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, 2021
or
For the transition period from to
Commission File Number: 001-12400
INCYTE CORPORATION
(Exact name of registrant as specified in its charter)
Delaware
(State of other jurisdiction
of incorporation or organization)
1801 Augustine Cut-Off
Wilmington, DE
(Address of principal executives offices)
94-3136539
(IRS Employer
Identification No.)
19803
(zip code)
(302) 498-6700
(Registrant’s telephone number, including area code)
Title of each class
Common Stock, $.001 par value per share
Trading Symbol(s)
INCY
Name of exchange on which registered
The Nasdaq Stock Market LLC
Securities registered pursuant to Section 12(b) of the Act:
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. ☒
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒
The aggregate market value of Common Stock held by non-affiliates (based on the closing sale price on The Nasdaq Global Select Market on June 30, 2021)
was approximately $16.0 billion.
As of February 1, 2022 there were 221,325,189 shares of Common Stock, $.001 par value per share, outstanding.
DOCUMENTS INCORPORATED BY REFERENCE
Items 10 (as to directors and Section 16(a) Beneficial Ownership Reporting Compliance), 11, 12, 13 and 14 of Part III incorporate by reference information
from the registrant’s proxy statement to be filed with the Securities and Exchange Commission in connection with the solicitation of proxies for the registrant’s 2022
Annual Meeting of Stockholders to be held on June 15, 2022.
Table of Contents
Forward-Looking Statements
Summary Risk Factors
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
Information about our Executive Officers
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
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, Financial Statement Schedules
Form 10-K Summary
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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.
PART III
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
PART IV
Item 15.
Item 16.
SIGNATURES
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1
Forward-Looking Statements
This report contains forward-looking statements that involve risks and uncertainties. These statements relate to
future periods, future events or our future operating or financial plans or performance. Often, these statements include the
words “believe,” “expect,” “target,” “anticipate,” “intend,” “plan,” “seek,” “estimate,” “potential,” or words of
similar meaning, or future or conditional verbs such as “will,” “would,” “should,” “could,” “might,” or “may,” or the
negative of these terms, and other similar expressions. These forward-looking statements include statements as to:
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the discovery, development, formulation, manufacturing and commercialization of our compounds, our drug
candidates and JAKAFI®/JAKAVI® (ruxolitinib), PEMAZYRE® (pemigatinib), ICLUSIG® (ponatinib),
MONJUVI®(tafasitamab-cxix) /MINJUVI® (tafasitamab), and OPZELURA™ (ruxolitinib) cream;
our plans to further develop our operations outside of the United States;
conducting clinical trials internally, with collaborators, or with clinical research organizations;
our collaboration and strategic relationship strategy, and anticipated benefits and disadvantages of entering
into collaboration agreements;
our licensing, investment and commercialization strategies, including our plans to commercialize our drug
products and drug candidates;
the regulatory approval process, including obtaining U.S. Food and Drug Administration and other
international health authorities’ approval for our products in the United States and abroad;
the safety, effectiveness and potential benefits and indications of our drug candidates and other compounds
under development;
the timing and size of our clinical trials; the compounds expected to enter clinical trials; timing of clinical
trial results;
our ability to manage expansion of our drug discovery and development operations;
future required expertise relating to clinical trials, manufacturing, sales and marketing;
obtaining and terminating licenses to products, drug candidates or technology, or other intellectual property
rights;
the receipt from or payments pursuant to collaboration or license agreements resulting from milestones or
royalties;
plans to develop and commercialize products on our own;
plans to use third-party manufacturers;
plans for our manufacturing operations;
expected expenses and expenditure levels; expected uses of cash; expected revenues and sources of revenues,
including milestone payments; expectations with respect to inventory;
expectations with respect to reimbursement for our products;
the expected impact of recent accounting pronouncements and changes in tax laws;
expected losses; fluctuation of losses; currency translation impact associated with collaboration royalties;
our profitability; the adequacy of our capital resources to continue operations;
the need to raise additional capital;
the costs associated with resolving matters in litigation and governmental proceedings;
our expectations regarding competition;
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expectations relating to the anticipated completion and GMP approval dates for our large molecule
production facility;
our investments, including anticipated expenditures, losses and expenses;
our patent prosecution and maintenance efforts; and
the potential effects of the COVID-19 pandemic and efforts undertaken or to be undertaken by us or
applicable governmental authorities on local and global economic conditions, and on our business, results
of operations and financial condition.
These forward-looking statements reflect our current views with respect to future events, are based on
assumptions and are subject to risks and uncertainties. These risks and uncertainties could cause actual results to differ
materially from those projected and include, but are not limited to:
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our ability to successfully commercialize our drug products and drug candidates;
our ability to obtain, or maintain at anticipated levels, coverage and reimbursement for our products from
government health administration authorities, private health insurers and other organizations;
our ability to establish and maintain effective sales, marketing and distribution capabilities;
the risk of reliance on other parties to manufacture our products, which could result in a short supply of our
products, increased costs, and withdrawal of regulatory approval;
our ability to maintain regulatory approvals to market our products;
our ability to achieve a significant market share in order to achieve or maintain profitability;
the risk of civil or criminal penalties if we market our products in a manner that violates health care fraud
and abuse and other applicable laws, rules and regulations;
our ability to discover, develop, formulate, manufacture and commercialize our drug candidates;
the risk of unanticipated delays in, or discontinuations of, research and development efforts;
the risk that previous preclinical testing or clinical trial results are not necessarily indicative of future
clinical trial results;
risks relating to the conduct of our clinical trials;
changing regulatory requirements;
the risk of adverse safety findings;
the risk that results of our clinical trials do not support submission of a marketing approval application for
our drug candidates;
the risk of significant delays or costs in obtaining regulatory approvals;
risks relating to our reliance on third-party manufacturers, collaborators, and clinical research
organizations;
risks relating to the development of new products and their use by us and our current and potential
collaborators;
risks relating to our inability to control the development of out-licensed compounds or drug candidates;
risks relating to our collaborators’ ability to develop and commercialize JAKAVI, OLUMIANT, TABRECTA
and the drug candidates licensed from us;
costs associated with prosecuting, maintaining, defending and enforcing patent claims and other intellectual
property rights;
our ability to maintain or obtain adequate product liability and other insurance coverage;
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the risk that our drug candidates may not obtain or maintain regulatory approval;
the impact of technological advances and competition, including potential generic competition;
our ability to compete against third parties with greater resources than ours;
risks relating to changes in pricing and reimbursement in the markets in which we may compete;
risks relating to governmental healthcare reform efforts, including efforts to control, set or cap pricing for
our commercial drugs in the U.S and abroad;
competition to develop and commercialize similar drug products;
our ability to obtain and maintain patent protection and freedom to operate for our discoveries and to
continue to be effective in expanding our patent coverage;
the impact of changing laws on our patent portfolio;
developments in and expenses relating to litigation;
our ability to in-license drug candidates or other technology;
unanticipated construction, other delays or changes in plans or regulatory agency interactions relating to
our large molecule production facility;
our ability to integrate successfully acquired businesses, development programs or technology;
our ability to obtain additional capital when needed;
fluctuations in net cash provided and used by operating, financing and investing activities;
our ability to analyze the effects of new accounting pronouncements and apply new accounting rules;
risks relating to our ability to sustain profitability;
risks related to public health pandemics such as the COVID-19 pandemic; and
the risks set forth under “Risk Factors.”
Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements.
Except as required by federal securities laws, we undertake no obligation to update any forward-looking statements for
any reason, even if new information becomes available or other events occur in the future.
In this report all references to “Incyte,” “we,” “us,” “our” or the “Company” mean Incyte Corporation and
our subsidiaries, except where it is made clear that the term means only the parent company.
Incyte, JAKAFI and PEMAZYRE are our registered trademarks and OPZELURA is our trademark. We also refer
to trademarks of other corporations and organizations in this Annual Report on Form 10-K.
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Summary Risk Factors
Our business is subject to numerous risks and uncertainties that could affect our ability to successfully implement
our business strategy and affect our financial results. You should carefully consider all of the information in this report
and, in particular, the following principal risks and all of the other specific factors described in Item 1A. of this report,
“Risk Factors,” before deciding whether to invest in our company.
• We depend heavily on JAKAFI/JAKAVI (ruxolitinib), and if we are not able to maintain revenues from
JAKAFI/JAKAVI or those revenues decrease, our business may be materially harmed.
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If we or our collaborators are unable to obtain, or maintain at anticipated levels, coverage and reimbursement for
our products from government and other third-party payors, our results of operations and financial condition could
be harmed.
• A limited number of specialty pharmacies and wholesalers represent a significant portion of revenues from
JAKAFI and most of our other products, and the loss of, or significant reduction in sales to, any one of these
specialty pharmacies or wholesalers could harm our operations and financial condition.
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If we are unable to establish and maintain effective sales, marketing and distribution capabilities, or to enter into
agreements with third parties to do so, we will not be able to successfully commercialize our products.
If we fail to comply with applicable laws and regulations, we could lose our approval to market our products or
be subject to other governmental enforcement activity.
If the use of our products harms or is perceived to harm patients, our regulatory approvals could be revoked or
otherwise negatively impacted or we could be subject to costly product liability claims.
If we market our products in a manner that violates various laws and regulations, we may be subject to civil or
criminal penalties.
• Competition for our products could harm our business and result in a decrease in our revenue.
• The COVID-19 pandemic and measures to address the pandemic have adversely affected and could in the future
adversely affect our business and results of operations.
• We or our collaborators may be unsuccessful in discovering and developing drug candidates, and we may spend
significant time and money attempting to do so, in particular with our later stage drug candidates.
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If we or our collaborators are unable to obtain regulatory approval in and outside of the United States for drug
candidates, we and our collaborators will be unable to commercialize those drug candidates.
• Health care reform measures could impact the pricing and profitability of pharmaceuticals, and adversely affect
the commercial viability of our or our collaborators’ products and drug candidates.
• Conflicts between us and our collaborators or termination of our collaboration agreements could limit future
development and commercialization of our drug candidates and harm our business.
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If we are unable to establish collaborations to fully exploit our drug discovery and development capabilities or if
future collaborations are unsuccessful, our future revenue prospects could be diminished.
If we fail to enter into additional in-licensing agreements or if these arrangements are unsuccessful, we may be
unable to increase our number of successfully marketed products and our revenues.
• Even if one of our drug candidates receives regulatory approval, we may determine that commercialization would
not be worth the investment.
• Any approved drug product that we bring to the market may not gain market acceptance by physicians, patients,
healthcare payors and others in the medical community.
• We have limited capacity to conduct preclinical testing and clinical trials, and our resulting dependence on other
parties could result in delays in and additional costs for our drug development efforts.
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• We face significant competition for our drug discovery and development efforts, and if we do not compete
effectively, our commercial opportunities will be reduced or eliminated.
• Our reliance on others to manufacture our drug products and drug candidates could result in drug supply
constraints, delays in clinical trials, increased costs, and withdrawal or denial of regulatory approvals.
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If we fail to comply with the extensive legal and regulatory requirements affecting the health care industry, we
could face increased costs, penalties and a loss of business.
• The illegal distribution and sale by third parties of counterfeit or unfit versions of our or our collaborators’
products or stolen products could harm our business and reputation.
• As most of our drug discovery and development operations are conducted at our headquarters in Wilmington,
Delaware, the loss of access to this facility would negatively impact our business.
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If we lose any of our key employees or are unable to attract and retain additional personnel, our business and
ability to achieve our objectives could be harmed.
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If we fail to manage our growth effectively, our ability to develop and commercialize products could suffer.
• We may acquire businesses or assets, form joint ventures or make investments in other companies that may be
unsuccessful, divert our management’s attention and harm our operating results and prospects.
• Risks associated with our operations outside of the United States could adversely affect our business.
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If product liability lawsuits are brought against us, we could face substantial liabilities and may be required to
limit commercialization of our products, and our results of operations could be harmed.
• Because our activities involve the use of hazardous materials, we may be subject to claims relating to improper
handling, storage or disposal of these materials that could be time consuming and costly.
• We expect to continue to incur significant expenses to discover and develop drugs, which could result in future
losses and impair our achievement of and ability to sustain profitability in the future.
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If we are unable to raise additional capital in the future when we require it, our efforts to broaden our product
portfolio or commercialization efforts could be limited.
• Our marketable securities and long term investments are subject to risks that could adversely affect our overall
financial position, and tax law changes could adversely affect our results of operations and financial condition.
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If we are unable to achieve milestones, develop product candidates to license or renew or enter into new
collaborations, our royalty and milestone revenues and future prospects for those revenues may decrease.
• Any arbitration or litigation involving us and regarding intellectual property infringement claims could be costly
and disrupt our drug discovery and development efforts.
• Our inability to adequately protect or enforce our proprietary information may result in loss of revenues or
otherwise reduce our ability to compete.
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If the effective term of our patents is decreased or if we need to refile some of our patent applications, the value
of our patent portfolio and the revenues we derive from it may be decreased.
International patent protection is particularly uncertain and costly, and our involvement in opposition proceedings
may result in the expenditure of substantial sums and management resources.
• Significant disruptions of information technology systems, breaches of data security, or unauthorized disclosures
of sensitive data could harm our business and subject us to liability or reputational damage.
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Increasing use of social media could give rise to liability, breaches of data security, or reputational damage, which
could harm our business and results of operations.
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Item 1. Business
Overview
Incyte is a biopharmaceutical company focused on the discovery, development and commercialization of
proprietary therapeutics. Our global headquarters is located in Wilmington, Delaware, where we conduct global clinical
development and commercial operations. We also conduct clinical development and commercial operations from our
country offices across Europe, including our European headquarters in Morges, Switzerland, our Japanese office in Tokyo
and our Canadian headquarters in Montreal.
As described in more detail below, we operate in two therapeutic areas that are defined by the indications of our
approved medicines and the diseases for which our clinical candidates are being developed. One therapeutic area is
Hematology/Oncology, which is comprised of Myeloproliferative Neoplasms (MPNs), Graft-Versus-Host Disease
(GVHD), as well as solid tumors and hematologic malignancies. The other therapeutic area is Inflammation and
Autoimmunity (IAI), which includes our newly established Dermatology commercial franchise. We are also eligible to
receive milestones and royalties on molecules discovered by us and licensed to third parties.
Hematology and Oncology
Our hematology and oncology franchise is comprised of four approved products, which are JAKAFI (ruxolitinib),
MONJUVI (tafasitamab-cxix)/MINJUVI (tafasitamab), PEMAZYRE (pemigatinib) and ICLUSIG (ponatinib), as well as
numerous clinical development programs.
JAKAFI (ruxolitinib)
JAKAFI (ruxolitinib) is our first product to be approved for sale in the United States. It was approved by the U.S.
Food and Drug Administration (FDA) in November 2011 for the treatment of adults with intermediate or high-risk
myelofibrosis (MF), in December 2014 for the treatment of adults with polycythemia vera (PV) who have had an
inadequate response to or are intolerant of hydroxyurea, in May 2019 for the treatment of steroid-refractory acute graft-
versus-host disease (GVHD) in adult and pediatric patients 12 years and older and in September 2021 for the treatment of
chronic GVHD after failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older.
Myelofibrosis and polycythemia vera are both myeloproliferative neoplasms (MPNs), a type of rare blood cancer, and
GVHD is an adverse immune response to an allogeneic hematopoietic stem cell transplant (HSCT). Under our
collaboration agreement with our collaboration partner Novartis Pharmaceutical International Ltd., Novartis received
exclusive development and commercialization rights to ruxolitinib outside of the United States for all hematologic and
oncologic indications and sells ruxolitinib outside of the United States under the name JAKAVI.
In 2003, we initiated a research and development program to explore the inhibition of enzymes called janus
associated kinases (JAK). The JAK family is composed of four tyrosine kinases—JAK1, JAK2, JAK3 and Tyk2—that are
involved in the signaling of a number of cytokines and growth factors. JAKs are central to a number of biologic processes,
including the formation and development of blood cells and the regulation of immune functions. Dysregulation of the
JAK-STAT signaling pathway has been associated with a number of diseases, including myeloproliferative neoplasms,
other hematological malignancies, rheumatoid arthritis and other chronic inflammatory diseases.
We have discovered multiple potent, selective and orally bioavailable JAK inhibitors that are selective for JAK1
or JAK1 and JAK2. JAKAFI is the most advanced compound in our JAK program. It is an oral JAK1 and JAK2 inhibitor.
JAKAFI is marketed in the United States through our own specialty sales force and commercial team. JAKAFI
was the first FDA-approved JAK inhibitor for any indication, was the first FDA-approved product in MF, PV and steroid-
refractory acute GVHD, and was recently approved in steroid-refractory chronic GVHD. JAKAFI remains the first-line
standard of care in MF and remains the only FDA-approved product for steroid-refractory acute GVHD. The FDA has
granted JAKAFI orphan drug status for MF, PV and GVHD.
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JAKAFI is distributed primarily through a network of specialty pharmacy providers and wholesalers that allow
for efficient delivery of the medication by mail directly to patients or direct delivery to the patient’s pharmacy. Our
distribution process uses a model that is well-established and familiar to physicians who practice within the oncology field.
To further support appropriate use and future development of JAKAFI, our U.S. Medical Affairs department is
responsible for providing appropriate scientific and medical education and information to physicians, preparing scientific
presentations and publications, and overseeing the process for supporting investigator sponsored trials.
Myelofibrosis. MF is a rare, life-threatening condition. MF, considered the most serious of the myeloproliferative
neoplasms, can occur either as primary MF, or as secondary MF that develops in some patients who previously had
polycythemia vera or essential thrombocythemia. We estimate there are between 16,000 and 18,500 patients with MF in
the United States. Based on the modern prognostic scoring systems referred to as International Prognostic Scoring System
and Dynamic International Prognostic Scoring System, we believe intermediate and high-risk patients represent 80% to
90% of all patients with MF in the United States and encompass patients over the age of 65, or patients who have or have
ever had any of the following: anemia, constitutional symptoms, elevated white blood cell or blast counts, or platelet counts
less than 100,000 per microliter of blood.
Most MF patients have enlarged spleens and many suffer from debilitating symptoms, including abdominal
discomfort, pruritus (itching), night sweats and cachexia (involuntary weight loss). There were no FDA approved therapies
for MF until the approval of JAKAFI.
The FDA approval was based on results from two randomized Phase III trials (COMFORT-I and COMFORT-II),
which demonstrated that patients treated with JAKAFI experienced significant reductions in splenomegaly (enlarged
spleen). COMFORT-I also demonstrated improvements in symptoms. The most common hematologic adverse reactions
in both trials were thrombocytopenia and anemia. These events rarely led to discontinuation of JAKAFI treatment. The
most common non-hematologic adverse reactions were bruising, dizziness and headache.
In August 2014, the FDA approved supplemental labeling for JAKAFI to include Kaplan-Meier overall survival
curves as well as additional safety and dosing information. The overall survival information is based on three-year data
from COMFORT-I and II, and shows that at three years the probability of survival for patients treated with JAKAFI in
COMFORT-I was 70% and for those patients originally randomized to placebo it was 61%. In COMFORT-II, at three
years the probability of survival for patients treated with JAKAFI was 79% and for patients originally randomized to best
available therapy it was 59%. In December 2016, we announced an exploratory pooled analysis of data from the five-year
follow-up of the COMFORT-I and COMFORT-II trials of patients treated with JAKAFI, which further supported
previously published overall survival findings.
In September 2016, we announced that JAKAFI had been included as a recommended treatment in the latest
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for myelofibrosis,
underscoring the important and long-term clinical benefits seen in patients treated with JAKAFI.
In October 2017, the FDA approved updated labeling for JAKAFI to include the addition of new patient-reported
outcome (PRO) data from the COMFORT-I study, as well as updating the warning related to progressive multifocal
leukoencephalopathy. An exploratory analysis of PRO data of patients with myelofibrosis receiving JAKAFI showed
improvement in fatigue-related symptoms at Week 24. Fatigue response (defined as a reduction of 4.5 points or more from
baseline in the PROMIS® Fatigue total score) was reported in 35% of patients treated with JAKAFI versus 14% of the
patients treated with placebo.
Polycythemia Vera. PV is a myeloproliferative neoplasm typically characterized by elevated hematocrit, the
volume percentage of red blood cells in whole blood, which can lead to a thickening of the blood and an increased risk of
blood clots, as well as an elevated white blood cell and platelet count. When phlebotomy can no longer control PV,
chemotherapy such as hydroxyurea, or interferon, is utilized. Approximately 25,000 patients with PV in the United States
are considered uncontrolled because they have an inadequate response to or are intolerant of hydroxyurea, the most
commonly used chemotherapeutic agent for the treatment of PV.
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In December 2014, the FDA approved JAKAFI for the treatment of patients with PV who have had an inadequate
response to or are intolerant of hydroxyurea. The approval of JAKAFI for PV was based on data from the pivotal Phase III
RESPONSE trial. In this trial, patients treated with JAKAFI demonstrated superior hematocrit control and reductions in
spleen volume compared to best available therapy. In addition, a greater proportion of patients treated with JAKAFI
achieved complete hematologic remission—which was defined as achieving hematocrit control, and lowering platelet and
white blood cell counts. In the RESPONSE trial, the most common hematologic adverse reactions (incidence > 20%) were
thrombocytopenia and anemia. The most common non-hematologic adverse events (incidence >10%) were headache,
abdominal pain, diarrhea, dizziness, fatigue, pruritus, dyspnea and muscle spasms.
In March 2016, the FDA approved supplemental labeling for JAKAFI to include additional safety data as well as
efficacy analyses from the RESPONSE trial to assess the durability of response in JAKAFI treated patients after 80 weeks.
At this time, 83% patients were still on treatment, and 76% of the responders at 32 weeks maintained their response through
80 weeks.
In June 2016, we announced data from the Phase III RESPONSE-2 study of JAKAFI in patients with inadequately
controlled PV that was resistant to or intolerant of hydroxyurea who did not have an enlarged spleen. These data showed
that JAKAFI was superior to best available therapy in maintaining hematocrit control (62.2% vs. 18.7%, respectively;
P<0.0001) without the need for phlebotomy.
In August 2017, we announced that JAKAFI had been included as a recommended treatment in the latest NCCN
Guidelines for patients with polycythemia vera who have had an inadequate response to first-line therapies, such as
hydroxyurea.
Graft-versus-host disease. GVHD is a condition that can occur after an allogeneic HSCT (the transfer of
genetically dissimilar stem cells or tissue). In GVHD, the donated bone marrow or peripheral blood stem cells view the
recipient’s body as foreign and attack various tissues. 12-month survival rates in patients with Grade III or IV steroid-
refractory acute GVHD are 50% or less, and the incidence of steroid-refractory acute and chronic GVHD is approximately
3,000 per year in the United States.
In June 2016, we announced that the FDA granted Breakthrough Therapy designation for ruxolitinib in patients
with acute GVHD. In May 2019, the FDA approved JAKAFI for the treatment of steroid-refractory acute GVHD in adult
and pediatric patients 12 years and older. The approval was based on data from REACH1, an open-label, single-arm,
multicenter study of JAKAFI in combination with corticosteroids in patients with steroid-refractory grade II-IV acute
GVHD. The overall response rate (ORR) in patients refractory to steroids alone was 57% with a complete response
(CR) rate of 31%. The most frequently reported adverse reactions among all study participants were infections (55%) and
edema (51%), and the most common laboratory abnormalities were anemia (75%), thrombocytopenia (75%) and
neutropenia (58%).
In September 2021, the FDA approved JAKAFI for the treatment of chronic GVHD after failure of one or two
lines of systemic therapy in adult and pediatric patients 12 years and older. This approval was based on data from REACH3,
a Phase III, randomized, open-label, multicenter study of JAKAFI in comparison to best available therapy for treatment of
steroid-refractory chronic GVHD after allogeneic stem cell transplantation. The overall response rate through Cycle 7
Day 1 was 70% for JAKAFI compared to 57% for best available therapy. The most common hematologic adverse reactions
(incidence > 35%) were anemia and thrombocytopenia. The most common nonhematologic adverse reactions (incidence
≥ 20%) were infections (pathogen not specified) and viral infection. In addition, the FDA updated labeling for JAKAFI to
include warnings of increased risk of major adverse cardiovascular events, thrombosis, and secondary malignancies related
to another JAK-inhibitor treating rheumatoid arthritis, a condition for which JAKAFI is not indicated. In patients with MF
and PV treated with JAKAFI in clinical trials, the rates of thromboembolic events were similar in JAKAFI and control
treated patients.
We have retained all development and commercialization rights to JAKAFI in the United States and are eligible
to receive development and sales milestones as well as royalties from product sales outside the United States. We hold
patents that cover the composition of matter and use of ruxolitinib, which patents, including applicable extensions, expire
in mid-2028.
9
MONJUVI (tafasitamab-cxix) / MINJUVI (tafasitamab)
In January 2020, we and MorphoSys AG entered into a collaboration and license agreement to further develop
and commercialize MorphoSys' proprietary anti-CD19 antibody tafasitamab (MOR208) globally. The agreement became
effective March 2020. Tafasitamab is an Fc-engineered antibody against CD19 currently in clinical development for the
treatment of B cell malignancies. We have rights to co-commercialize tafasitamab in the United States with MorphoSys,
and we have exclusive development and commercialization rights outside of the United States.
In July 2020, we and MorphoSys announced that the FDA approved MONJUVI (tafasitamab-cxix), which is
indicated in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-
cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not
eligible for autologous stem cell transplant (ASCT). MONJUVI was approved under accelerated approval based on overall
response rate from the MorphoSys-sponsored Phase II L-MIND study, an open label, multicenter, single arm trial of
MONJUVI in combination with lenalidomide as a treatment for adult patients with r/r DLBCL. Results from the study
showed an objective response rate (ORR) of 55% (39 out of 71 patients; primary endpoint) and a complete response
(CR) rate of 37% (26 out of 71 patients). The median duration of response (mDOR) was 21.7 months. The most frequent
serious adverse reactions were infections (26%), including pneumonia (7%) and febrile neutropenia (6%). Updated three-
year data from L-MIND were presented at the American Society of Clinical Oncology (ASCO) 2021.
In August 2020, we and MorphoSys announced that MONJUVI in combination with lenalidomide had been
included in the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for B-
cell Lymphomas.
In August 2021, we and MorphoSys announced that the European Commission (EC) granted conditional
marketing authorization for MINJUVI (tafasitamab) in combination with lenalidomide, followed by MINJUVI
monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for autologous
stem cell transplant (ASCT). The conditional approval was based on the three-year results from the L-MIND study
evaluating the safety and efficacy of MINJUVI in combination with lenalidomide as a treatment for patients with r/r
DLBCL who are not eligible for ASCT. The results showed best objective response rate (ORR) of 56.8% (primary
endpoint), including a complete response (CR) rate of 39.5% and a partial response rate (PR) of 17.3%, as assessed by an
independent review committee. The median duration of response (mDOR) was 43.9 months after a minimum follow up of
35 months (secondary endpoint). MINJUVI together with lenalidomide was shown to provide a clinically meaningful
response and the side effects were manageable. Warnings and precautions for MINJUVI include infusion-related reactions,
myelosuppression, including neutropenia and thrombocytopenia, infections and tumour lysis syndrome.
DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide, comprising 40% of all cases.
DLBCL is characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow
or other organs. It is an aggressive disease with ~40% of patients not responding to initial therapy or relapsing thereafter.
We estimate that there are ~10,000 patients diagnosed in the United States each year with r/r DLBCL who are not eligible
for ASCT. In the EU, we estimate there are ~14,000 patients diagnosed each year with r/r DLBCL who are not eligible for
ASCT.
PEMAZYRE (pemigatinib)
PEMAZYRE is the first internally discovered product to be internationally commercialized by us.
In April 2020, we announced that the FDA approved PEMAZYRE (pemigatinib), a selective fibroblast growth
factor receptor (FGFR) kinase inhibitor, for the treatment of adults with previously treated, unresectable locally advanced
or metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test.
PEMAZYRE is the first FDA-approved treatment for this indication, which was approved under accelerated approval
based on overall response rate and duration of response (DOR).
In March 2021, PEMAZYRE was approved by the Japanese Ministry of Health, Labour and Welfare (MHLW)
for the treatment of patients with unresectable biliary tract cancer (BTC) with an FGFR2 fusion gene, worsening after
10
cancer chemotherapy. Also in March 2021, PEMAZYRE was approved by the European Commission (EC) for the
treatment of adults with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement that
have progressed after at least one prior line of systemic therapy.
In July 2021, the UK’s National Institute for Health and Care Excellence (NICE) recommended PEMAZYRE for
patients with cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or rearrangement that have
progressed after at least one prior line of systemic therapy. NICE’s guidance enables all eligible patients in England and
Wales to have access to PEMAZYRE through the National Health Service (NHS).
Cholangiocarcinoma is a rare cancer that arises from the cells within the bile ducts. It is often diagnosed late
(stages III and IV) and the prognosis is poor. The incidence of cholangiocarcinoma with FGFR2 fusions or rearrangements
is increasing, and it is currently estimated that there are 2,000-3,000 patients in the United States, Europe and Japan.
