agreement, including maintaining an effective
registration statement covering the sale of shares under the Open Market Sale Agreement. In April 2021, the registration statement
registering the sale of shares under the Open Market Sale Agreement expired. From the time of implementation of the Open Market Sale
Agreement through expiration of the registration statement, no sales of shares occurred. On August 3, 2021, we filed a new automatic shelf
registration statement as a qualified WKSI, such term as defined in Rule 405 of the Securities Act. The automatic shelf registration
statement was filed to register, among other securities, the sale of up to a maximum aggregate offering price of $100.0 million of shares of
our common stock that may be issued and sold from time to time under the Open Market Sale Agreement; and a base prospectus which
covers the offering, issuance, and sale by us of the securities identified from time to time in one or more offerings. On March 1, 2022,
we filed a post-effective amendment to the automatic shelf registration statement immediately after filing our Annual Report on Form 10-K
for the year ended December 31, 2021, because we no longer qualified as a WKSI upon filing of such Annual Report. The post-effective
amendment was declared effective on May 3, 2022. The post-effective amendment registers, among other securities, a base prospectus
which covers the offering, issuance, and sale by us of up to $250.0 million in the aggregate of the securities identified from time to time in
one or more offerings, which include the $100.0 million of shares of our common stock that may be offered, issued and sold under the
Open Market Sale Agreement. As of December 31, 2022, no shares had been sold under the Open Market Sale Agreement.
135
Table of Contents
13. INCOME TAXES
For the years ended December 31, 2022 and 2020, we did not recognize provision for income taxes due to our pre-tax book losses
and a full valuation allowance was recorded against our deferred tax assets. For the year ended December 31, 2021, we recorded provision
for income tax of $0.6 million. This provision for income tax was related to the state tax liability primarily due to revenue recognized for
the Lilly Agreement. We did not have federal income taxes due to the sufficient NOL carryforwards that were generated prior to the
enactment of the Tax Act, as well as significant research and development credit carryforwards. We continue to record a full valuation
allowance on our deferred tax assets considering our cumulative losses in prior years and forecasted losses in the future.
Deferred income taxes reflect the net tax effects of temporary differences between the carrying amounts of assets and liabilities for
financial reporting purposes and the amounts used for income tax purposes. Significant components of our deferred tax assets are as follows
(in thousands):
Deferred tax assets
Net operating loss carryforwards
Orphan drug and research and development credits
Capitalized research and development credits
Deferred revenue
Deferred compensation
Other, net
Lease liabilities
Deferred tax liabilities
Operating lease right-of-use asset
Others
Total net deferred tax assets
Less: valuation allowance
Deferred tax assets, net of allowance
As of December 31,
2022
2021
$
230,373
68,646
15,680
11,234
9,620
2,494
504
$
229,364
66,616
150
16,297
8,819
1,523
2,564
(461)
(439)
337,651
(337,651)
$
— $
(2,335)
(607)
322,391
(322,391)
—
The reconciliation of the statutory federal income tax rate to the effective tax rate was as follows:
Federal statutory tax rate
State, net of federal benefit
Valuation allowance
Stock compensation
Orphan drug and research and development credits
Other, net
Effective tax rate
Year Ended December 31,
2022
(21.0)%
0.0 %
20.2 %
2.5 %
(2.6)%
1.0 %
0.1 %
2021
(21.0)%
2.8 %
27.5 %
5.6 %
(14.0)%
2.7 %
3.6 %
2020
(21.0)%
0.1 %
24.4 %
4.7 %
(12.7)%
4.6 %
0.1 %
In general, under Section 382 of the Internal Revenue Code (Section 382), a corporation that undergoes an ownership change is
subject to limitations on its ability to utilize its pre-change NOL carryovers and tax credits to offset future taxable income. Our existing
NOL carryforwards and tax credits are subject to limitations arising from ownership changes which occurred in previous periods. We
finalized our analysis of potential ownership changes and concluded our Section 382 owner shift analysis during the year ended December
31, 2012. We have updated our NOL carryforwards to reflect the results of the Section 382 owner shift analysis as of December 31, 2022.
We did not experience any significant changes in ownership in the periods presented. Future changes in our stock ownership, some of
which are outside of our control, could result in an ownership change under Section 382 and result in additional limitations.
136
Table of Contents
As of December 31, 2022, we had NOL carryforwards for federal income tax purposes of approximately $976.4 million. Of the
federal NOL carryforward, $837.9 million, which expire beginning in the year 2025 and the remaining NOL carryforwards can be carried
forward indefinitely, subject to annual limitation of 80% of taxable income. We also had state NOL carryforwards of approximately $379.4
million, which expire beginning in the year 2028.
We have general business credits of approximately $52.4 million, which will expire beginning in 2023, if not utilized, and is
consisted of research and development credits and orphan drug credits. We also have state research and development tax credits of
approximately $31.3 million, which have no expiration date.
Realization of deferred tax assets is dependent upon future earnings, if any, the timing and amount of which are uncertain.
Accordingly, our deferred tax assets have been fully offset by valuation allowance considering our cumulative losses in prior years and
forecasted losses in the future. The valuation allowance increased by approximately $15.3 million, $6.6 million and $4.1 million for the
years ended December 31, 2022, 2021 and 2020, respectively.
The following table summarizes the activity related to our gross unrecognized tax benefits (in thousands):
Balance at the beginning of the year
Increase related to current year tax positions
Balance at the end of the year
$
$
Year Ended December 31,
2021
8,901
285
9,186
2022
9,186
240
9,426
$
$
$
$
2020
8,358
543
8,901
During the years ended December 2022, 2021 and 2020, the amount of unrecognized tax benefits increased due to additional
research and development and orphan drug credits generated during those years. The reversal of the uncertain tax benefits would not affect
our effective tax rate to the extent that we continue to maintain a full valuation allowance against our deferred tax assets.
We are subject to federal income tax and various state taxes. Because of NOL and research credit carryovers, substantially all of
our tax years remain open to examination.
Our policy is to recognize interest and penalties accrued on any unrecognized tax benefits as a component of income tax expense.
We currently have no tax positions that would be subject to interest or penalties.
14. RESTRUCTURING CHARGES
In October 2022, we announced a reduction in our workforce primarily in our development and administration groups. We
recorded restructuring charges of $1.3 million in the statements of operations for the year ended December 31, 2022, comprised cash
severance, bonus and related employee benefits and taxes of affected employees. As of December 31, 2022, we had approximately $0.5
million outstanding unpaid cash severance, bonus and related employee benefits and taxes included within accrued compensation in the
balance sheet, which we expect to be paid out by the first quarter of 2023.
In November 2021, we announced a reduction in our workforce primarily in the research organization. We recorded restructuring
charges of $3.5 million in the statements of operations for the year ended December 31, 2021, comprised $2.9 million cash severance,
bonus and related employee benefits and taxes of affected employees, $0.4 million of stock-based compensation expense related to option
modification and $0.1 million impairment of certain property and equipment which was recorded within depreciation expense14. As of
December 31, 2021, we had approximately $2.2 million outstanding unpaid cash severance, bonus and related employee benefits and taxes
included within accrued compensation in the balance sheet, which were paid in the first quarter of 2022.
137
Table of Contents
SUPPLEMENTARY DATA
Schedule II - Valuation and Qualifying Accounts
All schedules are omitted because they are not applicable, or the required information is shown in the financial statements or notes
thereto.
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
None.
Item 9A. Controls and Procedures
Conclusion Regarding the Effectiveness of Disclosure Controls and Procedures
Under the supervision and with the participation of our management, including our principal executive officer and principal
financial officer, we conducted an evaluation of our disclosure controls and procedures, as such term is defined under Rule 13a-15(e)
promulgated under the Exchange Act. Based on this evaluation, our principal executive officer and our principal financial officer concluded
that our disclosure controls and procedures were effective as of the end of the period covered by this Annual Report.
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 such term is
defined in Exchange Act Rules 13a-15(f). Under the supervision and with the participation of our management, including our principal
executive officer and principal financial officer, we conducted an evaluation of the effectiveness of our internal control over financial
reporting based on the framework in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the
Treadway Commission (2013 framework). Based on our evaluation under the framework in Internal Control—Integrated Framework, our
management concluded that our internal control over financial reporting was effective as of December 31, 2022.
The effectiveness of our internal control over financial reporting as of December 31, 2022 has been audited by Ernst &
Young LLP, an independent registered public accounting firm, as stated in its attestation report which is set forth below in this Annual
Report on Form 10-K.
Changes in Internal Controls over Financial Reporting
There were no changes in our internal control over financial reporting that occurred during the fourth quarter of 2022 that have
materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
Limitations on Effectiveness of Controls and Procedures
In designing and evaluating the disclosure controls and procedures, management recognizes that any controls and procedures, no
matter how well designed and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the
design of disclosure controls and procedures must reflect the fact that there are resource constraints and that management is required to
apply judgment in evaluating the benefits of possible controls and procedures relative to their costs.
138
Table of Contents
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Rigel Pharmaceuticals, Inc.
Opinion on Internal Control over Financial Reporting
We have audited Rigel Pharmaceuticals, Inc.’s internal control over financial reporting as of December 31, 2022, based on criteria
established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission
(2013 framework) (the COSO criteria). In our opinion, Rigel Pharmaceuticals, Inc. (the Company) maintained, in all material respects,
effective internal control over financial reporting as of December 31, 2022, based on the COSO criteria.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States) (PCAOB), the
balance sheets of the Company as of December 31, 2022 and 2021, the related statements of operations, comprehensive loss, stockholders’
equity (deficit) and cash flows for each of the three years in the period ended December 31, 2022, and the related notes, and our report
dated March 7, 2023 expressed an unqualified opinion thereon.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its assessment of the
effectiveness of internal control over financial reporting included in the accompanying Management’s Annual Report on Internal Control
Over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control over financial reporting based on
our audit. We are a public accounting firm registered with the 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 audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to
obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all material respects.
Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness exists,
testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and performing such other
procedures as we considered necessary in the circumstances. We believe that our audit provides a reasonable basis for our opinion.
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 (1) pertain to the maintenance
of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the company; (2) 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 (3) 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.
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.
/s/ Ernst & Young LLP
San Francisco, California
March 7, 2023
139
Table of Contents
Item 9B. Other Information
None.
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Not applicable.
PART III
Item 10. Directors, Executive Officers and Corporate Governance
Information regarding our directors, executive officers and corporate governance is incorporated by reference to the information
set forth under the captions “Election of Directors” and “Management—Executive Officers” in our Proxy Statement for the 2023 Annual
Meeting of Stockholders to be filed with the SEC within 120 days of December 31, 2022. Such information is incorporated herein by
reference.
Information regarding compliance with Section 16(a) of the Exchange Act is incorporated by reference to the information set forth
under the caption “Delinquent Section 16(a) Reports” in our Proxy Statement for the 2023 Annual Meeting of Stockholders to be filed with
the SEC within 120 days of December 31, 2022. Such information, if any, is incorporated herein by reference.
Item 11. Executive Compensation
Information regarding executive and director compensation is incorporated by reference to the information set forth under the
captions “Compensation Discussion and Analysis,” “Executive Compensation” and “Director Compensation” in our Proxy Statement for
the 2023 Annual Meeting of Stockholders to be filed with the SEC within 120 days of December 31, 2022. Such information is
incorporated herein by reference.
Information regarding Compensation Committee interlocks and insider participation is incorporated by reference to the
information set forth under the caption “Compensation Committee Interlocks and Insider Participation” in our Proxy Statement for the 2023
Annual Meeting of Stockholders to be filed with the SEC within 120 days of December 31, 2022. Such information is incorporated herein
by reference.
Information regarding our Compensation Committee’s review and discussion of our Compensation Discussion and Analysis is
incorporated by reference to the information set forth under the caption “Compensation Committee Report” in our Proxy Statement for the
2023 Annual Meeting of Stockholders to be filed with the SEC within 120 days of December 31, 2022. Such information is incorporated
herein by reference.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Information regarding security ownership of certain beneficial owners and management and securities authorized for issuance
under our equity compensation plans is incorporated by reference to the information set forth under the caption “Security Ownership of
Certain Beneficial Owners and Management and Related Stockholder Matters” and “Equity Compensation Plan Information” in our Proxy
Statement for the 2023 Annual Meeting of Stockholders to be filed with the SEC within 120 days of December 31, 2022. Such information
is incorporated herein by reference.
Item 13. Certain Relationships and Related Transactions, and Director Independence
Information regarding certain relationships and related transactions and director independence is incorporated by reference to the
information set forth under the captions “Transactions with Related Persons” and “Information Regarding the Board of Directors and
Corporate Governance” in our Proxy Statement for the 2023 Annual Meeting of Stockholders to be filed with the SEC within 120 days of
December 31, 2022. Such information is incorporated herein by reference.
140
Table of Contents
Item 14. Principal Accountant Fees and Services
Information regarding principal accounting fees and services is incorporated by reference to the information set forth under the
caption “Ratification of Selection of Independent Registered Public Accounting Firm” in our Proxy Statement for the 2023 Annual Meeting
of Stockholders to be filed with the SEC within 120 days of December 31, 2022. Such information is incorporated herein by reference.
PART IV
Item 15. Exhibits, Financial Statement Schedules
The following documents are being filed as part of this Annual Report on Form 10-K:
1.
2.
Financial Statements—Index to Financial Statements in Part II, Item 8 of this Annual Report on Form 10-K.
See Exhibit Index at the end of this Annual Report, which is incorporated herein by reference. The Exhibits listed in the
accompanying Exhibit Index are filed as part of this report.
141
Table of Contents
EXHIBIT INDEX
3.1 Amended and Restated Certificate of Incorporation (filed as an exhibit to Rigel’s Current Report on Form 8- K dated June
24, 2003 and incorporated herein by reference).
3.2 Amended and Restated Bylaws (filed as an exhibit to Rigel’s Current Report on Form 8-K, dated November 3, 2022 and
incorporated herein by reference).
3.3 Certificate of Amendment to the Amended and Restated Certificate of Incorporation (filed as an exhibit to Rigel’s Current
Report on Form 8-K, dated May 29, 2012 and incorporated herein by reference).
3.4 Certificate of Amendment to the Amended and Restated Certificate of Incorporation (filed as an exhibit to Rigel’s Current
Report on Form 8-K, dated May 18, 2018 and incorporated herein by reference).
4.1 Description of Capital Stock (filed as an exhibit to Rigel’s Annual Report on Form 10-K for the year ended December 31,
2020 filed on February 27, 2020 and incorporated herein by reference).
4.2 Form of warrant to purchase shares of common stock (filed as an exhibit to Rigel’s Registration Statement on Form S-1,
filed on September 15, 2000, as amended and incorporated herein by reference).
4.3 Specimen Common Stock Certificate (filed as an exhibit to Rigel’s Current Report on Form 8-K dated June 24, 2003 and
incorporated herein by reference).
4.4 Warrant issued to HCP BTC, LLC for the purchase of shares of common stock (filed as an exhibit to Rigel’s Quarterly
Report on Form 10-Q for the quarter ended March 31, 2009 and incorporated herein by reference).
10.1+ Form of Stock Option Agreement pursuant to 2000 Equity Incentive Plan (filed as an exhibit to Rigel’s Registration
Statement on Form S-1, as amended and incorporated herein by reference).
10.2 Build-to-Suit Lease between Rigel and Slough BTC, LLC, dated May 16, 2001 (filed as an exhibit to Rigel’s Quarterly
Report on Form 10-Q for the quarter ended June 30, 2001 and incorporated herein by reference).
10.3 ˄ Amendment to Build-to-Suit Lease between Rigel and Slough BTC, LLC, dated October 18, 2002 (filed as an exhibit to
Rigel’s Annual Report on Form 10-K, as amended, for the fiscal year ended December 31, 2002 and incorporated herein
by reference).
10.4 Amendment No. Two to Build-to-Suit Lease between Rigel and Slough BTC, LLC, dated January 31, 2005 (filed as an
exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2009 and incorporated herein by
reference).
10.5 Amendment No. Three to Build-to-Suit Lease between Rigel and Slough BTC, LLC, dated January 31, 2005 (filed as an
exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2009 and incorporated herein by
reference).
10.6 Amendment No. Four to Build-to-Suit Lease between Rigel and HCP BTC, LLC, dated February 1, 2009 (filed as an
exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2009 and incorporated herein by
reference).
10.7 ˄ Collaboration Agreement between Rigel and Daiichi Pharmaceutical Co., Ltd., dated August 1, 2002 (filed as an exhibit to
Rigel’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2002 and incorporated herein by reference).
10.8+˄ Offer Letter from Rigel Pharmaceuticals, Inc. to Wolfgang Dummer, dated October 3, 2020 (filed as an exhibit to Rigel’s
Annual Report on Form 10-K for the year ended December 31, 2019 filed on February 27, 2020 and incorporated herein
by reference).
10.9+ Form of Indemnity Agreement (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended
March 31, 2007, as amended, and incorporated herein by reference).
142
Table of Contents
10.10+ 2000 Equity Incentive Plan, as amended (filed as an exhibit to Rigel’s Registration Statement on Form S-8 filed on
June 21, 2013 and incorporated herein by reference).
10.11+ 2000 Non-Employee Directors’ Stock Option Plan, as amended (filed as an exhibit to Rigel’s Quarterly Report on
Form 10-Q for the quarter ended June 30, 2017 filed on August 21, 2017 and incorporated herein by reference).
10.12+ Amended and Restated Change of Control Severance Plan (filed as an exhibit to Rigel’s Annual Report on Form 10-K for
the fiscal year ended December 31, 2010 and incorporated herein by reference).
10.13+ 2000 Employee Stock Purchase Plan, as amended (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the
quarter ended June 30, 2021 filed on August 3, 2021 and incorporated herein by reference).
10.14 ˄ License and Collaboration Agreement between Rigel and AstraZeneca AB, dated February 15, 2010 (filed as an exhibit to
Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2010 and incorporated herein by reference).
10.15+ 2011 Equity Incentive Plan, as amended (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter
ended June 30, 2017 filed on August 21, 2017 and incorporated herein by reference).
10.16+ Form of Stock Option Agreement pursuant to 2011 Equity Incentive Plan (filed as an exhibit to Rigel’s Quarterly Report
on Form 10-Q for the quarter ended September 30, 2011 and incorporated herein by reference).
10.17+ Form of Stock Option Grant Notice, Option Agreement and Notice of Exercise under the Rigel Inducement Plan (filed as
an exhibit to Rigel’s Current Report on Form 8-K filed on October 11, 2016, and incorporated herein by reference).
10.18 Amendment No. Five to Build-to-Suit Lease between Rigel Pharmaceuticals, Inc. and HCP BTC, LLC, dated July 24,
2017 (filed as an exhibit to Rigel’s Annual Report on Form 10-K for the fiscal year ended December 31, 2017 filed on
March 6, 2018 and incorporated herein by reference).
10.19+ Executive Severance Plan (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31,
2018 filed on May 1, 2018 and incorporated herein by reference).
10.20+ Executive Severance Plan (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31,
2020 filed on May 5, 2020 and incorporated herein by reference).
10.21+ 2018 Equity Incentive Plan, as amended (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter
ended June 30, 2022 filed on August 2, 2022 and incorporated herein by reference).
10.22+ ˄ Offer Letter from Rigel Pharmaceuticals, Inc. to Dean Schorno, dated May 22, 2018 (filed as an exhibit to Rigel’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2018 filed on August 8, 2018 and incorporated herein by
reference).
10.23 ˄ Collaboration and License Agreements with Kissei Pharmaceutical Co., Ltd., dated October 29, 2018 (filed as an exhibit to
Rigel’s Annual Report on Form 10-K for the year ended December 31, 2018 filed on February 28, 2019 and incorporated
herein by reference).
10.24 ˄ Supply Agreements with Kissei Pharmaceutical Co., Ltd., dated October 29, 2018 (filed as an exhibit to Rigel’s Annual
Report on Form 10-K for the year ended December 31, 2018 filed on February 28, 2019 and incorporated herein by
reference).
10.25 ˄ Credit and Security Agreement, dated as of September 27, 2019, among Rigel Pharmaceuticals, Inc. MidCap Financial
Trust, as agent and lender, and the additional lenders from time to time party thereto (filed as an exhibit to Rigel’s
Quarterly Report on Form 10-Q for the quarter ended September 30, 2019 filed on November 5, 2019 and incorporated
herein by reference).
143
Table of Contents
10.26 ˄ Exclusive Commercialization License Agreement with Grifols Worldwide Operations Limited, dated January 22, 2019
(filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2019 filed on May 7, 2019
and incorporated herein by reference).
10.27+ 2020 Cash Incentive Plan (filed as an exhibit to Rigel’s Current Report on Form 8-K filed on November 22, 2019 and
incorporated herein by reference).
10.28+ 2021 Cash Incentive Plan (filed as an exhibit to Rigel’s Current Report on Form 8-K filed on February 3, 2021 and
incorporated herein by reference).
10.29+˄ Offer Letter from Rigel Pharmaceuticals, Inc. to David Santos, dated July 13, 2020 (filed as an exhibit to Rigel’s Quarterly
Report on Form 10-Q for the quarter ended September 30, 2020 filed on November 5, 2020 and incorporated herein by
reference).
10.30 ˄ License and Collaboration Agreement between Rigel and Eli Lilly and Company, dated February 28, 2021 (filed as an
exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2021 filed on May 5, 2021 and
incorporated herein by reference).
10.31+ Non-Employee Director Compensation Policy, as amended (filed as an exhibit to Rigel’s Annual Report on Form 10-K for
the year ended December 31, 2021 filed on March 1, 2022 and incorporated herein by reference).
10.32+ 2022 Cash Incentive Plan (filed as an exhibit to Rigel’s Current Report on Form 8-K filed on January 28, 2022 and
incorporated herein by reference).
10.33 ˄ First Amendment to the Credit and Security Agreement with MidCap Financial Trust, dated March 29, 2021 (filed as an
exhibit to Rigel’s Annual Report on Form 10-K for the year ended December 31, 2021 filed on March 1, 2022 and
incorporated herein by reference).
10.34 ˄ Second Amendment to the Credit and Security Agreement with MidCap Financial Trust, dated February 11, 2022 (filed as
an exhibit to Rigel’s Annual Report on Form 10-K for the year ended December 31, 2021 filed on March 1, 2022 and
incorporated herein by reference).
10.35 ˄ Amendment No. Six to Build-to-Suit Lease between Rigel Pharmaceuticals, Inc. and HCP BTC, LLC, dated March 21,
2022 (filed as an exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2022 filed on May 3,
2022 and incorporated herein by reference).
10.36 ˄ License and Transition Services Agreement with Forma Therapeutics, Inc. dated July 27, 2022 (filed as an exhibit to
Rigel’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022 filed on November 3, 2022 and
incorporated herein by reference).
10.37 ˄ Third Amendment to the Credit and Security Agreement with MidCap Financial Trust, dated July 27, 2022 (filed as an
exhibit to Rigel’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2022 filed on November 3, 2022
and incorporated herein by reference).
10.38+# Rigel Pharmaceuticals, Inc. Inducement Plan, as amended.
10.39˄# Sublease Agreement with Atara Biotherapheutics, Inc., dated October 28, 2022.
10.40+ ˄ # Offer Letter from Rigel Pharmaceuticals, Inc. to Raymond Furey, dated November 17, 2022.
23.1# Consent of Independent Registered Public Accounting Firm.
24.1# Power of Attorney (included on signature page).
31.1# Certification required by Rule 13a-14(a) or Rule 15d-14(a).
31.2# Certification required by Rule 13a-14(a) or Rule 15d-14(a).
32.1*# Certification required by Rule 13a-14(b) or Rule 15d-14(b) and Section 1350 of Chapter 63 of Title 18 of the United States
Code (18 U.S.C. 1350).
144
Table of Contents
101.INS Inline XBRL Instance Document – the instance document does not appear in the Interactive Data File because its XBRL
tags are embedded within the Inline XBRL document.
101.SCH Inline XBRL Taxonomy Extension Schema Document.
101.CAL# Inline XBRL Taxonomy Extension Calculation Linkbase Document.
101.LAB# Inline XBRL Taxonomy Extension Labels Linkbase Document.
101.PRE# Inline XBRL Taxonomy Extension Presentation Linkbase Document.
101.DEF# Inline XBRL Taxonomy Extension Definition Linkbase Document.
104 Cover Page Interactive Data File (formatted as Inline XBRL and contained in Exhibit 101).
Indicates a management contract or compensatory plan or arrangement.
The certification attached as Exhibit 32.1 accompanies this Annual Report on Form 10-K pursuant to 18 U.S.C. Section 1350, as
adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, and shall not be deemed “filed” by the registrant for purposes
of Section 18 of the Exchange Act.
Certain marked information has been omitted from this exhibit because it is both not material and is the type that the registrant
treats as private and confidential.
Filed herewith.
+
*
˄
#
Item 16. Form 10-K Summary
None.
145
Table of Contents
Pursuant to the requirements of the Section 13 or 15(d) of the Securities Exchange Act of 1934, the Registrant has duly caused this Annual
Report on Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of South San Francisco, State of California, on
March 7, 2023.
SIGNATURES
RIGEL PHARMACEUTICALS, INC.
By:
By:
/s/ RAUL R. RODRIGUEZ
Raul R. Rodriguez
Chief Executive Officer
(Principal Executive Officer)
/s/ DEAN L. SCHORNO
Dean L. Schorno
Chief Financial Officer
(Principal Financial Officer)
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Raul R. Rodriguez
and Dean L. Schorno, and each of them, as his true and lawful attorneys-in-fact and agents, with full power of substitution and resubstitution, for him and
in his name, place, and stead, in any and all capacities, to sign any and all amendments to this Annual Report on Form 10-K, and to file the same, with all
exhibits thereto, and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and
agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection
therewith, as fully to all intents and purposes as he might or could do in person, hereby ratifying and confirming that all said attorneys-in-fact and agents,
or any of them or their or his substitute or substitutes, may lawfully do or cause to be done by virtue hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this Annual Report on Form 10-K has been signed below by the following
persons on behalf of the Registrant and in the capacities and on the dates indicated:
Signature
/s/ RAUL R. RODRIGUEZ
Raul R. Rodriguez
/s/ DEAN L. SCHORNO
Dean L. Schorno
/s/ GREGG LAPOINTE
Gregg Lapointe
/s/ KAMIL ALI-JACKSON
Kamil Ali-Jackson
/s/ ALISON L. HANNAH
Alison L. Hannah
/s/ BRIAN L. KOTZIN
Brian L. Kotzin
/s/ GARY A. LYONS
Gary A. Lyons
/s/ WALTER H. MOOS
Walter H. Moos
/s/ JANE WASMAN
Jane Wasman
Title
Chief Executive Officer and Director
(Principal Executive Officer)
Chief Financial Officer
(Principal Financial Officer)
Chairman of the Board
Director
Director
Director
Director
Director
Director
146
Date
March 7, 2023
March 7, 2023
March 7, 2023
March 7, 2023
March 7, 2023
March 7, 2023
March 7, 2023
March 7, 2023
March 7, 2023
Exhibit 10.38
RIGEL PHARMACEUTICALS, INC.
INDUCEMENT PLAN
ADOPTED BY THE COMPENSATION COMMITTEE: OCTOBER 10, 2016
AMENDED BY THE COMPENSATION COMMITTEE: JANUARY 3, 2017
AMENDED BY THE COMPENSATION COMMITTEE: AUGUST 16, 2017
AMENDED BY THE COMPENSATION COMMITTEE: NOVEMBER 7, 2017
AMENDED BY THE COMPENSATION COMMITTEE: DECEMBER 23, 2017
AMENDED BY THE COMPENSATION COMMITTEE: JANUARY 24, 2018
AMENDED BY THE COMPENSATION COMMITTEE: AUGUST 19, 2020
AMENDED BY THE COMPENSATION COMMITTEE: SEPTEMBER 30, 2021
AMENDED BY THE COMPENSATION COMMITTEE: JANUARY 4, 2022
AMENDED BY THE COMPENSATION COMMITTEE: APRIL 4, 2022
AMENDED BY THE COMPENSATION COMMITTEE: DECEMBER 8, 2022
1. GENERAL.
(a)
Eligible Stock Award Recipients. The only persons eligible to receive grants of Stock Awards under this Plan are
individuals who satisfy the standards for inducement grants under NASDAQ Marketplace Rule 5635(c)(4) and the related guidance
under NASDAQ IM 5635-1. A person who previously served as an Employee or Director will not be eligible to receive Stock Awards
under the Plan, other than following a bona fide period of non-employment. Persons eligible to receive grants of Stock Awards under
this Plan are referred to in this Plan as “Eligible Employees”. These Stock Awards must be approved by either a majority of the
Company's “Independent Directors” (as such term is defined in NASDAQ Listing Rule 5605(a)(2)) or the Company’s compensation
committee, provided such committee is comprised solely of Independent Directors (the “Independent Compensation Committee”) in
order to comply with the exemption from the stockholder approval requirement for “inducement grants” provided under Rule 5635(c)
(4) of the NASDAQ Listing Rules. NASDAQ Marketplace Rule 5635(c)(4) and the related guidance under NASDAQ IM 5635-1 are
referred to in this Plan as the “Inducement Award Rules”.
(b)
Available Awards. The Plan provides for the grant of Options and Restricted Stock Unit Awards. All Options will be
Nonstatutory Stock Options. Awards intended to qualify as stockholder-approved performance based compensation for purposes of
Section 162(m) of the Code may not be granted under this Plan.
(c)
Purpose. This Plan, through the granting of Stock Awards, is intended to provide (i) an inducement material for
certain individuals to enter into employment with the Company within the meaning of Rule 5635(c)(4) of the NASDAQ Listing Rules,
(ii) incentives for such persons to exert maximum efforts for the success of the Company and any Affiliate and (iii) a means by which
Eligible Employees may be given an opportunity to benefit from increases in value of the Common Stock through the granting of
Stock Awards.
2. ADMINISTRATION.
(a)
Administration by Board. The Board will administer the Plan, provided, however, that Stock Awards may only be
granted by either (i) a majority of the Company's Independent Directors or (ii) the Independent Compensation Committee. Subject to
those constraints and the other constraints of the Inducement Award Rules, the Board may delegate some of its powers of
administration of the Plan to a Committee, as provided in Section 2(c).