The approval of PEMAZYRE was based on data from FIGHT-202, a multi-center, open-label, single-arm study
evaluating PEMAZYRE as a treatment for adults with cholangiocarcinoma. In FIGHT-202, and in patients harboring
FGFR2 fusions or rearrangements (Cohort A), PEMAZYRE monotherapy resulted in an overall response rate of 36%
(primary endpoint), and median DOR of 9.1 months (secondary endpoint). FIGHT-302, a Phase III trial of pemigatinib for
the first-line treatment of patients with cholangiocarcinoma and FGFR2 fusions or rearrangements, is ongoing.
We have retained all rights to PEMAZYRE globally, other than those granted to Innovent Biologics, Inc. to
develop and commercialize pemigatinib in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.
ICLUSIG (ponatinib)
In June 2016, we acquired the European operations of ARIAD Pharmaceuticals, Inc. and obtained an exclusive
license to develop and commercialize ICLUSIG (ponatinib) in Europe and other select countries. ICLUSIG is a kinase
inhibitor. The primary target for ICLUSIG is BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic myeloid
leukemia (CML) and Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL).
In the European Union, ICLUSIG is approved for the treatment of adult patients with chronic phase, accelerated
phase or blast phase CML who are resistant to dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for
whom subsequent treatment with imatinib is not clinically appropriate; or who have the T315I mutation, or the treatment
of adult patients with Ph+ ALL who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent
treatment with imatinib is not clinically appropriate; or who have the T315I mutation.
Clinical Programs in Hematology and Oncology
Ruxolitinib and itacitinib
As part of our ongoing LIMBER (Leadership In MPNs BEyond Ruxolitinib) clinical development initiative,
which is designed to improve and expand therapeutic options for patients with myeloproliferative neoplasms, we are
evaluating combinations of ruxolitinib with other therapeutic modalities, as well as developing a once-a-day formulation
of ruxolitinib for potential use as monotherapy and combination therapy. Bioavailability and bioequivalence data were
published for ruxolitinib’s once-daily (QD) extended release (XR) formulation at the European Hematology Association
(EHA) 2021 Virtual Congress in June 2021.
Based on positive Phase II data, we opened two pivotal trials of ruxolitinib in combination with parsaclisib
(PI3Kδ) in first-line MF (LIMBER-313) and in MF patients with a suboptimal response to ruxolitinib monotherapy
(LIMBER-304), and both trials are ongoing. Additional Phase II trials combining ruxolitinib with investigational agents
from our portfolio such as INCB57643 (BET) and INCB00928 (ALK2) in patients with MF are in preparation, and
additional discovery and development initiatives are also ongoing within the LIMBER program, which are evaluating both
internally-discovered compounds, including itacitinib (JAK1), and candidates from collaboration partners.
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Itacitinib is a selective JAK1 inhibitor being evaluated in GRAVITAS-309, a Phase II/III trial of itacitinib in
patients with steroid-naïve chronic GVHD. The FDA has granted itacitinib orphan drug status for GVHD.
In September 2021, we and Syndax Pharmaceuticals, Inc. announced an exclusive worldwide collaboration and
license agreement to develop and commercialize axatilimab, Syndax’s anti-CSF-1R monoclonal antibody. Together, we
plan to develop axatilimab as a therapy for patients with chronic GVHD as well as in additional immune-mediated diseases
where CSF-1R-dependent monocytes and macrophages are believed to contribute to organ fibrosis. In December, updated
positive data were presented at ASH from the Phase I/II trial evaluating axatilimab as a monotherapy in patients with
recurrent or refractory chronic GVHD after two or more prior lines of therapy. A 68% overall response rate and broad
clinical benefit across multiple organs were observed at doses being assessed in AGAVE-201, a global pivotal trial
evaluating axatilimab monotherapy in patients with chronic GVHD in the third line setting. Additional trials of axatilimab
are planned in patients with chronic GVHD, including a Phase II trial in combination with a JAK inhibitor in patients with
steroid-refractory cGVHD.
Tafasitamab
Tafasitamab is an anti-CD19 antibody and is being investigated as a therapeutic option in B cell malignancies in
a number of ongoing and planned combination trials. An open-label Phase II combination trial (L-MIND) is investigating
the safety and efficacy of tafasitamab in combination with lenalidomide in patients with relapsed or refractory diffuse large
B-cell lymphoma (r/r DLBCL), and the ongoing Phase III B-MIND trial is assessing the combination of tafasitamab and
bendamustine versus rituximab and bendamustine in r/r DLBCL. firstMIND is a Phase Ib safety trial of tafasitamab as a
first-line therapy for patients with DLBCL, and frontMIND, a placebo-controlled Phase III trial evaluating tafasitamab in
combination with lenalidomide added to rituximab plus chemotherapy (R-CHOP) as a first-line therapy for patients with
DLBCL, is ongoing.
A placebo-controlled Phase III trial (inMIND) of tafasitamab added to lenalidomide plus rituximab (R2) in
patients with relapsed or refractory follicular or marginal zone lymphomas is ongoing, as is a proof-of-concept study
(topMIND) evaluating tafasitamab in combination with parsaclisib (PI3Kδ) in patients with relapsed or refractory B-cell
malignancies. We are also preparing to initiate a proof-of-concept study of tafasitamab, lenalidomide and plamotamab in
patients with r/r DLBCL.
In January 2021, the FDA granted orphan drug designation to tafasitamab as a treatment for patients with
follicular lymphoma.
Pemigatinib
Pemigatinib is a potent and selective inhibitor of the fibroblast growth factor receptor (FGFR) isoforms 1, 2 and
3 with demonstrated activity in preclinical studies. The FGFR family of receptor tyrosine kinases can act as oncogenic
drivers in a number of liquid and solid tumor types.
We initiated the FIGHT clinical program to evaluate pemigatinib across a spectrum of cancers that are driven by
FGF/FGFR alterations. The program initially included three Phase II trials – FIGHT-201 in patients with bladder cancer,
FIGHT-202 in patients with cholangiocarcinoma, and FIGHT-203 in patients with myeloid/lymphoid neoplasms with
FGFR1 rearrangement. Based on data generated from these ongoing trials, we have initiated additional trials. FIGHT-207,
a solid tumor-agnostic trial evaluating pemigatinib in patients with driver-alterations of FGF/FGFR, is now closed to
recruitment. Based on findings from this study, we have identified populations that may potentially benefit from treatment
with pemigatinib and intend to initiate Phase II studies in glioblastoma and non-small cell lung cancer.
Pemigatinib has Breakthrough Therapy designation as a treatment for patients with myeloid/lymphoid neoplasms
(MLN) with FGFR1 rearrangement who have relapsed or are refractory to initial chemotherapy.
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Parsaclisib
The PI3Kδ pathway mediates oncogenic signaling in B cell malignancies. Parsaclisib is a PI3Kδ inhibitor that
has demonstrated potency and selectivity in preclinical studies and has potential therapeutic utility in the treatment of
patients with lymphoma. We initiated the CITADEL clinical program to evaluate parsaclisib in non-Hodgkin lymphomas,
including Phase II trials in follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma. The FDA granted
orphan drug designation and Fast Track designation to parsaclisib as a treatment for patients with follicular lymphoma,
marginal zone lymphoma and mantle cell lymphoma.
In December 2020, we announced preliminary results from the ongoing CITADEL monotherapy development
program, which was designed to enable registration of parsaclisib. Results from four cohorts were presented at the
American Society of Hematology (ASH), including in r/r follicular lymphoma (CITADEL-203), in BTK-naïve r/r marginal
zone lymphoma (CITADEL-204) and in both BTK-naïve and BTK-experienced r/r mantle cell lymphoma
(CITADEL-205).
In October 2021, we announced the FDA acceptance of a NDA seeking approval of parsaclisib for the treatment
of patients with relapsed or refractory follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma. The
submission was based on data from several Phase 2 studies (CITADEL-203, -204 and -205) evaluating parsaclisib as a
treatment for relapsed or refractory NHLs (follicular, marginal zone and mantle cell). In January 2022, we announced that
we withdrew the NDA seeking approval of parsaclisib for the three indications in NHL. The decision to withdraw the NDA
followed discussions with FDA regarding confirmatory studies that we determined cannot be completed within a
reasonable time period to support an accelerated approval. We have an ongoing EMA submission under review for MZL.
A Phase II trial of parsaclisib in patients with autoimmune hemolytic anemia (AIHA), a rare red blood cell
disorder, is ongoing. In June 2021, data from the Phase II trial were presented at EHA. The majority of patients achieved
a response with parsaclisib over the initial 12-week treatment period and treatment with parsaclisib was generally well
tolerated. Based on these results, we initiated a Phase III trial in warm AIHA. The FDA has granted orphan drug designation
to parsaclisib as a treatment for patients with AIHA.
Retifanlimab
In October 2017, we and MacroGenics, Inc. announced an exclusive global collaboration and license agreement
for MacroGenics’ retifanlimab (formerly INCMGA0012), an investigational monoclonal antibody that inhibits PD-1.
Under this collaboration, we obtained exclusive worldwide rights for the development and commercialization of
retifanlimab in all indications. The molecule is currently being evaluated both as monotherapy and in combination therapy
across various tumor types. Potentially registration-enabling trials in microsatellite instability-high (MSI-H) endometrial
cancer and Merkel cell carcinoma are ongoing.
The Phase III POD1UM-303 trial of retifanlimab in combination with platinum-based chemotherapy as a first-
line treatment for patients with SCAC is underway. In July 2021, we announced that the FDA issued a complete response
letter (CRL) for the BLA of retifanlimab for the treatment of squamous cell carcinoma of the anal canal (SCAC). In
October 2021, we announced that we withdrew the Marketing Authorization Application (MAA) seeking approval of
retifanlimab in SCAC.
The Phase III POD1UM-304 trial is evaluating retifanlimab in combination with platinum-based chemotherapy
as a first-line treatment for patients with non-small cell lung cancer (NSCLC), and in October 2020, our collaboration
partner Zai Lab announced dosing of the first patient in China.
Retifanlimab has been granted Fast Track designation for the treatment of certain patients with advanced or
metastatic MSI-H or DNA mismatch repair (dMMR) endometrial cancer, for the treatment of certain patients with locally
advanced or metastatic SCAC and for the treatment of Merkel cell carcinoma (MCC). The FDA and EMA have granted
orphan drug designation to retifanlimab as a treatment for patients with locally advanced or metastatic SCAC and the FDA
has granted orphan drug designation to retifanlimab as a treatment for patients with MCC.
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Once-a-day ruxolitinib
(JAK1/JAK2)
Indication and status
Myelofibrosis, polycythemia vera and GVHD: clinical pharmacology studies
ruxolitinib + parsaclisib
(JAK1/JAK2 + PI3Kδ)
Myelofibrosis: Phase III (first-line therapy) (LIMBER-313)
Myelofibrosis: Phase III (suboptimal responders to ruxolitinib) (LIMBER-304)
ruxolitinib + INCB57643
(JAK1/JAK2 + BET)
ruxolitinib + INCB00928
(JAK1/JAK2 + ALK2)
ruxolitinib + CK08041
(JAK1/JAK2 + CB-Tregs)
Myelofibrosis: Phase II in preparation
Myelofibrosis: Phase II in preparation
Myelofibrosis: PoC in preparation
itacitinib (JAK1)
Treatment-naïve chronic GVHD: Phase II/III (GRAVITAS-309)
axatilimab (anti-CSF-1R)2
Chronic GVHD: Pivotal Phase II (third-line plus therapy) (AGAVE-201)
tafasitamab (CD19)3
r/r DLBCL: Phase II (L-MIND); Phase III (B-MIND)
1L DLBCL: Phase III (frontMIND)
r/r follicular & marginal zone lymphomas: Phase III (inMIND)
r/r B-cell malignancies: PoC with parsaclisib (PI3Kδ) (topMIND)
r/r B-cell malignancies: PoC with lenalidomide and plamotamab in preparation4
pemigatinib (FGFR1/2/3)
parsaclisib (PI3Kδ)
retifanlimab (PD-1)5
CCA: Phase III (FIGHT-302)
Myeloid/lymphoid neoplasms (MLN): Phase II (FIGHT-203)
Glioblastoma: Phase II in preparation
NSCLC: Phase II in preparation
Autoimmune hemolytic anemia: Phase III (PATHWAY)
SCAC: Phase III (PODIUM-303)
MSI-high endometrial cancer: Phase II (POD1UM-101, POD1UM-204)
Merkel cell carcinoma: Phase II (POD1UM-201)
NSCLC: Phase III (POD1UM-304)
1. Development collaboration with Cellenkos, Inc.
2. axatilimab development in collaboration with Syndax.
3. tafasitamab development in collaboration with MorphoSys.
4. Clinical collaboration with MorphoSys and Xencor, Inc. to investigate the combination of tafasitamab plus lenalidomide
in combination with Xencor’s CD20xCD3 XmAb bispecific antibody, plamotamab.
5. retifanlimab licensed from MacroGenics.
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Earlier-Stage Development Programs in Hematology and Oncology
We also have a number of other earlier-stage clinical programs in hematology and oncology, as detailed in the
table below. We intend to describe these programs more fully if we obtain clinical proof-of-concept and establish that a
program warrants further development in a specific indication or group of indications.
Modality
Small molecules
Candidates
INCB81776 (AXL/MER), epacadostat (IDO1), INCB86550 (PD-L1), INCB99280
(PD-L1), INCB99318 (PD-L1), INCB106385 (A2A/A2B)
Monoclonal antibodies1
INCAGN1876 (GITR), INCAGN2385 (LAG-3), INCAGN1949 (OX40),
INCAGN2390 (TIM-3), INCA00186 (CD73)
1. Discovery collaboration with Agenus Inc.
Inflammation and AutoImmunity (IAI)
Incyte Dermatology launched its first approved product, OPZELURA (ruxolitinib) cream, in October 2021,
following FDA approval in September 2021.
Incyte’s IAI efforts also include numerous clinical development programs.
OPZELURA (ruxolitinib) cream
In September 2021, we announced that the FDA approved OPZELURA (ruxolitinib) cream, a novel cream
formulation of Incyte’s selective JAK1/JAK2 inhibitor ruxolitinib, for the topical short-term and non-continuous chronic
treatment of mild to moderate atopic dermatitis (AD) in non-immunocompromised patients 12 years of age and older
whose disease is not adequately controlled with topical prescription therapies, or when those therapies are not advisable.
AD is a skin disorder that causes long term inflammation of the skin resulting in itchy, red, swollen and cracked
skin. Onset can occur at any age, but is more common in infants and children. In the United States, we estimate that there
are approximately 10 million diagnosed adolescent and adult patients with AD.
The approval of OPZELURA was based on data from two randomized, double-blind, vehicle-controlled Phase
III studies (TRuE-AD1 and TRuE-AD 2) evaluating the safety and efficacy of OPZELURA in adolescents and adults with
mild to moderate AD. Significantly more patients treated with OPZELURA achieved Investigator’s Global Assessment
(IGA) Treatment Success at Week 8 (defined as an IGA score of 0 or 1 with at least a 2-point improvement from baseline,
the primary endpoint: 53.8% in TRuE-AD1 and 51.3% in TRuE-AD2, compared to vehicle (15.1% in TRuE-AD1, 7.6%
in TRuE-AD2; P<0.0001). Significantly more patients treated with OPZELURA experienced a clinically meaningful
reduction in itch from baseline at Week 8, as measured by a ≥4-point reduction in the itch Numerical Rating Scale (itch
NRS4): 52.2% in TRuE-AD1 and 50.7% in TRuE-AD2, compared to vehicle (15.4% in TRuE-AD1, 16.3% in TRuE-AD2;
P<0.0001), among patients with an NRS score of at least 4 at baseline. The most common (≥1%) treatment-emergent
adverse reactions in patients treated with OPZELURA were nasopharyngitis, diarrhea, bronchitis, ear infection, eosinophil
count increased, urticaria, folliculitis, tonsillitis and rhinorrhea.
Clinical Programs in Dermatology
Ruxolitinib cream is a potent, selective inhibitor of JAK1 and JAK2 that provides the opportunity to directly
target diverse pathogenic pathways that underlie certain dermatologic conditions, including atopic dermatitis, vitiligo and
chronic hand eczema.
We are currently evaluating ruxolitinib cream in a Phase III trial, TRuE-AD3, in pediatric atopic dermatitis
patients ages ≥2 years to < 12 years. A Phase III trial evaluating ruxolitinib cream in chronic hand eczema is in preparation.
15
In May 2021, we announced positive topline results from the Phase III TRuE-V program evaluating ruxolitinib
cream as a treatment for adolescent and adult patients with vitiligo. Both TRuE-V1 and TRuE-V2 studies met the primary
and key secondary endpoints, including patient reported outcomes. The overall efficacy and safety profile of ruxolitinib
cream was consistent with previously reported Phase II data, and no new safety signals were observed.
In October 2021, data from the Week 24 analysis of the Phase III TRuE-V program were presented at the
European Academy of Dermatology and Venereology Congress (EADV). Treatment with 1.5% ruxolitinib cream twice
daily (BID) resulted in greater improvement versus vehicle for the primary and all key secondary endpoints in both the
TRuE-V1 and TRuE-V2 studies. Results, which were consistent across both studies, showed that 29.9% of patients
applying ruxolitinib cream achieved ≥75% improvement from baseline in the facial Vitiligo Area Scoring Index
(F-VASI75), the primary endpoint. The overall safety profile of ruxolitinib cream in vitiligo was consistent with previous
study data. In the TRuE-V studies, patients using ruxolitinib cream did not report clinically significant application site
reactions. Treatment-emergent adverse events were consistent with previous studies, with no serious treatment-related
adverse events reported.
In October 2021, we announced the validation of the European Marketing Authorization Application (MAA) for
ruxolitinib cream as a potential treatment for adolescents and adults (age ≥12 years) with non-segmental vitiligo with facial
involvement. In December 2021, we announced that the U.S. FDA accepted for Priority Review the sNDA for ruxolitinib
cream as a potential treatment for adolescents and adults (age ≥ 12 years) with vitiligo. The Prescription Drug User Fee
Act (PDUFA) target action date is April 18, 2022.
Vitiligo is a long-term skin condition characterized by patches of the skin losing their pigment. It is estimated that
vitiligo affects 0.5-2% of the US population and, therefore, there are at least 1.5 million patients in the United States with
this disorder. There are no FDA approved treatments for repigmentation of vitiligo lesions.
We are also developing INCB54707, which is an oral small molecule selective JAK1 inhibitor. INCB54707 is
undergoing evaluation in patients with hidradenitis suppurativa (HS), a chronic skin condition where lesions develop as a
result of inflammation and infection of the sweat glands. In October 2020, initial results from the clinical program were
presented and a randomized Phase IIb trial of INCB54707 is underway in patients with HS. In March 2021, we initiated a
Phase II trial evaluating INCB54707 in patients with vitiligo. A Phase II trial evaluating INCB54707 in patients with
prurigo nodularis is ongoing.
ruxolitinib cream1
(JAK1/JAK2)
INCB54707 (JAK1)
Indication and status
Atopic dermatitis: Phase III pediatric study (TRuE-AD3)
Chronic hand eczema: Phase III in preparation
Vitiligo: Phase III (TRuE-V1, TRuE-V2; primary endpoint met in both studies); sNDA
under Priority Review and MAA under review
Hidradenitis suppurativa: Phase II
Vitiligo: Phase II
Prurigo nodularis: Phase II
1. Novartis’ rights for ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis
do not include topical administration.
Clinical Programs in Other IAI
A Phase II trial of INCB00928 is in preparation for patients with fibrodysplasia ossificans progressiva (FOP), a
disorder in which muscle tissue and connective tissue are gradually replaced by bone. The FDA has granted Fast Track
designation and orphan drug designation to INCB00928 as a treatment for patients with FOP.
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INCB00928 (ALK2)
Indication and status
Fibrodysplasia ossificans progressiva: Phase II in preparation
Collaborative Partnered Programs
As described below under “—License Agreements and Business Relationships,” we are eligible for milestone
payments and royalties on certain products that we licensed to third parties. These include OLUMIANT (baricitinib),
which is licensed to our collaborative partner Eli Lilly and Company, and JAKAVI (ruxolitinib) and TABRECTA
(capmatinib), which are licensed to Novartis.
Baricitinib
We have a second JAK1 and JAK2 inhibitor, baricitinib, which is subject to our collaboration agreement with
Lilly, in which Lilly received exclusive worldwide development and commercialization rights to the compound for
inflammatory and autoimmune diseases.
Rheumatoid Arthritis. Rheumatoid arthritis is an autoimmune disease characterized by aberrant or abnormal
immune mechanisms that lead to joint inflammation and swelling and, in some patients, the progressive destruction of
joints. Rheumatoid arthritis can also affect connective tissue in the skin and organs of the body.
Current rheumatoid arthritis
the use of non-steroidal anti-inflammatory drugs,
disease-modifying anti-rheumatic drugs, such as methotrexate, and the newer biological response modifiers that target
pro-inflammatory cytokines, such as tumor necrosis factor, implicated in the pathogenesis of rheumatoid arthritis. None
of these approaches to treatment is curative; therefore, there remains an unmet need for new safe and effective treatment
options for these patients. Rheumatoid arthritis is estimated to affect about 1% of the world’s population.
treatments
include
The Phase III program of baricitinib in patients with rheumatoid arthritis incorporated all three rheumatoid
arthritis populations (methotrexate naïve, biologic naïve, and tumor necrosis factor (TNF) inhibitor inadequate responders);
used event rates to fully power the baricitinib program for structural comparison and non-inferiority vs. adalimumab; and
evaluated patient-reported outcomes. All four Phase III trials met their respective primary endpoints.
In January 2016, Lilly submitted an NDA to the FDA and an MAA to the EMA for baricitinib as treatment for
rheumatoid arthritis. In February 2017, we and Lilly announced that the European Commission approved baricitinib as
OLUMIANT for the treatment of moderate-to-severe rheumatoid arthritis in adult patients who have responded
inadequately to, or who are intolerant to, one or more disease-modifying antirheumatic drugs (DMARDs). In July 2017,
the Japanese Ministry of Health, Labour and Welfare (MHLW) granted marketing approval for OLUMIANT for the
treatment of rheumatoid arthritis (including the prevention of structural injury of joints) in patients with inadequate
response to standard-of-care therapies. In June 2018, the FDA approved the 2mg dose of OLUMIANT for the treatment
of adults with moderately-to-severely active rheumatoid arthritis (RA) who have had an inadequate response to one or
more tumor necrosis factor (TNF) inhibitor therapies.
Atopic Dermatitis. Lilly has conducted a Phase IIa trial and a Phase III program to evaluate the safety and efficacy
of baricitinib in patients with moderate-to-severe atopic dermatitis. The JAK-STAT pathway has been shown to play an
essential role in the dysregulation of immune responses in atopic dermatitis. Therefore, we believe that inhibiting cytokine
pathways dependent on JAK1 and JAK2 may lead to positive clinical outcomes in AD.
In February 2019, we and Lilly announced that baricitinib met the primary endpoint in BREEZE-AD1 and
BREEZE-AD2, two Phase III studies evaluating the efficacy and safety of baricitinib monotherapy for the treatment of
adult patients with moderate-to-severe AD and, in August 2019, we and Lilly announced that baricitinib met the primary
endpoint in BREEZE-AD7, a Phase III study evaluating the efficacy and safety of baricitinib in combination with
standard-of-care topical corticosteroids in patients with moderate-to-severe AD. In January 2020, we and Lilly announced
that baricitinib met the primary endpoint in both BREEZE-AD4 and BREEZE-AD5, the results of which completed the
placebo-controlled data program intended to support global registrations. An sNDA for baricitinib has been submitted by
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Lilly for the treatment of patients with moderate to severe AD. In April 2021, we and Lilly announced the FDA extended
the review period for the sNDA for baricitinib for the treatment of moderate to severe AD by three months to allow time
for additional data analyses. In July 2021, we and Lilly announced that the FDA will not meet the PDUFA action date for
the sNDA for baricitinib for the treatment of adults with moderate to severe AD due to the FDA's ongoing assessment of
JAK inhibitors. In January 2022, Lilly provided a regulatory update on the sNDA based on ongoing discussions with the
FDA. Lilly announced that alignment with the FDA on the indicated population had not yet been reached and given the
FDA’s position, there would be the possibility of a Complete Response Letter (CRL).
In January 2020, Lilly announced that baricitinib had been submitted for regulatory review in Europe as a
treatment for patients with moderate-to-severe AD. In October 2020, Lilly announced that the European Commission
approved baricitinib as OLUMIANT for the treatment of moderate-to-severe AD in adult patients who are candidates for
systemic therapy. In December 2020, baricitinib was approved by the MHLW for the treatment of patients with moderate-
to-severe AD.
Systemic Lupus Erythematosus. Systemic lupus erythematosus (SLE) is a chronic disease that causes
inflammation. In addition to affecting the skin and joints, it can affect other organs in the body such as the kidneys, the
tissue lining the lungs and heart, and the brain. Lilly has conducted a Phase II trial to evaluate the safety and efficacy of
baricitinib in patients with SLE. Baricitinib’s activity profile suggests that it inhibits cytokines implicated in SLE such as
type I interferon (IFN), type II IFN-γ, IL-6, and IL-23 as well as other cytokines that may have a role in SLE, including
granulocyte macrophage colony stimulating factor (GM-CSF) and IL-12.
In January 2022, Lilly announced the discontinuation of the Phase III development program for baricitinib in SLE
based on top-line efficacy results from two pivotal Phase III trials (SLE-BRAVE-I and –II). The primary endpoint of SRI-4
response was reached in SLE-BRAVE-I but was not reached in SLE-BRAVE-II and key secondary endpoints were not
met in either study.
Alopecia Areata. Alopecia areata is an autoimmune disorder in which the immune system attacks the hair follicles,
causing hair loss in patches. In March 2020, Lilly announced that baricitinib received Breakthrough Therapy designation
for the treatment of alopecia areata, based on the positive Phase II results of Lilly’s adaptive Phase II/III study
BRAVE-AA1. In March 2021, we and Lilly announced positive results from BRAVE-AA2, the Phase III trial evaluating
the efficacy and safety of once-daily baricitinib in adults with severe alopecia areata. In April 2021, we and Lilly
announced positive results from the Phase III portion of BRAVE-AA1. In September 2021, we and Lilly announced
detailed results from BRAVE-AA1 and BRAVE-AA2 at the European Academy of Dermatology and Venereology
Congress (EADV). The two studies showed statistically significant improvement in scalp hair regrowth across both
baricitinib dosing groups when compared to placebo. Regulatory applications for baricitinib as a treatment for alopecia
areata have been submitted in the U.S., Europe and Japan.
COVID-19. In May 2020, we amended our agreement with Lilly to enable Lilly to commercialize baricitinib for
the treatment of COVID-19. In November 2020, we and Lilly announced that the FDA issued an Emergency Use
Authorization (EUA) for the distribution and emergency use of baricitinib to be used in combination with remdesivir in
hospitalized adult and pediatric patients two years of age or older with suspected or laboratory confirmed COVID-19 who
require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. In
December 2020, we and Lilly announced that data from ACTT-2 supportive of the EUA were published in the New
England Journal of Medicine. In July 2021, we and Lilly announced that the FDA broadened the EUA for baricitinib to
allow for treatment with or without remdesivir. The EUA now provides for the use of baricitinib for treatment of
COVID-19 in hospitalized adults and pediatric patients two years of age or older requiring supplemental oxygen,
non-invasive or invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO).
Capmatinib
Capmatinib is a potent and highly selective MET inhibitor. The investigational compound has demonstrated
inhibitory activity in cell-based biochemical and functional assays that measure MET signaling and MET dependent cell
proliferation, survival and migration. Under our agreement, Novartis received worldwide exclusive development and
commercialization rights to capmatinib and certain back-up compounds in all indications. Capmatinib is being evaluated
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in patients with hepatocellular carcinoma, non-small cell lung cancer and other solid tumors, and may have potential utility
as a combination agent.
MET is a clinically validated receptor kinase cancer target. Abnormal MET activation in cancer correlates with
poor prognosis. Dysregulation of the MET pathway triggers tumor growth, formation of new blood vessels that supply the
tumor with nutrients, and causes cancer to spread to other organs. Dysregulation of the MET pathway is seen in many
types of cancers, including lung, kidney, liver, stomach, breast and brain.
In May 2020, we and Novartis announced the FDA approval of capmatinib as TABRECTA for the treatment of
adult patients with metastatic NSCLC whose tumors have a mutation that leads to MET exon 14 skipping (METex14) as
detected by an FDA-approved test. TABRECTA is the first and only treatment approved to specifically target NSCLC
with this driver mutation and is approved for first-line and previously treated patients regardless of prior treatment type.
The FDA approval of TABRECTA was based on results from the pivotal GEOMETRY mono-1 study. In the
METex14 population (n=97), the confirmed overall response rate was 68% and 41% among treatment-naive (n=28) and
previously treated patients (n=69), respectively, based on the Blinded Independent Review Committee (BIRC) assessment
per RECIST v1.1. In patients taking TABRECTA, the study also demonstrated a median duration of response of 12.6
months in treatment-naive patients (19 responders) and 9.7 months in previously treated patients (28 responders). The most
common treatment-related adverse events (AEs) (incidence ≥20%) are peripheral edema, nausea, fatigue, vomiting,
dyspnea, and decreased appetite. In September 2020, we and Novartis announced that GEOMETRY mono-1 results were
published in The New England Journal of Medicine.