1
(b)
Powers of Board. The Board will have the power, subject to, and within the limitations of, the express provisions of
the Plan and the Inducement Award Rules:
(i)
To determine: (A) who will be granted Stock Awards; (B) when and how each Stock Award will be granted;
(C) what type of Stock Award will be granted; (D) the provisions of each Stock Award (which need not be identical), including when a
person will be permitted to exercise or otherwise receive cash or Common Stock under the Stock Award; (E) the number of shares of
Common Stock subject to, or the cash value of, a Stock Award; and (F) the Fair Market Value applicable to a Stock Award; provided,
however, that Stock Awards may only be granted by either (i) a majority of the Company's Independent Directors or (ii) the
Independent Compensation Committee.
(ii)
To construe and interpret the Plan and Stock Awards granted under it, and to establish, amend and revoke
rules and regulations for administration of the Plan and Stock Awards. The Board, in the exercise of these powers, may correct any
defect, omission or inconsistency in the Plan or in any Stock Award Agreement, in a manner and to the extent it will deem necessary
or expedient to make the Plan or Stock Award fully effective.
(iii)
To settle all controversies regarding the Plan and Stock Awards granted under it.
(iv)
To accelerate, in whole or in part, the time at which a Stock Award may be exercised or vest (or at which
cash or shares of Common Stock may be issued).
To suspend or terminate the Plan at any time. Except as otherwise provided in the Plan or a Stock Award
Agreement, suspension or termination of the Plan will not materially impair a Participant’s rights under his or her then-outstanding
Stock Award without his or her written consent except as provided in subsection (viii) below.
(v)
(vi)
To amend the Plan in any respect the Board deems necessary or advisable, including, without limitation,
adopting amendments relating to nonqualified deferred compensation under Section 409A of the Code and/or making the Plan or
Stock Awards granted under the Plan exempt from or compliant with the requirements for nonqualified deferred compensation under
Section 409A of the Code, subject to the limitations, if any, of applicable law. If required by applicable law or listing requirements,
and except as provided in Section 9(a) relating to Capitalization Adjustments, the Company will seek stockholder approval of any
amendment of the Plan that (A) materially increases the number of shares of Common Stock available for issuance under the Plan,
(B) materially expands the class of individuals eligible to receive Stock Awards under the Plan, (C) materially increases the benefits
accruing to Participants under the Plan, (D) materially reduces the price at which shares of Common Stock may be issued or purchased
under the Plan, (E) materially extends the term of the Plan, or (F) materially expands the types of Stock Awards available for issuance
under the Plan. Except as otherwise provided in the Plan (including subsection (viii) below) or a Stock Award Agreement, no
amendment of the Plan will materially impair a Participant’s rights under an outstanding Stock Award without the Participant’s written
consent.
(vii)
To submit any amendment to the Plan for stockholder approval, including, but not limited to, amendments
to the Plan intended to satisfy the requirements of Rule 16b-3 of Exchange Act or any successor rule.
(viii)
To approve forms of Stock Award Agreements for use under the Plan and to amend the terms of any one or
more outstanding Stock Awards, including, but not limited to, amendments to provide terms more favorable to the Participant than
previously provided in the Stock Award Agreement, subject to any specified limits in the Plan that are not subject to Board discretion.
A Participant’s rights under any Stock Award will not be impaired by any such amendment unless the Company requests the consent
of the affected Participant, and the Participant consents in writing. However, a Participant’s rights will not be deemed to have been
impaired by any such amendment if the Board, in its sole discretion, determines that the amendment, taken as a whole, does not
materially impair the Participant’s rights. In addition, subject to the limitations of applicable law, if any, the Board may amend the
terms of any one or more Stock Awards without the affected Participant’s consent (A) to clarify the manner of exemption from, or to
bring the Stock Award into compliance with, Section 409A of the Code, or (B) to comply with other applicable laws or listing
requirements.
2
Generally, to exercise such powers and to perform such acts as the Board deems necessary or expedient to
promote the best interests of the Company and that are not in conflict with the provisions of the Plan and/or Stock Award Agreements.
(ix)
(x)
To adopt such procedures and sub-plans as are necessary or appropriate (A) to permit participation in the
Plan by individuals who are foreign nationals or employed outside the United States or (B) allow Stock Awards to qualify for special
tax treatment in a foreign jurisdiction; provided that Board approval will not be necessary for immaterial modifications to the Plan or
any Stock Award Agreement that are required for compliance with the laws of the relevant foreign jurisdiction.
(c)
Delegation to Committee.
(i)
General. The Board may delegate some or all of the administration of the Plan to a Committee or
Committees. If administration of the Plan is delegated to a Committee, the Committee will have, in connection with the administration
of the Plan, the powers theretofore possessed by the Board that have been delegated to the Committee, including the power to delegate
to a subcommittee of the Committee any of the administrative powers the Committee is authorized to exercise (and references in this
Plan to the Board will thereafter be to the Committee or subcommittee). Any delegation of administrative powers will be reflected in
resolutions, not inconsistent with the provisions of the Plan, adopted from time to time by the Board or Committee (as applicable). The
Committee may, at any time, abolish the subcommittee and/or revest in the Committee any powers delegated to the subcommittee. The
Board may retain the authority to concurrently administer the Plan with the Committee and may, at any time, revest in the Board some
or all of the powers previously delegated.
accordance with Rule 16b-3 of the Exchange Act.
(ii)
Rule 16b-3 Compliance. The Committee may consist solely of two or more Non-Employee Directors, in
(d)
Effect of Board’s Decision. All determinations, interpretations and constructions made by the Board in good faith
will not be subject to review by any person and will be final, binding and conclusive on all persons.
(e)
Cancellation and Re-Grant of Stock Awards. Neither the Board nor any Committee will have the authority to: (i)
reduce the exercise, purchase or strike price of any outstanding Option, or (ii) cancel any outstanding Option that has an exercise price
or strike price greater than the current Fair Market Value of the Common Stock in exchange for cash or other Stock Awards under the
Plan, unless the stockholders of the Company have approved such an action within twelve (12) months prior to such an event.
3. SHARES SUBJECT TO THE PLAN.
(a)
Share Reserve.
(i)
Subject to Section 9(a) relating to Capitalization Adjustments, the aggregate number of shares of Common
Stock that may be issued pursuant to Stock Awards will not exceed 4,428,000 shares (the “Share Reserve”).
Shares may be issued under the terms of this Plan in connection with a merger or acquisition as permitted
by NASDAQ Listing Rule 5635(c), NYSE Listed Company Manual Section 303A.08, AMEX Company Guide Section 711 or other
applicable rule, and such issuance will not reduce the number of shares available for issuance under the Plan.
(ii)
(b)
Reversion of Shares to the Share Reserve. If a Stock Award or any portion of a Stock Award (i) expires or
otherwise terminates without all of the shares covered by the Stock Award having been issued or (ii) is settled in cash (i.e., the
Participant receives cash rather than stock), such expiration, termination or settlement will nevertheless reduce (or otherwise offset)
the number of shares of Common Stock that are available for issuance under the Plan. If any shares of Common Stock issued under a
Stock Award are forfeited back to or repurchased by the Company because of the failure to meet a contingency or condition required
to vest such shares in the Participant, then the shares that are forfeited or repurchased will not revert to and again become available for
issuance under the Plan.
3
Any shares reacquired by the Company in satisfaction of tax withholding obligations on a Stock Award or as consideration for the
exercise or purchase price of a Stock Award will not again become available for issuance under the Plan.
(c)
Source of Shares. The stock issuable under the Plan will be shares of authorized but unissued or reacquired
Common Stock, including shares repurchased by the Company on the open market or otherwise.
4. ELIGIBILITY.
(a)
Eligibility for Specific Stock Awards. Stock Awards may only be granted to persons who are Eligible Employees
described in Section 1(a) of the Plan, where the Stock Award is an inducement material to the individual’s entering into employment
with the Company or an Affiliate within the meaning of Rule 5635(c)(4) of the NASDAQ Listing Rules, provided however, that Stock
Awards may not be granted to Eligible Employees who are providing Continuous Service only to any “parent” of the Company, as
such term is defined in Rule 405 of the Securities Act, unless (i) the stock underlying such Stock Awards is treated as “service
recipient stock” under Section 409A of the Code (for example, because the Stock Awards are granted pursuant to a corporate
transaction such as a spin off transaction), or (ii) the Company, in consultation with its legal counsel, has determined that such Stock
Awards are otherwise exempt from or comply with the distribution requirements of Section 409A of the Code.
(b)
Approval Requirements. All Stock Awards must be granted either by a majority of the Company’s independent
directors or the Independent Compensation Committee.
5. PROVISIONS RELATING TO OPTIONS.
Each Option will be in such form and will contain such terms and conditions as the Board deems appropriate. All Options
will be Nonstatutory Stock Options. The provisions of separate Options need not be identical; provided, however, that each Option
Agreement will conform to (through incorporation of provisions hereof by reference in the applicable Option Agreement or otherwise)
the substance of each of the following provisions:
(a)
Term. No Option will be exercisable after the expiration of 10 years from the date of its grant or such shorter period
specified in the Option Agreement.
(b)
Exercise Price. The exercise or strike price of each Option will be not less than 100% of the Fair Market Value of
the Common Stock subject to the Option on the date the Option is granted. Notwithstanding the foregoing, an Option may be granted
with an exercise price lower than 100% of the Fair Market Value of the Common Stock subject to the Option if such Option is granted
pursuant to an assumption of or substitution for another option or stock appreciation right pursuant to a Corporate Transaction and in a
manner consistent with the provisions of Section 409A of the Code.
(c)
Purchase Price for Options. The purchase price of Common Stock acquired pursuant to the exercise of an Option
may be paid, to the extent permitted by applicable law and as determined by the Board in its sole discretion, by any combination of the
methods of payment set forth below. The Board will have the authority to grant Options that do not permit all of the following
methods of payment (or otherwise restrict the ability to use certain methods) and to grant Options that require the consent of the
Company to use a particular method of payment. The permitted methods of payment are as follows:
(i)
by cash, check, bank draft or money order payable to the Company;
(ii)
pursuant to a program developed under Regulation T as promulgated by the Federal Reserve Board that,
prior to the issuance of the stock subject to the Option, results in either the receipt of cash (or check) by the Company or the receipt of
irrevocable instructions to pay the aggregate exercise price to the Company from the sales proceeds;
4
(iii)
by delivery to the Company (either by actual delivery or attestation) of shares of Common Stock;
(iv)
by a “net exercise” arrangement pursuant to which the Company will reduce the number of shares of
Common Stock issuable upon exercise by the largest whole number of shares with a Fair Market Value that does not exceed the
aggregate exercise price; provided, however, that the Company will accept a cash or other payment from the Participant to the extent
of any remaining balance of the aggregate exercise price not satisfied by such reduction in the number of whole shares to be issued.
Shares of Common Stock will no longer be subject to an Option and will not be exercisable thereafter to the extent that (A) shares
issuable upon exercise are used to pay the exercise price pursuant to the “net exercise,” (B) shares are delivered to the Participant as a
result of such exercise, and (C) shares are withheld to satisfy tax withholding obligations; or
Option Agreement.
(v)
in any other form of legal consideration that may be acceptable to the Board and specified in the applicable
(d)
Transferability of Options. The Board may, in its sole discretion, impose such limitations on the transferability of
Options as the Board will determine. In the absence of such a determination by the Board to the contrary, the following restrictions on
the transferability of Options will apply:
(i)
Restrictions on Transfer. An Option will not be transferable except by will or by the laws of descent and
distribution (or pursuant to subsections (ii) and (iii) below), and will be exercisable during the lifetime of the Participant only by the
Participant. The Board may permit transfer of the Option in a manner that is not prohibited by applicable tax and securities laws.
Except as explicitly provided in the Plan, an Option may not be transferred for consideration.
Domestic Relations Orders. Subject to the approval of the Board or a duly authorized Officer, an Option
may be transferred pursuant to the terms of a domestic relations order, official marital settlement agreement or other divorce or
separation instrument.
(ii)
(iii)
Beneficiary Designation. Subject to the approval of the Board or a duly authorized Officer, a Participant
may, by delivering written notice to the Company, in a form approved by the Company (or the designated broker), designate a third
party who, on the death of the Participant, will thereafter be entitled to exercise the Option and receive the Common Stock or other
consideration resulting from such exercise. In the absence of such a designation, the executor or administrator of the Participant’s
estate will be entitled to exercise the Option and receive the Common Stock or other consideration resulting from such exercise.
However, the Company may prohibit designation of a beneficiary at any time, including due to any conclusion by the Company that
such designation would be inconsistent with the provisions of applicable laws.
(e)
Vesting Generally. The total number of shares of Common Stock subject to an Option may vest and therefore
become exercisable in periodic installments that may or may not be equal. The Option may be subject to such other terms and
conditions on the time or times when it may or may not be exercised (which may be based on the satisfaction of performance goals or
other criteria) as the Board may deem appropriate. The vesting provisions of individual Options may vary. The provisions of this
Section 5(e) are subject to any Option provisions governing the minimum number of shares of Common Stock as to which an Option
may be exercised.
(f)
Termination of Continuous Service. Except as otherwise provided in the applicable Option Agreement or other
agreement between the Participant and the Company, if a Participant’s Continuous Service terminates (other than for Cause and other
than upon the Participant’s death or Disability), the Participant may exercise his or her Option (to the extent that the Participant was
entitled to exercise such Option as of the date of termination of Continuous Service) within the period of time ending on the earlier of
(i) the date which occurs 3 months following the termination of the Participant’s Continuous Service, and (ii) the expiration of the
term of the Option as set forth in the Option Agreement. If, after termination of Continuous Service, the Participant does not exercise
his or her Option within the applicable time frame, the Option will terminate.
5
(g)
Extension of Termination Date. Except as otherwise provided in the applicable Stock Award Agreement, if the
exercise of an Option following the termination of the Participant’s Continuous Service (other than for Cause and other than upon the
Participant’s death or Disability) would be prohibited at any time solely because the issuance of shares of Common Stock would
violate the registration requirements under the Securities Act, then the Option will terminate on the earlier of (i) the expiration of a
total period of time (that need not be consecutive) equal to the applicable post-termination exercise period after the termination of the
Participant’s Continuous Service during which the exercise of the Option would not be in violation of such registration requirements,
and (ii) the expiration of the term of the Option as set forth in the applicable Option Agreement. In addition, unless otherwise provided
in a Participant’s Option Agreement, if the sale of any Common Stock received upon exercise of an Option following the termination
of the Participant’s Continuous Service (other than for Cause) would violate the Company’s insider trading policy, then the Option will
terminate on the earlier of (i) the expiration of a period of days or months (that need not be consecutive) equal to the applicable post-
termination exercise period after the termination of the Participant’s Continuous Service during which the sale of the Common Stock
received upon exercise of the Option would not be in violation of the Company’s insider trading policy, or (ii) the expiration of the
term of the Option as set forth in the applicable Option Agreement.
(h)
Disability of Participant. Except as otherwise provided in the applicable Option Agreement or other agreement
between the Participant and the Company, if a Participant’s Continuous Service terminates as a result of the Participant’s Disability,
the Participant may exercise his or her Option (to the extent that the Participant was entitled to exercise such Option as of the date of
termination of Continuous Service), but only within such period of time ending on the earlier of (i) the date 12 months following such
termination of Continuous Service and (ii) the expiration of the term of the Option as set forth in the Option Agreement. If, after
termination of Continuous Service, the Participant does not exercise his or her Option within the applicable time frame, the Option
will terminate.
(i)
Death of Participant. Except as otherwise provided in the applicable Option Agreement or other agreement
between the Participant and the Company, if (i) a Participant’s Continuous Service terminates as a result of the Participant’s death, or
(ii) the Participant dies within the period (if any) specified in the Option Agreement for exercisability after the termination of the
Participant’s Continuous Service for a reason other than death, then the Option may be exercised (to the extent the Participant was
entitled to exercise such Option as of the date of death) by the Participant’s estate, by a person who acquired the right to exercise the
Option by bequest or inheritance or by a person designated to exercise the Option upon the Participant’s death, but only within the
period ending on the earlier of (i) the date 18 months following the date of death, and (ii) the expiration of the term of such Option as
set forth in the Option Agreement. If, after the Participant’s death, the Option is not exercised within the applicable time frame, the
Option will terminate.
(j)
Termination for Cause. Except as explicitly provided otherwise in a Participant’s Stock Award Agreement or other
individual written agreement between the Company or any Affiliate and the Participant, if a Participant’s Continuous Service is
terminated for Cause, the Option will terminate upon the date on which the event giving rise to the termination for Cause first
occurred, and the Participant will be prohibited from exercising his or her Option from and after the date on which the event giving
rise to the termination for Cause first occurred (or, if required by applicable law, the date of termination of Continuous Service). If a
Participant’s Continuous Service is suspended pending an investigation of the existence of Cause, all of the Participant’s rights under
the Option will also be suspended during the investigation period, except to the extent prohibited by applicable law.
(k)
Non-Exempt Employees. If an Option is granted to an Employee who is a non-exempt employee for purposes of
the Fair Labor Standards Act of 1938, as amended, the Option will not be first exercisable for any shares of Common Stock until at
least 6 months following the date of grant of the Option (although the Option may vest prior to such date). Consistent with the
provisions of the Worker Economic Opportunity Act, (i) if such non-exempt Employee dies or suffers a Disability, (ii) upon a
Corporate Transaction in which such Option is not assumed, continued, or substituted, or (iii) upon the non-exempt Employee’s
retirement (as such term may be defined in the non-exempt Employee’s Option Agreement in another agreement between the non-
exempt Employee and the Company, or, if no such definition, in accordance with the Company's then current employment policies and
guidelines), the vested portion of any Options may be exercised earlier than 6 months following the date of grant. The foregoing
provision is intended to operate so that any income derived by a non-exempt employee in connection with the exercise or vesting of an
Option will be exempt from his or her regular rate of pay. To the extent permitted and/or required for compliance with the Worker
Economic Opportunity Act to ensure that any income derived by a non-
6
exempt Employee in connection with the exercise, vesting or issuance of any shares under any other Option will be exempt from such
Employee’s regular rate of pay, the provisions of this paragraph will apply to all Options and are hereby incorporated by reference into
such Option Agreements.
6. PROVISIONS RELATING TO RESTRICTED STOCK UNIT AWARDS.
Each Restricted Stock Unit Award Agreement will be in such form and will contain such terms and conditions as the Board
deems appropriate. The terms and conditions of Restricted Stock Unit Award Agreements may change from time to time, and the terms
and conditions of separate Restricted Stock Unit Award Agreements need not be identical. Each Restricted Stock Unit Award
Agreement will conform to (through incorporation of the provisions hereof by reference in the Agreement or otherwise) the substance
of each of the following provisions:
(a)
Consideration. At the time of grant of a Restricted Stock Unit Award, the Board will determine the consideration, if
any, to be paid by the Participant upon delivery of each share of Common Stock subject to the Restricted Stock Unit Award. The
consideration to be paid (if any) by the Participant for each share of Common Stock subject to a Restricted Stock Unit Award may be
paid in any form of legal consideration that may be acceptable to the Board, in its sole discretion, and permissible under applicable
law.
(b)
Vesting. At the time of the grant of a Restricted Stock Unit Award, the Board may impose such restrictions on or
conditions to the vesting of the Restricted Stock Unit Award as it, in its sole discretion, deems appropriate.
(c)
Payment. A Restricted Stock Unit Award may be settled by the delivery of shares of Common Stock, their cash
equivalent, any combination thereof or in any other form of consideration, as determined by the Board and contained in the Restricted
Stock Unit Award Agreement.
(d)
Additional Restrictions. At the time of the grant of a Restricted Stock Unit Award, the Board, as it deems
appropriate, may impose such restrictions or conditions that delay the delivery of the shares of Common Stock (or their cash
equivalent) subject to a Restricted Stock Unit Award to a time after the vesting of such Restricted Stock Unit Award.
(e)
Dividend Equivalents. Dividend equivalents may be credited in respect of shares of Common Stock covered by a
Restricted Stock Unit Award, as determined by the Board and contained in the Restricted Stock Unit Award Agreement. At the sole
discretion of the Board, such dividend equivalents may be converted into additional shares of Common Stock covered by the
Restricted Stock Unit Award in such manner as determined by the Board. Any additional shares covered by the Restricted Stock Unit
Award credited by reason of such dividend equivalents will be subject to all of the same terms and conditions of the underlying
Restricted Stock Unit Award Agreement to which they relate.
(f)
Termination of Participant’s Continuous Service. Except as otherwise provided in the applicable Restricted Stock
Unit Award Agreement, such portion of the Restricted Stock Unit Award that has not vested will be forfeited upon the Participant’s
termination of Continuous Service.
7. COVENANTS OF THE COMPANY.
(a)
Availability of Shares. The Company will keep available at all times the number of shares of Common Stock
reasonably required to satisfy then-outstanding Stock Awards.
(b)
Securities Law Compliance. The Company will seek to obtain from each regulatory commission or agency having
jurisdiction over the Plan such authority as may be required to grant Stock Awards and to issue and sell shares of Common Stock upon
exercise of the Stock Awards; provided, however, that this undertaking will not require the Company to register under the Securities
Act the Plan, any Stock Award or any Common Stock issued or issuable pursuant to any such Stock Award. If, after reasonable efforts
and at a reasonable cost, the Company is unable to obtain from any such regulatory commission or agency the authority that counsel
for the Company deems necessary for the lawful issuance and sale of Common Stock under the Plan, the Company will be relieved
from any liability for
7
failure to issue and sell Common Stock upon exercise of such Stock Awards unless and until such authority is obtained. A Participant
will not be eligible for the grant of a Stock Award or the subsequent issuance of cash or Common Stock pursuant to the Stock Award if
such grant or issuance would be in violation of any applicable securities law.
(c)
No Obligation to Notify or Minimize Taxes. The Company will have no duty or obligation to any Participant to
advise such holder as to the time or manner of exercising such Stock Award. Furthermore, the Company will have no duty or
obligation to warn or otherwise advise such holder of a pending termination or expiration of a Stock Award or a possible period in
which the Stock Award may not be exercised. The Company has no duty or obligation to minimize the tax consequences of a Stock
Award to the holder of such Stock Award.
8. MISCELLANEOUS.
(a)
Use of Proceeds from Sales of Common Stock. Proceeds from the sale of shares of Common Stock pursuant to
Stock Awards will constitute general funds of the Company.
(b)
Corporate Action Constituting Grant of Stock Awards. Corporate action constituting a grant by the Company of
a Stock Award to any Participant will be deemed completed as of the date of such corporate action, unless otherwise determined by the
Board, regardless of when the instrument, certificate, or letter evidencing the Stock Award is communicated to, or actually received or
accepted by, the Participant. In the event that the corporate records (e.g., Board consents, resolutions or minutes) documenting the
corporate action constituting the grant contain terms (e.g., exercise price, vesting schedule or number of shares) that are inconsistent
with those in the Stock Award Agreement as a result of a clerical error in the papering of the Stock Award Agreement, the corporate
records will control and the Participant will have no legally binding right to the incorrect term in the Stock Award Agreement.
(c)
Stockholder Rights. No Participant will be deemed to be the holder of, or to have any of the rights of a holder with
respect to, any shares of Common Stock subject to a Stock Award unless and until (i) such Participant has satisfied all requirements for
exercise of, or the issuance of shares of Common Stock under, the Stock Award pursuant to its terms, and (ii) the issuance of the
Common Stock subject to such Stock Award has been entered into the books and records of the Company.
(d)
No Employment or Other Service Rights. Nothing in the Plan, any Stock Award Agreement or any other
instrument executed thereunder or in connection with any Stock Award granted pursuant thereto will confer upon any Participant any
right to continue to serve the Company or an Affiliate in the capacity in effect at the time the Stock Award was granted or will affect
the right of the Company or an Affiliate to terminate (i) the employment of an Employee with or without notice and with or without
cause, including, but not limited to, Cause, (ii) the service of a Consultant pursuant to the terms of such Consultant’s agreement with
the Company or an Affiliate, or (iii) the service of a Director pursuant to the bylaws of the Company or an Affiliate, and any
applicable provisions of the corporate law of the state in which the Company or the Affiliate is incorporated, as the case may be.
(e)
Change in Time Commitment. In the event a Participant’s regular level of time commitment in the performance of
his or her services for the Company and any Affiliates is reduced (for example, and without limitation, if the Participant is an
Employee of the Company and the Employee has a change in status from a full-time Employee to a part-time Employee or takes an
extended leave of absence) after the date of grant of any Stock Award to the Participant, the Board has the right in its sole discretion to
(i) make a corresponding reduction in the number of shares or cash amount subject to any portion of such Stock Award that is
scheduled to vest or become payable after the date of such change in time commitment, and (ii) in lieu of or in combination with such
a reduction, extend the vesting or payment schedule applicable to such Stock Award. In the event of any such reduction, the
Participant will have no right with respect to any portion of the Stock Award that is so reduced or extended.
(f)
Investment Assurances. The Company may require a Participant, as a condition of exercising or acquiring
Common Stock under any Stock Award, (i) to give written assurances satisfactory to the Company as to the Participant’s knowledge
and experience in financial and business matters and/or to employ a purchaser representative reasonably satisfactory to the Company
who is knowledgeable and experienced in financial and business matters and that he or she is capable of evaluating, alone or together
with the purchaser representative, the merits and risks of exercising the Stock Award, and (ii) to give written assurances satisfactory to
the Company stating that the Participant is acquiring Common Stock subject to the Stock Award for the Participant’s own account and
not with any present
8
intention of selling or otherwise distributing the Common Stock. The foregoing requirements, and any assurances given pursuant to
such requirements, will be inoperative if (i) the issuance of the shares upon the exercise of a Stock Award or acquisition of Common
Stock under the Stock Award has been registered under a then currently effective registration statement under the Securities Act, or
(ii) as to any particular requirement, a determination is made by counsel for the Company that such requirement need not be met in the
circumstances under the then applicable securities laws. The Company may, upon advice of counsel to the Company, place legends on
stock certificates issued under the Plan as such counsel deems necessary or appropriate in order to comply with applicable securities
laws, including, but not limited to, legends restricting the transfer of the Common Stock.
(g)
Withholding Obligations. Unless prohibited by the terms of a Stock Award Agreement, the Company may, in its
sole discretion, satisfy any U.S. federal, state, local, foreign or other tax withholding obligation relating to a Stock Award by any of the
following means or by a combination of such means: (i) causing the Participant to tender a cash payment; (ii) withholding shares of
Common Stock from the shares of Common Stock issued or otherwise issuable to the Participant in connection with the Stock Award;
provided, however, that no shares of Common Stock are withheld with a value exceeding the minimum amount of tax required to be
withheld by law (or such other amount as may be necessary to avoid classification of the Stock Award as a liability for financial
accounting purposes); (iii) withholding cash from a Stock Award settled in cash; (iv) withholding payment from any amounts
otherwise payable to the Participant, including proceeds from the sale of shares of Common Stock issued pursuant to a Stock Award;
or (v) by such other method as may be set forth in the Stock Award Agreement.
(h)
Electronic Delivery. Any reference herein to a “written” agreement or document will include any agreement or
document delivered electronically, filed publicly at www.sec.gov (or any successor website thereto), or posted on the Company’s
intranet (or other shared electronic medium controlled by the Company to which the Participant has access).
(i)
Deferrals. To the extent permitted by applicable law, the Board, in its sole discretion, may determine that the
delivery of Common Stock or the payment of cash, upon the exercise, vesting or settlement of all or a portion of any Stock Award may
be deferred and may establish programs and procedures for deferral elections to be made by Participants. Deferrals by Participants will
be made in accordance with Section 409A of the Code (to the extent applicable to a Participant). Consistent with Section 409A of the
Code, the Board may provide for distributions while a Participant is still an employee or otherwise providing services to the Company.
The Board is authorized to make deferrals of Stock Awards and determine when, and in what annual percentages, Participants may
receive payments, including lump sum payments, following the Participant’s termination of Continuous Service, and implement such
other terms and conditions consistent with the provisions of the Plan and in accordance with applicable law.
(j)
Compliance with Section 409A. Unless otherwise expressly provided for in a Stock Award Agreement and the Plan
will be interpreted to the greatest extent possible in a manner that makes the Plan and the Stock Awards granted hereunder exempt
from Section 409A of the Code, and, to the extent not so exempt, in compliance with Section 409A of the Code. If the Board
determines that any Stock Award granted hereunder is not exempt from and is therefore subject to Section 409A of the Code, the Stock
Award Agreement evidencing such Stock Award will incorporate the terms and conditions necessary to avoid the consequences
specified in Section 409A(a)(1) of the Code, and to the extent a Stock Award Agreement is silent on terms necessary for compliance,
such terms are hereby incorporated by reference into the Stock Award Agreement. Notwithstanding anything to the contrary in this
Plan (and unless the Stock Award Agreement specifically provides otherwise), if the shares of Common Stock are publicly traded, and
if a Participant holding a Stock Award that constitutes “deferred compensation” under Section 409A of the Code is a “specified
employee” for purposes of Section 409A of the Code, no distribution or payment of any amount that is due because of a “separation
from service” (as defined in Section 409A of the Code) will be issued or paid before the date that is six (6) months following the date
of such Participant’s “separation from service” or, if earlier, the date of the Participant’s death, unless such distribution or payment can
be made in a manner that complies with Section 409A of the Code, and any amounts so deferred will be paid in a lump sum on the day
after such six (6) month period elapses, with the balance paid thereafter on the original schedule.
(k)
Clawback/Recovery. All Stock Awards granted under the Plan will be subject to recoupment in accordance with
any clawback policy that the Company is required to adopt pursuant to the listing standards of any national securities exchange or
association on which the Company’s securities are listed or as is otherwise required
9
by the Dodd-Frank Wall Street Reform and Consumer Protection Act or other applicable law. In addition, the Board may impose such
other clawback, recovery or recoupment provisions in a Stock Award Agreement as the Board determines necessary or appropriate,
including, but not limited to, a reacquisition right in respect of previously acquired shares of Common Stock or other cash or property
upon the occurrence of an event constituting Cause. No recovery of compensation under such a clawback policy will be an event
giving rise to a right to resign for “good reason” or “constructive termination” (or similar term) under any agreement with the
Company or an Affiliate.