In June 2020, we and Novartis announced that the MHLW approved TABRECTA for METex14 mutation-
positive advanced and/or recurrent unresectable NSCLC.
NSCLC is the most common type of lung cancer, impacting more than 2 million people per year globally.
Approximately 3-4 percent of all patients with NSCLC have tumors with a mutation that leads to MET exon 14 skipping.
Though rare, this mutation is an indicator of especially poor prognosis and poor responses to standard therapies, including
immunotherapy.
baricitinib
(JAK1/JAK2)1
Indication and status
Atopic dermatitis: Phase III (BREEZE-AD); approved in European Union and Japan
Severe alopecia areata: Phase III (BRAVE-AA1, BRAVE-AA2); submissions in U.S., EU,
and Japan
capmatinib (MET)2 NSCLC (with MET exon 14 skipping mutations): approved in United States and Japan; MAA
under review
ruxolitinib
(JAK1/JAK2)3
Acute and chronic GVHD: MAA and J-NDA under review
1. baricitinib licensed to Lilly.
2. capmatinib licensed to Novartis.
3. ruxolitinib licensed to Novartis ex-US for use in hematology and oncology excluding topical administration.
License Agreements and Business Relationships
We establish business relationships, including collaborative arrangements with other companies and medical
research institutions to assist in the clinical development and/or commercialization of certain of our drugs and drug
candidates and to provide support for our research programs. We also evaluate opportunities for acquiring products or
rights to products and technologies that are complementary to our business from other companies and medical research
institutions.
Below is a brief description of our significant business relationships and collaborations and related license
agreements that expand our pipeline and provide us with certain rights to existing and potential new products and
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technologies. Additional information regarding our collaboration agreements, including their financial and accounting
impact on our business and results of operations, can be found in Note 6 of notes to the consolidated financial statements
included in Item 8 of this report.
Out-License Agreements
Novartis
In November 2009, we entered into a Collaboration and License Agreement with Novartis. Under the terms of
the agreement, Novartis received exclusive development and commercialization rights outside of the United States to
ruxolitinib and certain back up compounds for hematologic and oncology indications, including all hematological
malignancies, solid tumors and myeloproliferative diseases. We retained exclusive development and commercialization
rights to JAKAFI (ruxolitinib) in the United States and in certain other indications. Novartis also received worldwide
exclusive development and commercialization rights to our MET inhibitor compound capmatinib and certain back up
compounds in all indications. We retained options to co-develop and to co-promote capmatinib in the United States. In
April 2016, we amended this agreement to provide that Novartis has exclusive research, development and
commercialization rights outside of the United States to ruxolitinib (excluding topical formulations) in the GVHD field.
Lilly
In December 2009, we entered into a License, Development and Commercialization Agreement with Lilly. Under
the terms of the agreement, Lilly received exclusive worldwide development and commercialization rights to baricitinib
and certain back up compounds for inflammatory and autoimmune diseases. In March 2016, we entered into an amendment
to the agreement with Lilly that allows us to engage in the development and commercialization of ruxolitinib in the GVHD
field. In May 2020, we amended our agreement with Lilly to enable Lilly to commercialize baricitinib for the treatment of
COVID-19.
Innovent
In December 2018, we entered into a Research Collaboration and Licensing Agreement with Innovent Biologics,
Inc. Under the terms of this agreement, Innovent received exclusive development and commercialization rights to
pemigatinib and our clinical-stage product candidates itacitinib and parsaclisib in hematology and oncology indications in
mainland China, Hong Kong, Macau and Taiwan.
Zai Lab
In July 2019, we entered into a Collaboration and License Agreement with a subsidiary of Zai Lab Limited. Under
the terms of this agreement, Zai Lab’s subsidiary received development and exclusive commercialization rights to
retifanlimab in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan. We retained an option to
assist in the promotion of retifanlimab in Zai Lab’s licensed territories.
InnoCare
In August 2021, we entered into a Collaboration and License Agreement with a subsidiary of InnoCare Pharma
Limited. Under the terms of this agreement, InnoCare’s subsidiary received development and exclusive commercialization
rights to tafasitamab in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.
In-License Agreements
Agenus
In January 2015, we entered into a License, Development and Commercialization Agreement with Agenus Inc.
and its wholly-owned subsidiary, 4-Antibody AG (now known as Agenus Switzerland Inc.), which we collectively refer
to as Agenus. Under this agreement, the parties have agreed to collaborate on the discovery of novel immuno-therapeutics
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using Agenus’ antibody discovery platforms. Under the terms of this agreement, as amended in February 2017, we received
exclusive worldwide development and commercialization rights to four checkpoint modulators directed against GITR,
OX40, LAG-3 and TIM-3. In addition to the initial four program targets, we and Agenus have the option to jointly nominate
and pursue additional targets within the framework of the collaboration, and in November 2015, three more targets were
added, two of which were removed from the collaboration under the February 2017 amendments.
Takeda (ARIAD)
In June 2016, we acquired from ARIAD Pharmaceuticals, Inc. all of the outstanding shares of ARIAD
Pharmaceuticals (Luxembourg) S.à.r.l., the parent company of ARIAD’s European subsidiaries responsible for the
development and commercialization of ICLUSIG in the European Union and other countries. We obtained an exclusive
license to develop and commercialize ICLUSIG in Europe and other select countries. ARIAD was subsequently acquired
by Takeda Pharmaceutical Company Limited in 2017.
Merus
In December 2016, we entered into a Collaboration and License Agreement with Merus N.V. Under this
agreement, which became effective in January 2017, the parties have agreed to collaborate with respect to the research,
discovery and development of bispecific antibodies utilizing Merus’ technology platform. The collaboration encompasses
up to eleven independent programs.
In January 2022, we decided to opt-out of the continued development of MCLA-145, a bispecific antibody
targeting PD-L1 and CD137. We continue to collaborate with Merus and leverage the Merus platform to develop a pipeline
of novel agents, as we continue to hold worldwide exclusive development and commercialization rights to up to ten
additional programs.
Calithera
In January 2017, we entered into a Collaboration and License Agreement with Calithera Biosciences, Inc. Under
this agreement, we received an exclusive, worldwide license to develop and commercialize small molecule arginase
inhibitors, including INCB01158 (CB-1158), which is currently in Phase II clinical trials, for multiple myeloma.
MacroGenics
In October 2017, we entered into a Global Collaboration and License Agreement with MacroGenics. Under this
agreement, we received exclusive development and commercialization rights worldwide to MacroGenics’ INCMGA0012,
an investigational monoclonal antibody that inhibits PD-1. MacroGenics has retained the right to develop and
commercialize, at its cost and expense, its pipeline assets in combination with INCMGA0012.
Syros
In January 2018, we entered into a Target Discovery, Research Collaboration and Option Agreement with Syros
Pharmaceuticals, Inc. Under this agreement, Syros will use its proprietary gene control platform to identify novel
therapeutic targets with a focus in myeloproliferative neoplasms and we have received options to obtain exclusive
worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets. We will have
exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those
validated targets.
MorphoSys
In January 2020, we entered into a Collaboration and License Agreement with MorphoSys AG and MorphoSys
US Inc., a wholly-owned subsidiary of MorphoSys AG, covering the worldwide development and commercialization of
MOR208 (tafasitamab), an investigational Fc engineered monoclonal antibody directed against the target molecule CD19.
Under the terms of this agreement, we received exclusive commercialization rights outside of the United States, and
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MorphoSys and we have co-commercialization rights in the United States, with respect to tafasitamab.
Syndax
In September 2021, we entered into a Collaboration and License Agreement with Syndax covering the worldwide
development and commercialization of SNDX-6352 (axatilimab), Syndax’s anti-CSF-1R monoclonal antibody. In
March 2021, axatilimab was granted Orphan Drug Designation by the FDA for the treatment of chronic GVHD and a
second designation in April 2021 for treatment of idiopathic pulmonary fibrosis. The Agreement became effective in
December 2021 with the expiration of the initial waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
Under the terms of this agreement, we received exclusive commercialization rights outside of the United States, and
Syndax has co-commercialization rights in the United States with respect to axatilimab.
COVID-19
In December 2019, coronavirus disease of 2019, or COVID-19, was first reported in Wuhan, China. In
March 2020, the World Health Organization declared COVID-19 a pandemic. We and our collaboration partners Lilly
and Novartis initiated a number of clinical trials to address COVID-19.
In April 2020, we announced the initiation of a Phase III clinical trial (RUXCOVID) to evaluate the efficacy and
safety of ruxolitinib plus standard-of-care (SoC), compared to SoC therapy alone, in patients not on mechanical ventilation
and who have COVID-19 associated cytokine storm. We sponsored this collaborative study in the United States and our
collaboration partner Novartis International Pharmaceutical Ltd. sponsored the study outside of the United States.
In December 2020, we announced initial results from RUXCOVID, where treatment with ruxolitinib plus SoC
did not prevent complications compared to SoC treatment alone in patients with COVID-19 associated cytokine storm.
The RUXCOVID study has been completed and the data will be further analyzed to determine any potential impact on
other studies of ruxolitinib in patients with COVID-19, including our Expanded Access Program in the United States,
which allows eligible patients with severe COVID-19 associated cytokine storm to receive ruxolitinib.
In March 2021, results from a second Phase III clinical trial to evaluate the efficacy and safety of ruxolitinib plus
SoC, compared to SoC therapy alone, in COVID-19 patients on mechanical ventilation and who have acute respiratory
distress syndrome (ARDS), a type of respiratory failure characterized by rapid onset of widespread inflammation in the
lungs were announced. Ruxolitinib failed to reduce mortality due to any cause through Day 29 although in the U.S. study
population (91% of total study patients), there was a clinically and statistically significant improvement in mortality in
each of the 5mg and 15mg ruxolitinib arms.
In April 2020, Lilly announced that it has entered into an agreement with the National Institute of Allergy and
Infectious Diseases (NIAID), part of the National Institutes of Health, to study baricitinib as an arm in NIAID's Adaptive
COVID-19 Treatment Trial (ACTT-2). The study is investigating the efficacy and safety of baricitinib as a potential
treatment for hospitalized patients diagnosed with COVID-19 in the United States, and Lilly is also planning an expansion
to include Europe and Asia.
In September 2020, we and Lilly announced initial results from ACTT-2, where baricitinib in combination with
remdesivir reduced the time to recovery in comparison with remdesivir alone. Additional data announced in October 2020
showed that baricitinib plus remdesivir resulted in a numerical decrease in mortality through Day 29 compared to
remdesivir alone, with a more pronounced reduction seen in more severely ill patients.
In November 2020, we and Lilly announced that the FDA issued an Emergency Use Authorization (EUA) for the
distribution and emergency use of baricitinib to be used in combination with remdesivir in hospitalized adult and pediatric
patients two years of age or older with suspected or laboratory confirmed COVID-19 who require supplemental oxygen,
invasive mechanical ventilation, or extracorporeal membrane oxygenation. In December 2020, we and Lilly announced
that data from ACTT-2 supportive of the EUA were published in the New England Journal of Medicine. In July 2021, we
and Lilly announced that the FDA broadened the EUA for baricitinib to allow for treatment with or without remdesivir.
The EUA now provides for the use of baricitinib for treatment of COVID-19 in hospitalized adults and pediatric patients
22
two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation or extracorporeal
membrane oxygenation (ECMO).
In April 2021, we and Lilly announced that the primary endpoint was not met in COV-BARRIER, the Phase III
randomized, double-blind, placebo–controlled study to evaluate the efficacy and safety of baricitinib in hospitalized adults
not on mechanical ventilation and who have COVID-19. There was, however, a 38% reduction in mortality by Day 28 in
patients treated with baricitinib in addition to SoC. In August 2021, we and Lilly announced new data from an additional
cohort of 101 adult patients from the COV-BARRIER trial. In this sub-study, patients with COVID-19 on mechanical
ventilation or extracorporeal membrane oxygenation (ECMO) who received baricitinib plus standard of care were 46%
less likely to die by Day 28 compared to patients who received placebo plus standard of care.
Incyte’s Approach to Drug Discovery and Development
Our productivity in drug discovery is primarily a result of our core competency in medicinal chemistry which is
tightly integrated with, and supported by, an experienced team of biologists and pharmaceutical scientists with expertise
in multiple therapeutic areas. This discovery team operates in concert with an equally experienced drug development
organization with expertise in clinical sciences, statistics, and regulatory affairs. Our drug development organization
manages our clinical programs and utilizes clinical research organizations (CROs), expert scientific advisory boards, and
leading consultants and suppliers as appropriate to ensure our clinical trials are conducted efficiently, effectively, and in
accordance with regulatory and compliance guidelines.
To succeed in our objective to discover and advance novel therapeutics that address serious unmet medical needs,
we have established a broad range of discovery capabilities in-house, including target validation, high-throughput
screening, medicinal chemistry, computational chemistry, pharmacological and translational sciences, ADME (absorption,
distribution, metabolism and excretion) and toxicology assessment. We augment these capabilities through collaborations
with academic and contract laboratory resources with relevant expertise.
In addition to our small molecules expertise, we have added a biologics discovery capability in-house and have
expanded our discovery scope to include bispecific antibodies through a collaboration with Merus. We are complementing
these collaborations by establishing in-house pharmacology, ADME and CMC capabilities.
Driven by a target- and pathway-centric discovery process, our pipeline has grown and is currently focused
primarily in the area of oncology. We conduct a limited number of discovery programs in parallel at any one time. This
focus allows us to allocate resources to our selected programs at a level that we believe is competitive with larger
pharmaceutical companies. We continually modify the resourcing of our discovery efforts with the goals of maximizing
information content when and where we need it and ensuring that each program, regardless of stage, is executed in the
most efficient and data-rich manner possible. We believe this approach has played a critical role in the development of our
product portfolio.
Once our compounds reach clinical development, our objective is to rapidly progress the lead candidate into a
proof-of-concept clinical trial to quickly assess the therapeutic potential of the clinical candidate itself as well as its
underlying mechanism of action. This information is then used to evaluate the compound’s development opportunities,
identify the most appropriate indication or indications to pursue, and develop a clinical and regulatory plan to advance the
molecule forward.
Our development teams are responsible for ensuring that our clinical candidates are expeditiously progressed
through clinical safety, proof-of-concept, and formal efficacy/pivotal trials. Our development teams include employees
with expertise in drug development, including clinical trial design, statistics, regulatory affairs, medical affairs,
pharmacovigilance and project management. We have also built internal process chemistry and formulation teams that
work closely with external GMP contract manufacturers to support our drug development efforts.
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Incyte’s Commercial Strategy
Our strategy is to develop and commercialize compounds that we have internally discovered or have acquired
rights to in the markets where we believe that a company of our size can successfully compete. We currently commercialize
four compounds in the United States, three in Europe and one in Japan.
In November 2011, we received regulatory approval of JAKAFI (ruxolitinib) in the United States for the treatment
of intermediate or high-risk myelofibrosis. In December 2014, JAKAFI was approved for the treatment of patients with
polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea. In May 2019, JAKAFI was
approved for the treatment of steroid‐refractory acute GVHD in adult and pediatric patients 12 years and older. In
September 2021, JAKAFI was approved for the treatment of chronic GVHD after failure of one or two lines of systemic
therapy in adult and pediatric patients 12 years and older. As a result of these approvals, we have focused on increasing
utilization of JAKAFI in these patient populations.
In April 2020, we received regulatory approval of PEMAZYRE (pemigatinib) in the United States for the
treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) with
an FGFR2 fusion or other rearrangement. We are focused on increasing the utilization of molecular profiling in CCA to
support identification of appropriate patients for PEMAZYRE. In March 2021, PEMAZYRE was approved by the
Japanese Ministry of Health, Labour and Welfare for the treatment of patients with unresectable biliary tract cancer with
an FGFR2 fusion gene, worsening after cancer chemotherapy. Also in March 2021, PEMAZYRE was approved by the
European Commission for the treatment of adults with locally advanced or metastatic cholangiocarcinoma with an FGFR2
fusion or rearrangement that have progressed after at least one prior line of systemic therapy.
In January 2020, we and MorphoSys AG entered into a collaboration and license agreement to further develop
and commercialize MorphoSys' proprietary anti-CD19 antibody tafasitamab globally. In July of 2020, MONJUVI
(tafasitamab-cxix), in combination with lenalidomide, was FDA approved for the treatment of adult patients with relapsed
or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade
lymphoma, and who are not eligible for autologous stem cell transplant. MONJUVI is being co-commercialized by us and
MorphoSys in the United States. In August 2021, the European Commission granted conditional marketing authorization
for MINJUVI (tafasitamab) in combination with lenalidomide, followed by MINJUVI monotherapy, for the treatment of
adult patients with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant.
topical short-term and non-continuous chronic
In September 2021, we received regulatory approval of OPZELURA (ruxolitinib) cream in the United States for
the
in
non-immunocompromised patients 12 years of age and older whose disease is not adequately controlled with topical
prescription therapies, or when those therapies are not advisable.
to moderate atopic dermatitis
treatment of mild
We established Incyte Dermatology as a new commercial franchise, which includes the marketing, medical, sales
and operational infrastructure, to support the commercialization of OPZELURA in the United States.
ICLUSIG is approved in the European Union for the treatment of adult patients with CML who are resistant to
dasatinib or nilotinib; who are intolerant to dasatinib or nilotinib and for whom subsequent treatment with imatinib is not
clinically appropriate, or who have the T315I mutation. ICLUSIG is also indicated in adult patients with Philadelphia
positive AML who are resistant to dasatinib; who are intolerant to dasatinib and for whom subsequent treatment with
imatinib is not clinically appropriate, or who have the T315I mutation. We are focused on increasing the utilization of
ICLUSIG in this patient population within our territory as appropriate.
We are continuing to expand our marketing, medical and operational infrastructure within the United States and
outside of the United States to prepare for potential approval of other products.
For certain other compounds, including rights to ruxolitinib outside the United States and global rights to
capmatinib, which have both been licensed to Novartis, and global rights to baricitinib, which have been licensed to Lilly,
we have established and may in the future establish collaborations or strategic relationships to support development and
commercialization in certain territories or therapeutic areas where we do not have or do not want to build expertise. We
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believe the key benefits to entering into such strategic relationships include the potential to expedite the development and
commercialization of certain of our compounds, as well as the opportunity to receive upfront payments and future
milestones and royalties in exchange for certain rights to those compounds.
Patents and Other Intellectual Property
We regard the protection of patents and other enforceable intellectual property rights that we own or license as
critical to our business and competitive position. Accordingly, we rely on patent, trademark, trade secret and copyright
law, as well as nondisclosure and other contractual arrangements, to protect our intellectual property. We have established
a patent portfolio of patents and patent applications owned or licensed by us that cover aspects of all our drug products and
drug candidates. The patents and patent applications relating to our drug products and drug candidates generally include
claims directed to the compounds, methods of using the compounds, formulations of the compounds, pharmaceutical salt
forms of the compounds, and methods of manufacturing the compounds. Our policy is to pursue patent applications on
inventions and discoveries that we believe are commercially important to the development and growth of our business.
The following table sets forth the status of the patents and patent applications in the United States, the European Union,
and Japan for our approved medicines and for those compounds in our portfolio that have been submitted to regulatory
authorities seeking approval or are in registration-directed clinical trials:
Drug/Drug Candidate (Target)
ruxolitinib (JAK)1,2
baricitinib (JAK)
itacitinib (JAK)
capmatinib (MET)
parsaclisib (PI3Kδ)
pemigatinib (FGFR)
ponatinib (BCRABL)
retifanlimab (PD-1)6
tafasitamab (CD19)7
axatilimab (CSF-1R)8
Status of U.S. Composition of
Matter Patent Estate
(Earliest Anticipated Expiration
Including PTE Extensions
where granted)3
Granted and pending (2027)9
Granted and pending (2030)5
Granted and pending (2032)4
Granted and pending (2027)5
Granted and pending (2033)4
Granted and pending (2035)5
Granted and pending (2036)4
Granted and pending (2029)5
Granted (2034)4
Status of EU Composition of
Matter Patent Estate (Earliest
Anticipated Expiration
Including SPC Extensions
where granted)3
Granted and pending (2027) 9
Granted and pending (2032)
Granted and pending (2031)4
Granted and pending (2027)4
Granted and pending (2032)4
Granted and pending (2033)4
Granted and pending (2026)
Granted and pending (2036)4
Granted (2027)4
Granted and pending (2034)4
Status of Japan Composition
of Matter Patent Estate
(Earliest Anticipated
Expiration Including SPC
Extensions where granted)3
Granted and pending (2028) 9
Granted and pending (2033)
Granted and pending (2031)4
Granted and pending (2027)4
Granted and pending (2032)4
Granted and pending (2033)4
Granted and pending (2036)4
Granted (2027)4
Granted and pending (2034)4
1. Ruxolitinib cream formulation patents are issued in the United States, European Union and Japan with anticipated
expiration dates of 2031 respectively, not including patent term extensions that will be sought upon regulatory
approval.
2. Once-a-day (QD) ruxolitinib formulation patents are issued in the United States and the European Union, but pending
in Japan with anticipated expiration dates of 2033 respectively, not including patent term extensions that will be sought
upon regulatory approval.
3. Subject to the payment of maintenance fees.
4. Respective patent term extension/supplementary protection certificate (SPC) will be sought upon approval by the
respective regulatory agency.
5. Patent term extension has been applied for and being sought.
6. Retifanlimab licensed from MacroGenics.
7. Tafasitamab licensed from MorphoSys.
8. Axatilimab licensed from Syndax.
9. Ruxolitinib phosphate salt patents are issued in the United States, European Union and Japan with anticipated
expiration dates of mid-2028, not including patent term extensions.
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. The actual protection afforded by a patent, which can vary from
country to country, depends on the type of patent, the scope of its coverage and the availability of legal remedies in the
country.
We may seek to license rights relating to technologies, drug candidates or drug products in connection with our
drug discovery and development programs and commercialization activities. Under these licenses, such as our licenses
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from Agenus, ARIAD/Takeda, Calithera, MacroGenics, MorphoSys, Merus, and Syndax, we may be required to pay
up-front fees, license fees, milestone payments and royalties on sales of future products.
Although we believe our rights under patents and patent applications provide a competitive advantage, the patent
positions of pharmaceutical and biotechnology companies are highly uncertain and involve complex legal and factual
questions. We may not be able to develop patentable products or processes, and may not be able to obtain patents in the
United States or elsewhere from pending applications. Even if patent claims are allowed, the claims may not issue, or in
the event of issuance, may not be valid or enforceable or may not be sufficient to protect the technology owned by or
licensed to us or provide us with a competitive advantage. Any patent or other intellectual property rights that we own or
obtain may be circumvented, challenged or invalidated by our competitors. Others may have patents that relate to our
business or technology and that may prevent us from marketing our drug candidates unless we are able to obtain a license
to those patents. In addition, litigation or other proceedings may be necessary to defend against claims of infringement, to
enforce patents, to protect our other intellectual property rights, to determine the scope and validity of the proprietary rights
of third parties or to defend ourselves in patent or other intellectual property right suits brought by third parties. We could
incur substantial costs in such litigation or other proceedings. An adverse outcome in any such litigation or proceeding
could subject us to significant liability.
With respect to proprietary information that is not patentable, and for inventions for which patents are difficult to
enforce, we rely on trade secret protection and confidentiality agreements to protect our interests. While we require all
employees, consultants and potential business partners to enter into confidentiality agreements, we may not be able to
adequately protect our trade secrets or other proprietary information. Others may independently develop substantially
equivalent proprietary information and techniques or otherwise gain access to our trade secrets.
Competition
Our drug discovery, development and commercialization activities face, and will continue to face, intense
competition from organizations such as pharmaceutical and biotechnology companies, as well as academic and research
institutions and government agencies. We face significant competition from organizations, particularly fully integrated
pharmaceutical companies, that are pursuing pharmaceuticals that are competitive with JAKAFI, ICLUSIG, PEMAZYRE,
MONJUVI/MINJUVI, OPZELURA and our drug candidates.
Many companies and institutions, either alone or together with their collaborative partners, have substantially
greater financial resources, larger drug discovery, development and commercial staffs and significantly greater experience
than we do in:
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drug discovery;
developing products;
undertaking preclinical testing and clinical trials;
obtaining FDA and other regulatory approvals of products; and
• manufacturing, marketing, distributing and selling products.
Accordingly, our competitors may succeed in obtaining patent protection, receiving FDA and other regulatory
approval or commercializing products that compete with JAKAFI, ICLUSIG, PEMAZYRE, MONJUVI/MINJUVI,
OPZELURA or our drug candidates.
In addition, any drug candidate that we successfully develop may compete with existing therapies that have long
histories of safe and effective use. Competition may also arise from:
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other drug development technologies and methods of preventing or reducing the incidence of disease;
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new compounds; or
other classes of therapeutic agents.
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 drug candidates or proprietary technology. These competitors, either alone or with their collaborative
partners, may succeed in developing products that are more effective or commercially successful than ours.
Our ability to compete successfully will depend, in part, on our ability to:
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develop proprietary products;
develop and maintain products that reach the market first, are technologically superior to and/or are of lower
cost than other products in the market;
attract and retain scientific, product development and sales and marketing personnel;
obtain patent or other proprietary protection for our products and technologies;
obtain required regulatory approvals; and
• manufacture, market, distribute and sell any products that we develop.
In a number of countries, including in particular, developing countries, government officials and other groups
have suggested that pharmaceutical companies should make drugs available at a low cost. In some cases, governmental
authorities have indicated that where pharmaceutical companies do not do so, their patents might not be enforceable to
prevent generic competition. Some major pharmaceutical companies have greatly reduced prices for their drugs in certain
developing countries. If certain countries do not permit enforcement of any of our patents, sales of our products in those
countries, and in other countries by importation from low-price countries, could be reduced by generic competition or by
parallel importation of our product. Alternatively, governments in those countries could require that we grant compulsory
licenses to allow competitors to manufacture and sell their own versions of our products in those countries, thereby
reducing our product sales, or we could respond to governmental concerns by reducing prices for our products. In all of
these situations, our results of operations could be adversely affected.
Government Regulation
Our ongoing research and development activities and any manufacturing and marketing of our approved drug
products and our drug candidates are subject to extensive regulation by numerous governmental authorities in the United
States and other countries. Before marketing in the United States, any drug developed by us must undergo rigorous
preclinical testing, clinical trials, and an extensive regulatory clearance process implemented by the FDA under the United
States Food, Drug and Cosmetic Act and its implementing regulations and, in the case of biologics, the Public Health
Service Act. The FDA regulates, among other things, the research, development, testing, manufacture, safety, efficacy,
record-keeping, labeling, storage, approval, advertising, promotion, sale and distribution and import and export, of these
products.
FDA Review and Approval Process
The regulatory review and approval process is lengthy, expensive and uncertain. The steps generally required
before a drug may be marketed in the United States include:
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preclinical laboratory tests, animal studies and formulation studies in compliance with the FDA’s Good
Laboratory Practice and Good Manufacturing Practice regulations;
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submission to the FDA of an Investigational New Drug application (IND) for human clinical testing, which
must become effective before human clinical trials may commence;
performance of adequate and well-controlled clinical trials in three phases, as described below, to establish
the safety and efficacy of the drug for each indication;
submission of an NDA or Biologics License Application (BLA) to the FDA for review;
random inspections of clinical sites to ensure validity of clinical safety and efficacy data;
satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is
produced to assess compliance with current good manufacturing practices;
• FDA approval of the NDA or BLA; and
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payment of user and program fees, if applicable.
Similar requirements exist within foreign agencies as well. The time required to satisfy FDA requirements or
similar requirements of foreign regulatory agencies may vary substantially based on the type, complexity and novelty of
the product or the targeted disease.
Preclinical testing includes laboratory evaluation of product pharmacology, drug metabolism, and toxicity which
includes animal studies, to assess potential safety and efficacy as well as product chemistry, stability, formulation,
development, and testing. The results of the preclinical tests, together with manufacturing information and analytical data,
are submitted to the FDA as part of an IND. An IND will automatically become effective 30 days after receipt by the FDA,
unless before that time, the FDA raises safety concerns or questions about the conduct of the clinical trial(s) included in
the IND. In the latter case, the IND sponsor and the FDA must resolve any outstanding FDA concerns or questions before
clinical trials can proceed. We cannot be sure that submission of an IND will result in the FDA allowing clinical trials to
commence.
Clinical trials involve the administration of the investigational drug to human subjects under the supervision of
qualified investigators and in accordance with Good Clinical Practice regulations covering the protection of human
subjects. These regulations require all research subjects to provide informed consent. Clinical trials are conducted under
protocols detailing the objectives of the study, the parameters to be used in monitoring safety, and the effectiveness criteria
to be evaluated. Each protocol must be submitted to the FDA as part of the IND and each trial must be reviewed and
approved by an institutional review board (IRB) before it can begin.
Clinical trials typically are conducted in three sequential phases, but the phases may overlap or be combined.
Phase I usually involves the initial introduction of the investigational drug into healthy volunteers to evaluate its safety,
dosage tolerance, absorption, metabolism, distribution and excretion. Phase II usually involves clinical trials in a limited
patient population to evaluate dosage tolerance and optimal dosage, identify possible adverse effects and safety risks, and
evaluate and gain preliminary evidence of the efficacy of the drug for specific indications. Phase III clinical trials usually
further evaluate clinical efficacy and safety by testing the drug in its final form in an expanded patient population, providing
statistical evidence of efficacy and safety, and providing an adequate basis for labeling. We cannot guarantee that Phase I,
Phase II or Phase III testing will be completed successfully within any specified period of time, if at all. Furthermore, we,
the IRB, or the FDA may suspend clinical trials at any time on various grounds, including a finding that the subjects or
patients are being exposed to an unacceptable health risk.