9. ADJUSTMENTS UPON CHANGES IN COMMON STOCK; OTHER CORPORATE EVENTS.
(a)
Capitalization Adjustments. In the event of a Capitalization Adjustment, the Board will appropriately and
proportionately adjust: (i) the class(es) and maximum number of securities subject to the Plan pursuant to Section 3(a) and (ii) the
class(es) and number of securities and price per share of stock subject to outstanding Stock Awards. The Board will make such
adjustments, and its determination will be final, binding and conclusive.
(b)
Dissolution or Liquidation. In the event of a dissolution or liquidation of the Company, then all outstanding Stock
Awards shall terminate immediately prior to such event.
(c)
Corporate Transaction. In the event of (i) a sale, lease or other disposition of all or substantially all of the
securities or assets of the Company, (ii) a merger or consolidation in which the Company is not the surviving corporation or (iii) a
reverse merger in which the Company is the surviving corporation but the shares of Common Stock outstanding immediately
preceding the merger are converted by virtue of the merger into other property, whether in the form of securities, cash or otherwise (a
“Corporate Transaction”), then any surviving corporation or acquiring corporation may assume any Stock Awards outstanding under
the Plan or may substitute similar stock awards (including an award to acquire the same consideration paid to the stockholders in such
Corporate Transaction) for those outstanding under the Plan. In the event any surviving corporation or acquiring corporation does not
assume such Stock Awards or substitute similar stock awards for those outstanding under the Plan, then with respect to Stock Awards
held by Participants whose Continuous Service has not terminated, the vesting of such Stock Awards (and, if applicable, the time
during which such Stock Awards may be exercised) shall be accelerated in full, and the Stock Awards shall terminate if not exercised
(if applicable) at or prior to such event. With respect to any other Stock Awards outstanding under the Plan, such Stock Awards shall
terminate if not exercised (if applicable) prior to such event.
10. TERMINATION OR SUSPENSION OF THE PLAN.
The Board may suspend or terminate the Plan at any time. No Stock Awards may be granted under the Plan while the Plan is
suspended or after it is terminated.
11. EFFECTIVE DATE OF PLAN; TIMING OF FIRST GRANT OR EXERCISE.
The Plan will come into existence on the Effective Date. No Stock Award may be granted prior to the Effective Date.
12. CHOICE OF LAW.
The laws of the State of Delaware will govern all questions concerning the construction, validity and interpretation of this
Plan, without regard to that state’s conflict of laws rules.
13. DEFINITIONS. As used in the Plan, the following definitions will apply to the capitalized terms indicated below:
(a) “Affiliate” means, at the time of determination, any “parent” or “subsidiary” of the Company, as such terms are defined
in Rule 405 of the Securities Act. The Board will have the authority to determine the time or times at which “parent” or
“subsidiary” status is determined within the foregoing definition.
(b) “Board” means the Board of Directors of the Company.
10
(c) “Capitalization Adjustment” means any change that is made in, or other events that occur with respect to, the Common
Stock subject to the Plan or subject to any Stock Award after the Effective Date without the receipt of consideration by
the Company through merger, consolidation, reorganization, recapitalization, reincorporation, stock dividend, dividend
in property other than cash, large nonrecurring cash dividend, stock split, reverse stock split, liquidating dividend,
combination of shares, exchange of shares, change in corporate structure or other similar equity restructuring transaction,
as that term is used in Financial Accounting Standards Board Accounting Standards Codification Topic 718 (or any
successor thereto). Notwithstanding the foregoing, the conversion of any convertible securities of the Company will not
be treated as a Capitalization Adjustment.
(d) “Cause” will have the meaning ascribed to such term in any written agreement between the Participant and the Company
or any Affiliate defining such term and, in the absence of such agreement, such term means, with respect to a Participant,
the occurrence of any of the following events: (i) such Participant’s conviction of any felony or any crime involving
moral turpitude or dishonesty, (ii) such Participant’s participation in a fraud or act of dishonesty against the Company,
(iii) such Participant’s conduct that, based upon a good faith and reasonable factual investigation and determination by
the Board, demonstrates the Participant’s gross unfitness to serve, or (iv) such Participant’s intentional, material violation
of any contract between the Company and the Participant or any statutory duty that the Participant has to the Company
that the Participant does not correct within 30 days after written notice to the Participant thereof. The determination as to
whether a Participant is being terminated for Cause will be made in good faith by the Company and will be final and
binding on the Participant. Any determination by the Company that the Continuous Service of a Participant was
terminated with or without Cause for the purposes of outstanding Stock Awards held by such Participant will have no
effect upon any determination of the rights or obligations of the Company, any Affiliate or such Participant for any other
purpose.
(e) “Code” means the U.S. Internal Revenue Code of 1986, as amended, including any applicable regulations and guidance
thereunder.
(f) “Committee” means a committee of one (1) or more Independent Directors to whom authority has been delegated by the
Board in accordance with Section 2(c).
(g) “Common Stock” means the common stock of the Company.
(h) “Company” means Rigel Pharmaceuticals, Inc., a Delaware corporation.
(i) “Consultant” means any person, including an advisor, who is (i) engaged by the Company or an Affiliate to render
consulting or advisory services and is compensated for such services, or (ii) serving as a member of the board of
directors of an Affiliate and is compensated for such services. However, service solely as a Director, or payment of a fee
for such service, will not cause a Director to be considered a “Consultant” for purposes of the Plan. Notwithstanding the
foregoing, a person is treated as a Consultant under this Plan only if a Form S-8 Registration Statement under the
Securities Act is available to register either the offer or the sale of the Company’s securities to such person.
(j) “Continuous Service” means that the Participant’s service with the Company or an Affiliate, whether as an Employee,
Director or Consultant, is not interrupted or terminated. A change in the capacity in which the Participant renders service
to the Company or an Affiliate as an Employee, Consultant or Director or a change in the Entity for which the Participant
renders such service, provided that there is no interruption or termination of the Participant’s service with the Company
or an Affiliate, will not terminate a Participant’s Continuous Service. For example, a change in status from an Employee
of the Company to a Consultant of an Affiliate or to a Director will not constitute an interruption of Continuous Service.
If the Entity for which a Participant is rendering services ceases to qualify as an Affiliate, as determined by the Board in
its sole discretion, such Participant’s Continuous Service will be considered to have terminated on the date such Entity
ceases to qualify as an Affiliate. To the extent permitted by law, the Board or the chief executive officer of the Company,
in that party’s sole discretion, may determine whether Continuous Service will be considered interrupted in the case of
(i) any leave of absence
11
approved by the Board or chief executive officer, including sick leave, military leave or any other personal leave, or
(ii) transfers between the Company, an Affiliate, or their successors. In addition, if required for exemption from or
compliance with Section 409A of the Code, the determination of whether there has been a termination of Continuous
Service will be made, and such term will be construed, in a manner that is consistent with the definition of “separation
from service” as defined under Treasury Regulation Section 1.409A-1(h). A leave of absence will be treated as
Continuous Service for purposes of vesting in a Stock Award only to such extent as may be provided in the Company’s
leave of absence policy, in the written terms of any leave of absence agreement or policy applicable to the Participant, or
as otherwise required by law.
(k) “Director” means a member of the Board. Directors are not eligible to receive Stock Awards under the Plan with respect
to their service in such capacity.
(l) “Disability” means the permanent and total disability of a person within the meaning of Section 22(e)(3) of the Code.
(m) “Effective Date” means October 10, 2016.
(n) “Employee” means any person employed by the Company or an Affiliate. However, service solely as a Director, or
payment of a fee for such services, will not cause a Director to be considered an “Employee” for purposes of the Plan.
(o) “Entity” means a corporation, partnership, limited liability company or other entity.
(p) “Exchange Act” means the Securities Exchange Act of 1934, as amended, and the rules and regulations promulgated
thereunder.
(q) “Fair Market Value” means, as of any date, the value of the Common Stock determined as follows:
(i)
If the Common Stock is listed on any established stock exchange or traded on any established market, the
Fair Market Value of a share of Common Stock will be, unless otherwise determined by the Board, the closing sales price for such
stock as quoted on such exchange or market (or the exchange or market with the greatest volume of trading in the Common Stock) on
the last market trading day prior to the date of determination, as reported in a source the Board deems reliable.
Unless otherwise provided by the Board, if there is no closing sales price for the Common Stock on the
date of determination, then the Fair Market Value will be the closing selling price on the last preceding date for which such quotation
exists.
(ii)
Board in good faith and in a manner that complies with Section 409A of the Code.
(iii)
In the absence of such markets for the Common Stock, the Fair Market Value will be determined by the
(r) “Independent Director” has the meaning set forth in Section 1(a) above.
(s) “Non-Employee Director” means a Director who either (i) is not a current employee or officer of the Company or an
Affiliate, does not receive compensation, either directly or indirectly, from the Company or an Affiliate for services
rendered as a consultant or in any capacity other than as a Director (except for an amount as to which disclosure would
not be required under Item 404(a) of Regulation S-K promulgated pursuant to the Securities Act (“Regulation S-K”)),
does not possess an interest in any other transaction for which disclosure would be required under Item 404(a) of
Regulation S-K, and is not engaged in a business relationship for which disclosure would be required pursuant to
Item 404(b) of Regulation S-K; or (ii) is otherwise considered a “non-employee director” for purposes of Rule 16b-3 of
the Exchange Act.
12
(t) “Nonstatutory Stock Option” means any option granted pursuant to Section 4(b) of the Plan that does not qualify as an
“incentive stock option” within the meaning of Section 422 of the Code.
(u) “Officer” means a person who is an officer of the Company within the meaning of Section 16 of the Exchange Act.
(v) “Option” means a Nonstatutory Stock Option to purchase shares of Common Stock granted pursuant to the Plan.
(w) “Option Agreement” means a written agreement between the Company and an Optionholder evidencing the terms and
conditions of an Option grant. Each Option Agreement will be subject to the terms and conditions of the Plan.
(x) “Optionholder” means a person to whom an Option is granted pursuant to the Plan or, if applicable, such other person
who holds an outstanding Option.
(y) “Participant” means a person to whom a Stock Award is granted pursuant to the Plan or, if applicable, such other person
who holds an outstanding Stock Award.
(z) “Plan” means this Rigel Pharmaceuticals, Inc. Inducement Plan, as it may be amended.
(aa) “Restricted Stock Unit Award” means a right to receive shares of Common Stock which is granted pursuant to the terms
and conditions of Section 6(b).
(bb)“Restricted Stock Unit Award Agreement” means a written agreement between the Company and a holder of a
Restricted Stock Unit Award evidencing the terms and conditions of a Restricted Stock Unit Award grant. Each
Restricted Stock Unit Award Agreement will be subject to the terms and conditions of the Plan.
(cc) “Rule 16b-3” means Rule 16b-3 promulgated under the Exchange Act or any successor to Rule 16b-3, as in effect from
time to time.
(dd)“Securities Act” means the Securities Act of 1933, as amended.
(ee) “Stock Award” means any right to receive Common Stock granted under the Plan, including an Option or a Restricted
Stock Unit Award.
(ff) “Stock Award Agreement” means a written agreement between the Company and a Participant evidencing the terms and
conditions of a Stock Award grant. Each Stock Award Agreement will be subject to the terms and conditions of the Plan.
13
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT
MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.
Exhibit 10.39
SUBLEASE AGREEMENT
This Sublease Agreement (“Sublease”), dated as of October 28, 2022, is by and between ATARA BIOTHERAPEUTICS,
INC., a Delaware corporation, having an office at 611 Gateway Boulevard, Suite 900, South San Francisco, CA 94080
(“Sublandlord”) and RIGEL PHARMACEUTICALS, INC., a Delaware corporation (“Subtenant”), having an office at 1180
Veterans Blvd, South San Francisco, CA 94080.
RECITALS
WHEREAS, Sublandlord, as tenant, and 611 Gateway Center LP, LLC, a Delaware limited partnership (as successor-in-
interest to BXP 611 Gateway Center LP) (“Prime Landlord”), as landlord, are parties to that certain Office Lease dated as of
November 25, 2015 (the “Original Primary Lease”), as amended by that certain First Amendment to Lease Agreement dated
October 21, 2020 (the “First Amendment to Original Primary Lease”), as further amended by that certain Second Amendment to
Lease Agreement dated December 9, 2021 (the “Second Amendment to Original Primary Lease” and, collectively with the
Original Primary Lease and the First Amendment to Original Primary Lease, the “Primary Lease”).
WHEREAS, pursuant to the Primary Lease, Sublandlord leases from Prime Landlord those certain premises comprised of
approximately 13,670 rentable square feet (the “Rentable Area”) of space located on the ninth (9th) floor and commonly known as
Suite 900 (“Demised Premises”), as more particularly described in the Primary Lease and located in the building having a street
address of 611 Gateway Boulevard, South San Francisco, CA 94080 (“Building”).
WHEREAS, Sublandlord desires to sublease all of the Demised Premises leased under the Primary Lease to Subtenant, and
Subtenant desires to sublease all of the Demised Premises from Sublandlord, in accordance with the terms and conditions of this
Sublease.
AGREEMENT
NOW, THEREFORE, in consideration of the mutual covenants, terms and conditions set forth herein, and for other good
and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties agree as follows:
1.
Demise and Existing FF&E. Subject to the terms below, Sublandlord hereby leases to Subtenant, and Subtenant
hereby leases from Sublandlord, the entire Demised Premises (also referred to herein as the “Subleased Premises”) as more
particularly shown on Exhibit A attached to and made a part of this Sublease, together with the right to use the common areas of the
Building as described in the Primary Lease. Sublandlord and Subtenant agree that the Rentable Area is conclusive for all purposes of
this Sublease and is not subject to remeasurement. On the Sublease Expiration Date (as hereinafter defined), Sublandlord shall
convey all existing furniture, fixtures, and equipment located in the Subleased Premises, including but not limited to all private
office, conference rooms, and cubicle furniture all of which are reflected on Schedule I attached hereto and made part hereof (the
“Existing FF&E”) to Subtenant. Sublandlord shall deliver all Existing FF&E to Subtenant in as-is condition via a quit claim bill of
sale. Subtenant shall: (i) pay Sublandlord Ten Dollars ($10.00) for the Existing FF&E on the Sublease Expiration Date; and (ii) remove
the Existing FF&E from the Subleased Premises in accordance with Section 23 of this Sublease by the Sublease Expiration Date.
2.
Term.
(a)
The term of this Sublease (the “Sublease Term”) shall commence on the date immediately following the
parties’ receipt of the Prime Landlord’s Consent (as defined below), but no sooner than November 1, 2022 (the “Sublease
Commencement Date”) and shall expire on May 24, 2025 (i.e., the date that is one (1) week prior to the scheduled expiration date
of the term of the Primary Lease ) (the “Sublease Expiration Date”), unless sooner terminated or cancelled in accordance with the
terms and conditions of this Sublease.
If for any reason the term of the Primary Lease is terminated prior to the Sublease Expiration Date, this Sublease
shall automatically terminate on the date of such termination and, unless resulting from a default by Sublandlord under this Sublease
and/or the Primary Lease, Sublandlord shall not be liable to Subtenant for such termination.
(b)
3.
Permitted Use. Subtenant shall use and occupy the Subleased Premises solely in accordance with, and as permitted
under, the terms of the Primary Lease and for no other purpose. Subtenant shall (i) not conduct, nor permit to be conducted, on the
Subleased Premises, any business which is in violation of any law or governmental regulation, and (ii) to the extent the responsibility of
Sublandlord under the Primary Lease and provided Sublandlord delivers the Subleased Premises in the condition required hereunder,
maintain the Subleased Premises in accordance with the terms of the Primary Lease.
4.
Payment of Base Rent and Additional Rent.
(a)
Throughout the Sublease Term, Subtenant shall pay to Sublandlord fixed base rent (“Base Rent”) at the rate
of: (i) $59,464.50 per month on a full-service basis from the Sublease Commencement Date to the Sublease Expiration Date, payable in
equal monthly installments, in advance, on the first day of each calendar month during the Sublease Term, pro rated on a per diem basis
for any partial calendar month(s). The Base Rent shall be subject to an annual three (3%) percent escalation effective on each anniversary
of Sublease Commencement Date, as more particularly set forth on the Base Rent table attached hereto as Schedule II. Subtenant shall
pay to Sublandlord the first monthly installment of Base Rent concurrently with the execution and delivery of this Sublease by Subtenant
to Sublandlord. Notwithstanding anything to the contrary herein, the Base Rent shall be abated in full for the first three full calendar
months of the Sublease Term.
(b)
In addition to Base Rent, commencing on the Sublease Commencement Date and continuing throughout the
Sublease Term, Subtenant shall pay to Sublandlord at the place where Base Rent is payable all Direct Expenses and all other Additional
Rent payable by Sublandlord under the Primary Lease. For all such Additional Rent, Sublandlord will be responsible for any underpaid
amounts, as well as entitled to reimbursement of overpaid amounts, relating to the period prior to the Sublease Commencement Date.
Subtenant will be responsible for any underpaid amounts, as well as entitled to reimbursement of overpaid amounts, first arising or
accruing during the period from and after the Sublease Commencement Date. Notwithstanding the foregoing or anything herein to the
contrary, rent under this Sublease shall not include, and Subtenant shall have no responsibility or liability for the payment of any cost,
expense, and/or charge arising from Sublandlord’s failure to perform its obligations under this Sublease or the Primary Lease.
(c)
All Base Rent and Additional Rent shall be due and payable without demand therefor and without any
deduction, offset, abatement, counterclaim or defense, except as otherwise expressly set forth herein. The monthly installments of Base
Rent and Additional Rent payable on account of any partial calendar month during the Sublease Term, if any, shall be prorated on a per
diem basis. Subtenant shall make payment for such rent by ACH payment or electronic funds transfer, provided that Sublandlord has
provided its account information. Any rent paid directly by Subtenant to Prime Landlord at Prime Landlord’s or Sublandlord’s request
shall be credited to Subtenant’s corresponding rent obligation under this Sublease.
5.
Security Deposit. Simultaneously with the execution and delivery of this Sublease, Subtenant shall deposit with
Sublandlord a security deposit (“Security Deposit”) in the amount of One Hundred Fifty Thousand and 00/100 Dollars ($150,000.00) in
cash as security for the full and faithful performance by Subtenant of Subtenant’s obligations hereunder. Sublandlord shall return the
Security Deposit, reduced by the amounts, if any, that have been applied to remedy defaults of this Sublease by Subtenant, to Subtenant
within ten (10) business days after the expiration or earlier termination of this Sublease.
6.
Incorporation of Primary Lease by Reference.
(a)
The terms, covenants and conditions of the Primary Lease are incorporated herein by reference, except to the
extent they are expressly deleted or modified by the provisions of this Sublease. Except as set forth herein, every term, covenant and
condition of the Primary Lease binding upon or inuring to the benefit of Prime Landlord shall, in respect of this Sublease, be binding upon
or inure to the benefit of Sublandlord and every term, covenant and condition of the Primary Lease binding upon or inuring to the benefit
of Sublandlord shall, in respect of this Sublease, be binding upon and inure to the benefit of Subtenant. Whenever the term “Lessor” or
“Landlord” appears in the Primary Lease, the word “Sublandlord” shall be substituted therefor; whenever the term “Lessee” or
“Tenant” appears in the Primary Lease, the word “Subtenant” shall be substituted therefor; whenever the word “Premises” appears in the
Primary Lease, the word “Subleased Premises” shall be substituted therefor. With respect to work, services, and utilities that are
obligations of Prime Landlord under the Primary Lease, the sole responsibility of Sublandlord shall be to use commercially reasonable
efforts to obtain Prime Landlord’s performance
(b)
Notwithstanding the foregoing, (i) the following numbered paragraphs of the Primary Lease shall not apply to
this Sublease: The Summary of Basic Lease Information, excepting Sections 2, 7 and 12; Section 1.3 (Right of First Offer), Section 2.2
(Occurrence of Delivery Date); Article 3 (Base Rent), Article 14 (Assignment and Subletting) other than Section 14.8, Section 18.2
((Notice to Lienholder or Ground Lessor), Article 20 (Covenant of Quiet Enjoyment), Article 21 (Letter of Credit), Article 23 (Signs),
Article 28 (Notices), Section 29.24 (Brokers), Section 29.29 (Development of the Project), Exhibits B and H of the Original Primary
Lease, the first sentence of Section 1 and Sections 2, 3, 4, 5, and 6 of the First Amendment to Original Primary Lease, and the first
sentence of Section 1 and Sections 2.a, 5, 6 and 7 of the Second Amendment to Original Primary Lease, and (ii) the time limits contained
in the Primary Lease for Sublandlord, as tenant, to give notices, make demands or perform any act, covenant or condition or to exercise
any right, remedy or option, are modified herein by shortening the same in each instance by two (2) days, and (iii) references in the
following sections of the Primary Lease to “Landlord” shall refer only to Prime Landlord (as opposed to Prime Landlord and
Sublandlord): Article 6, Sections 10.1 and 10.12, and the first sentence of Section 3 of the Second Amendment to Original Primary Lease.
If any of the express provisions of this Sublease shall conflict with any of the provisions of the Primary Lease, the provisions of this
Sublease shall govern as between Sublandlord and Subtenant.
7.
Subordination to Primary Lease. This Sublease and all of Subtenant’s rights hereunder are subject and subordinate to the
Primary Lease. So long as Subtenant is not in default hereunder (beyond applicable notice and cure periods), Sublandlord shall not
terminate the Primary Lease without the prior consent of Subtenant (which may be granted or withheld in Subtenant’s sole discretion)
unless Prime Landlord agrees to recognize Subtenant as a direct tenant on the terms of this Sublease in conjunction with such termination.
8.
Reimbursement. If Sublandlord is required by Prime Landlord pursuant to the terms of the Prime Lease to reimburse
Prime Landlord for expenditures made by Prime Landlord resulting from Subtenant’s breach of the terms of this Sublease, Subtenant shall
pay to Sublandlord all amounts demanded by Prime Landlord no later than the earlier of (i) thirty (30) days after written demand by
Sublandlord, which demand shall include reasonable supporting documentation therefor, and (ii) two (2) days prior to the date when such
payment is required to be made by Sublandlord to Prime Landlord.
9.
AS-IS Condition. Subtenant acknowledges that, except as set forth in this Sublease, neither Sublandlord nor any of
Sublandlord’s agents, employees or representatives have made any representation or warranty, either express or implied, with respect
to the Premises, the condition of the Premises or the use of the Premises by Subtenant, and Subtenant accepts the Subleased Premises
in its current, “as-is” “where is” and “with all faults” condition. Sublandlord shall have no obligation to furnish or supply any work,
services, furniture, fixtures, equipment or decorations, provided, however, that Sublandlord shall deliver the Subleased Premises in
broom clean condition with all systems in good working order and condition. On or before the Sublease Expiration Date or earlier
termination or expiration of this Sublease, Subtenant shall restore the Subleased Premises to the condition existing as of the Sublease
Commencement Date, ordinary wear and tear, damage from casualty and condemnation, and, except to the extent removal is required
by Prime Landlord, permitted alterations and improvements excepted. The obligations of Subtenant hereunder shall survive the
expiration or earlier termination of this Sublease.
10.
Performance By Sublandlord. Notwithstanding any other provision of this Sublease but provided Sublandlord delivers
the Subleased Premises and the Existing FF&E in the condition required hereunder, Sublandlord shall have no obligation (a) to furnish or
provide, or cause to be furnished or provided, any repairs, restoration, alterations or other work, or electricity, heating, ventilation, air-
conditioning, water, elevator, cleaning or other utilities or services, or (b) to comply with or perform or, except as expressly provided in
this Sublease, to cause the compliance with or performance of, any of the terms and conditions required to be performed by Prime
Landlord pursuant to the terms of the Primary Lease. Subtenant hereby agrees that Prime Landlord is solely responsible for the
performance of the foregoing obligations. Notwithstanding the foregoing, upon the written request of Subtenant, Sublandlord shall make
written demand upon and otherwise use commercially reasonable efforts to cause Prime Landlord to perform its obligations under the
Primary Lease with respect to the Subleased Premises if Prime Landlord fails to perform same within the time frame and in the manner
required pursuant to the Primary Lease provided, however, Sublandlord shall not be required to bring any action against the Prime
Landlord to enforce its obligations; further provided, however, that if Primary Landlord defaults under the Primary Lease or fails to
perform any of its
obligations under the Primary Lease after receipt of written notice from Sublandlord of such failure, Sublandlord shall either institute legal
proceedings against Primary Landlord directly or assign Sublandlord's rights under the Primary Lease to Subtenant to the extent necessary
to permit Subtenant to institute legal proceedings against Primary Landlord to obtain performance of Primary Landlord’s obligations
under the Primary Lease; provided Subtenant agrees to indemnify and hold harmless Sublandlord for all claims, liabilities and damages
that Sublandlord may sustain as a result of, arising out of, or in connection therewith and pays Sublandlord all costs and expenses
reasonably incurred by Sublandlord in connection therewith. In the event Sublandlord brings an action against Prime Landlord to enforce
Prime Landlord’s obligations under the Primary Lease with respect to the Subleased Premises, all costs and expenses (including, without
limitation, reasonable attorneys’ fees and expenses) incurred by Sublandlord in connection therewith shall be deemed Additional Rent
and shall be due and payable by Subtenant to Sublandlord within thirty (30) days of demand (which shall include reasonable supporting
documentation) therefor. This Section 10 shall survive the expiration or earlier termination of the Sublease Term.
11.
No Privity of Estate; No Privity of Contract. Nothing in this Sublease shall be construed to create privity of estate or
privity of contract between Subtenant and Prime Landlord.
12.
No Breach of Primary Lease. Subtenant shall not do or permit (by its agents, employees and contractors) to be done any
act or thing, or omit to do anything required of it by the terms of this Sublease, which may constitute a breach or violation of any term,
covenant or condition of the Primary Lease, notwithstanding such act, thing or omission is permitted under the terms of this Sublease.
13.
Subtenant Defaults. If Subtenant fails to cure a default under this Sublease within any applicable notice, grace or cure
period contained in the Primary Lease (as such applicable notice, grace or cure period is modified by Section 6 herein), Sublandlord shall
have the right, but not the obligation, to seek to remedy any such default on the behalf of, and at the expense of, Subtenant, on the terms
of Article 19 of the Primary Lease, as incorporated herein. Any reasonable out-of-pocket cost and expense (including without limitation
reasonable attorneys’ fees and expenses) actually incurred by Sublandlord shall be deemed Additional Rent and shall be due and payable
by Subtenant to Sublandlord within thirty (30) days after notice from Sublandlord. If Sublandlord actually receives under the Primary
Lease an abatement of rent or any portion thereof resulting from any casualty, condemnation, interruption of services, of default by Prime
Landlord, then Subtenant shall be entitled to receive from Sublandlord the same such abatement.
14.
Consents. Whenever the consent or approval of Sublandlord is required under this Sublease, to the extent Prime
Landlord’s consent or approval is also required pursuant to the terms of the Primary Lease, Sublandlord shall promptly make such
consent or approval request of Prime Landlord and use commercially reasonable efforts to obtain such consent or approval, and
Subtenant shall use commercially reasonable efforts to promptly provide any information or documentation that Prime Landlord may
request in connection therewith. Subtenant shall reimburse Sublandlord, not later than thirty (30) days after written demand by
Sublandlord, for any actual and reasonable fees and disbursements of attorneys, architects, engineers or others charged by Prime
Landlord in connection with any such consent or approval. Sublandlord shall have no liability of any kind to Subtenant for Prime
Landlord’s failure to give its consent or approval so long as Sublandlord uses commercially reasonable efforts to obtain the same. In no
event shall Subtenant or Sublandlord be liable to the other for any consequential, special or punitive damages arising out of or in
connection with this Sublease, except to the extent Sublandlord is obligated to Prime Landlord for the same as a result of Subtenant’s
default under this Sublease.
15.
Prime Landlord Consent to Sublease.
(a)
This Sublease is expressly conditioned upon obtaining the written consent of Prime Landlord (“Prime
Landlord Consent”) in form and substance reasonably approved by Sublandlord and Subtenant. The parties acknowledge that Subtenant
shall request Prime Landlord to consent in the Prime Landlord Consent to permit Subtenant all of the parking and signage rights of
Sublandlord, as tenant under Section 29.18 and Article 23 of the Primary Lease, respectively, and that Subtenant may (at its option)
condition its approval of the Prime Landlord Consent on receipt thereof. For purposes of this Sublease, the Prime Landlord Consent shall
be deemed to have been given as of the date when the Prime Landlord Consent has been fully executed and delivered by Prime Landlord,
Sublandlord and Subtenant.
(b)
Notwithstanding Section 14 above to the contrary, any fees and expenses incurred by the Prime Landlord or any
mortgagee, ground lessor or other third party in connection with requesting and obtaining the Prime Landlord Consent shall be paid by
Sublandlord. Subtenant agrees to reasonably cooperate with Sublandlord and use commercially reasonable efforts to supply all
information and documentation requested by Prime Landlord within thirty (30) days of request therefor. Subtenant shall have no right to
any claim against Sublandlord in the
event the Prime Landlord Consent is not obtained, provided Sublandlord uses commercially reasonable efforts to obtain such consent.
(c)
If the Prime Landlord Consent is not obtained within thirty (30) days from the date of this Sublease, either
party may terminate this Sublease upon written notice to the other, whereupon Sublandlord shall promptly refund (but in any event within
10 business days) to Subtenant the first month’s Base Rent and the Security Deposit paid to Sublandlord, and neither party shall have any
further obligation to the other under this Sublease, except to the extent that the provisions of this Sublease expressly survive the
termination of this Sublease.
(d)
This Section 15 shall survive the expiration or earlier termination of this Sublease.
16.