As a separate amendment to an IND, a clinical trial sponsor may submit to the FDA a request for a Special
Protocol Assessment (SPA). Under the SPA procedure, a sponsor may seek the FDA’s agreement on the design and size
of a clinical trial intended to form the primary basis of an effectiveness claim. If the FDA agrees in writing, its agreement
may not be changed after the trial begins, except when agreed by FDA or in limited circumstances, such as when a
substantial scientific issue essential to determining the safety and effectiveness of a drug candidate is identified after a
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Phase III clinical trial is commenced and agreement is obtained with the FDA. If the outcome of the trial is successful, the
sponsor will ordinarily be able to rely on it as the primary basis for approval with respect to effectiveness. However,
additional trials could also be requested by the FDA to support approval, and the FDA may make an approval decision
based on a number of factors, including the degree of clinical benefit as well as safety. The FDA is not obligated to approve
an NDA or BLA as a result of an SPA agreement, even if the clinical outcome is positive.
Even after initial FDA approval has been obtained, post-approval trials, or Phase IV studies, may be required to
provide additional data, and will be required to obtain approval for the sale of a product as a treatment for a clinical
indication other than that for which the product was initially tested and approved. Also, the FDA will require post-approval
safety reporting to monitor the side effects of the drug. Results of post-approval programs may limit or expand the
indication or indications for which the drug product may be marketed. Further, if there are any requests for modifications
to the initial FDA approval for the drug, including changes in indication, manufacturing process, manufacturing facilities,
or labeling, a supplemental NDA or BLA may be required to be submitted to the FDA.
The length of time and related costs necessary to complete clinical trials varies significantly and may be difficult
to predict. Clinical results are frequently susceptible to varying interpretations that may delay, limit or prevent regulatory
approvals. Additional factors that can cause delay or termination of our clinical trials, or cause the costs of these clinical
trials to increase, include:
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slow patient enrollment due to the nature of the protocol, the proximity of patients to clinical sites, the
eligibility criteria for the study, competition with clinical trials for other drug candidates or other factors;
inadequately trained or insufficient personnel at the study site to assist in overseeing and monitoring clinical
trials;
delays in approvals from a study site’s IRB;
longer than anticipated treatment time required to demonstrate effectiveness or determine the appropriate
product dose;
lack of sufficient supplies of the drug candidate for use in clinical trials;
adverse medical events or side effects in treated patients; and
lack of effectiveness of the drug candidate being tested.
Any drug is likely to produce some toxicities or undesirable side effects in animals and in humans when
administered at sufficiently high doses and/or for sufficiently long periods of time. Unacceptable toxicities or side effects
may occur at any dose level, and at any time in the course of animal studies designed to identify unacceptable effects of a
drug candidate, known as toxicological studies, or in clinical trials of our drug candidates. The appearance of any
unacceptable toxicity or side effect could cause us or regulatory authorities to interrupt, limit, delay or abort the
development of any of our drug candidates, and could ultimately prevent their marketing approval by the FDA or foreign
regulatory authorities for any or all targeted indications.
The FDA’s fast track, breakthrough therapy, accelerated approval, and priority review designation programs are
intended to facilitate the development and expedite the review and approval of drug candidates intended for the treatment
of serious or life-threatening conditions and that demonstrate the potential to address unmet medical needs for these
conditions. Under these programs, FDA can, for example, review portions of an NDA or BLA for a drug candidate before
the entire application is complete, thus potentially beginning the review process at an earlier time. The FDA, however, can
mandate, and has mandated, post-approval requirements that could include lengthy and extensive confirmatory clinical
trials. The FDA has recently increased its focus on accelerated approvals for oncology drugs and the confirmatory trials
required for those drugs.
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We cannot guarantee that the FDA will grant any of our requests for any of these expedited program designations,
that any such designations would affect the time of review or that the FDA will approve the NDA or BLA submitted for
any of our drug candidates, whether or not these designations are granted. Additionally, FDA approval of a product can
include restrictions on the product’s use or distribution (such as permitting use only for specified medical conditions or
limiting distribution to physicians or facilities with special training or experience). Approval of such designated products
can be conditioned on additional clinical trials after approval.
Sponsors submit the results of preclinical studies and clinical trials to the FDA as part of an NDA or BLA. NDAs
and BLAs must also contain extensive product manufacturing information and proposed labeling. Upon receipt, the FDA
initially reviews the NDA or BLA to determine whether it is sufficiently complete to initiate a substantive review. If the
FDA identifies deficiencies that would preclude substantive review, the FDA will refuse to accept the NDA or BLA and
will inform the sponsor of the deficiencies that must be corrected prior to resubmission. If the FDA accepts the submission
for review (then deemed a “filing”), the FDA typically completes the NDA or BLA review within a pre-determined time
frame. Under the Prescription Drug User Fee Act, the FDA agrees to review NDAs and BLAs under either a standard
review or priority review. FDA procedures provide for priority review of NDAs and BLAs submitted for drugs that,
compared to currently marketed products, if any, offer a significant improvement in the treatment, diagnosis or prevention
of a disease. The FDA seeks to review NDAs and BLAs that are granted priority status more quickly than NDAs and BLAs
given standard review status. The FDA’s stated policy is to act on 90% of priority NDAs and BLAs within eight months
of receipt (or six months after filing, which occurs within 60 days after NDA or BLA submission). Although the FDA
historically has not met these goals, the agency has made significant improvements in the timeliness of the review process.
NDA and BLA review often extends beyond anticipated completion dates due to FDA requests for additional data or
clarification, the submission of a major amendment by the Sponsor, the FDA’s decision to have an advisory committee
review, and difficulties in scheduling an advisory committee meeting. The recommendations of an advisory committee are
not binding on the FDA.
To obtain FDA approval to market a product, we must demonstrate that the product is safe and effective for the
patient population that will be treated. If regulatory approval of a product is granted, the approval will be limited to those
disease states and conditions for which the product is safe and effective, as demonstrated through clinical trials. Marketing
or promoting a drug for an unapproved indication is prohibited. Furthermore, approval may entail requirements for
post-marketing studies or risk evaluation and mitigation strategies, including the need for patient and/or physician
education, patient registries, medication or similar guides, or other restrictions on the distribution of the product. If an
NDA or BLA does not satisfy applicable regulatory criteria, the FDA may deny approval of an NDA or BLA or may issue
a complete response, and require, among other things, additional clinical data or analyses.
The Orphan Drug Act provides incentives to manufacturers to develop and market drugs for rare diseases and
conditions affecting fewer than 200,000 persons in the United States at the time of application for orphan drug designation
or conditions affecting 200,000 or more people in the United States where the disease or condition occurs so infrequently
that there is no reasonable expectation that the costs of drug development and marketing will be recovered in future sales
of the drug in the United States. The first developer to receive FDA marketing approval for an orphan drug is entitled to a
seven year exclusive marketing period in the United States for the orphan drug indication. However, a drug that the FDA
considers to be clinically superior to, or different from, another approved orphan drug, even though for the same indication,
may also obtain approval in the United States during the seven year exclusive marketing period.
Regulation of Manufacturing Process
Even when NDA or BLA approval is obtained, a marketed product, such as JAKAFI, its manufacturer and its
manufacturing facilities are subject to continual review and periodic inspections by the FDA. The manufacturing process
for pharmaceutical products is highly regulated and regulators may shut down manufacturing facilities that they believe
do not comply with regulations. Discovery of previously unknown problems with a product, manufacturer or facility may
result in restrictions on the product, manufacturer or facility, including costly recalls or withdrawal of the product from the
market. Manufacturing facilities are always subject to inspection by the applicable regulatory authorities.
We and our third-party manufacturers are subject to current Good Manufacturing Practices, or GMP, which are
extensive regulations governing manufacturing processes, including but not limited to stability testing, record keeping and
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quality standards as defined by the International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use, or ICH, FDA and the European Medicines Agency. Similar regulations are in effect in
other countries. Manufacturing facilities are subject to inspection by the applicable regulatory authorities and are subject
to manufacturing licenses where applicable. These facilities, whether our own or our contract manufacturers, must be
inspected before we can use them in commercial manufacturing of our related products. We or our contract manufacturers
may not be able to comply with applicable GMP and FDA or other regulatory requirements. If we or our contract
manufacturers fail to comply, we or our contract manufacturers may be subject to legal or regulatory action, such as
suspension of manufacturing license, seizure of product, or voluntary recall of product. Furthermore, continued compliance
with applicable GMP will require continual expenditure of time, money and effort on the part of us or our contract
manufacturers in the areas of production and quality control and record keeping and reporting, in order to ensure full
compliance.
Post-Approval Regulation
Any products manufactured or distributed by us pursuant to FDA approvals are subject to pervasive and
continuing regulation by the FDA, including record-keeping requirements, reporting of adverse experiences with the drug
and other reporting, advertising and promotion restrictions. The FDA’s rules for advertising and promotion require, among
other things, that our promotion be fairly balanced and adequately substantiated by clinical studies, and that we not promote
our products for unapproved uses. We must also submit appropriate new and supplemental applications and obtain FDA
approval for certain changes to the approved product, product labeling or manufacturing process. On its own initiative, the
FDA may require changes to the labeling of an approved drug if it becomes aware of new safety information that the
agency believes should be included in the approved drug’s labeling. The FDA also enforces the requirements of the
Prescription Drug Marketing Act, or PDMA, which, among other things, imposes various requirements in connection with
the distribution of product samples to physicians.
In addition to inspections related to manufacturing, we are subject to periodic unannounced inspections by the
FDA and other regulatory bodies related to the other regulatory requirements that apply to marketed drugs manufactured
or distributed by us. The FDA also may conduct periodic inspections regarding our review and reporting of adverse events,
or related to compliance with the requirements of the PDMA concerning the handling of drug samples. When the FDA
conducts an inspection, the inspectors will identify any deficiencies they believe exist in the form of a notice of inspectional
observations. The observations may be more or less significant. If we receive a notice of inspectional observations, we
likely will be required to respond in writing, and may be required to undertake corrective and preventive actions in order
to address the FDA’s concerns.
There are a variety of state laws and regulations that apply in the states or localities where JAKAFI and our drug
candidates are or may be marketed. For example, we must comply with state laws that require the registration of
manufacturers and wholesale distributors of pharmaceutical products in that state, including, in certain states,
manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of
business within the state. Some states also impose requirements on manufacturers and distributors to establish the pedigree
of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology
capable of tracking and tracing product as it moves through the distribution chain. Any applicable state or local regulations
may hinder our ability to market, or increase the cost of marketing, our products in those states or localities.
The FDA’s policies may change and additional government regulations may be enacted which could impose
additional burdens or limitations on our ability to market products after approval. Moreover, increased attention to the
containment of health care costs in the United States and in foreign markets could result in new government regulations
which could have a material adverse effect on our business. We cannot predict the likelihood, nature or extent of adverse
governmental regulation which might arise from future legislative or administrative action, either in the United States or
abroad.
Marketing Exclusivity
The FDA may grant five years of exclusivity in the United States for the approval of NDAs for new chemical
entities, and three years of exclusivity for supplemental NDAs, for among other things, new indications, dosages or dosage
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forms of an existing drug if new clinical investigations that were conducted or sponsored by the applicant are essential to
the approval of the supplemental application. Additionally, six months of marketing exclusivity in the United States is
available if, in response to a written request from the FDA, a sponsor submits and the agency accepts requested information
relating to the use of the approved drug in the pediatric population. The six month pediatric exclusivity is added to any
existing patent or non-patent exclusivity period for which the drug is eligible. Orphan drug products are also eligible for
pediatric exclusivity if the FDA requests and the company completes pediatric clinical trials. Under the Biologics Price
Competition and Innovation Act, the FDA may grant 12 years of data exclusivity for innovative biological products.
Foreign Regulation
Outside the United States, our ability to market a product is contingent upon receiving a marketing authorization
from the appropriate regulatory authorities. The requirements governing the conduct of clinical trials, marketing
authorization, pricing and reimbursement vary widely from country to country. At present, foreign marketing
authorizations are applied for at a national level, although within the European Union (EU) regional registration procedures
are available to companies wishing to market a product in more than one EU member state. If the competent regulatory
authority is satisfied that adequate evidence of safety, quality and efficacy has been presented, a marketing authorization
may be granted. This foreign regulatory approval process involves all of the risks associated with FDA approval discussed
above and may also include additional risks.
Whether or not we obtain FDA approval for a product, we must obtain the requisite approvals from regulatory
authorities in non-US countries prior to the commencement of clinical trials or marketing of the product in those countries.
Certain countries outside of the United States have a process that requires the submission of a clinical trial application, or
CTA, much like an IND prior to the commencement of human clinical trials. In Europe, a CTA must be submitted for each
trial to the competent national health authority and to independent ethics committees in each country in which a company
plans to conduct clinical trials. Once the CTA is approved in accordance with a country’s requirements, clinical trial
development may proceed in that country and are conducted in accordance with GCP and other applicable regulatory
requirements.
To obtain regulatory approval of an investigational drug under EU regulatory systems, we must submit a
marketing authorization application (MAA). This application is similar to the NDA in the United States, with the exception
of, among other things, regional and/or country-specific document requirements. Drugs can be authorized in the EU by
using (i) the centralized authorization procedure, (ii) the mutual recognition procedure, (iii) the decentralized procedure or
(iv) national authorization procedures.
The European Medicines Agency implemented the centralized procedure for the approval of human drugs to
facilitate marketing authorizations that are valid throughout the EU. This procedure results in a single marketing
authorization granted by the European Commission that is valid across the EU. Under the centralized procedure, the
maximum timeframe for the evaluation of a marketing authorization application by the EMA is 210 days (excluding clock
stops, when additional written or oral information is to be provided by the applicant in response to questions asked by the
Committee for Medicinal Products for Human Use). A positive opinion on the MAA by the CHMP then needs to be
endorsed by the European Commission. Accelerated assessment might be granted by the CHMP in exceptional cases, in
which case the EMA ensures that the evaluation for the opinion of the CHMP is completed within 150 days (excluding
clock stops) and the opinion issued thereafter.
The mutual recognition procedure (MRP) for the approval of human drugs is an alternative approach to facilitate
individual national marketing authorizations within the EU. The MRP may be applied for all human drugs for which the
centralized procedure is not obligatory. The MRP is based on the principle of the mutual recognition by EU member states
of their respective national marketing authorizations. Based on a marketing authorization in the reference member state,
the applicant may apply for marketing authorizations in other member states. In such case, the reference member state
shall update its existing assessment report about the drug. After the assessment is completed, copies of the report are sent
to all member states, together with the approved summary of product characteristics, labeling and package leaflet. The
concerned member states then recognize the decision of the reference member state and the summary of product
characteristics, labeling and package leaflet. National marketing authorizations shall be granted within 30 days after
acknowledgement of the agreement.
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Should any Member State refuse to recognize the marketing authorization by the reference member state, the
member states shall make all efforts to reach a consensus. If this fails, the procedure is submitted to an EMA scientific
committee for arbitration. The opinion of this EMA Committee is then forwarded to the Commission, for the start of the
decision making process. As in the centralized procedure, this process entails consulting various European Commission
Directorates General and the Standing Committee on Human Medicinal Products or Veterinary Medicinal Products, as
appropriate.
Legislation similar to the Orphan Drug Act has been enacted in other countries outside of the United States,
including the EU. The orphan legislation in the EU is available for therapies addressing conditions that affect five or fewer
out of 10,000 persons, are life-threatening or chronically debilitating conditions and for which no satisfactory treatment is
authorized. The market exclusivity period is for ten years, although that period can be reduced to six years if, at the end of
the fifth year, available evidence establishes that the product does not justify maintenance of market exclusivity.
For other countries outside of the EU, such as non-EU countries in Eastern Europe, Middle-East, Latin America,
Japan or other countries in Asia, the requirements governing the conduct of clinical trials, product licensing, pricing and
reimbursement vary. In all cases, again, the clinical trials are conducted in accordance with GCP and the other applicable
regulatory requirements.
If we fail to comply with applicable foreign regulatory requirements, we may be subject to, among other things,
fines, suspension of clinical trials, suspension or withdrawal of regulatory approvals, product recalls, seizure of products,
operating restrictions and criminal prosecution.
Manufacturing
Our manufacturing strategy is to contract with third parties to manufacture the raw materials, our active
pharmaceutical ingredients, or API, and finished dosage form for clinical and commercial uses. We currently do not operate
manufacturing facilities for clinical or commercial production of JAKAFI, ICLUSIG, PEMAZYRE, OPZELURA and
MONJUVI/MINJUVI or our drug candidates. As such, we expect to continue to rely on third parties for the manufacture
of commercial supplies of the raw materials, API and finished drug product for drugs that we successfully develop and are
approved for commercial sale. In this manner, we continue to build and maintain our supply chain and quality assurance
resources.
In July 2018, we purchased land located in Yverdon, Switzerland for construction of a large molecule production
facility to manufacture biologic drug substances for our drug candidates. Construction activity commenced in July 2018
and we currently expect the facility to be GMP approved in the second half of 2022, after the inspection and approval from
the competent authorities.
Manufacturing of our Products
Our supply chain for manufacturing raw materials, API and drug product ready for distribution and
commercialization is a multi-step international process. Establishing and managing the supply chain requires a significant
financial commitment and the creation and maintenance of numerous third-party contractual relationships.
We contract with third parties to manufacture JAKAFI, ICLUSIG, PEMAZYRE, OPZELURA and our drug
candidates for clinical and commercial purposes. Our collaborator MorphoSys is currently responsible for sourcing
manufacturing of MONJUVI/MINJUVI. Third-party manufacturers supply raw materials, and other third-party
manufacturers convert these raw materials into API or convert the API into final dosage form. For most of our drug
candidates, once our raw materials are produced, we rely on one third-party to manufacture the API, another to make
finished drug product and a third to package and label the finished product. For ruxolitinib phosphate, the API for JAKAFI
and OPZELURA, we have two qualified third-party contract manufacturers from which we can source drug substance.
The manufacturing of ponatinib, the API for ICLUSIG, is the sole responsibility of Takeda, the intellectual property holder.
We procure API from Takeda, which outsources the API manufacturing to a third party. For pemigatinib, the API for
PEMAZYRE, we have one qualified third-party contract manufacturer from which we can source drug substance.
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We also rely on third-party contract manufacturers to tablet or capsulate all of our active pharmaceutical
ingredients for clinical and commercial uses. For JAKAFI and ICLUSIG, we have two qualified third-party manufacturers
from which we can source commercial drug product. Secondary packaging of ICLUSIG is performed by a qualified third-
party manufacturer. Primary packaged product for ICLUSIG can be used for clinical and commercial purposes. For
PEMAZYRE, we have one qualified third-party manufacturer from which we can source commercial drug product. For
OPZELURA, we have one qualified third-party manufacturer from which we can source commercial drug product.
We may not be able to obtain sufficient quantities of any of our raw materials, drug candidates, API, or finished
goods if our designated manufacturers do not have the capacity or capability to manufacture our products according to our
schedule and specifications. If any of these single source suppliers were to become unable or unwilling to supply us with
API or finished product that complies with applicable regulatory requirements, we could incur significant delays in our
clinical trials or interruption of commercial supply which could have a material adverse effect on our business. Similar
risks apply to our supply of MONJUVI/MINJUVI under our collaboration with MorphoSys.
We have established a quality assurance program intended to ensure that our third-party manufacturers and service
providers produce materials and provide services, as applicable, in accordance with the FDA and EMA’s current Good
Manufacturing Practices and other applicable regulations. Our quality assurance program extends to our licensed facilities
that oversee the manufacturing and distribution activities.
For our future products, we intend to continue to establish third-party suppliers to manufacture sufficient
quantities of our drug candidates to undertake clinical trials and to manufacture sufficient quantities of any product that is
approved for commercial sale. If we are unable to contract for large scale manufacturing with third parties on acceptable
terms for our future products or develop manufacturing capabilities internally, our ability to conduct large scale clinical
trials and meet customer demand for commercial products will be adversely affected.
Third-party Manufacturers
Our third-party manufacturers are independent entities, under contract with us, who are subject to their own
unique operational and financial risks which are out of our control. If we or any of our third-party manufacturers fail to
perform as required, this could impair our ability to deliver our products on a timely basis or cause delays in our clinical
trials and applications for regulatory approval. To the extent these risks materialize and affect their performance obligations
to us, our financial results may be adversely affected.
For products manufactured by our third-party manufacturers, we have licensed the necessary aspects of this
manufacturing technology that we believe is proprietary to us to enable them to manufacture the products for us. We have
agreements with these third-party manufacturers that are intended to restrict these manufacturers from using or revealing
our technology, but we cannot be certain that these third-party manufacturers will comply with these restrictions.
While we believe there are multiple third parties capable of providing most of the materials and services we need
in order to manufacture API and distribute finished goods, and that supply of materials that cannot be second sourced can
be managed with inventory planning, there is always a risk that we may underestimate demand, and that our manufacturing
capacity through third-party manufacturers may not be sufficient. In addition, because of the significant lead times involved
in our supply chain for ruxolitinib phosphate, we may have less flexibility to adjust our supply in response to changes in
demand than if we had shorter lead times. Our strategy is to maintain 18 to 24 months of safety stock of API to be able to
respond to changes in demand to provide on-time supply of drug product as well as at least 6 months of semi-finished
goods inventory.
Access to Supplies and Materials
Our third-party manufacturers need access to certain supplies and products to manufacture our products and drug
candidates. If delivery of material from their suppliers were interrupted for any reason or if they are unable to purchase
sufficient quantities of raw materials used to manufacture our products and drug candidates, they may be unable to ship
our products for commercial supply or to supply our drug candidates in development for clinical trials. For example,
currently raw materials used to manufacture ruxolitinib phosphate, the API in JAKAFI and OPZELURA, are supplied by
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Chinese-based companies. As a result, an international trade dispute between China and the United States or any other
actions by the Chinese government that would limit or prevent Chinese companies from supplying these materials would
adversely affect our ability to manufacture and supply our products to meet market needs and have a material and adverse
effect on our operating results.
Human Capital
Our human capital management philosophy is committed to promoting an environment where our colleagues are
fulfilled and valued. We promote a company culture based on scientific excellence as we seek to create new treatments;
we are creative in our development strategies; and we seek positive collaboration with each other. Working collaboratively
is of the utmost importance as we aim to change the treatment landscape for patients with cancer and inflammatory and
autoimmune diseases. It is our goal to conduct business in a manner that does not compromise the health of people nor the
state of the environment. It is our policy to comply with all applicable environmental, health and safety (EHS) regulatory
requirements and seek to continually improve our EHS management systems. A strong safety culture is a fundamental part
of how we work, and our philosophy is that everyone at Incyte has a responsibility to create and maintain a safe and healthy
workplace with a goal to reduce risk and prevent injuries.
We appreciate one another’s differences and strengths and are proud to be an Equal Opportunity Employer. We
value diversity of backgrounds and perspectives and our policy is that we do not discriminate based on race, religious
creed, color, national origin, ancestry, physical disability, mental disability, medical condition, genetic information, marital
status, sex, gender, gender identity, gender expression, age, military and veteran status, sexual orientation or any other
protected characteristic as established by federal, state or local laws. Further, we have policies in place that prohibit
harassment of all kinds. At Incyte, we prohibit retaliation in all forms and are committed to encouraging a culture where
employees can freely ask questions and raise concerns. Our management team makes themselves available to all employees
and quarterly global Town Hall events allow for open question and answer dialogue.
We believe that creative solutions are best achieved by diverse teams working together, and inclusion is therefore
essential to Incyte. Diversity of thoughts, backgrounds, perceptions and ideas help us create the medical solutions that
patients require, and represent the lifeblood of organizations such as ours. We have an Inclusion Committee, which is co-
chaired by our Chief Executive Officer and Chief Human Resources Officer, to bring forth actionable plans across multiple
focus areas. We have continued to expand our recruitment searches to include organizations and websites dedicated to
Black candidates. We have partnered with Jopwell, to aid connections with Black and other underrepresented candidates
for non-science jobs and we are participating in the reputable Scientific Mentoring & Diversity Program (SMDP)
mentoring program that pairs primarily Black and Brown students, who are post baccalaureate and graduate students with
mentors who work at biopharmaceutical companies. We additionally post all of our open positions on the Historically
Black Colleges and Universities career pages and participate in diversity career fairs with national organizations such as
National Black MBA Association and National Sales Network in order to expand our recruitment reach.
We offer what we believe is a competitive compensation package, which allows 100% of global Incyte employees
to participate in our annual incentive compensation plan as well as annual equity-based grants. We seek to ensure our
compensation package remains competitive by benchmarking against our peers several times annually as well as
conducting twice per year compensation reviews to confirm that our employees are being compensated fairly, equitably
and in accordance with our pay structures and job levels. In addition, we offer what we believe is a competitive benefits
package, which includes an option to participate in our Employee Stock Purchase Plan for both full-time and part-time
employees working at least 20 hours per week. We believe that our health insurance coverage is industry-leading, as it
provides 100% coverage for full-time employees and is 95% subsidized for part-time employees working at least 20 hours
per week in the United States. Beyond compensation and benefits, we are committed to supporting our colleagues in their
professional development. Opportunities for growth are provided through challenging job assignments, performance
management and training opportunities. Globally, all full-time employees are eligible for tuition reimbursement. We
believe these professional opportunities enhance our colleagues’ skills, career aspirations and job satisfaction as well as
provide personal enrichment.
As of December 31, 2021, we had 2,094 employees representing an 18% increase over our 1,773 employees as
of the end of the prior year. This growth is largely as result of preparations for the commercial launch of OPZELURA
35
(ruxolitinib) cream in the second half of 2021. Among our employees, 989 are in research and development, 187 in medical
affairs, 638 in sales and marketing and 280 in operations support, finance and administrative positions. Geographically,
75% of our employees were based in the United States and Canada, 22% in Europe and 3% employees were based in Asia.
In terms of gender diversity, 51% are female and 49% are male. None of our employees are covered by collective
bargaining agreements, and management considers relations with our employees to be good.
Available Information
We were incorporated in Delaware in 1991 and our website is located at www.incyte.com. We make available
free of charge on our website our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on
Form 8-K and amendments to those reports, as soon as reasonably practicable after we electronically file or furnish such
materials to the Securities and Exchange Commission. Our website and the information contained therein or connected
thereto are not intended to be incorporated into this Annual Report on Form 10-K.
Item 1A. Risk Factors
RISKS RELATING TO COMMERCIALIZATION OF OUR PRODUCTS
We depend heavily on our lead product, JAKAFI (ruxolitinib), which is marketed as JAKAVI outside the United States.
If we are unable to maintain revenues from JAKAFI or those revenues decrease, our business may be materially
harmed.
JAKAFI is our first product marketed by us that is approved for sale in the United States. JAKAFI was approved
by the U.S. Food and Drug Administration, or FDA, in November 2011 for the treatment of patients with intermediate or
high-risk myelofibrosis, in December 2014 for the treatment of patients with polycythemia vera who have had an
inadequate response to or are intolerant of hydroxyurea, which we refer to as uncontrolled polycythemia vera, in May 2019
for the treatment of steroid-refractory acute graft-versus-host disease in adult and pediatric patients 12 years and older and
in September 2021 for the treatment of steroid-refractory chronic graft-versus-host disease in adult and pediatric patients
12 years and older. Although we have received regulatory approval for these indications, such approval does not guarantee
future revenues. While we also sell ICLUSIG in the European Union, or EU, and other countries for the treatment of certain
types of leukemia, PEMAZYRE in the United States, Europe and Japan for the treatment of certain metastatic
cholangiocarcinoma indications, MONJUVI in the United States and MINJUVI in the European Union for the treatment
of certain lymphoma indications, and OPZELURA in the Unites States for the treatment of certain indications of atopic
dermatitis, and our exclusive licensees sell OLUMIANT (baricitinib) for the treatment of specified rheumatoid arthritis
and atopic dermatitis indications and TABRECTA for the treatment of a certain type of non small-cell lung cancer, we
anticipate that JAKAFI product sales will continue to contribute a significant percentage of our total revenues over the
next several years.
The commercial success of JAKAFI and our ability to maintain and continue to increase revenues from the sale
of JAKAFI will depend on a number of factors, including:
•
•
the number of patients with intermediate or high-risk myelofibrosis, uncontrolled polycythemia vera or
steroid-refractory acute graft-versus-host disease who are diagnosed with the diseases and the number of such
patients that may be treated with JAKAFI;
the acceptance of JAKAFI by patients and the healthcare community;
• whether physicians, patients and healthcare payors view JAKAFI as therapeutically effective and safe relative
to cost and any alternative therapies;
•
the ability to obtain and maintain sufficient coverage or reimbursement by third-party payors and pricing;
36
•
•
•
•
•
•
the ability of our third-party manufacturers to manufacture JAKAFI in sufficient quantities that meet all
applicable quality standards;
the ability of our company and our third-party providers to provide marketing and distribution support for
JAKAFI;
the effects of the COVID-19 pandemic, any associated quarantine, travel restriction, stay-at-home or
shutdown orders, guidelines or practices, and any disruption in our supply chain for JAKAFI on our ability
to provide marketing and distribution support for JAKAFI, our ability to produce sufficient quantities of
JAKAFI that meet all applicable quality standards, patient demand (including new patient prescriptions) and
other risks detailed further below under “—Other Risks Relating to our Business—Public health epidemics,
such as the COVID-19 pandemic, could adversely affect our business, results of operations, and financial
condition”;
the label and promotional claims allowed by the FDA;
the maintenance of regulatory approval for the approved indications in the United States; and
our ability to develop, obtain regulatory approval for and commercialize ruxolitinib in the United States for
additional indications.
If we are not able to maintain revenues from JAKAFI in the United States, or our revenues from JAKAFI decrease,
our business may be materially harmed and we may need to delay other drug discovery, development and
commercialization initiatives or even significantly curtail operations, and our ability to license or acquire new products to
diversify our revenue base could be limited.
In addition, revenues from our other products and our receipt of royalties under our collaboration agreements with
Novartis for sales of JAKAVI outside the United States and TABRECTA globally and with Eli Lilly and Company for
worldwide sales of OLUMIANT will depend on factors similar to those listed above, with similar regulatory, pricing and
reimbursement issues driven by applicable regulatory authorities and governmental and third-party payors affecting
jurisdictions outside the United States.
If we are unable to obtain, or maintain at anticipated levels, coverage and reimbursement for our products from
government health administration authorities, private health insurers and other organizations, our pricing may be
affected and our product sales, results of operations and financial condition could be harmed.
Our ability to commercialize our current and any future approved products successfully will depend in part on
the prices we are able to charge for these products and the extent to which adequate coverage and reimbursement levels
for the cost of our products and related treatment are obtained from third-party payors, such as private insurers, government
insurance programs, including Medicare and Medicaid, health maintenance organizations (HMOs) and other health care
related organizations in the United States and abroad. We may not be able to sell our products on a profitable basis or our
profitability may be reduced if we are required to sell our products at lower than anticipated prices or reimbursement is
unavailable or limited in scope or amount. The costs of JAKAFI, ICLUSIG, PEMAZYRE, MONJUVI/MINJUVI and
OPZELURA are not insignificant and almost all patients will require some form of third-party coverage to afford their
cost. Our future revenues and profitability will be adversely affected if we cannot depend on government and other
third-party payors to defray the cost of our products to the patient.
Governments and other third-party payors continue to pursue initiatives to manage drug costs. Pricing and
reimbursement for our products may be adversely affected by a number of factors, including;
•
actions of federal, state and foreign governments and other third-party payors to implement or modify laws,
regulations or policies addressing payment and reimbursement for drugs;
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•
•
pressure by employers on private health insurance plans to reduce costs or moderate cost increases, as well
as continued public scrutiny of the price of drugs and other healthcare costs; and
consolidation of third-party payors and continued initiatives of government and other third-party payors to
reduce costs by seeking price discounts or rebates, reducing reimbursement rates or imposing restrictions on
access to or coverage of particular drugs based on perceived value.
In many markets outside of the United States, including countries of the EU, drug pricing and reimbursement are
subject to government control, and government authorities are making greater efforts to limit or regulate the price of drug
products. Reimbursement systems in international markets vary significantly by country and by region, and reimbursement
approvals must be obtained on a country-by-country basis. Reimbursement in the EU must be negotiated on a country-by-
country basis and in many countries a drug product cannot be commercially launched until reimbursement is approved.
The timing to complete the negotiation process in each country is highly uncertain, and in some countries, we expect that
it may exceed 12 months. Some countries set prices by reference to prices in other countries, and countries may refuse to
reimburse or may restrict the reimbursed population for a drug product based on their national health technology
assessments and cost effectiveness thresholds. In addition, governmental authorities in many countries may reduce prices
for approved drug products from previously established prices.
Third-party payors are increasingly challenging the prices charged for medical products and services, and payors
and employers are adopting benefit plan changes that shift a greater portion of prescription drug costs to patients. Third
party pharmacy benefit managers, or PBMs, other similar organizations and payors can limit coverage to specific products
on an approved list, or formulary, which might not include all of the approved products for a particular indication, and to
exclude drugs from their formularies in favor of competitor drugs or alternative treatments, or place drugs on formulary
tiers with higher patient co-pay obligations, and/or to mandate stricter utilization criteria. Formulary exclusion effectively
encourages patients and providers to seek alternative treatments, make a complex and time-intensive request for medical
exemptions, or pay 100% of the cost of a drug. In addition, in many instances, certain PBMs, other similar organizations
and third party payors may exert negotiating leverage by requiring incremental rebates, discounts or other concessions
from manufacturers in order to maintain formulary positions, which could continue to result in higher gross to net
deductions for affected products. There has been significant consolidation in the health insurance industry, resulting in
large insurers and PBMs exerting greater pressure and leverage in pricing and usage negotiations with drug manufacturers.
In this regard, we are in the process of negotiating agreements with PBMs and payor accounts to provide rebates to those
entities related to formulary coverage for OPZELURA, but we cannot guarantee that we will be able to agree to coverage
terms with these PBMs and other third party payors. Payors could decide to exclude OPZELURA from formulary coverage
lists, impose step edits that require patients to try alternative, including generic, treatments before authorizing payment for
OPZELURA, limit the types of diagnoses for which coverage will be provided or impose a moratorium on coverage for
products while the payor makes a coverage decision. An inability to maintain adequate formulary positions could increase
patient cost-sharing for OPZELURA and cause some patients to determine not to use OPZELURA. Any delays or
unforeseen difficulties in reimbursement approvals could limit patient access, depress therapy adherence rates, and
adversely impact our ability to successfully commercialize OPZELURA. If we are unsuccessful in obtaining and
maintaining broad coverage and reimbursement for OPZELURA, our anticipated revenue from and growth prospects for
OPZELURA could be negatively affected.
If third parties institute high co-payment amounts or other benefit limits for our products, the demand for our
products and, accordingly, our revenues and results of operations, could be adversely affected. Our patient assistance
programs have provided support for non-profit organizations that provide financial assistance to eligible patients or in
some cases, we have provided our products without charge to eligible patients who have no insurance coverage or are
underinsured. Substantial support in this manner could harm our profitability in the future. Further, non-profit
organizations’ ability to provide assistance to patients is dependent on funding from external sources, and we cannot
guarantee that such funding will be provided at adequate levels, or at all.
Risks related to proposed changes in government regulations and health care reform measures are described below
under “—Other Risks Relating to our Business—Health care reform measures could impact the pricing and profitability
of pharmaceuticals, and adversely affect the commercial viability of our or our collaborators’ products and drug candidates.
” If government and other third-party payors refuse to provide coverage and reimbursement with respect to our products,
38
determine to provide a lower level of coverage and reimbursement than anticipated, reduce previously approved levels of
coverage and reimbursement, or delay reimbursement payments due to budgetary constraints relating to the COVID-19
pandemic, then our pricing or reimbursement for our products may be affected and our product sales, results of operations
or financial condition could be harmed. Our collaborators Novartis and Eli Lilly are affected by similar considerations for
the drugs that they market and for which we may receive royalties.
We depend upon a limited number of specialty pharmacies and wholesalers for a significant portion of any revenues
from JAKAFI and most of our other drug products, and the loss of, or significant reduction in sales to, any one of these
specialty pharmacies or wholesalers could adversely affect our operations and financial condition.
We sell JAKAFI and our other drug products other than OPZELURA primarily to specialty pharmacies and
wholesalers. Specialty pharmacies dispense JAKAFI and our other drug products to patients in fulfillment of prescriptions
and wholesalers sell JAKAFI and our other drug products to hospitals and physician offices. We do not promote JAKAFI
or our other drug products to specialty pharmacies or wholesalers, and they do not set or determine demand for JAKAFI
or our other drug products. Our ability to successfully commercialize JAKAFI and our other drug products will depend, in
part, on the extent to which we are able to provide adequate distribution of JAKAFI and our other drug products to patients.
Although we have contracted with a number of specialty pharmacies and wholesalers, they are expected generally to carry
a very limited inventory and may be reluctant to be part of our distribution network in the future if demand for the product
does not increase. Further, it is possible that these specialty pharmacies and wholesalers could decide to change their
policies or fees, or both, at some time in the future. This could result in their refusal to carry smaller volume products such
as JAKAFI and our other drug products, or lower margins or the need to find alternative methods of distributing our
product. Although we believe we can find alternative channels to distribute JAKAFI or our other drug products on
relatively short notice, our revenue during that period of time may suffer and we may incur additional costs to replace any
such specialty pharmacy or wholesaler. The loss of any large specialty pharmacy or wholesaler as part of our distribution
network, a significant reduction in sales we make to specialty pharmacies or wholesalers, or any failure to pay for the
products we have shipped to them could materially and adversely affect our results of operations and financial condition.
If we are unable to establish and maintain effective sales, marketing and distribution capabilities, or to enter into
agreements with third parties to do so, we will not be able to successfully commercialize our products.
We have established commercial capabilities in the United States and outside of the United States, but cannot
guarantee that we will be able to enter into and maintain any marketing, distribution or third-party logistics agreements
with third-party providers on acceptable terms, if at all. We may not be able to correctly judge the size and experience of
the sales and marketing force and the scale of distribution capabilities necessary to successfully market and sell any new
products. Establishing and maintaining sales, marketing and distribution capabilities are expensive and time-consuming.
Competition for personnel with experience in sales and marketing can be high. Our expenses associated with building and
maintaining the sales force and distribution capabilities may be disproportional compared to the revenues we may be able
to generate on sales of our products.
We are working to establish and maintain sales, marketing and distribution capabilities for OPZELURA that will
generally be separate from our existing capabilities for oncology indications, and we have no prior experience in
commercializing products for dermatology indications. Successful commercialization of our drug candidates for
dermatology indications requires us to establish new physician and payor relationships, reimbursement strategies and
governmental interactions. Our inability to commercialize successfully products in indications outside of oncology could
harm our business and operating results.
If we fail to comply with applicable laws and regulations, we could lose our approval to market our products or be
subject to other governmental enforcement activity.
We cannot guarantee that we will be able to maintain regulatory approval to market our products in the
jurisdictions in which they are currently marketed. If we do not maintain our regulatory approval to market our products,
in particular JAKAFI, our results of operations will be materially harmed. We and our collaborators, third-party
manufacturers and suppliers are subject to rigorous and extensive regulation by the FDA and other federal and state
agencies as well as foreign governmental agencies. These regulations continue to apply after product marketing approval,
39
and cover, among other things, testing, manufacturing, quality control and assurance, labeling, advertising, promotion, risk
mitigation, and adverse event reporting requirements.
The commercialization of our products is subject to post-regulatory approval product surveillance, and our
products may have to be withdrawn from the market or subject to restrictions if previously unknown problems occur.
Regulatory agencies may also require additional clinical trials or testing for our products, and our products may be recalled
or may be subject to reformulation, additional studies, changes in labeling, warnings to the public and negative publicity.
For example, from late 2013 through 2014, ICLUSIG was subject to review by the European Medicines Agency, or EMA,
of the benefits and risks of ICLUSIG to better understand the nature, frequency and severity of events obstructing the
arteries or veins, the potential mechanism that leads to these side effects and whether there needed to be a revision in the
dosing recommendation, patient monitoring and a risk management plan for ICLUSIG. This review was completed in
January 2015, with additional warnings in the product information but without any change in the approved indications.
The EMA could take additional actions in the future that reduce the commercial potential of ICLUSIG. In addition, in
September 2021, the FDA approved a labeling update for JAKAFI, adding warnings of increased risk of major adverse
cardiovascular events, thrombosis, and secondary malignancies related to another JAK-inhibitor treating rheumatoid
arthritis, a condition for which JAKAFI is not indicated. As part of the FDA labeling update for oral JAK inhibitors in
treating inflammatory conditions, class “boxed” warnings were also included in the OPZELURA label. We cannot predict
the effects on sales of JAKAFI with the updated warnings or OPZELURA as a result of the “boxed” warnings, but it is
possible that future sales of JAKAFI and OPZELURA can be negatively affected, which could have a material and adverse
effect on our business, results of operations and prospects.
Failure to comply with the laws and regulations administered by the FDA or other agencies could result in:
•
•
•
•
•
•
•
•
administrative and judicial sanctions, including warning letters;
fines and other civil penalties;
suspension or withdrawal of regulatory approval to market or manufacture our products;
interruption of production;
operating restrictions;
product recall or seizure;
injunctions; and
criminal prosecution.
The occurrence of any such event may have a material adverse effect on our business.
If the use of our products harms patients, or is perceived to harm patients even when such harm is unrelated to our
products, our regulatory approvals could be revoked or otherwise negatively impacted or we could be subject to costly
and damaging product liability claims.
The testing of JAKAFI, ICLUSIG, PEMAZYRE, MONJUVI/MINJUVI and OPZELURA, the manufacturing,
marketing and sale of JAKAFI, PEMAZYRE and OPZELURA and the marketing and sale of ICLUSIG and
MONJUVI/MINJUVI expose us to product liability and other risks. Side effects and other problems experienced by
patients from the use of our products could:
•
lessen the frequency with which physicians decide to prescribe our products;
40
•
•
•
encourage physicians to stop prescribing our products to their patients who previously had been prescribed
our products;
cause serious harm to patients that may give rise to product liability claims against us; and
result in our need to withdraw or recall our products from the marketplace.
If our products are used by a wide patient population, new risks and side effects may be discovered, the rate of
known risks or side effects may increase, and risks previously viewed as less significant could be determined to be
significant.
Previously unknown risks and adverse effects of our products may also be discovered in connection with
unapproved, or off-label, uses of our products. We are prohibited by law from promoting or in any way supporting or
encouraging the promotion of our products for off-label uses, but physicians are permitted to use products for off-label
purposes. In addition, we are studying and expect to continue to study JAKAFI in diseases for potential additional
indications in controlled clinical settings, and independent investigators are doing so as well. In the event of any new risks
or adverse effects discovered as new patients are treated for intermediate or high-risk myelofibrosis, uncontrolled
polycythemia vera or acute graft-versus-host disease and as JAKAFI is studied in or used by patients for off-label
indications, regulatory authorities may delay or revoke their approvals, we may be required to conduct additional clinical
trials, make changes in labeling of JAKAFI, reformulate JAKAFI or make changes and obtain new approvals. We may
also experience a significant drop in the sales of JAKAFI, experience harm to our reputation and the reputation of JAKAFI
in the marketplace or become subject to lawsuits, including class actions. Any of these results could decrease or prevent
sales of JAKAFI or substantially increase the costs and expenses of commercializing JAKAFI. Similar results could occur
with respect to our commercialization of ICLUSIG, PEMAZYRE, MONJUVI/MINJUVI and OPZELURA.
Patients who have been enrolled in our clinical trials or who may use our products in the future often have severe
and advanced stages of disease and known as well as unknown significant pre-existing and potentially life-threatening
health risks. During the course of treatment, patients may suffer adverse events, including death, for reasons that may or
may not be related to our products. Such events could subject us to costly litigation, require us to pay substantial amounts
of money to injured patients, delay, negatively impact or end our opportunity to receive or maintain regulatory approval
to market our products, or require us to suspend or abandon our commercialization efforts. Even in a circumstance in which
we do not believe that an adverse event is related to our products, the investigation into the circumstance may be time
consuming or inconclusive. These investigations may interrupt our sales efforts, impact and limit the type of regulatory
approvals our products receive or maintain, or delay the regulatory approval process in other countries.
Factors similar to those listed above also apply to our collaborator Novartis for jurisdictions in which it has
development and commercialization rights, to ICLUSIG for jurisdictions outside the United States, to our collaborator
Lilly for all jurisdictions and to our collaborator Innovent for PEMAZYRE in the jurisdictions in which it has development
and commercialization rights.
If we market our products in a manner that violates various laws and regulations, we may be subject to civil or criminal
penalties.
In addition to FDA and related regulatory requirements, we are subject to health care “fraud and abuse” laws,
such as the federal False Claims Act, the anti-kickback provisions of the federal Social Security Act, and other state and
federal laws and regulations. Federal and state anti-kickback laws prohibit, among other things, knowingly and willfully
offering, paying, soliciting or receiving remuneration to induce, or in return for purchasing, leasing, ordering or arranging
for the purchase, lease or order of any health care item or service reimbursable under Medicare, Medicaid, or other
federally- or state-financed health care programs. Federal false claims laws prohibit any person from knowingly presenting,
or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be
made, a false statement to get a false claim paid. Pharmaceutical companies have been prosecuted under these laws for a
variety of alleged promotional and marketing activities.
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Although physicians are permitted, based on their medical judgment, to prescribe products for indications other
than those approved by the FDA, manufacturers are prohibited from promoting their products for such off-label uses. We
market JAKAFI for intermediate or high-risk myelofibrosis, uncontrolled polycythemia vera and acute graft-versus-host
disease and provide promotional materials to physicians regarding the use of JAKAFI for these indications. Although we
believe that our promotional materials for physicians do not constitute improper promotion of JAKAFI, the FDA or other
agencies may disagree. If the FDA or another agency determines that our promotional materials or other activities
constitute improper promotion of JAKAFI, it could request that we modify our promotional materials or other activities or
subject us to regulatory enforcement actions, including the issuance of a warning letter, injunction, seizure, civil fine and
criminal penalties. It is also possible that other federal, state or foreign enforcement authorities might take action if they
believe that the alleged improper promotion led to the submission and payment of claims for an unapproved use, which
could result in significant fines or penalties under other statutory authorities, such as laws prohibiting false claims for
reimbursement. Even if it is later determined we are not in violation of these laws, we may be faced with negative publicity,
incur significant expenses defending our position and have to divert significant management resources from other matters.
Similar risks exist for our marketing of PEMAZYRE and OPZELURA and our collaborator MorphoSys’s marketing of
MONJUVI.
The European Union and member countries, as well as governmental authorities in other countries, impose similar
strict restrictions on the promotion and marketing of drug products. The off-label promotion of medicinal products is
prohibited in the EU and in other territories, and the EU also maintains strict controls on advertising and promotional
materials. The promotion of medicinal products that are not subject to a marketing authorization is also prohibited in the
EU. Violations of the rules governing the promotion of medicinal products in the EU and in other territories could be
penalized by administrative measures, fines and imprisonment.
The majority of states also have statutes or regulations similar to the federal anti-kickback law and false claims
laws, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply
regardless of the payor. Numerous states and localities have enacted or are considering enacting legislation requiring
pharmaceutical companies to establish marketing compliance programs, file periodic reports or make periodic public
disclosures on sales, marketing, pricing, clinical trials, and other activities. Additionally, as part of the Patient Protection
and Affordable Care Act, the federal government has enacted the Physician Payment Sunshine provisions. The Sunshine
provisions and similar laws and regulations in other jurisdictions where we do business require manufacturers to publicly
report certain payments or other transfers of value made to physicians and teaching hospitals. Many of these requirements
are new and uncertain, and the penalties for failure to comply with these requirements are unclear. Nonetheless, if we are
found not to be in full compliance with these laws, we could face enforcement action and fines and other penalties, which
could be significant in amount or result in exclusion from federal healthcare programs such as Medicare and Medicaid.
Any action initiated against us for violation of these laws, even if we successfully defend against it, could require the
expenditure of significant resources and generate negative publicity, which could harm our business and operating results.
See also “—Other Risks Relating to our Business—If we fail to comply with the extensive legal and regulatory
requirements affecting the health care industry, we could face increased costs, penalties and a loss of business” below.
Competition for our products could harm our business and result in a decrease in our revenue.
Our products compete, and our product candidates may in the future compete, with currently existing therapies,
including generic drugs, product candidates currently under development by us and others, or future product candidates,
including new chemical entities that may be safer or more effective or more convenient than our products. Any products
that we develop may be commercialized in competitive markets, and our competitors, which include large global
pharmaceutical and biopharmaceutical companies and smaller research-based biotechnology companies, may succeed in
developing products that render our products obsolete or noncompetitive. Many of our competitors, particularly large
pharmaceutical and biopharmaceutical companies, have substantially greater financial, operational and human resources
than we do. Smaller or earlier stage companies may also prove to be significant competitors, particularly through focused
development programs and collaborative arrangements with large, established companies. In addition, many of our
competitors deploy more personnel to market and sell their products than we do, and we compete with other companies to
recruit, hire, train and retain pharmaceutical sales and marketing personnel. If our sales force and sales support organization
are not appropriately resourced and sized to adequately promote our products, the commercial potential of our current and
any future products may be diminished. In any event, the commercial potential of our current products and any future
42
products may be reduced or eliminated if our competitors develop or acquire and commercialize generic or branded
products that are safer or more effective, are more convenient or are less expensive than our products. See “Item 1.
Business —Competition” in this Annual Report on Form 10-K for additional information regarding the effects of
competition. If we are unable to compete successfully, our commercial opportunities will be reduced and our business,
results of operations and financial conditions may be materially harmed.
Present and potential competitors for JAKAFI could include major pharmaceutical and biotechnology companies,
as well as specialty pharmaceutical firms. For example, in August 2019, Celgene Corporation, now a subsidiary of Bristol-
Myers Squibb Company, announced that the FDA had approved INREBIC (fedratinib) for the treatment of myelofibrosis.
See “—Other Risks Relating to our Business— We face significant competition for our drug discovery and development
efforts, and if we do not compete effectively, our commercial opportunities will be reduced or eliminated” for a description
of risks relating to this type of competition. In addition, JAKAFI could face competition from generic products. As a
result of the Drug Price Competition and Patent Term Restoration Act of 1984, commonly known as the Hatch-Waxman
Act, in the United States, generic manufacturers may seek approval of a generic version of an innovative pharmaceutical
by filing with the FDA an Abbreviated New Drug Application, or ANDA. The Hatch-Waxman Act provides significant
incentives to generic manufacturers to challenge U.S. patents on successful innovative pharmaceutical products. In
February 2016, we received a notice letter regarding an ANDA that requested approval to market a generic version of
JAKAFI and purported to challenge patents covering ruxolitinib phosphate and its use that expire in 2028. The notice letter
does not challenge the ruxolitinib composition of matter patent, which expires in December 2027. To date, to our
knowledge, the FDA has taken no action with respect to this ANDA. Separately, in January 2018 the Patent Trial and
Appeal Board (PTAB) of United States Patent and Trademark Office denied a petition challenging our patent covering
deuterated ruxolitinib analogs and the PTAB subsequently denied the petitioner’s request for rehearing in May 2018.
Nevertheless, the petitioner still has the right separately to challenge the validity of our patent in federal court. There can
be no assurance that our patents will be upheld or that any litigation in which we might engage with any such generic
manufacturer would be successful in protecting JAKAFI’s exclusivity. The entry of a competitive drug product from
another company or a generic version of JAKAFI could result in a decrease in JAKAFI sales and materially harm our
business, operating results and financial condition.
ICLUSIG currently competes with existing therapies that are approved for the treatment of patients with chronic
myeloid leukemia, or CML, who are resistant or intolerant to prior tyrosine kinase inhibitor, or TKI, therapies, on the basis
of, among other things, efficacy, cost, breadth of approved use and the safety and side-effect profile. In addition, generic
versions of imatinib are available and, while we currently believe that generic versions of imatinib will not materially
impact our commercialization of ICLUSIG, given ICLUSIG’s various indication statements globally that are currently
focused on resistant or intolerant CML, we cannot be certain how physicians, payors, patients, regulatory authorities and
other market participants will respond to the availability of generic versions of imatinib.
MONJUVI/MINJUVI currently competes with existing therapies that are approved for the treatment of patients
with diffuse large B-cell lymphoma on the basis of, among other things, efficacy, cost, breadth of approved use and the
safety and side-effect profile. These existing therapies are offered by major pharmaceutical and biotechnology companies,
as well as specialty pharmaceutical firms. Competitors and potential competitors for PEMAZYRE include major
pharmaceutical and biotechnology companies, as well as specialty pharmaceutical firms. Competitors for OPZELURA
include existing over-the-counter topical treatments, prescription topical treatments, including generic versions, such as
tacrolimus, pimecrolimus, topical steroids, and EUCRISA (crisaborole) from Pfizer Inc., as well as oral and injectable
therapies such as prednisone and other oral steroids and injectable DUPIXENT (dupilimab) from Sanofi and Regeneron
Pharmaceuticals, Inc.
OTHER RISKS RELATING TO OUR BUSINESS
Public health epidemics, such as the COVID-19 pandemic, have adversely affected and could in the future adversely
affect our business, results of operations, and financial condition.
Our global operations expose us to risks associated with public health epidemics, such as the COVID-19 pandemic
that has spread globally. The extent to which the COVID-19 pandemic and the measures taken to limit COVID-19’s
spread impact our operations and those of our suppliers, collaborators, service providers and healthcare organizations
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serving patients, as well as demand for our drug products, will depend on future developments, which are highly uncertain
and cannot be predicted with confidence, including the duration of the outbreak and any future resurgence of the outbreak,
additional or modified government actions, including any further restrictions or reopening of local, state or national social
or economic activity, new information that may emerge concerning the severity of COVID-19 and the actions taken to
contain COVID-19 or treat its impact, among others.
As a result of the COVID-19 pandemic, we have experienced and may in the future experience disruptions that
could severely impact our business, results of operations and financial condition, including the following:
• When the COVID-19 pandemic commenced, to protect the health of our employees and their families, and our
communities, in accordance with – and in some cases in advance of – direction from state and local government
authorities, we limited access to our facilities and a significant percentage of our personnel worked remotely. In
the event that governmental authorities were to re-establish workplace restrictions, our employees conducting
research and development activities may not be able to access our laboratory space or access may be limited, and
our research and development activities may be significantly limited or curtailed, possibly for an extended period
of time. These research and development activities could include completing Investigational New Drug
(IND)/Clinical Trial Application (CTA)-enabling studies, our ability to select future development candidates, and
initiation of additional clinical trials for our development programs. Having a significant portion of our employees
work from home can strain our information technology infrastructure, which may affect our ability to operate
effectively, may make us more susceptible to communications disruptions, and expose us to greater cybersecurity
risks.
• Our sales and marketing activities, including our interactions with healthcare professionals, have been limited
and made more difficult by government or employer imposed work from home orders and travel and workplace
visitor restrictions resulting from measures to address the COVID-19 pandemic, as well as employee-initiated
remote work and travel limitations resulting from, among other things, the spread of the COVID-19 variants. In
addition, demand for our products has been affected by decreases in new patients, which we believe resulted in
large part from decreases in patient visits to healthcare professionals and prioritization of hospital resources for
the COVID-19 pandemic, resulting in decreases in disease screening and diagnosis. We cannot predict the effects
on patient demand or future sales if there are prolonged quarantines, work from home orders or travel restrictions.
• Our clinical trials have been and will likely continue to be affected by delays in site initiation, patient screening,
patient enrollment, and monitoring and data collection as a result of prioritization of hospital resources for the
COVID-19 pandemic, difficulty in recruiting and retaining healthcare providers and staff due to their diversion
toward treating COVID-19 patients, the potential unwillingness of patients to enroll or continue in clinical trials
for fear of exposure to COVID-19 at sites, and the inability to access sites for initiation and monitoring. In
addition, some patients may be unable to comply with clinical trial protocols if quarantines or travel restrictions
impede patient movement or interrupt health services, we may be unable to obtain blood samples for testing, and
we may not be able to provide the trial drug candidate to patients. Also, we rely on independent clinical
investigators, contract research organizations and other third-party service providers to assist us in managing,
monitoring and otherwise carrying out our preclinical studies and clinical trials, and the COVID-19 pandemic has
affected and may continue to affect their ability to devote sufficient time and resources to our programs or to
travel to sites to perform work for us.
• Health regulatory agencies globally have experienced disruptions in their operations as a result of the coronavirus
pandemic. The FDA and comparable foreign regulatory agencies may have slower response times or be under-
resourced to continue to monitor our clinical trials and, as a result, review, inspection, and other timelines may
be materially delayed. If any of these disruptions occur or continue to occur, we cannot predict how long they
may last. Our drug candidate application reviews and potential approvals could be impacted or delayed by these
disruptions, if they occur or continue to occur.
• The outbreak and measures taken to limit the spread of the outbreak, especially if prolonged, could also disrupt
our supply chain or limit our ability to obtain sufficient materials for our drug products and product candidates,
which could adversely affect our revenues and clinical trial timelines. Currently, our supply chain for our drug
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products and product candidates depends on operations by us and by other companies in multiple countries around
the world, and the effects of the COVID-19 pandemic on any or all of these countries is uncertain and
unpredictable and potential disruption is possible. In addition, our third-party manufacturers might experience
capacity constraints and delays in producing materials for our drug products and product candidates if they are
required, under the U.S. Defense Production Act or similar governmental mandates, to prioritize production of
raw materials, supplies, drugs or vaccines to address COVID-19. And, for JAKAFI, while our strategy is to
maintain a 24 month stock of active pharmaceutical ingredient, or API, inclusive of finished product, ruxolitinib
phosphate might be used by us either to make JAKAFI or for ruxolitinib drug candidates in clinical trials.
• Any deterioration of worldwide credit and financial markets could result in losses on our holdings of cash and
investments due to failures of financial institutions and other parties, and interruptions and delays in our ability
to collect, or potential losses on, our accounts receivable.