Assignment or Subletting. Subtenant shall not sublet all or any portion of the Subleased Premises or assign, encumber,
mortgage, pledge or otherwise transfer this Sublease (by operation of law or otherwise) or any interest therein, without the prior written
consent of: (a) Sublandlord, which consent may be withheld in its sole and absolute discretion, except in connection with a transfer
effected pursuant to the terms of Section 14.8 of the Original Primary Lease, and (b) Prime Landlord.
17.
Indemnity. Subtenant shall indemnify and hold harmless Sublandlord from any claims, liabilities and damages that
Sublandlord may sustain as a result of, arising out of, or in connection with: (i) the use or occupancy of the Subleased Premises by
Subtenant, its agents, contractors, employees, invitees, licensees, servants, subcontractors or subtenants, (ii) any gross negligence or
willful misconduct of Subtenant or any of Subtenant’s agents, contractors, employees, invitees, licensees, subcontractors or subtenants,
and (iii) any failure by Subtenant to fully and promptly perform any of Subtenant’s obligations under this Sublease. Sublandlord shall
indemnify and hold harmless Subtenant from any claims, liabilities and damages that Subtenant may sustain as a result of, arising out of,
or in connection with: (i) the use or occupancy of the Subleased Premises by Sublandlord, its agents, contractors, employees, invitees,
licensees, servants, subcontractors or subtenants prior to the Sublease Commencement Date, (ii) any gross negligence or willful
misconduct of Sublandlord or any of Sublandlord's agents, contractors, employees, invitees, licensees, subcontractors or subtenants, and
(iii) any failure by Sublandlord to fully and promptly perform any of Sublandlord's obligations under this Sublease. This Section 17 shall
survive the expiration or earlier termination of the Sublease Term.
18.
Insurance.
(a)
Subtenant shall, at its sole cost, and with respect to the Subleased Premises, maintain throughout the Sublease
Term any insurance coverage required to be maintained by Sublandlord under the Primary Lease.
(b)
The insurance that Subtenant is required to maintain shall name Sublandlord and Prime Landlord as “additional
insureds.” Subtenant shall deliver certificates of all insurance required of Subtenant to Sublandlord and Prime Landlord no later than the
Sublease Commencement Date. Notwithstanding anything to the contrary contained herein, in no event shall Subtenant be required to
provide a copy of any insurance policy unless and to the extent actually required by Prime Landlord.
19.
Sublandlord Improvement Allowance. Subject to receipt of the Prime Landlord Consent, Subtenant shall be allowed the
use of the full amount of the remaining (as of the date of this Sublease) Tenant Improvement Allowance for Subtenant’s improvements to
the Subleased Premises to be performed in accordance with the terms of the Prime Lease, including the Work Letter attached as Exhibit A
to the Second Amendment to Original Primary Lease (the “Work Letter”), as incorporated herein, and Sublandlord shall promptly
cooperate with Subtenant in connection therewith and shall not withhold its consent to any design or construction of any Tenant
Improvements (as defined in the Work Letter) provided Prime Landlord consents to the same (to the extent the consent or approval of
Prime Landlord is required under the terms of said Work Letter). Additionally, upon written request from Subtenant, Sublandlord shall
make available to the Subtenant the Additional Tenant Improvement Allowance (as defined in the Work Letter) provided Prime Landlord
consents to the same pursuant to the Prime Landlord’s Consent, subject to the terms of the Primary Lease; provided that Subtenant shall
be responsible for any amounts in respect thereof required to be paid to Prime Landlord pursuant to the terms of the Primary Lease,
which amounts shall be payable hereunder as Additional Rent upon 30 days demand therefor.
20.
Surrender of the Subleased Premises. During the last week of the Sublease Term and upon not less than 24 hours’ prior
notice to Subtenant, Sublandlord may inspect the Premises to determine the work needed to be done to restore the Subleased Premises to
the condition required by the Primary Lease.
21.
Release. Subtenant hereby releases Sublandlord or anyone claiming through or under Sublandlord by way of
subrogation or otherwise. Subtenant hereby releases Prime Landlord or anyone claiming through or under Prime Landlord by way of
subrogation or otherwise to the extent that Sublandlord releases Prime Landlord pursuant to the terms of the Primary Lease. Subtenant
shall cause its insurance carriers to include any clauses or endorsements in favor of Sublandlord, Prime Landlord and any additional
parties, which Sublandlord is required to provide pursuant to the provisions of the Primary Lease.
22.
Notices. All notices and other communications required or permitted under this Sublease shall be addressed to the
addresses set forth below:
To Subtenant prior to the Sublease Commencement Date at: 1180 Veterans Blvd., South San Francisco, CA 94080, email:
[***]
To Subtenant after the Sublease Commencement Date at: 611 Gateway Boulevard, Suite 900, South San Francisco, CA 94080,
email: [***]
To Sublandlord at: 2380 Conejo Spectrum Street, Suite 200, Thousand Oaks, CA 91320
Either party may change its address(es) for notice on not less than five (5) business days’ notice to the other party. All notices,
demands or communications in connection with this Sublease shall be properly addressed and delivered as follows: (a) personally delivered;
or (b) submitted to an overnight courier service, charges prepaid; or (c) deposited in the mail (certified, return-receipt requested, and
postage prepaid); or (d) email, with a hard copy sent within one (1) day pursuant to (a), (b) or (c) above. Notices shall be deemed delivered
upon (i) receipt, if personally delivered, (ii) one (1) business day after being submitted to an overnight courier service or sent by email, and
(iii) three (3) business days after mailing, if mailed as set forth above.
23.
Holding Over. In the event Subtenant fails to vacate the Subleased Premises and remove the Existing FF&E at the end
of the Sublease Term, then in addition to Subtenant’s obligations and Sublandlord’s rights and remedies under Article 16 of the Primary
Lease, as incorporated by Section 6 (the “Incorporated Holdover Provision”), Subtenant shall be liable for and indemnify Sublandlord
for any and all costs and expenses actually incurred by Sublandlord under the Primary Lease, including, but not limited to, all rent and
other amounts owed by Sublandlord to Prime Landlord under the Primary Lease as a result of Subtenant’s holding over, but amounts
under this Section 23 shall be reduced by the amount required to be paid, and which is actually paid, by Subtenant to Sublandlord
pursuant to the Incorporated Holdover Provision so there is no duplication.
24.
Brokers. Sublandlord and Subtenant each represent to the other that it has not dealt with any other broker other than
Kidder Mathews representing Subtenant (“Subtenant’s Broker”) and Cushman & Wakefield representing Sublandlord (“Sublandlord’s
Broker”, and collectively with Subtenant’s Broker, “Broker”) in connection with this Sublease and the transactions contemplated hereby.
Sublandlord shall compensate Subtenant’s Broker and Sublandlord’s Broker each in accordance with a separate agreement. Sublandlord
and Subtenant each indemnify and hold harmless the other from and against all claims, liabilities, damages, costs and expenses (including
without limitation reasonable attorneys’ fees and other charges) arising out of any claim, demand or proceeding for commissions, fees,
reimbursement for expenses or other compensation by any person or entity who shall claim to have dealt with the indemnifying party in
connection with the Sublease other than Broker. This Section 24 shall survive the expiration or earlier termination of this Sublease.
25.
Signage. Subtenant shall have all of the signage rights granted to Sublandlord under the Primary Lease (including but
not limited to Article 23 of the Original Primary Lease), subject to Prime Landlord’s consent to the extent required under the Primary
Lease. Further, Subtenant acknowledges that Sublandlord’s signage rights for the Monument pursuant to Section 23.5 of the Original
Primary Lease are personal to Sublandlord and may not be assigned to any sublessee without the express consent of Prime Landlord.
26.
Parking. Subject to the terms of the Primary Lease, Subtenant shall have the exclusive right to use at all times during the
Sublease Term all of the parking spaces made available under the Primary Lease to Sublandlord. Further, Subtenant acknowledges that
Sublandlord’s parking passes pursuant to Section 29.18 of the Primary Lease may not be transferred, assigned, subleased or otherwise
alienated by Sublandlord without the express consent of Prime Landlord.
27.
Representations and Warranties. Subtenant represents and warrants to Sublandlord that Subtenant is authorized to enter
into this Sublease, that the person executing this Sublease on behalf of Subtenant is properly authorized to do so, and that Subtenant is a
validly existing entity authorized to do business in California. Sublandlord represents and warrants to Subtenant that Sublandlord is
authorized to enter into this Sublease, that the person executing this Sublease on behalf of Sublandlord is properly authorized to do so,
and that Sublandlord is a validly existing entity authorized to do business in California. Sublandlord further represents and warrants that, as
of the date hereof, (a) the Primary Lease is in full force and effect, and to the knowledge of Sublandlord, no defaults or events that, with the
passage of time or the giving of notice, or both, would constitute a default, exist thereunder on the part of Prime Landlord or Sublandlord,
(b) except for obtaining the Prime Landlord’s consent hereto, Sublandlord has the right to grant Subtenant the rights granted in this
Sublease, (c) the copy of the Primary Lease attached hereto as Exhibit B is a true, correct and complete copy of the Primary Lease and as
of the date hereof, there exist no other amendments or modifications to the Primary Lease except as expressly set forth therein, (d) the
expiration date under the Primary Lease is May 31, 2025. Sublandlord warrants that during the Sublease Term, Sublandlord shall, except
to the extent the same is an obligation of Subtenant hereunder, comply with the Primary Lease and make all payments to Prime Landlord
required thereunder (other than payments made directly by Subtenant to Prime Landlord, if any) and shall commit no default thereunder
(other than a default resulting from Subtenant’s default hereunder) beyond the expiration of any applicable notice and cure periods.
Sublessor shall perform all of its covenants and obligations under the Primary Lease that do not require for their performance possession
of the Subleased Premises and that are not otherwise to be performed by Sublessee under this Sublease on behalf of Sublessor to the
extent that Sublessor’s failure to perform would adversely affect Sublessee’s use or occupancy of the Subleased Premises. Sublessor shall
not agree to any amendment or modification of the Primary Lease that adversely affects Sublessee’s occupancy of and/or access to the
Subleased Premises, unless Sublessor first obtains Sublessee’s written approval of such amendment or modification.
28.
Entire Agreement. This Sublease contains the entire agreement between the parties with respect to the subject matter
contained herein and all prior negotiations and agreements are merged herein. In the event any provisions of this Sublease are held to be
invalid or unenforceable in any respect, the validity, legality or enforceability of the remaining provisions of this Sublease shall remain
unaffected.
29.
Amendments and Modifications. This Sublease may not be modified or amended in any manner other than by a written
agreement signed by Sublandlord and Subtenant.
30.
Successors and Assigns. The covenants and agreements contained in this Sublease shall bind and inure to the benefit of
Sublandlord and Subtenant and their respective permitted successors and assigns.
31.
Counterparts. This Sublease may be executed in any number of counterparts, each of which when so executed and
delivered shall be deemed an original for all purposes, and all such counterparts shall together constitute but one and the same instrument.
A manual signature on this Sublease, an image of which shall have been transmitted electronically, shall constitute an original signature
for all purposes. The delivery of copies of this Sublease, including executed signature pages where required, by electronic transmission
will constitute effective delivery of this Sublease for all purposes. The words “executed”, “execution”, “signed”, “signature”, and words
of like import in this Sublease shall include images of manually executed signatures transmitted by facsimile or other electronic format
(including, without limitation, “pdf”, “tiff” or “jpg”) and other electronic signatures (including, without limitation, DocuSign and
AdobeSign). The use of electronic signatures and electronic records (including, without limitation, any contract or other record created,
generated, sent, communicated, received, or stored by electronic means) shall be of the same legal effect, validity and enforceability as a
manually executed signature or use of a paper-based record-keeping system to the fullest extent permitted by applicable law, including
the Federal Electronic Signatures in Global and National Commerce Act, and any other applicable law, including, without limitation, any
state law based on the Uniform Electronic Transactions Act or the Uniform Commercial Code.
32.
Cumulative Remedies. All rights and remedies of Sublandlord and Subtenant under this Sublease, at law and in equity
are cumulative, and the exercise of one or more rights or remedies shall not be taken to exclude or waive the right to the exercise of any
other.
33.
Non-Waiver. No right or remedy under this Sublease shall be waived unless the waiver is in writing and signed by the
party claimed to have made the waiver, and such waiver shall not be interpreted as a continuing waiver.
34.
Interpretation. There shall be no presumption applied in the construction of this Sublease against the party that initially
drafted this Sublease. Except as otherwise specified in this Sublease: (i) “includes” and “including” mean includes or including by way of
illustration and not by way of limitation; (ii) “may” is permissive; (iii) references to Exhibits, Sections, or subsections are to those
attached to or included in this Sublease, and all Exhibits are incorporated into this Sublease; and (iv) the section and other headings in this
Sublease are for convenience only and do not limit or expand any provisions of this Sublease. Time is of the essence with respect to this
Sublease.
35.
Defined Terms. All capitalized terms not otherwise defined in this Sublease shall have the definitions contained in the
Primary Lease.
36.
Choice of Law. This Sublease shall be governed by, and construed in accordance with, the laws of the State of
California, without regard to conflict of law rules.
37.
Covenant of Quiet Enjoyment. Provided that Subtenant is not in default hereunder beyond applicable notice and cure
periods, Subtenant’s quiet enjoyment of the Subleased Premises shall not be interfered with or disturbed by Sublandlord, provided,
however, if the Primary Lease has been terminated for a reason other than (i) casualty or condemnation, or (ii) a default by Sublandlord in
performing in obligations thereunder (excluding any default that is caused by Subtenant’s failure to perform its obligations under this
Sublease) or under this Sublease (including Section 7 hereof), the termination of this Sublease as a consequence of the termination of the
Primary Lease shall not constitute a breach of this covenant of quiet enjoyment.
38.
Mail Delivery. Subtenant grants Sublandlord a right to: (i) continue to use the address of the Subleased Premises and
receive mail at the Subleased Premises until December 31, 2022; and (ii) pick up such mail from the Subleased Premises at mutually
convenient times and location agreed to by the parties until January 31, 2023. Prior to the date of this Sublease, Sublandlord has used
commercially reasonable efforts to update its labeling and mail addresses.
[Signature Page Follows]
IN WITNESS WHEREOF, the parties hereto have executed this Sublease as of the date first above written.
SUBLANDLORD:
ATARA BIOTHERAPEUTICS., INC.,
a Delaware corporation
By:/s/ Amar Murugan
Name: Amar Murugan
Title: SVP, General Counsel
SUBTENANT:
RIGEL PHARMACEUTICALS, INC.,
a Delaware corporation
By:/s/ Dean Schorno
Name: Dean Schorno
Title: Chief Financial Officer
EXHIBIT A DESCRIPTION OF LEASED PREMISES
Exhibit A of the Primary Lease is incorporated herein by reference.
EXHIBIT B
PRIMARY LEASE
See Attached.
SCHEDULE I EXISTING FF&E
All furniture, fixtures, and equipment located in the Subleased Premises as of the Sublease Commencement Date shall be considered
Existing FF&E. However, the IT equipment listed in that separate purchase agreement mutually agreed to by the parties shall not be
considered Existing FF&E.