Our collaborators could be affected by similar factors as those that have or could affect our business. The ultimate
impact of the COVID-19 pandemic or a similar health epidemic is highly uncertain and subject to change. We do not yet
know the full extent of potential impacts or delays on our or our collaborators’ businesses, our revenues, including
milestone and royalty revenues from our collaborators, our and our collaborators’ clinical trials, healthcare systems or the
global economy as a whole. However, these effects could have a material adverse impact on our business, results of
operations, and financial condition.
We may be unsuccessful in our efforts to discover and develop drug candidates and commercialize drug products.
Our long-term success, revenue growth and diversification of revenues depends on our ability to obtain regulatory
approval for new drug products and additional indications for our existing drug products. Our ability to discover and
develop drug candidates and to commercialize additional drug products and indications will depend on our ability to:
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hire and retain key employees;
identify high quality therapeutic targets;
identify potential drug candidates;
develop products internally or license or acquire drug candidates from others;
identify and enroll suitable human subjects, either in the United States or abroad, for our clinical trials;
complete laboratory testing;
commence, conduct and complete safe and effective clinical trials on humans;
obtain and maintain necessary intellectual property rights to our products;
obtain and maintain necessary regulatory approvals for our products, both in the United States and abroad;
enter into arrangements with third parties to provide services or to manufacture our products on our behalf;
deploy sales, marketing, distribution and manufacturing resources effectively or enter into arrangements with
third parties to provide these functions in compliance with all applicable laws;
obtain appropriate coverage and reimbursement levels for the cost of our products from governmental
authorities, private health insurers and other third-party payors;
lease facilities at reasonable rates to support our growth; and
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enter into arrangements with third parties to license and commercialize our products.
We may not be successful in discovering, developing, or commercializing additional drug products or our existing
drug products in new indications. Discovery and development of drug candidates are expensive, uncertain and
time-consuming, and we do not know if our efforts will lead to discovery of any drug candidates that can be successfully
developed and marketed. Of the compounds or biologics that we identify as potential drug products or that we may
in-license from other companies, including potential products for which we are conducting clinical trials, only a few, if
any, are likely to lead to successful drug development programs and commercialized drug products.
We depend heavily on the success of our most advanced drug candidates. We and our collaborators might not be able
to commercialize any of our or their drug candidates successfully, and we may spend significant time and money
attempting to do so.
We have invested significant resources in the development of our most advanced drug candidates. We have a
number of drug candidates in Phase III clinical trials as monotherapies or in combination with other drugs and drug
candidates, including itacitinib, parsaclisib, pemigatinib, ruxolitinib, ruxolitinib cream and tafasitamab. Our ability to
generate product revenues will depend on the successful development and eventual commercialization of our most
advanced drug candidates. We, or our collaborators or licensees, may decide to discontinue development of any or all of
our drug candidates at any time for commercial, scientific or other reasons. For example, in April 2018, we along with
Merck stopped the ECHO-301 study with epacadostat, and we also significantly downsized the epacadostat development
program. If a product is developed but not approved or marketed, or becomes approved for a narrower set of indications
than those for which we initially conducted clinical trials, we may have spent significant amounts of time and money on it
without achieving potential returns initially anticipated, which could adversely affect our operating results and financial
condition as well as our business plans.
If we or our collaborators are unable to obtain regulatory approval for our drug candidates in the United States and
foreign jurisdictions, we or our collaborators will not be permitted to commercialize products resulting from our
research.
In order to commercialize drug products in the United States, drug candidates will have to obtain regulatory
approval from the FDA. Satisfaction of regulatory requirements typically takes many years. To obtain regulatory approval,
we or our collaborators, as the case may be, must first show that our or our collaborators’ drug candidates are safe and
effective for target indications through preclinical testing (animal testing) and clinical trials (human testing). Preclinical
testing and clinical development are long, expensive and uncertain processes, and we do not know whether the FDA will
allow us or our collaborators to undertake clinical trials of any drug candidates in addition to our or our collaborators’
compounds currently in clinical trials. If regulatory approval of a product is granted, this approval will be limited to those
disease states and conditions for which the product is demonstrated through clinical trials to be safe and effective.
Completion of clinical trials may take several years and failure may occur at any stage of testing. The length of
time required varies substantially according to the type, complexity, novelty and intended use of the drug candidate. Interim
results of a preclinical test or clinical trial do not necessarily predict final results, and acceptable results in early clinical
trials may not be repeated in later clinical trials. For example, a drug candidate that is successful at the preclinical level
may cause harmful or dangerous side effects when tested at the clinical level. Our rate of commencement and completion
of clinical trials may be delayed, and existing clinical trials with our or our collaborators’ drug candidates may be stopped,
due to many potential factors, including:
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the high degree of risk and uncertainty associated with drug development;
our inability to formulate or manufacture sufficient quantities of materials for use in clinical trials;
variability in the number and types of patients available for each study;
difficulty in maintaining contact with patients after treatment, resulting in incomplete data;
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unforeseen safety issues or side effects;
poor or unanticipated effectiveness of drug candidates during the clinical trials; or
government or regulatory delays.
Data obtained from clinical trials are susceptible to varying interpretation, which may delay, limit or prevent
regulatory approval. Many companies in the pharmaceutical and biopharmaceutical industry, including our company, have
suffered significant setbacks in advanced clinical trials, even after achieving promising results in earlier clinical trials. In
addition, regulatory authorities may refuse or delay approval as a result of other factors, such as changes in regulatory
policy during the period of product development and regulatory agency review. For example, the FDA has in the past
required, and could in the future require, that we or our collaborators conduct additional trials of any of our drug candidates,
which would result in delays. In April 2017, we and our collaborator Lilly announced that the FDA had issued a complete
response letter for the New Drug Application, or NDA, of OLUMIANT as a once-daily oral medication for the treatment
of moderate-to-severe rheumatoid arthritis. The letter indicated that additional clinical data were needed to determine the
most appropriate doses and to further characterize safety concerns across treatment arms. In June 2018, after a
resubmission of the NDA, the FDA approved the 2mg dose of OLUMIANT for the treatment of adults with moderately-
to-severely active rheumatoid arthritis who have had an inadequate response to one or more tumor necrosis factor inhibitor
therapies. The FDA did not at that time approve any higher dose of OLUMIANT and required a warning label in
connection with its approval. In addition, in January 2022, we announced that we withdrew the NDA seeking approval of
parsaclisib for the treatment of patients with relapsed or refractory follicular lymphoma, marginal zone lymphoma and
mantle cell lymphoma. The decision to withdraw the NDA followed discussions with FDA regarding confirmatory clinical
trials that we determined cannot be completed within the time period to support the investment.
Compounds or biologics developed by us or with or by our collaborators and licensees may not prove to be safe
and effective in clinical trials and may not meet all of the applicable regulatory requirements needed to receive marketing
approval. For example, in January 2016, a Phase II trial that was evaluating ruxolitinib in combination with regorafenib in
patients with relapsed or refractory metastatic colorectal cancer and high C-reactive protein was stopped early after a
planned analysis of interim efficacy data determined that the likelihood of the trial meeting its efficacy endpoint was
insufficient. In addition, in February 2016, we made a decision to discontinue our JANUS 1 study, our JANUS 2 study,
our other studies of ruxolitinib in colorectal, breast and lung cancer, and our study of INCB39110 in pancreatic cancer
after a planned analysis of interim efficacy data of JANUS 1 demonstrated that ruxolitinib plus capecitabine did not show
a sufficient level of efficacy to warrant continuation. Also, in April 2018, we along with Merck announced that the
ECHO-301 study had been stopped and we also significantly downsized the epacadostat development program and in
January 2020 we stopped our Phase III trial of itacitinib for the treatment of acute graft-versus-host-disease. If clinical
trials of any of our or our collaborators’ compounds or biologics are stopped for safety, efficacy or other reasons or fail to
meet their respective endpoints, our overall development plans, business, prospects, expected operating results and
financial condition could be materially harmed and the value of our company could be negatively affected.
Even if any of our applications receives an FDA Fast Track or priority review designation (including based on a
priority review voucher, one of which we recently acquired and used in connection with our submission seeking FDA
approval of ruxolitinib cream for atopic dermatitis), these designations may not result in faster review or approval for our
product candidate compared to product candidates considered for approval under conventional FDA procedures and, in
any event, do not assure ultimate approval of our product candidate by FDA. For example, in June 2021 we were informed
by the FDA that the FDA had extended by three months the review period for the NDA for ruxolitinib cream for atopic
dermatitis. Also, in July 2021, we announced that the FDA issued a complete response letter for the BLA of retifanlimab
for the treatment of squamous cell carcinoma of the anal canal, in which the FDA stated it cannot approve the BLA and
that additional data are needed. In addition, while the FDA had granted orphan drug designation and Fast Track designation
to parsaclisib as a treatment for patients with follicular lymphoma, marginal zone lymphoma and mantle cell lymphoma,
as discussed above we withdrew our NDA seeking approval for treatment of patients with those lymphomas. The FDA has
recently increased its attention on mandated confirmatory trials for oncology drug candidates with accelerated approvals,
and the logistics, cost and timing required for confirmatory trials may conflict with the investment thesis for drug
candidates, resulting in withdrawal of approval applications.
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Outside the United States, our and our collaborators’ ability to market a product is contingent upon receiving a
marketing authorization from the appropriate regulatory authorities. This foreign regulatory approval process typically
includes all of the risks associated with the FDA approval process described above and may also include additional risks.
The requirements governing the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from
country to country and may require us to perform additional testing and expend additional resources. Approval by the FDA
does not ensure approval by regulatory authorities in other countries, and approval by one foreign regulatory authority
does not ensure approval by regulatory authorities in other countries or by the FDA.
Health care reform measures could impact the pricing and profitability of pharmaceuticals, and adversely affect the
commercial viability of our or our collaborators’ products and drug candidates.
In recent years, through legislative and regulatory actions and executive orders, the U.S. federal government has
made substantial changes to various payment systems under the Medicare and other federal health care programs.
Comprehensive reforms to the U.S. healthcare system were enacted, including changes to the methods for, and amounts
of, Medicare reimbursement. For example, a provision in the American Rescue Plan Act of 2021 that is expected to be
implemented in 2024 will have the effect of increasing the Medicaid rebate liability for some medicines that increase prices
in excess of inflation. While there is currently significant uncertainty regarding the implementation of some of these
reforms or the scope of amended or additional reforms, the implementation of reforms could significantly reduce payments
from Medicare and Medicaid. Reforms or other changes to these payment systems may change the availability, methods
and rates of reimbursements from Medicare, private insurers and other third-party payors for our current and any future
approved products. Some of these changes and proposed changes could result in reduced reimbursement rates or in
eliminating dual sources of payment, which could reduce the price that we or any of our collaborators or licensees receive
for any products in the future, and which would adversely affect our business strategy, operations and financial results.
In addition, there has been an increasing legislative and enforcement interest in the United States with respect to
drug pricing practices. This has resulted in significant legislative activity and proposals from the prior and current
Administrations relating to prescription drug prices and reimbursement, any of which, if enacted, could impose downward
pressure on the prices that we can charge for our products and may further limit the commercial viability of our products
and drug candidates. Specifically, there have been ongoing federal congressional inquiries and proposed and enacted
federal and state legislation, executive orders and administrative agency rules designed to, among other things, bring more
transparency to drug pricing, reduce drug prices, reform government program reimbursement methodologies for
prescription drugs, expand access to government-mandated discounted pricing (known as 340B pricing) through broader
contract pharmacy arrangements, allow importation of drugs into the United States from other countries, and limit
allowable prices for drugs through reference to an average price from foreign markets that may be substantially lower than
what we currently or would otherwise charge. In certain foreign markets, pricing or profitability of prescription
pharmaceuticals is subject to government control. We expect that the health care reform measures that have been adopted
in the United States and in foreign markets, and further reforms that may be adopted in the future, could result in more
rigorous coverage criteria and additional downward pressure on the prices that we may receive for our approved products.
If reimbursement for our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels,
our business could be materially harmed, including by our revenue potentially being materially adversely affected and our
research and development efforts potentially being materially curtailed or, in some cases, ceasing. There may be future
changes that result in reductions in current prices, coverage and reimbursement levels for our current or any future
approved products, and we cannot predict the scope of any future changes or the impact that those changes would have on
our operations.
The consequences of the COVID-19 pandemic, including the economic effect on government budgets in the
United States and elsewhere, may accelerate any of the healthcare reform efforts described above or result in future reform
efforts, any of which could have adverse effects on our business, including higher costs for us, lower reimbursement rates
for our products and lower demand for our products.
Further, if we become the subject of any governmental or other regulatory hearing or investigation with respect
to the pricing of our products or other business practices, we could incur significant expenses and could be distracted from
the operation of our business and execution of our business strategy. Any such hearing or investigation could also result
in significant negative publicity and harm to our reputation, reduced market acceptance and demand, which could adversely
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affect our financial results and growth prospects.
In addition, the trend toward managed health care in the United States, the organizations for which could control
or significantly influence the purchase of health care services and products, as well as legislative and regulatory proposals
to reform health care or address the cost of government insurance programs, may all result in lower prices for or rejection
of our products. Adoption of our products by the medical community and patients may be limited without adequate
reimbursement for those products. Cost control initiatives may decrease coverage and payment levels for our products and,
in turn, the price that we will be able to charge for any product. Our products may not be considered cost-effective, and
coverage and reimbursement may not be available or sufficient to allow us to sell our products on a profitable basis. We
are unable to predict all changes to the coverage or reimbursement methodologies that will be applied by private or
government payors to our current and any future approved products.
The continuing efforts of legislatures, health agencies and third-party payors to contain or reduce the costs of
health care, any denial of private or government payor coverage or inadequate reimbursement for our drug candidates
could materially and adversely affect our business strategy, operations, future revenues and profitability, and the future
revenues and profitability of our potential customers, suppliers, collaborators and licensees and the availability of capital.
The same risks apply to our compounds developed and marketed by our collaborators, and our future potential milestone
and royalty revenues could be affected in a similar manner.
We depend on our collaborators and licensees for the future development and commercialization of some of our drug
candidates. Conflicts may arise between our collaborators and licensees and us, or our collaborators and licensees may
choose to terminate their agreements with us, which may adversely affect our business.
We have licensed to Novartis rights to ruxolitinib outside of the United States and worldwide rights to our MET
inhibitor compounds, including TABRECTA, and licensed to Lilly worldwide rights to baricitinib. In addition, we have
licensed to Innovent, Zai Lab and InnoCare certain Asian rights to some of our clinical stage compounds. Under the terms
of our agreements with these collaborators, we have no or limited control over the further clinical development of these
drug candidates in the relevant territories and any revenues we may receive if these drug candidates receive regulatory
approval and are commercialized in the relevant territories will depend primarily on the development and
commercialization efforts of others. While OLUMIANT was approved by the European Commission in February 2017 for
the treatment of moderate-to-severe rheumatoid arthritis in adult patients and by Japan’s Ministry of Health, Labor and
Welfare in July 2017 for the treatment of rheumatoid arthritis in patients with inadequate response to standard-of-care
therapies, the NDA for OLUMIANT for the treatment of moderate-to-severe rheumatoid arthritis was approved in
June 2018, and only in the lower dosage tablet and with a warning label. Delays in any marketing approval by the FDA,
European or other regulatory authorities, or any label modifications or restrictions in connection with any such approval,
or the existence of other risks relating to approved drug products, including those described under “Risks Relating to
Commercialization of Our Products,” could delay the receipt of and reduce resulting potential royalty and milestone
revenue from baricitinib or any of our other out-licensed drug candidates.
Conflicts may arise with our collaborators and licensees if they pursue alternative technologies or develop
alternative products either on their own or in collaboration with others as a means for developing treatments for the diseases
that we have targeted. Competing products and product opportunities may lead our collaborators and licensees to withdraw
their support for our drug candidates. Any failure of our collaborators and licensees to perform their obligations under our
agreements with them or otherwise to support our drug candidates could negatively impact the development of our drug
candidates, lead to our loss of potential revenues from product sales and milestones and delay our achievement, if any, of
profitability. Additionally, conflicts have from time to time occurred, and may in the future arise, relating to, among other
things, disputes about the achievement and payment of milestone amounts and royalties owed, the ownership of intellectual
property that is developed during the course of a collaborative relationship or the operation or interpretation of other
provisions in our collaboration agreements. These disputes have led and could in the future lead to litigation or arbitration,
which could be costly and divert the efforts of our management and scientific staff, and could diminish the expected
effectiveness of the collaboration.
Our existing collaborative and license agreements can be terminated by our collaborators and licensees for
convenience, among other circumstances. If any of our collaborators or licensees terminates its agreement with us, or
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terminates its rights with respect to certain indications or drug candidates, we may not be able to find a new collaborator
for them, and our business could be adversely affected. Should an agreement be terminated before we have realized the
benefits of the collaboration or license, our reputation could be harmed, we may not obtain revenues that we anticipated
receiving, and our business could be adversely affected.
The success of our drug discovery and development efforts may depend on our ability to find suitable collaborators to
fully exploit our capabilities. If we are unable to establish collaborations or if these future collaborations are
unsuccessful in the development and commercialization of our drug candidates, our research, development and
commercialization efforts may be unsuccessful, which could adversely affect our results of operations, financial
condition and future revenue prospects.
An element of our business strategy is to enter into collaborative or license arrangements with other parties, under
which we license our drug candidates to those parties for development and commercialization or under which we study
our drug candidates in combination with other parties’ compounds or biologics. For example, in addition to our Novartis,
Lilly, Innovent, Zai Lab and InnoCare collaborations, we have entered into clinical study relationships with respect to
several of our programs, including epacadostat, and are evaluating strategic relationships with respect to several of our
other programs. However, because collaboration and license arrangements are complex to negotiate, we may not be
successful in our attempts to establish these arrangements. Also, we may not have drug candidates that are desirable to
other parties, or we may be unwilling to license a drug candidate to a particular party because such party interested in it is
a competitor or for other reasons. The terms of any such arrangements that we establish may not be favorable to us.
Alternatively, potential collaborators may decide against entering into an agreement with us because of our financial,
regulatory or intellectual property position or for scientific, commercial or other reasons. If we are not able to establish
collaboration or license arrangements, we may not be able to develop and commercialize a drug product, which could
adversely affect our business, our revenues and our future revenue prospects.
We will likely not be able to control the amount and timing of resources that our collaborators or licensees devote
to our programs or drug candidates. If our collaborators or licensees prove difficult to work with, are less skilled than we
originally expected, do not devote adequate resources to the program, are unable to obtain regulatory approval of our drug
candidates, pursue alternative technologies or develop alternative products, or do not agree with our approach to
development or manufacturing of the drug candidate, the relationship could be unsuccessful. Our collaborations with
respect to epacadostat involved the study of our collaborators’ drugs used in combination with epacadostat on a number
of indications or tumor types, many of which were the same across multiple collaborations. We cannot assure you that
potential conflicts will not arise or be alleged among these or future collaborations. If a business combination involving a
collaborator or licensee and a third-party were to occur, the effect could be to terminate or cause delays in development of
a drug candidate.
If we fail to enter into additional licensing agreements or if these arrangements are unsuccessful, our business and
operations might be adversely affected.
In addition to establishing collaborative or license arrangements under which other parties license our drug
candidates for development and commercialization or under which we study our drug candidates in combination with such
parties’ compounds or biologics, we may explore opportunities to develop our clinical pipeline by in-licensing drug
candidates or therapeutics targets that fit within our focus on oncology, such as our collaborations with Agenus Inc.,
Calithera Biosciences, Inc., MacroGenics, Inc., Merus N.V., MorphoSys, and Syros Pharmaceuticals, Inc. and Syndax
Pharmaceuticals, Inc., or explore additional opportunities to further develop and commercialize existing drug candidates
in specific jurisdictions, such as our June 2016 acquisition of the development and commercialization rights to ICLUSIG
in certain countries. We may be unable to enter into any additional in-licensing agreements because suitable drug
candidates that are within our expertise may not be available to us on terms that are acceptable to us or because competitors
with greater resources seek to in-license the same drug candidates. Drug candidates that we would like to develop or
commercialize may not be available to us because they are controlled by competitors who are unwilling to license the
rights to the drug candidate to us. In addition, we may enter into license agreements that are unsuccessful and our business
and operations might be adversely affected if we are unable to realize the expected economic benefits of a collaboration
or other licensing arrangement, by the termination of a drug candidate and termination and winding down of the related
license agreement, or due to other business or regulatory issues, including financial difficulties, that may adversely affect
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a licensor’s ability to continue to perform its obligations under an in-license agreement. For example, in January 2022, we
decided to opt-out of the continued development with Merus of MCLA-145, which was the most advanced compound
under our collaboration with Merus. If we make or incur contractual obligations to make significant upfront payments in
connection with licenses for late-stage drug candidates, as we did in March 2020 in connection with the effectiveness of
our collaboration agreement with MorphoSys, and if any of those drug candidates do not receive marketing approval or
commercial sales as anticipated or we have to fund additional clinical trials before marketing approval can be obtained,
we will have expended significant funds that might otherwise be applied for other uses or have to expend funds that were
not otherwise budgeted or anticipated in connection with the collaboration, and such developments could have a material
adverse effect on our stock price and our ability to pursue other transactions. As discussed above under “We depend on
our collaborators and licensees for the future development and commercialization of some of our drug candidates. Conflicts
may arise between our collaborators and licensees and us, or our collaborators and licensees may choose to terminate their
agreements with us, which may adversely affect our business,” conflicts or other issues may arise with our licensors. Those
conflicts could result in delays in our plans to develop drug candidates or result in the expenditure of additional funds to
resolve those conflicts that could have an adverse effect on our results of operations. We may also need to license drug
delivery or other technology in order to continue to develop our drug candidates. If we are unable to enter into additional
agreements to license drug candidates, drug delivery technology or other technology or if these arrangements are
unsuccessful, our research and development efforts could be adversely affected, and we may be unable to increase our
number of successfully marketed products and our revenues.
Even if a drug candidate that we develop receives regulatory approval, we may decide not to commercialize it if we
determine that commercialization of that product would require more money and time than we are willing to invest.
Even if any of our drug candidates receives regulatory approval, it could be subject to post-regulatory surveillance,
and may have to be withdrawn from the market or subject to restrictions if previously unknown problems occur. Regulatory
agencies may also require additional clinical trials or testing, and the drug product may be recalled or may be subject to
reformulation, additional studies, changes in labeling, warnings to the public and negative publicity. As a result, we may
not continue to commercialize a product even though it has obtained regulatory approval. Further, we may decide not to
continue to commercialize a product if the market does not accept the product because it is too expensive or because third
parties such as insurance companies or Medicare, will not cover it for substantial reimbursement. In addition, we may
decide not to continue to commercialize a product if competitors develop and commercialize similar or superior products
or have proprietary rights that preclude us from ultimately marketing our products.
Any approved drug product that we bring to the market may not gain market acceptance by physicians, patients,
healthcare payors and others in the medical community.
Even if we or our collaborators are successful in gaining regulatory approval of any of our or our collaborators’
drug candidates in addition to JAKAFI, OLUMIANT, PEMAZYRE, MONJUVI/MINJUVI and OPZELURA or acquire
rights to approved drug products in addition to ICLUSIG, we may not generate significant product revenues if these drug
products do not achieve an adequate level of acceptance. Physicians may not recommend our or our collaborators’ drug
products until longer-term clinical data or other factors demonstrate the safety and efficacy of our or our collaborators’
drug products as compared to other alternative treatments. Even if the clinical safety and efficacy of our or our
collaborators’ drug products is established, physicians may elect not to prescribe these drug products for a variety of
reasons, including the reimbursement policies of government and other third-party payors and the effectiveness of our or
our collaborators’ competitors in marketing their products.
Market acceptance of our drug products, if approved for commercial sale, will depend on a number of factors,
including the following, and market acceptance of our collaborators’ drug products will depend on similar factors:
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the willingness and ability of patients and the healthcare community to use our drug products;
the ability to manufacture our drug products in sufficient quantities that meet all applicable quality standards
and to offer our drug products for sale at competitive prices;
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the perception of patients and the healthcare community, including third-party payors, regarding the safety,
efficacy and benefits of our drug products compared to those of competing products or therapies;
the label and promotional claims allowed by the FDA;
the pricing and reimbursement of our drug products relative to existing treatments; and
• marketing and distribution support for our drug products.
In September 2021, the FDA updated labeling for JAKAFI and other JAK-inhibitor drugs to include warnings of
increased risk of major adverse cardiovascular events, thrombosis, and secondary malignancies related to another JAK-
inhibitor treating rheumatoid arthritis, a condition for which JAKAFI is not indicated. The label for OPZELURA contains
similar warnings seen with JAK inhibitors for inflammatory conditions. We cannot predict the effects on sales of JAKAFI
as a result of the labeling change or OPZELURA as a result of warning included in its label, but it is possible that future
sales of JAKAFI and the commercial success of OPZELURA can be negatively affected by the updated labeling, which
could have a material and adverse effect on our business, results of operations and prospects.
We have limited capacity to conduct preclinical testing and clinical trials, and our resulting dependence on other parties
could result in delays in and additional costs for our drug development efforts.
We have limited internal resources and capacity to perform preclinical testing and clinical trials. As part of our
development strategy, we often hire contract research organizations, or CROs, to perform preclinical testing and clinical
trials for drug candidates. If the CROs that we hire to perform our preclinical testing and clinical trials do not meet
deadlines, do not follow proper procedures, or a conflict arises between us and our CROs, our preclinical testing and
clinical trials may take longer than expected, may cost more, may be delayed or may be terminated. If we were forced to
find a replacement entity to perform any of our preclinical testing or clinical trials, we may not be able to find a suitable
entity on favorable terms, or at all. Even if we were able to find another company to perform a preclinical test or clinical
trial, the delay in the test or trial may result in significant additional expenditures. Events such as these may result in delays
in our obtaining regulatory approval for our drug candidates or our ability to commercialize our products and could result
in increased expenditures that would adversely affect our operating results.
We face significant competition for our drug discovery and development efforts, and if we do not compete effectively,
our commercial opportunities will be reduced or eliminated.
The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant
technological change. Our drug discovery and development efforts may target diseases and conditions that are already
subject to existing therapies or that are being developed by our competitors, many of which have substantially greater
resources, larger research and development staffs and facilities, more experience in completing preclinical testing and
clinical trials, and formulation, marketing and manufacturing capabilities. As a result of these resources, our competitors
may develop drug products that render our products obsolete or noncompetitive by developing more effective drugs,
developing their products more efficiently or pricing their products more competitively. Our ability to develop competitive
products would be limited if our competitors succeeded in obtaining regulatory approvals for drug candidates more rapidly
than we were able to or in obtaining patent protection or other intellectual property rights that limited our drug development
efforts. Any drug products resulting from our research and development efforts, or from our joint efforts with collaborators
or licensees, might not be able to compete successfully with our competitors’ existing and future products, or obtain
regulatory approval in the United States or elsewhere. The development of products or processes by our competitors with
significant advantages over those that we are developing could harm our future revenues and profitability.
Our reliance on other parties to manufacture our drug products and drug candidates could result in a short supply of
the drugs, delays in clinical trials or drug development, increased costs, and withdrawal or denial of a regulatory
authority’s approval.
We do not currently operate manufacturing facilities for clinical or commercial production of JAKAFI,
PEMAZYRE, OPZELURA and our other drug candidates or for ICLUSIG or MONJUVI/MINJUVI. We currently hire
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third parties to manufacture the raw materials, API and finished drug product of JAKAFI, ICLUSIG, PEMAZYRE,
OPZELURA and our other drug candidates for clinical trials and our collaborator MorphoSys is currently responsible for
sourcing manufacturing of MONJUVI/MINJUVI. In addition, we expect to continue to rely on third parties for the
manufacture of commercial supplies of raw materials, API and finished drug product for any drugs that we successfully
develop. We also hire third parties to package and label the finished product. The FDA requires that the raw materials, API
and finished product for drug products such as JAKAFI, PEMAZYRE and OPZELURA and our other drug candidates be
manufactured according to its current Good Manufacturing Practices regulations and regulatory authorities in other
countries have similar requirements. There are only a limited number of manufacturers that comply with these
requirements. Failure to comply with current Good Manufacturing Practices and the applicable regulatory requirements of
other countries in the manufacture of our drug candidates and products could result in the FDA or a foreign regulatory
authority halting our clinical trials, withdrawing or denying regulatory approval of our drug product, enforcing product
recalls or other enforcement actions, which could have a material adverse effect on our business.
We may not be able to obtain sufficient quantities of our drug candidates or any drug products we may develop
if our designated manufacturers do not have the capacity or capability to manufacture them according to our schedule and
specifications. Manufacturers of pharmaceutical products often encounter difficulties in production, especially in scaling
up initial production to commercial quantities from clinical quantities. These problems include difficulties with production
costs and yields, quality control and assurance and shortages of qualified personnel. To the extent problems are
experienced, we could encounter difficulties in supplying sufficient product to meet demand or incur additional costs to
remedy the problems or to recall defective products. Any such recall could also harm our sales efforts and our reputation.
To the extent our supply chain involves parties in China or materials originating in areas of China that are or could be
affected by disease outbreaks such as the COVID-19 pandemic, we could see disruptions to our supply chain. Currently,
our supply chain for our drug products and product candidates depends on operations by us and by other companies in
multiple countries around the world, and the effects of the COVID-19 pandemic and measures to address the COVID-19
pandemic on any or all of these countries is uncertain and unpredictable and potential disruption is possible. And, for
JAKAFI, while our strategy is to maintain a 24 months stock of API, inclusive of finished product, ruxolitinib phosphate
might be used by us either to make JAKAFI or for ruxolitinib drug candidates in clinical trials. In addition, we may not be
able to arrange for our drug candidates or any drug products that we may develop to be manufactured by one of these
parties on reasonable terms, if at all. We generally have a single source or a limited number of suppliers that are qualified
to supply each of the API and finished product of our drug products and our other drug candidates and, in the case of
JAKAFI, we only have a single source for its raw materials. If any of these suppliers were to become unable or unwilling
to supply us with raw materials, API or finished product that complies with applicable regulatory requirements, we could
incur significant delays in our clinical trials or interruption of commercial supply that could have a material adverse effect
on our business. If we have promised delivery of a drug candidate or drug product and are unable to meet the delivery
requirement due to manufacturing difficulties, our development programs could be delayed, we may have to expend
additional sums in order to ensure that manufacturing capacity is available when we need it even if we do not use all of
the manufacturing capacity, and our business and operating results could be harmed.
We may not be able to adequately manage and oversee the manufacturers we choose, they may not perform as
agreed or they may terminate their agreements with us. Foreign manufacturing approval processes typically include all of
the risks associated with the FDA approval process for manufacturing and may also include additional risks.
A number of our collaborations involve the manufacture of antibodies. Either we or our collaborators have
primary responsibility for manufacturing activities, and we intend to continue to use third-party contract manufacturing
organizations for the manufacture of antibodies even after we finalize the qualification of our manufacturing facility in
Switzerland. Manufacturing antibodies and products containing antibodies is a more complex process than manufacturing
small molecule drugs and subject to additional risks. The process of manufacturing antibodies and products containing
antibodies is highly susceptible to product loss due to contamination, equipment failure or improper installation or
operation of equipment, vendor or operator error, inconsistency in yields, variability in product characteristics, and
difficulties in scaling up the production process. Even minor deviations from normal manufacturing processes could result
in reduced production yields, product defects and other supply disruptions. If microbial, viral or other contaminations are
discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, such
manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.
We may encounter delays and difficulties in scaling up production at our new facility, once completed.
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If we fail to comply with the extensive legal and regulatory requirements affecting the health care industry, we could
face increased costs, penalties and a loss of business.
Our activities, and the activities of our collaborators, partners and third-party providers, are subject to extensive
government regulation and oversight both in the United States and in foreign jurisdictions. The FDA and comparable
agencies in other jurisdictions directly regulate many of our most critical business activities, including the conduct of
preclinical and clinical studies, product manufacturing, advertising and promotion, product distribution, adverse event
reporting and product risk management. States increasingly have been placing greater restrictions on the marketing
practices of healthcare companies and have instituted pricing disclosure and other requirements for companies selling
pharmaceuticals. In addition, pharmaceutical and biotechnology companies have been the target of lawsuits and
investigations alleging violations of government regulations, including claims asserting submission of incorrect pricing
information, improper promotion of pharmaceutical products, payments intended to influence the referral of federal or
state healthcare business, submission of false claims for government reimbursement, antitrust violations, violations of the
U.S. Foreign Corrupt Practices Act, the U.K. Bribery Act and similar anti-bribery or anti-corruption laws, or violations
related to environmental matters. There is also enhanced scrutiny of company-sponsored patient assistance programs,
including insurance premium and co-pay assistance programs and donations to third-party charities that provide such
assistance. In December 2018, we received a civil investigative demand from the U.S. Department of Justice, or DOJ, for
documents and information relating to our speaker programs and patient assistance programs, including our support of
non-profit organizations that provide financial assistance to eligible patients and in November 2019, the qui tam complaint
underlying the DOJ inquiry was unsealed, at which time we learned that a former employee whom we had terminated had
made certain allegations relating to the programs described above. While we deny that any improper claims were submitted
to government payers, we agreed in May 2021 to settle the matter with the DOJ Civil Division for $12.6 million, plus
certain statutory fees. Violations of governmental regulation by us, our vendors or donation recipients may be punishable
by criminal and civil sanctions, including damages, fines and penalties and exclusion from participation in government
programs, including Medicare and Medicaid. In addition to damages, fines and penalties for violation of laws and
regulations, we could be required to repay amounts we received from government payors, or pay additional rebates and
interest if we are found to have miscalculated the pricing information we have submitted to the government. Actions taken
by federal or local governments, legislative bodies and enforcement agencies with respect to these legal and regulatory
compliance matters could also result in reduced demand for our products, reduced coverage of our products by health care
payors, or both. We cannot ensure that our compliance controls, policies, and procedures will in every instance protect us
from acts committed by our employees, collaborators, partners or third-party providers that would violate the laws or
regulations of the jurisdictions in which we operate. Whether or not we have complied with the law, an investigation into
alleged unlawful conduct could increase our expenses, damage our reputation, divert management time and attention and
adversely affect our business, and any settlement of these proceedings could result in significant payments by us. Risks
relating to compliance with laws and regulations may be heightened as we continue to expand our global operations and
enter new therapeutic areas with different patient populations, which due to different product distribution methods,
marketing programs or patient assistance programs may result in additional regulatory burdens and obligations.
The illegal distribution and sale by third parties of counterfeit or unfit versions of our or our collaborators’ products
or stolen products could harm our business and reputation.
We are aware that counterfeit versions of our products have been distributed or sold by entities not authorized by
us using product packaging suggesting that the product was provided by us. If unauthorized third parties illegally distribute
and sell counterfeit versions of our or our collaborators’ products, those products may not meet our or our collaborators’
rigorous manufacturing, distribution and handling standards. In addition, inventory that is stolen from warehouses, plants
or while in-transit, and that is subsequently improperly stored and sold through unauthorized channels, may not meet our
or our collaborators’ distribution and handling standards. A patient who receives a counterfeit or unfit drug may suffer
dangerous health consequences. Our reputation and business could suffer harm as a result of counterfeit or unfit drugs
sold under our brand name and could result in lost sales for us and decreased revenues. If counterfeit or unfit drugs are
sold under our or our collaborators’ brand names, our reputation and business could suffer harm and we could experience
decreased royalty revenues.
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As most of our drug discovery and development operations are conducted at our headquarters in Wilmington, Delaware,
the loss of access to this facility would negatively impact our business.
Our facility in Wilmington, Delaware is our headquarters and is also where we conduct most of our drug
discovery, research, development and marketing activities. In addition, natural disasters, the effects of or measures taken
to limit the effects of health epidemics such as the COVID-19 pandemic, or actions of activists opposed to aspects of
pharmaceutical research may disrupt our experiments or our ability to access or use our facility. The loss of access to or
use of our Wilmington, Delaware facility, either on a temporary or permanent basis, would result in an interruption of our
business and, consequently, would adversely affect our overall business.
We depend on key employees in a competitive market for skilled personnel, and the loss of the services of any of our
key employees or our inability to attract and retain additional personnel would affect our ability to expand our drug
discovery and development programs and achieve our objectives.
We are highly dependent on the members of our executive management team and principal members of our
commercial, development, medical, operations and scientific staff. We experience intense competition for qualified
personnel. Our future success also depends in part on the continued service of our executive management team and key
personnel and our ability to recruit, train and retain essential personnel for our drug discovery and development programs,
and for our medical affairs and commercialization activities. If we lose the services of any of these people or if we are
unable to recruit sufficient qualified personnel, our research and product development goals, and our commercialization
efforts could be delayed or curtailed. We do not maintain “key person” insurance on any of our employees.
If we fail to manage our growth effectively, our ability to develop and commercialize products could suffer.
We expect that if our drug discovery efforts continue to generate drug candidates, our clinical drug candidates
continue to progress in development, and we continue to build our development, medical and commercial organizations,
we will require significant additional investment in personnel, management and resources. Our ability to achieve our
research, development and commercialization objectives depends on our ability to respond effectively to these demands
and expand our internal organization, systems, controls and facilities to accommodate additional anticipated growth. If we
are unable to manage our growth effectively, our business could be harmed and our ability to execute our business strategy
could suffer.
We may acquire businesses or assets, form joint ventures or make investments in other companies that may be
unsuccessful, divert our management’s attention and harm our operating results and prospects.
As part of our business strategy, we may pursue additional acquisitions of what we believe to be complementary
businesses or assets or seek to enter into joint ventures. We also may pursue strategic alliances in an effort to leverage our
existing infrastructure and industry experience to expand our product offerings or distribution, or make investments in
other companies. For example, in June 2016, we completed the acquisition of the European operations of ARIAD. The
success of our acquisitions, joint ventures, strategic alliances and investments will depend on our ability to identify,
negotiate, complete and, in the case of acquisitions, integrate those transactions and, if necessary, obtain satisfactory debt
or equity financing to fund those transactions. We may not realize the anticipated benefits of any acquisition, joint venture,
strategic alliance or investment. We may not be able to integrate acquisitions successfully into our existing business,
achieve planned synergies or cost savings, maintain the key business relationships of businesses we acquire, or retain key
personnel of an acquired business, and we could assume unknown or contingent liabilities or incur unanticipated expenses.
Integration of acquired companies or businesses also may require management resources that otherwise would be available
for ongoing development of our existing business. Any acquisitions or investments made by us also could result in
significant write-offs or the incurrence of debt and contingent liabilities, any of which could harm our operating results.
For example, in the three month periods ended March 31, 2020, September 30, 2020, March 31, 2021 and September 31,
2021 we recorded unrealized losses related to our investments in our collaboration partners, and we may in experience
additional losses related to our investments in future period. In addition, if we choose to issue shares of our stock as
consideration for any acquisition, dilution to our stockholders could result.
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Risks associated with our operations outside of the United States could adversely affect our business.
Our acquisition of ARIAD’s European operations significantly expanded our operations in Europe, and we plan
to continue to expand our operations and conduct certain development activities outside of the United States. For example,
as part of our plans to expand our activities outside of the United States, we now conduct some of our operations in Canada,
commercial and clinical development activities in Japan and have opened an office in China. International operations and
business expansion plans are subject to numerous additional risks, including:
• multiple, conflicting and changing laws and regulations such as tax laws, privacy regulations, tariffs, export
and import restrictions, employment, immigration and labor laws, regulatory requirements, and other
governmental approvals, permits and licenses, compliance with which can increase in complexity as we enter
into additional jurisdictions;
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difficulties in staffing and managing operations in diverse countries and difficulties in connection with
assimilating and integrating any operations and personnel we might acquire into our company;
risks associated with obtaining and maintaining, or the failure to obtain or maintain, regulatory approvals for
the sale or use of our products in various countries;
complexities associated with managing government payor systems, multiple payor-reimbursement regimes
or patient self-pay systems;
financial risks, such as longer payment cycles, difficulty obtaining financing in foreign markets, difficulty
enforcing contracts and intellectual property rights, difficulty collecting accounts receivable and exposure to
foreign currency exchange rate fluctuations;
general political and economic conditions in the countries in which we operate, including terrorism and
political unrest, curtailment of trade and other business restrictions, and uncertainties associated with the
implementation of the relationship between the United Kingdom and the European Union;
public health risks, such as the effects of the COVID-19 pandemic, and related effects on new patient starts,
clinical trial activity, regulatory agency response times, supply chain, travel and employee health and
availability; and
regulatory and compliance risks that relate to maintaining accurate information and control over activities
that may fall within the purview of the U.S. Foreign Corrupt Practices Act, its books and records provisions
or its anti-bribery provisions, or similar anti-bribery or anti-corruption laws and regulations in other countries,
such as the U.K. Anti-Bribery Act and the U.K. Criminal Finances Act, which may have similarly broad
extraterritorial reach.
In addition, our revenues are subject to foreign currency exchange rate fluctuations due to the global nature of
our operations. To the extent that our non-U.S. source revenues represent a more significant portion of our total revenues,
these fluctuations could materially affect our operating results. Any of the risks described above, if encountered, could
significantly increase our costs of operating internationally, prevent us from operating in certain jurisdictions, or otherwise
significantly harm our future international expansion and operations, which could have a material adverse effect on our
business, financial condition and results of operations.
If product liability lawsuits are brought against us, we could face substantial liabilities and may be required to limit
commercialization of our products and our results of operations could be harmed.
In addition to the risks described above under “—Risks Relating to Commercialization of Our Products—If the
use of our products harms patients, or is perceived to harm patients even when such harm is unrelated to our products, our
regulatory approvals could be revoked or otherwise negatively impacted or we could be subject to costly and damaging
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product liability claims,” the conduct of clinical trials of medical products that are intended for human use entails an
inherent risk of product liability. If any product that we or any of our collaborators or licensees develops causes or is
alleged to cause injury during clinical trials or commercialization, we may be held liable. If we cannot successfully defend
ourselves against product liability claims, we may incur substantial liabilities, including substantial damages to be paid to
the plaintiffs and legal costs, or we may be required to limit further development and commercialization of our products.
Additionally, any product liability lawsuit could cause injury to our reputation, participants and investigators to withdraw
from clinical trials, and potential collaborators or licensees to seek other partners, any of which could impact our results
of operations.
Our product liability insurance policy may not fully cover our potential liabilities. In addition, we may determine
that we should increase our coverage, and this insurance may be prohibitively expensive to us or our collaborators or
licensees and may not fully cover our potential liabilities. Since December 30, 2017, we elected to self-insure a portion of
our exposure to product liability risks through our wholly-owned captive insurance subsidiary, in tandem with third-party
insurance policies. Our inability to obtain sufficient product liability insurance at an acceptable cost to protect against
potential product liability claims could prevent or inhibit the development or commercialization of our drug candidates
and products, and if our liabilities from any such claims exceed our third-party insurance limits and self-insurance reserves,
our results of operations, cash flows and financial condition could be adversely impacted.
Because our activities involve the use of hazardous materials, we may be subject to claims relating to improper handling,
storage or disposal of these materials that could be time consuming and costly.
We are subject to various environmental, health and safety laws and regulations governing, among other things,
the use, handling, storage and disposal of regulated substances and the health and safety of our employees. Our research
and development processes involve the controlled use of hazardous and radioactive materials and biological waste resulting
in the production of hazardous waste products. We cannot completely eliminate the risk of accidental contamination or
discharge and any resultant injury from these materials. If any injury or contamination results from our use or the use by
our collaborators or licensees of these materials, we may be sued and our liability may exceed our insurance coverage and
our total assets. Further, we may be required to indemnify our collaborators or licensees against all damages and other
liabilities arising out of our development activities or products produced in connection with these collaborations or licenses.
Compliance with the applicable environmental and workplace laws and regulations is expensive. Future changes to
environmental, health, workplace and safety laws could cause us to incur additional expense or may restrict our operations
or impair our research, development and production efforts.
RISKS RELATING TO OUR FINANCIAL RESULTS
We may incur losses in the future, and we expect to continue to incur significant expenses to discover and develop
drugs, which may make it difficult for us to achieve sustained profitability on a quarterly or annual basis in the future.
Due to historical net losses, we had an accumulated deficit of $0.8 billion as of December 31, 2021. We intend to
continue to spend significant amounts on our efforts to discover and develop drugs. As a result, we may incur losses in
future periods as well. Our revenues, expenses and net income (loss) may fluctuate, even significantly, due to the risks
described in these “Risk Factors” and factors discussed in “Management’s Discussion and Analysis of Financial Condition
and Results of Operations” as well as the timing of charges and expenses that we may take, including those relating to
transactions such as acquisitions and the entry into collaborative agreements.
We anticipate that our drug discovery and development efforts and related expenditures will increase as we focus
on the studies, including preclinical tests and clinical trials prior to seeking regulatory approval, that are required before
we can sell a drug product.
The development of drug products will require us to spend significant funds on research, development, testing,
obtaining regulatory approvals, manufacturing and marketing. To date, we do not have any drug products that have
generated significant revenues other than from sales of JAKAFI and we cannot assure you that we will generate substantial
revenues from the drug candidates that we license or develop, including ICLUSIG, PEMAZYRE, MONJUVI/MINJUVI,
and OPZELURA, for several years, if ever.
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We cannot be certain whether or when we will achieve sustained or increased profitability on a quarterly or annual
basis because of the factors discussed under “Risks Relating to Commercialization of our Products” and in the above
paragraphs and the significant uncertainties relating to our ability to generate commercially successful drug products. Even
if we are successful in obtaining regulatory approvals for manufacturing and commercializing drug products in addition to
JAKAFI, ICLUSIG, PEMAZYRE, MONJUVI/MINJUVI, and OPZELURA, we may incur losses if our drug products do
not generate significant revenues.
We may need additional capital in the future. If we are unable to generate sufficient funds from operations, the capital
markets may not permit us to raise additional capital at the time that we require it, which could result in limitations on
our research and development or commercialization efforts or the loss of certain of our rights in our technologies or
drug candidates.
Our future funding requirements will depend on many factors and we anticipate that we may need to raise
additional capital to fund our business plan and research and development efforts going-forward.
Additional factors that may affect our future funding requirements include:
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the acquisition of businesses, technologies, or drug candidates, or the licensing of technologies or drug
candidates, if any;
the amount of revenues generated from our business activities;
any changes in the breadth of our research and development programs;
the results of research and development, preclinical testing and clinical trials conducted by us or our current
or future collaborators or licensees, if any;
our exercise of any co-development options with collaborators that may require us to fund future
development;
costs for future facility requirements;
our ability to maintain and establish new corporate relationships and research collaborations;
competing technological and market developments;
the time and costs involved in filing, prosecuting, defending and enforcing patent and intellectual property
claims;
the receipt or payment of contingent licensing or milestone fees or royalties on product sales from our current
or future collaborative and license arrangements, if established; and
the timing of regulatory approvals, if any.
If we require additional capital at a time when investment in companies such as ours, or in the marketplace
generally, is limited due to the then prevailing market or other conditions, we may have to scale back our operations,
eliminate one or more of our research or development programs, or attempt to obtain funds by entering into an agreement
with a collaborator or licensee that would result in terms that are not favorable to us or relinquishing our rights in certain
of our proprietary technologies or drug candidates. If we are unable to raise funds at the time that we desire or at any time
thereafter on acceptable terms, we may not be able to continue to develop our drug candidates. The sale of equity or equity-
linked securities in the future may be dilutive to our stockholders and may provide for rights, preferences or privileges
senior to those of our holders of common stock, and debt financing arrangements may require us to pledge certain assets
or enter into covenants that could restrict our operations or our ability to pay dividends or other distributions on our
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common stock or incur further indebtedness.
Our marketable securities and long term investments are subject to risks that could adversely affect our overall financial
position.
We invest our cash in accordance with an established internal policy and customarily in instruments, money
market funds, U.S. government backed-funds and Treasury assets, which historically have been highly liquid and carried
relatively low risk. In recent periods, similar types of investments and money market funds have experienced losses in
value or liquidity issues that differ from their historical pattern.
Should a portion of our cash or marketable securities lose value or have their liquidity impaired, it could adversely
affect our overall financial position by imperiling our ability to fund our operations and forcing us to seek additional
financing sooner than we would otherwise. Such financing, if available, may not be available on commercially attractive
terms.
As discussed under “Other Risks Relating to Our Business— We may acquire businesses or assets, form joint
ventures or make investments in other companies that may be unsuccessful, divert our management’s attention and harm
our operating results and prospects,” any investments that we may make in companies with which we have strategic
alliances, such as Agenus, Merus and MorphoSys, could result in our recognition of losses on those investments. In
addition, to the extent we may seek to sell or otherwise monetize those investments, we may not be able to do so at our
desired price or valuation levels, or at all, due to the limited liquidity of some or all of those investments.
Any loss in value of our long term investments could adversely affect our financial position on the consolidated
balance sheets and consolidated statements of operations.
Changes in tax laws or regulations could adversely affect our results of operations, business and financial condition.
New tax laws or regulations could be enacted at any time, and existing tax laws or regulations could be interpreted,
modified or applied in a manner that is adverse to us or our customers, which could adversely affect our results of
operations, business and financial condition. The Administration and Congress are considering significant changes to
existing U.S. tax law, including an increase in the corporate tax rate and the effective tax rate on foreign earnings. These
changes could substantially increase U.S. taxation of our operations. In addition, the Organisation for Economic Co-
Operation and Development (OECD) in October 2021 announced an agreement on an outline for new tax rules that would
align countries on a minimum corporate tax rate and an expansion of the taxing rights of market countries. If enacted by
member countries, this agreement could result in tax increases in both the United States and many foreign jurisdictions
where we operate or have a presence. These initiatives not only could significantly increase our tax provision, cash tax
liabilities, and effective tax rate, but could also significantly increase tax uncertainty due to differing interpretations and
increased audit scrutiny.
We derive a substantial portion of our revenues from royalties, milestone payments and other payments under our
collaboration agreements. If we are unable to achieve milestones, develop product candidates to license or renew or
enter into new collaborations, our revenues may decrease, and future milestone and royalty payments may not
contribute significantly to revenues for several years, and may never result in revenues.
We derived a substantial portion of our revenues for the year ended December 31, 2021 from JAKAVI and
OLUMIANT product royalties and from milestone payments under our collaboration agreements. Future revenues from
research and development collaborations depend upon continuation of the collaborations, the achievement of milestones
and royalties we earn from any future products developed from our research. If we are unable to successfully achieve
milestones or our collaborators fail to develop successful products, we will not earn the future revenues contemplated
under our collaborative agreements. For example, delays in or other limitations with respect to the approval of baricitinib
in the United States for the treatment of moderate-to-severe rheumatoid arthritis, or the failure to obtain such approval as
a first line therapy, as discussed under “—We depend on our collaborators and licensees for the future development and
commercialization of some of our drug candidates. Conflicts may arise between our collaborators and licensees and us, or
our collaborators and licensees may choose to terminate their agreements with us, which may adversely affect our
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business.” could affect potential future royalty and milestone and contract revenue.
RISKS RELATING TO INTELLECTUAL PROPERTY AND LEGAL MATTERS
If we are subject to arbitration, litigation and infringement claims, they could be costly and disrupt our drug discovery
and development efforts.
The technology that we use to make and develop our drug products, the technology that we incorporate in our
products, and the products we are developing may be subject to claims that they infringe the patents or proprietary rights
of others. The success of our drug discovery and development efforts will also depend on our ability to develop new
compounds, drugs and technologies without infringing or misappropriating the proprietary rights of others. We are aware
of patents and patent applications filed in certain countries claiming intellectual property relating to some of our drug
discovery targets and drug candidates. While the validity of issued patents, patentability of pending patent applications
and applicability of any of them to our programs are uncertain, if any of these patents are asserted against us or if we
choose to license any of these patents, our ability to commercialize our products could be harmed or the potential return
to us from any product that may be successfully commercialized could be diminished.
From time to time we have received, and we may in the future receive, notices from third parties offering licenses
to technology or alleging patent, trademark, or copyright infringement, claims regarding trade secrets or other contract
claims. Receipt of these notices could result in significant costs as a result of the diversion of the attention of management
from our drug discovery and development efforts. Parties sending these notices may have brought and in the future may
bring litigation against us or seek arbitration relating to contract claims.
We may be involved in future lawsuits or other legal proceedings alleging patent infringement or other intellectual
property rights or contract violations. In addition, litigation or other legal proceedings may be necessary to:
•
•
•
•
assert claims of infringement;
enforce our patents or trademarks;
protect our trade secrets or know-how; or
determine the enforceability, scope and validity of the proprietary rights of others.
We may be unsuccessful in defending or pursuing these lawsuits, claims or other legal proceedings. Regardless
of the outcome, litigation or other legal proceedings can be very costly and can divert management’s efforts. An adverse
determination may subject us to significant liabilities or require us or our collaborators or licensees to seek licenses to
other parties’ patents or proprietary rights. We or our collaborators or licensees may also be restricted or prevented from
manufacturing or selling a drug or other product that we or they develop. Further, we or our future collaborators or licensees
may not be able to obtain any necessary licenses on acceptable terms, if at all. If we are unable to develop non-infringing
technology or license technology on a timely basis or on reasonable terms, our business could be harmed.
We may be unable to adequately protect or enforce our proprietary information, which may result in its unauthorized
use, a loss of revenue under a collaboration agreement or loss of sales to generic versions of our products or otherwise
reduce our ability to compete in developing and commercializing products.
Our business and competitive position depends in significant part upon our ability to protect our proprietary
technology, including any drug products that we create. Despite our efforts to protect this information, unauthorized parties
may attempt to obtain and use information that we regard as proprietary. For example, one of our collaborators may
disclose proprietary information pertaining to our drug discovery efforts. In addition, while we have filed numerous patent
applications with respect to ruxolitinib and our drug candidates in the United States and in foreign countries, our patent
applications may fail to result in issued patents. In addition, because patent applications can take several years to issue as
patents, there may be pending patent applications of others that may later issue as patents that cover some aspect of
ruxolitinib and our drug candidates. Our existing patents and any future patents we may obtain may not be broad enough
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to protect our products or all of the potential uses of our products, or otherwise prevent others from developing competing
products or technologies. In addition, our patents may be challenged and invalidated or may fail to provide us with any
competitive advantages if, for example, others were first to invent or first to file a patent application for the technologies
and products covered by our patents. As noted above under “—Risks Relating to Commercialization of Our Products—
Competition for our products could potentially harm our business and result in a decrease in our revenue,” a potential
generic drug company competitor has challenged certain patents relating to JAKAFI.
Additionally, when we do not control the prosecution, maintenance and enforcement of certain important
intellectual property, such as a drug candidate in-licensed to us or subject to a collaboration with a third-party, the
protection of the intellectual property rights may not be in our hands. If we do not control the intellectual property rights
in-licensed to us with respect to a drug candidate and the entity that controls the intellectual property rights does not
adequately protect those rights, our rights may be impaired, which may impact our ability to develop, market and
commercialize the in-licensed drug candidate.
Our means of protecting our proprietary rights may not be adequate, and our competitors may:
•
•
•
independently develop substantially equivalent proprietary information, products and techniques;
otherwise gain access to our proprietary information; or
design around patents issued to us or our other intellectual property.
We pursue a policy of having our employees, consultants and advisors execute proprietary information and
invention agreements when they begin working for us. However, these agreements may not provide meaningful protection
for our trade secrets or other proprietary information in the event of unauthorized use or disclosure. If we fail to maintain
trade secret and patent protection, our potential future revenues may be decreased.
If the effective term of our patents is decreased due to changes in the United States patent laws or if we need to refile
some of our patent applications, the value of our patent portfolio and the revenues we derive from it may be decreased.
The value of our patents depends, in part, on their duration. A shorter period of patent protection could lessen the
value of our rights under any patents that we obtain and may decrease the revenues we derive from our patents. The United
States patent laws provide a term of patent protection of 20 years from the earliest effective filing date of the patent
application. Because the time from filing to issuance of biotechnology applications may be more than three years depending
on the subject matter, a 20-year patent term from the filing date may result in substantially shorter patent protection.
Additionally, United States patent laws were amended in 2011 with the enactment of the America Invents Act
and third parties are now able to challenge the validity of issued U.S. patents through various review proceedings; thus
rendering the validity of U.S. patents more uncertain. We may be obligated to participate in review proceedings to
determine the validity of our U.S. patents. We cannot predict the ultimate outcome of these proceedings, the conduct of
which could result in substantial costs and diversion of our efforts and resources. If we are unsuccessful in these
proceedings some or all of our claims in the patents may be narrowed or invalidated and the patent protection for our
products and drug candidates in the United States could be substantially shortened. Further, if all of the patents covering
one of our products are invalidated, the FDA could approve requests to manufacture a generic version of that product prior
to the expiration date of those patents.
Other changes in the United States patent laws or changes in the interpretation of patent laws could diminish the
value of our patents or narrow the scope of our patent protection. For example, the Supreme Court of the United States
resolved a split among the circuit courts of appeals regarding antitrust challenges to settlements of patent infringement
lawsuits under the Hatch-Waxman Act between brand-name drug companies and generic drug companies. The Court
rejected the “scope of the patent” test and ruled that settlements involving “reverse payments” from brand-name drug
companies to generic drug companies should be analyzed under the rule of reason. This ruling may create uncertainty and
make it more difficult to settle patent litigation if a company seeking to manufacture a generic version of one of our
products challenges the patents covering that product prior to the expiration date of those patents.
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International patent protection is particularly uncertain and costly, and our involvement in opposition proceedings in
foreign countries may result in the expenditure of substantial sums and management resources.
Biotechnology and pharmaceutical patent law outside the United States is even more uncertain and costly than in
the United States and is currently undergoing review and revision in many countries. Further, the laws of some foreign
countries may not protect our intellectual property rights to the same extent as United States laws. For example, certain
countries do not grant patent claims that are directed to the treatment of humans. We have participated, and may in the
future participate, in opposition proceedings to determine the validity of our foreign patents or our competitors’ foreign
patents, which could result in substantial costs and diversion of our efforts. Successful challenges to our patent or other
intellectual property rights through these proceedings could result in a loss of rights in the relevant jurisdiction and allow
third parties to use our proprietary technologies without a license from us or our collaborators, which may also result in
loss of future royalty payments. In addition, successful challenges may jeopardize or delay our ability to enter into new
collaborations or commercialize potential products, which could harm our business and results of operations.