SCHEDULE II BASE RENT TABLE
Months During Term
Monthly Base Rent
Month 1* - Month 12
$59,464.50**
Months 13 - 24
$61,248.44
Month 25 -Sublease Expiration Date
$63,085.89
*If the Sublease Commencement Date is not the first day of a calendar month, “Month 1”
shall be the period from the Sublease Commencement Date through the last day of the first full
calendar month thereafter.
**Subject to abatement pursuant to Section 4(a) above.
13
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED BECAUSE IT IS BOTH (I) NOT
MATERIAL AND (II) IS THE TYPE THAT THE REGISTRANT TREATS AS PRIVATE OR CONFIDENTIAL.
Exhibit 10.40
November 17, 2022
Raymond Furey
[***]
Re: Employment Terms
Dear Raymond:
Rigel Pharmaceuticals, Inc. (the Company) is pleased to offer you the position of Executive Vice President and General Counsel on the
terms set forth in this letter.
This is a full-time, exempt position reporting to me. You will be responsible for all duties customarily associated with this position and
such duties as may be assigned to you by the Company from time to time. You will work at our facility located at 1180 Veterans
Boulevard, South San Francisco, California through the end of the year and thereafter at 611 Gateway Boulevard, South San Francisco,
California. Of course, the Company may change your position, duties and work location from time to time, as it deems necessary.
If you accept this offer (the “Agreement”), your annual salary will be $440,000 (Four Hundred Forty Thousand Dollars and No Cents),
less all required withholdings and any voluntary payroll deductions, which salary will be reviewed periodically. In addition, you will be
eligible for a Company bonus of 50%, based on achievement of your individual and the Company’s goals, determined in the sole
discretion of the Company, as well as such other criteria as determined by the Company. Additionally, under the Company's Amended
and Restated Severance Plan of 1/24/18, in the instance of a termination in the case of a change-in-control, you will qualify for a
severance of 2.5x (salary + eligible bonus), vesting of all stock options, 1 year period to exercise options, and 1.5 years of COBRA, all
under certain conditions, and in the absence of a change-in-control, you will qualify for a severance of 1 year (paid monthly), vesting of
stock in the amount of that which would vest over the next year, a 2 year period to exercise options, and 1 year of COBRA, all under
certain conditions. The Company may modify compensation and benefits from time to time, as it deems necessary.
You will be eligible for the Company’s standard benefits, available to similarly situated employees, including medical insurance,
vacation, sick leave, and holidays, subject to the terms and conditions of such plans. Details about these benefits are included for your
review. The Company may modify compensation and benefits from time to time, as it deems necessary.
Additionally, you will be granted the following equity grant after commencement of your employment: an option to purchase (1)
187,500 (One hundred and eighty-seven thousand, five hundred) shares of the Company's common stock, which has a four year vesting
period initiated on your start-date, 1/4th (one-fourth) of the shares vest one year after your hire date, and 1/48th (one forty-eighth) of the
shares vest monthly thereafter over the next three years (“time-based option grant”), (2) 93,750 (Ninety three thousand, seven hundred
fifty) shares of the Company’s common stock which will vest upon [***](“performance-based option grants”) and (3) 93,750 (Ninety
three thousand, seven hundred fifty) shares of the Company’s common stock which will vest upon achieving [***] (“performance-based
option grants”). The strike price for the time-based and performance-based option grant shall be the same as the close price on
NASDAQ on the day that your equity grant is approved by the Rigel Compensation Committee.
This offer is contingent upon Rigel receiving successful results from a background check conducted on you by our third-party vendor
and your compliance with our COVID-19 vaccination policy.
As a Rigel employee, you will be required to sign and comply with the Company Proprietary Information and Inventions Agreement,
attached hereto as Exhibit 1, which prohibits unauthorized use or disclosure of Company proprietary information.
You may terminate your employment with the Company at any time and for any reason whatsoever simply by notifying the Company.
Likewise, the Company may terminate your employment at any time and for any reason whatsoever, with or without cause or advance
notice. This at-will employment relationship cannot be changed except in writing signed by you and a Company officer.
1
You agree that, for one (1) year following the termination of your employment with the Company, you will not personally initiate or
participate in the solicitation of any employee of the Company or any of its affiliates to terminate his or her relationship with the
Company or any of its affiliates in order to become an employee for any other person or business entity.
To ensure rapid and economical resolution of any disputes which may arise under this Agreement, you and the Company agree that any
and all disputes or controversies, whether of law or fact of any nature whatsoever (including, but not limited to, all state and federal
statutory and discrimination claims) arising from or regarding your employment or the termination thereof, or the interpretation,
performance, enforcement or breach of this Agreement shall be resolved, pursuant to the Federal Arbitration Act, 9 U.S.C. § 1-16, to the
fullest extent permitted by law, by confidential, final and binding arbitration conducted by JAMS or its successor, under JAMS’ then
applicable rules and procedures for employment disputes before a single arbitrator (available upon request and also currently available at
http://www.jamsadr.com/rules-employment-arbitration/) and conducted in San Francisco, California. You acknowledge that by
agreeing to this arbitration procedure, both you and the Company waive the right to resolve any such dispute through a trial by
jury or judge or administrative proceeding. In addition, all claims, disputes, or causes of action under this section, whether by you or
the Company, must be brought in an individual capacity, and shall not be brought as a plaintiff (or claimant) or class member in any
purported class or representative proceeding, nor joined or consolidated with the claims of any other person or entity. The arbitrator may
not consolidate the claims of more than one person or entity, and may not preside over any form of representative or class proceeding.
To the extent that the preceding sentences regarding class claims or proceedings are found to violate applicable law or are otherwise
found unenforceable, any claim(s) alleged or brought on behalf of a class shall proceed in a court of law rather than by arbitration. This
paragraph shall not apply to any action or claim that cannot be subject to mandatory arbitration as a matter of law, including, without
limitation, claims brought pursuant to the California Private Attorneys General Act of 2004, as amended, the California Fair
Employment and Housing Act, as amended, and the California Labor Code, as amended, to the extent such claims are not permitted by
applicable law(s) to be submitted to mandatory arbitration and the applicable law(s) are not preempted by the Federal Arbitration Act or
otherwise invalid (collectively, the “Excluded Claims”). In the event you intend to bring multiple claims, including one of the Excluded
Claims listed above, the Excluded Claims may be filed with a court, while any other claims will remain subject to mandatory arbitration.
You will have the right to be represented by legal counsel at any arbitration proceeding. Questions of whether a claim is subject to
arbitration under this agreement shall be decided by the arbitrator. Likewise, procedural questions which grow out of the dispute and
bear on the final disposition are also matters for the arbitrator. The arbitrator shall: (a) have the authority to compel adequate discovery
for the resolution of the dispute and to award such relief as would otherwise be permitted by law; and (b) issue a written statement
signed by the arbitrator regarding the disposition of each claim and the relief, if any, awarded as to each claim, the reasons for the award,
and the arbitrator’s essential findings and conclusions on which the award is based. The arbitrator shall be authorized to award all relief
that you or the Company would be entitled to seek in a court of law. The Company shall pay all JAMS arbitration fees in excess of the
administrative fees that you would be required to pay if the dispute were decided in a court of law. Nothing in this Agreement is
intended to prevent either you or the Company from obtaining injunctive relief in court to prevent irreparable harm pending the
conclusion of any such arbitration. Any awards or orders in such arbitrations may be entered and enforced as judgments in the federal
and state courts of any competent jurisdiction.
This Agreement, including Exhibit 1, constitutes the complete, final and exclusive embodiment of the entire agreement between you and
the Company with respect to the terms and conditions of your employment. This Agreement is entered into without reliance upon any
promise, warranty or representation, written or oral, other than those expressly contained herein, and it supersedes any other such
promises, warranties, representations or agreements. It may not be amended or modified except by a written instrument signed by you
and a duly authorized representative of the Company (except with respect to terms reserved to the Company’s discretion). This
Agreement may be delivered and executed via facsimile, electronic mail (including pdf or any electronic signature complying with the
U.S. federal ESIGN Act of 2000, Uniform Electronic Transactions Act or other applicable law) or other transmission method and shall
be deemed to have been duly and validly delivered and executed and be valid and effective for all purposes.
If any provision of this Agreement is determined to be invalid or unenforceable, in whole or in part, this determination will not affect
any other provision of this Agreement. This Agreement shall be construed and interpreted in accordance with the laws of the State of
California and shall be deemed drafted by both parties.
As required by law, this offer is subject to satisfactory proof of your right to work in the United States.
We are very excited about your joining our team and being part of Rigel's plan for success. As discussed, we expect your start date to be
on November 21, 2022. Please formalize your acceptance by providing us with your signature on this letter and the Exhibit 1.
2
Sincerely,
/s/ Raul Rodriquez
Raul Rodriguez
CEO, Rigel Pharmaceuticals, Inc.
Accepted:
/s/ Raymond Furey
Raymond Furey
Date: November 18, 2022
3
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We consent to the incorporation by reference in the following Registration Statements:
Exhibit 23.1
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Registration Statements (Form S-8 Nos. 333-51184, 333-106532, 333-125895 and 333-148132) pertaining to the 2000 Equity
Incentive Plan, the 2000 Employee Stock Purchase Plan and the 2000 Non-Employee Directors’ Stock Option Plan of Rigel
Pharmaceuticals, Inc.,
Registration Statements (Form S-8 Nos. 333-155031 and 333-168495) pertaining to the 2000 Equity Incentive Plan and the
2000 Non-Employee Directors’ Stock Option Plan of Rigel Pharmaceuticals, Inc.,
Registration Statement (Form S-8 No. 333-134622) pertaining to the 2000 Equity Incentive Plan and 2000 Employee Stock
Purchase Plan of Rigel Pharmaceuticals, Inc.,
Registration Statement (Form S-8 No. 333-72492) pertaining to the 2001 Non-Officer Equity Incentive Plan of Rigel
Pharmaceuticals, Inc.,
Registration Statements (Form S-8 Nos. 333-107062, 333-139516 and 333-196535) pertaining to the 2000 Employee Stock
Purchase Plan of Rigel Pharmaceuticals, Inc.,
Registration Statement (Form S-8 No. 333-111782) pertaining to the 2000 Equity Incentive Plan of Rigel
Pharmaceuticals, Inc.,
Registration Statements (Form S-8 Nos. 333-175977 and 333-189523) pertaining to the 2011 Equity Incentive Plan, the 2000
Equity Incentive Plan and the 2000 Non-Employee Directors’ Stock Option Plan of Rigel Pharmaceuticals, Inc.,
Registration Statement (Form S-8 Nos. 333-212878 and 333-183130) pertaining to the 2011 Equity Incentive Plan of Rigel
Pharmaceuticals, Inc.,
Registration Statements (Form S-8 Nos. 333-214370, 333-216516, 333-221400 and 333-263187) pertaining to the Rigel
Pharmaceuticals, Inc. Inducement Plan,
(10) Registration Statement (Form S-8 No. 333-219610) pertaining to the 2000 Non-Employee Directors’ Stock Option Plan and
the 2011 Equity Incentive Plan of Rigel Pharmaceuticals, Inc.,
(11)
(12)
(13)
Registration Statement (Form S-8 No. 333-226700 and 333-266501) pertaining to the 2018 Equity Incentive Plan and the
Inducement Plan of Rigel Pharmaceuticals, Inc.,
Registration Statements (Form S-8 Nos. 333-233064 and 333-240371) pertaining to the 2018 Equity Incentive Plan of Rigel
Pharmaceuticals, Inc.,
Registration Statements (Form S-8 No. 333-257226) pertaining to the 2018 Equity Incentive Plan and the 2000 Employee
Stock Purchase Plan of Rigel Pharmaceuticals, Inc., and
(14)
Registration Statement (Form S-3 No.333-258426) of Rigel Pharmaceuticals, Inc. and in the related Prospectuses;
of our reports dated March 7, 2023, with respect to the financial statements of Rigel Pharmaceuticals, Inc. and the effectiveness of internal
control over financial reporting of Rigel Pharmaceuticals, Inc. included in this Annual Report (Form 10-K) of Rigel Pharmaceuticals, Inc. for the
year ended December 31, 2022.
/s/ Ernst & Young LLP
San Francisco, California
March 7, 2023
Exhibit 31.1
I, Raul R. Rodriguez, certify that:
CERTIFICATION
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Rigel Pharmaceuticals, Inc.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to
make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the
period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material
respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as
defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act
Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a)
b)
c)
d)
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made
known to us by others within those entities, particularly during the period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed
under our supervision, 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;
Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions
about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on
such evaluation; and
Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the
registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially
affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5.
The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial
reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent
functions):
a)
b)
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting
which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial
information; and
Any fraud, whether or not material, that involves management or other employees who have a significant role in the
registrant’s internal control over financial reporting.
Date: March 7, 2023
R
/s/ RAUL R. RODRIGUEZ
Raul R. Rodriguez
Chief Executive Officer
Exhibit 31.2
I, Dean L. Schorno, certify that:
CERTIFICATION
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Rigel Pharmaceuticals, Inc.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to
make the statements made, in light of the circumstances under which such statements were made, not misleading with respect to the
period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material
respects the financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as
defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act
Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
a)
b)
c)
d)
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made
known to us by others within those entities, particularly during the period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed
under our supervision, 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;
Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions
about the effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on
such evaluation; and
Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the
registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially
affected, or is reasonably likely to materially affect, the registrant’s internal control over financial reporting; and
5.
The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial
reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent
functions):
a)
b)
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting
which are reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial
information; and
Any fraud, whether or not material, that involves management or other employees who have a significant role in the
registrant’s internal control over financial reporting.
Date: March 7, 2023
/s/ DEAN L. SCHORNO
Dean L. Schorno
Executive Vice President and Chief Financial Officer
CERTIFICATIONS OF CHIEF EXECUTIVE OFFICER AND CHIEF FINANCIAL OFFICER
PURSUANT TO
18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
Pursuant to the requirement set forth in Rule 13a-14(b) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), and
Section 1350 of Chapter 63 of Title 18 of the United States Code (18 U.S.C. §1350), Raul R. Rodriguez, Chief Executive Officer of Rigel
Pharmaceuticals, Inc. (the “Company”), and Dean L. Schorno, Executive Vice President and Chief Financial Officer of the Company, each
hereby certifies that, to the best of his knowledge:
1.
2.
The Company’s Annual Report on Form 10-K for the period ended December 31, 2022, to which this Certification is attached
as Exhibit 32.1 (the “Annual Report”), fully complies with the requirements of Section 13(a) or Section 15(d) of the Exchange
Act; and
The information contained in the Annual Report fairly presents, in all material respects, the financial condition and results of
operations of the Company.
In Witness Whereof, the undersigned have set their hands hereto as of March 7, 2023.
/s/ RAUL R. RODRIGUEZ
Raul R. Rodriguez
Chief Executive Officer
/s/ DEAN L. SCHORNO
Dean L. Schorno
Executive Vice President and Chief Financial Officer
This certification accompanies the Form 10-K to which it relates, is not deemed filed with the Securities and Exchange Commission
and is not to be incorporated by reference into any filing of Rigel Pharmaceuticals, Inc. under the Securities Act of 1933, as amended, or the
Securities Exchange Act of 1934, as amended (whether made before or after the date of the Form 10- K), irrespective of any general
incorporation language contained in such filing.