RISKS RELATING TO INFORMATION TECHNOLOGY AND DATA PRIVACY
Significant disruptions of information technology systems, breaches of data security, or unauthorized disclosures of
sensitive data or personally identifiable information or individually identifiable health information could adversely
affect our business, and could subject us to liability or reputational damage.
Our business is increasingly dependent on critical, complex, and interdependent information technology
(IT) systems, including Internet-based systems, some of which are managed or hosted by third parties, to support business
processes as well as internal and external communications. The size and complexity of our IT systems make us potentially
vulnerable to IT system breakdowns, malicious intrusion, and computer viruses, which may result in the impairment of
our ability to operate our business effectively. In addition, having a significant portion of our employees work remotely
due to the COVID-19 pandemic can strain our information technology infrastructure, which may affect our ability to
operate effectively, may make us more susceptible to communications disruptions, and expose us to greater cybersecurity
risks.
We are continuously evaluating and, where appropriate, enhancing our IT systems to address our planned growth,
including to support our planned manufacturing operations. In particular, we are currently in the process of implementing
a new enterprise resource planning system. There are inherent costs and risks associated with implementing the
enhancements to our IT systems, including potential delays in access to, or errors in, critical business and financial
information, substantial capital expenditures, additional administrative time and operating expenses, retention of
sufficiently skilled personnel to implement and operate the enhanced systems, demands on management time, and costs of
delays or difficulties in transitioning to the enhanced systems, any of which could harm our business and results of
operations. In addition, the implementation of enhancements to our IT systems may not result in productivity
improvements at a level that outweighs the costs of implementation, or at all.
In addition, our systems and the systems of our third-party providers and collaborators are potentially vulnerable
to data security breaches which may expose sensitive data to unauthorized persons or to the public. Such data security
breaches could lead to the loss of confidential information, trade secrets or other intellectual property, could lead to the
public exposure of personal information (including personally identifiable information or individually identifiable health
information) of our employees, clinical trial patients, customers, business partners, and others, could lead to potential
identity theft, or could lead to reputational harm. Data security breaches could also result in loss of clinical trial data or
damage to the integrity of that data. In addition, the increased use of social media by our employees and contractors could
result in inadvertent disclosure of sensitive data or personal information, including but not limited to, confidential
information, trade secrets and other intellectual property.
Any such disruption or security breach, as well as any action by us or our employees or contractors that might be
inconsistent with the rapidly evolving data privacy and security laws and regulations applicable within the United States
and elsewhere where we conduct business, could result in enforcement actions by U.S. states, the U.S. Federal government
or foreign governments, liability or sanctions under data privacy laws, including healthcare laws such as HIPAA, that
protect certain types of sensitive information, regulatory penalties, other legal proceedings such as but not limited to private
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litigation, the incurrence of significant remediation costs, disruptions to our development programs, business operations
and collaborations, diversion of management efforts and damage to our reputation, which could harm our business and
operations. Because of the rapidly moving nature of technology and the increasing sophistication of cybersecurity threats,
our measures to prevent, respond to and minimize such risks may be unsuccessful.
In addition, the European Parliament and the Council of the European Union has adopted a comprehensive general
data privacy regulation, known as the GDPR, which governs the collection and use of personal data in the European Union.
The GDPR, which is wide-ranging in scope, imposes several requirements relating to the consent of the individuals to
whom the personal data relates, the information provided to the individuals, the security and confidentiality of the personal
data, data breach notification and the use of third party processors in connection with the processing of the personal data.
The GDPR also imposes strict rules on the transfer of personal data out of the European Union to the United States,
provides an enforcement authority and imposes large penalties for noncompliance, including the potential for fines of up
to €20 million or 4% of the annual global revenues of the infringer, whichever is greater. Moreover, the European Court
of Justice in July 2020 invalidated the Privacy Shield framework that had been in place between the European Union and
the United States, which invalidation has created uncertainty about how data can now be shared in a compliant manner.
Additionally, the California Consumer Privacy Act (CCPA) affords a private right of action to such consumers if certain
data breaches result in the loss or theft of their personal information. The GDPR, CCPA and other similar laws or
regulations enacted in the United States or other jurisdictions associated with the enhanced protection of certain types of
sensitive data, including healthcare data or other personal information, may increase our costs of doing business, and the
differing requirements of these laws and regulations can complicate our compliance efforts.
Increasing use of social media could give rise to liability, breaches of data security, or reputational damage.
We and our employees are increasingly utilizing social media tools as a means of communication both internally
and externally. Despite our efforts to monitor evolving social media communication guidelines and comply with applicable
rules, there is risk that the use of social media by us or our employees to communicate about our products or business may
cause us to be found in violation of applicable requirements. In addition, our employees may knowingly or inadvertently
make use of social media in ways that may not comply with our social media policy or other legal or contractual
requirements, which may give rise to liability, lead to the loss of trade secrets or other intellectual property, or result in
public exposure of personal information of our employees, clinical trial patients, customers, and others. Furthermore,
negative posts or comments about us or our products in social media could seriously damage our reputation, brand image,
and goodwill.
Item 1B. Unresolved Staff Comments
None.
Item 2. Properties
Our global headquarters is located in Wilmington, Delaware, where we conduct global clinical development and
commercial operations. We own three buildings comprising approximately 544,000 square feet of laboratory and office
space at this site. Also in October 2019, we entered into an agreement to purchase additional adjacent property for $50.0
million to expand our global headquarters. Under that agreement, closing of the purchase is subject to certain standard
closing conditions, including an initial diligence period and a subsequent approval period.
We lease approximately 112,000 square feet of office space in Chadds Ford, Pennsylvania and approximately
84,000 square feet of additional laboratory and office space in Wilmington, Delaware.
We also conduct clinical development and commercial operations from our European headquarters in Morges,
Switzerland and our Japanese office in Tokyo. In July 2018, we purchased land in Yverdon, Switzerland upon which we
are building a large molecule production facility. Construction commenced in July 2018 and we currently expect the
facility will be operational in the second half of 2022. Our Canadian office is in Montreal.
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Item 3. Legal Proceedings
From time to time, we are party to legal proceedings in the course of our business. The outcome of any such
proceedings, regardless of the merits, is inherently uncertain. Legal proceedings, including litigation, government
investigations and enforcement actions, can result in significant costs and occupy significant management resources. We
do not expect any such current legal proceedings to have a material adverse impact on our business or financial condition.
Item 4. Mine Safety Disclosures
Not applicable.
Information about our Executive Officers
Our executive officers are as follows:
Hervé Hoppenot, age 62, joined Incyte as President and Chief Executive Officer and a Director, in January 2014
and was appointed Chairman of the Board in May 2015. Mr. Hoppenot served as the President of Novartis Oncology,
Novartis Pharmaceuticals Corporation, the U.S. subsidiary of Novartis AG, a pharmaceutical company, from January 2010
to January 2014. Prior to that, Mr. Hoppenot served in other executive positions at Novartis Pharmaceuticals Corporation,
serving from September 2006 to January 2010 as Executive Vice President, Chief Commercial Officer of Novartis
Oncology and Head of Global Product Strategy & Scientific Development of Novartis Pharmaceuticals Corporation and
from 2003 to September 2006 as Senior Vice President, Head of Global Marketing of Novartis Oncology. Prior to joining
Novartis, Mr. Hoppenot served in various increasingly senior roles at Aventis S.A. (formerly Rhône-Poulenc S.A.), a
pharmaceutical company, including as Vice President Oncology US of Aventis Pharmaceuticals, Inc. from 2000 to 2003
and Vice President US Oncology Operations of Rhone-Poulenc Rorer Pharmaceuticals, Inc. from 1998 to 2000.
Mr. Hoppenot holds a Diploma from ESSEC International Business School. Mr. Hoppenot is also a director of Cellectis
S.A.
Dashyant Dhanak, age 61, joined Incyte in December 2018 as Executive Vice President, Chief Scientific Officer.
Prior to joining Incyte, Dr. Dhanak served as Vice President and Head of Discovery Sciences of Janssen Research &
Development, LLC, a wholly-owned subsidiary of Johnson & Johnson, a pharmaceutical company, from 2013 until
November 2018. Prior to his tenure at Janssen, Dr. Dhanak spent 25 years at GlaxoSmithKline, a pharmaceutical company,
in positions of increased responsibility across multiple disease areas, including his last position as Vice President and Head
of the Cancer Epigenetics Discovery Performance Unit. Dr. Dhanak received a B.S. in Chemistry from the University of
Manchester Institute of Science and Technology and his Ph.D. from the University of London. He completed his
postdoctoral research in natural product synthesis at Northwestern University.
Jonathan E. Dickinson, age 54, has served as Executive Vice President and General Manager, Europe since
June 2019 and joined Incyte as Senior Vice President and General Manager, Europe in June 2016. Mr. Dickinson joined
Incyte from ARIAD Pharmaceuticals (Luxembourg) S.à.r.l, the parent company of ARIAD Pharmaceuticals, Inc.’s
European subsidiaries responsible for the development and commercialization of Iclusig in the European Union and other
countries, where he most recently held the position of Senior Vice President and General Manager, Europe. Prior to joining
ARIAD in February 2013, Mr. Dickinson served as European oncology brand lead at Bristol-Myers Squibb, a
pharmaceutical company, and before that, he held several key leadership positions, including lifecycle leader, during his
13-year tenure at Hoffmann-La Roche, a pharmaceutical company. At Roche, he had assignments both in the United States
and Switzerland that included leadership roles for Roche’s three leading oncology medicines. Mr. Dickinson began his
career at Novartis, where he held commercial roles in its oncology and endocrinology businesses, including medical sales,
product manager and business director in the United Kingdom. Mr. Dickinson received a B.S. in Genetics and an M.B.A.
from the University of Nottingham.
Barry P. Flannelly, age 64, has served as Executive Vice President and General Manager, North America since
June 2015 and joined Incyte as Executive Vice President, Business Development and Strategic Planning in August 2014.
Prior to joining Incyte, he served as Chief Executive Officer of OSS Healthcare Inc., a biotechnology start-up company,
from August 2013 to July 2014. He served as Vice President, Global Product Strategy and Commercial Planning of Nektar
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Therapeutics, a biopharmaceutical company, from April 2011 until April 2013, and as Senior Vice President, Commercial,
of Onyx Pharmaceuticals, Inc., a biopharmaceutical company, from August 2008 until January 2011. Prior thereto,
Dr. Flannelly held key positions at biopharmaceutical and pharmaceutical companies such as Abraxis BioScience, Inc. and
Novartis. Dr. Flannelly earned his doctorate in pharmacy from the University of Maryland, School of Pharmacy, his
master’s degree in business administration from the University of Baltimore, and his B.S. degree in Pharmacy from
Massachusetts College of Pharmacy.
Vijay Iyengar, age 49, joined Incyte in May 2016 as Executive Vice President, Global Strategy and Corporate
Development. Prior to joining Incyte, from April 2014 to April 2016, he was the President of Genoptix Corporation, a
Novartis Company. From December 2011 to March 2014, he was the Vice President and Rare Diseases Franchise Head
at Novartis Oncology and from July 2009 to December 2011, he was the Vice President and Oncology General Manager
of Novartis Greece. From October 2007 to June 2009, he was the Global Brand Executive Director at Novartis
Pharmaceuticals, and from January 2006 to October 2007, he was the Global Brand Director, Oncology at Novartis
Pharmaceuticals. Dr. Iyengar received his B.S. degree in Biology from Stanford University and earned his M.D. from
Harvard Medical School.
Michael Morrissey, age 58, has served as Executive Vice President and Head of Global Technical Operations
since June 2019 and joined Incyte in January 2016 as Corporate Senior Vice President and Head of Global Technical
Operations. He has more than 30 years of global pharmaceutical industry experience through his prior positions in
Research and Development, Quality Assurance, and Manufacturing. From February 2005 until joining Incyte,
Mr. Morrissey worked at Celgene International, a subsidiary of Celgene Corporation, a biopharmaceutical company, where
he last served as Corporate Vice President, Head of International Technical Operations. Prior to Celgene, he worked for
Roche for 15 years in various positions. Mr. Morrissey received a B.Sc. in Physics and Applied Mathematics from the
University of London, United Kingdom.
Maria E. Pasquale, age 56, joined Incyte in April 2018 as Executive Vice President and General Counsel. Prior
to joining Incyte, Ms. Pasquale joined Incyte from Celgene Corporation, a biopharmaceutical company, where for 17 years
she held positions of increasing levels of responsibility, including Chief Counsel; Senior Vice President, Legal and Deputy
General Counsel and Assistant Corporate Secretary, and, most recently, Executive Vice President and Global Chief
Compliance Officer. Prior to her tenure at Celgene, Ms. Pasquale spent a decade supporting pharmaceutical clients as a
global patent and litigation attorney at Pennie & Edmonds LLP in New York (now part of Jones Day). Before her career
in law, Ms. Pasquale was an Assistant Research Scientist at the Institute for Basic Research and the Cold Spring Harbor
Laboratory. Ms. Pasquale holds a J.D. from Brooklyn Law School and a B.S. in biochemistry from the State University
of New York at Stony Brook.
Christiana Stamoulis, age 51, joined Incyte in February 2019 as Executive Vice President and Chief Financial
Officer. Prior to joining Incyte, she served as President from February 2018 until January 2019 and Chief Financial Officer
from January 2015 to January 2019 of Unum Therapeutics Inc., a biopharmaceutical company. From January 2014 until
she joined Unum, Ms. Stamoulis was an independent advisor to biopharmaceutical companies. From 2009 until
December 2013, Ms. Stamoulis was a Senior Vice President of Corporate Strategy and Business Development at Vertex
Pharmaceuticals, Inc., a biopharmaceutical company. Prior to joining Vertex, Ms. Stamoulis spent nearly 15 years in the
investment banking and management consulting industries. She was a Managing Director in the Investment Banking
division of Citigroup and, prior to that, she was a senior investment banker in the Healthcare Investment Banking Group
of Goldman, Sachs & Co., where she spent the majority of her investment banking career. Ms. Stamoulis started her career
as a strategy consultant at The Boston Consulting Group. Ms. Stamoulis holds two B.S. degrees from the Massachusetts
Institute of Technology (MIT) and an M.B.A. from the MIT Sloan School of Management.
Steven Stein, age 55, has served as Executive Vice President and Chief Medical Officer since May 2016 and
joined Incyte as Senior Vice President and Chief Medical Officer in March 2015. Prior to joining Incyte, from May 2011
to February 2015, he was the Senior Vice President, US Clinical Development & Medical Affairs at Novartis
Pharmaceuticals. From February 2004 to April 2011, Dr. Stein was the Vice President, Global Oncology, Clinical
Development and the Head of Medicines Development for Hematology and Supportive Care for GlaxoSmithKline.
Dr. Stein held a post-doctoral fellowship in hematology/oncology at the University of Pennsylvania from 1998 to 2001,
and earned his M.D. from the University of Witwatersrand in Johannesburg, South Africa in 1990.
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Paula J. Swain, age 64, has served as Executive Vice President, Human Resources since August 2002 and joined
Incyte as Senior Vice President of Human Resources in January 2002. Ms. Swain served as Senior Vice President of
Human Resources at Bristol-Myers Squibb Company from October 2001 to January 2002, after it acquired DuPont
Pharmaceuticals Company. From July 1998 to October 2001, Ms. Swain was Senior Vice President of Human Resources
at DuPont Pharmaceuticals. From October 1992 to July 1998, Ms. Swain held a variety of human resources positions of
increasing responsibility at DuPont Pharmaceuticals. Ms. Swain received her B.A. in Psychology and Industrial Relations
from Rockhurst University.
PART II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity
Securities
Our common stock, $.001 par value per share, is traded on The Nasdaq Global Select Market under the symbol
“INCY.” As of December 31, 2021, our common stock was held by 120 stockholders of record. We have never declared
or paid dividends on our capital stock and do not anticipate paying any dividends in the foreseeable future.
Item 6. [Reserved]
Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations
The following discussion and analysis of our financial condition and results of operations should be read in
conjunction with “Selected Consolidated Financial Data” and the Consolidated Financial Statements and related Notes
included elsewhere in this Report.
A discussion of our financial performance for the year ended December 31, 2021 as compared to the year ended
December 31, 2020 appears below under the captions “Results of Operations” and “Liquidity and Capital Resources.” A
discussion of our financial performance for the year ended December 31, 2020 compared to the year ended December 31,
2019 can be found under the same captions in Item 7 of our Annual Report on Form 10-K for the year ended December 31,
2020, filed with the SEC on February 9, 2021, which is available free of charge on the SEC’s website at www.sec.gov and
our Investor Relations website at investor.incyte.com/financial-information/annual-reports. These website addresses are
intended to be inactive, textual references only. None of the materials on, or accessible through, these websites are part of
this report or are incorporated by reference herein.
Overview
Incyte is a biopharmaceutical company focused on the discovery, development and commercialization of
proprietary therapeutics. Our global headquarters is located in Wilmington, Delaware, where we conduct global clinical
development and commercial operations. We also conduct commercial and clinical development operations from our
European headquarters in Morges, Switzerland and our Japanese office in Tokyo.
Our portfolio includes compounds in various stages, ranging from preclinical to late stage development, and
commercialized products JAKAFI® (ruxolitinib), ICLUSIG® (ponatinib), PEMAZYRE® (pemigatinib), OPZELURA™
(ruxolitinib) cream, MINJUVI® (tafasitamab) and MONJUVI® (tafasitamab-cxix), which is co-commercialized.
Effects of the COVID-19 Pandemic on Our Business
In December 2019, coronavirus disease of 2019, or COVID-19, was first reported in Wuhan, China. In
March 2020, the World Health Organization declared COVID-19 a pandemic and certain governments, including the State
of Delaware where our primary offices and laboratory spaces are located, enacted stay-at-home orders and sweeping
restrictions to travel and business activity were initiated by corporations and governments.
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We took aggressive, proactive actions early on to protect the health of our employees, and their families, including
voluntarily requiring almost all personnel across our global enterprise to work remotely and restricting access to our sites
to personnel who were required to perform critical business continuity activities. In May 2020, we initiated a return to full
laboratory work at our facilities in Wilmington, Delaware, as well as a gradual return to office-based working, where
allowed under local guidelines, at our offices in North America, Europe and Asia. However, the spread of the Omicron
variant beginning late in 2021 has led to renewed restrictions in some jurisdictions and a voluntary reduction in travel and
in-person meetings even where restrictions were not imposed.
While we currently believe we are well-positioned to function in a hybrid on-site and virtual or remote fashion,
the extent of the COVID-19 Pandemic’s effect on our operational and financial performance will depend on future
developments, including the duration, spread and intensity of the pandemic, protective measures, and the reimposition of
protective measures, implemented by governmental authorities or by us to protect our employees, and effects of the
pandemic and such protective measures on our suppliers, collaborators, services providers and healthcare organizations
serving patients, all of which are uncertain and difficult to predict considering the rapidly evolving landscape. As a result,
it is not currently possible to ascertain or predict the overall long-term impact of the COVID-19 pandemic on our business.
To date, we have not experienced a material effect on the results of our commercial operations, or our
manufacturing supply chain. New patient starts for treatment decreased as a result of shelter in place and other protective
measures, and if decreases in new patient starts occur in future periods, our revenues in future periods could be adversely
affected. We continue to anticipate that short-term effects may continue to emerge across different aspects of our global
clinical trial programs. For example, while we expect ongoing monitoring of already-enrolled patients to continue,
difficulties in monitoring may result as a consequence of shelter in place orders and other protective measures implemented
by governmental authorities or clinical trial sites. In addition, new patient recruitment in certain clinical trials has been
and may in the future be impacted, in particular with respect to our earlier stage clinical trials. We also expect the conduct
of clinical trials may continue to vary by disease state and by severity of disease, as well as by geography, as some regions
are more adversely impacted. Until our return to full laboratory work, our discovery laboratories were staffed by essential
personnel, and hence certain discovery programs experienced delays. Still, we caution that the duration and severity of the
continuing COVID-19 pandemic remains uncertain and we may not yet be able to assess its consequences accurately or
fully at this time.
Regulatory Achievements
In March 2021, PEMAZYRE (pemigatinib) was approved by the Japanese Ministry of Health, Labour and
Welfare for the treatment of patients with unresectable biliary tract cancer with an FGFR2 fusion gene, worsening after
cancer chemotherapy. Also in March 2021, PEMAZYRE was approved by the European Commission for the treatment of
adults with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement that have
progressed after at least one prior line of systemic therapy. PEMAZYRE was approved by the Food and Drug
Administration (FDA) in April 2020 for the treatment of adults with previously treated, unresectable locally advanced or
metastatic cholangiocarcinoma with an FGFR2 fusion or other rearrangement as detected by an FDA-approved test. We
have retained all rights to PEMAZYRE globally, other than those granted to Innovent Biologics, Inc. to develop and
commercialize pemigatinib in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.
In August 2021, under our collaboration and license agreement with MorphoSys AG, the European Commission
granted conditional marketing authorization for MINJUVI (tafasitamab) in combination with lenalidomide, followed by
MINJUVI monotherapy, for the treatment of adult patients with relapsed or refractory DLBCL who are not eligible for
autologous stem cell transplant. MONJUVI (tafasitamab-cxix) was approved by the FDA in July 2020 in combination
with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL)
not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous
stem cell transplant. We have rights to co-commercialize tafasitamab in the United States with MorphoSys, and we have
exclusive development and commercialization rights outside of the United States.
In September 2021, the FDA approved JAKAFI for the treatment of chronic GVHD after failure of one or two
lines of systemic therapy in adult and pediatric patients 12 years and older. We have retained all development and
commercialization rights to JAKAFI in the United States and are eligible to receive development and sales milestones as
67
well as royalties from product sales outside the United States.
In September 2021, the FDA approved OPZELURA (ruxolitinib) cream, a novel cream formulation of our
selective JAK1/JAK2 inhibitor ruxolitinib, for the topical short-term and non-continuous chronic treatment of mild to
moderate atopic dermatitis in non-immunocompromised patients 12 years of age and older whose disease is not adequately
controlled with topical prescription therapies, or when those therapies are not advisable.
License Agreements and Business Relationships
We establish business relationships, including collaborative arrangements with other companies and medical
research institutions to assist in the clinical development and/or commercialization of certain of our drugs and drug
candidates and to provide support for our research programs. We also establish business relationships with other companies
and medical research institutions to acquire products or rights to products and technologies that are complementary to our
business. Summarized below are the significant achievements under our existing collaboration and license agreements and
additional agreements we entered into during the year ended December 31, 2021.
Innovent
In June 2021, we recognized a $10.0 million milestone for approval of PEMAZYRE in Taiwan, which was
recorded in milestone and contract revenues.
InnoCare
In August 2021, we entered into a Collaboration and License Agreement with a subsidiary of InnoCare Pharma
Limited. Under the terms of this agreement, InnoCare’s subsidiary received development and exclusive commercialization
rights to tafasitamab in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan. In September 2021,
we recognized an upfront payment under this agreement of $35.0 million upon our transfer of technology related to the
licensed product candidate to InnoCare which was recorded in milestone and contract revenues. Under the terms of this
agreement, we are eligible to receive up to an additional $45.0 million in potential development and regulatory milestones
and up to $37.5 million in potential sales milestones from InnoCare. We are also eligible to receive tiered royalties from
the low to mid-twenties on future product sales resulting from the collaboration.
Syndax
In September 2021, we entered into a Collaboration and License Agreement with Syndax covering the worldwide
development and commercialization of SNDX-6352 (axatilimab), Syndax’s anti-CSF-1R monoclonal antibody. The
Agreement became effective in December 2021 with the expiration of the initial waiting period under the Hart-Scott-
Rodino Antitrust Improvements Act. Under the terms of this agreement, we received exclusive commercialization rights
outside of the United States, and Syndax has co-commercialization rights in the United States with respect to axatilimab.
We paid Syndax an upfront payment of $117.0 million upon effectiveness of the agreement. Syndax is eligible to receive
up to $220.0 million in future contingent development and regulatory milestones and $230.0 million in sales milestones as
well as tiered royalties ranging in the mid-teens on net sales in Europe and Japan and low double digit percentage on net
sales in the rest of the world outside of the United States.
Lilly
In December 2021, we recognized a $50.0 million sales milestone for Lilly achieving annual net sales of a licensed
product of $1.0 billion.
Additional information regarding our collaboration agreements, including their financial and accounting impact
on our business and results of operations, can be found in Note 6 of Notes to the Consolidated Financial Statements.
68
Critical Accounting Policies and Significant Estimates
The preparation of financial statements requires us to make estimates, assumptions and judgments that affect the
reported amounts of assets, liabilities, revenues and expenses, and related disclosures of contingent assets and liabilities.
On an ongoing basis, we evaluate our estimates. We base our estimates on historical experience and various other
assumptions that we believe to be reasonable under the circumstances, the results of which form our 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 those estimates under different assumptions or conditions. We believe the following critical accounting
policies reflect the more significant judgments and estimates used in the preparation of the consolidated financial
statements. See Note 1 of Notes to the Consolidated Financial Statements for a complete list of our significant accounting
policies.
Revenue Recognition. We recognize revenue only when we have satisfied a performance obligation through
transferring control of the promised good or service to a customer in an amount that reflects the consideration we expect
to receive in exchange for those goods or services. We apply the following five-step model in order to determine this
amount: (i) identification of the promised goods or services in the contract; (ii) determination of whether the promised
goods or services are performance obligations, including whether they are distinct in the context of the contract; (iii)
measurement of the transaction price, including the constraint on variable consideration; (iv) allocation of the transaction
price to the performance obligations; and (v) recognition of revenue when (or as) the Company satisfies each performance
obligation, which for the Company is at a point in time. We also assess collectability based primarily on the customer’s
payment history and on the creditworthiness of the customer.
Product Revenues
Our product revenues consist of sales of JAKAFI, OPZELURA, PEMAZYRE, ICLUSIG, and MINJUVI.
Product revenues are recognized once we satisfy the performance obligation at a point in time under the revenue
recognition criteria as described above. We recognize revenues for product received by our customers net of allowances
for customer credits, including estimated rebates, chargebacks, discounts, returns, distribution service fees, patient
assistance programs, and government rebates, such as Medicare Part D coverage gap reimbursements in the United States.
These sales allowances and accruals are recorded based on estimates which are described in detail below. Estimates are
assessed as of the end of each reporting period and are updated to reflect current information. We believe that our sales
allowances and accruals are reasonable and appropriate based on current facts and circumstances. As of December 31,
2021, a 5% change in our sales allowance and accruals would have had an approximate $29.2 million impact on our income
before taxes.
Customer Credits: Our customers are offered various forms of consideration, including allowances, service fees
and prompt payment discounts. We expect our customers will earn prompt payment discounts and, therefore, we deduct
the full amount of these discounts from total product sales when revenues are recognized. Service fees are also deducted
from total product sales as they are earned.
Rebates and Discounts: We accrue rebates for mandated discounts under the Medicaid Drug Rebate Program in
the United States and mandated discounts in Europe in markets where government-sponsored healthcare systems are the
primary payers for healthcare. These accruals are based on statutory discount rates and expected utilization as well as
historical data we have accumulated since product launch. Our estimates for expected utilization of rebates are based on
data received from our customers. Rebates are generally invoiced and paid in arrears so that the accrual balance consists
of an estimate of the amount expected to be incurred for the current quarter’s activity, plus an accrual balance for known
prior quarters’ unpaid rebates. If actual future rebates vary from estimates, we may need to adjust prior period accruals,
which would affect revenue in the period of adjustment.
Chargebacks: Chargebacks are discounts that occur when certain contracted customers purchase directly from
our wholesalers at a discounted price. The wholesalers, in turn, charges back to us the difference between the price initially
paid by the wholesalers and the discounted price paid by the contracted customers. In addition to actual chargebacks
received, we maintain an accrual for chargebacks based on the estimated contractual discounts on the inventory levels on
hand in our distribution channel. If actual future chargebacks vary from these estimates, we may need to adjust prior
69
period accruals, which would affect revenue in the period of adjustment.
Medicare Part D Coverage Gap: Medicare Part D prescription drug benefit mandates manufacturers to fund 70%
of the Medicare Part D insurance coverage gap for prescription drugs sold to eligible patients. Our estimates for the
expected Medicare Part D coverage gap are based on historical invoices received and in part from data received from our
customers. Funding of the coverage gap is generally invoiced and paid in arrears so that the accrual balance consists of an
estimate of the amount expected to be incurred for the current quarter’s activity, plus an accrual balance for known prior
quarters. If actual future funding varies from estimates, we may need to adjust prior period accruals, which would affect
revenue in the period of adjustment. Additionally, beginning in January 2020, the amount of spending required by eligible
patients in the Medicare Part D insurance coverage gap increased 30% due to the expiration of a provision in the Patient
Protection and Affordable Care Act, which now results in a change in the True Out of Pocket (TrOOP) calculation
methodology. The methodological change has resulted in an increase in required spending by patients and, in turn, an
increase in manufacturers’ contributions on behalf of patients in the Medicare Part D insurance coverage gap.
Co-payment Assistance: Patients who have commercial insurance and meet certain eligibility requirements may
receive co-payment assistance. We accrue a liability for co-payment assistance based on actual program participation and
estimates of program redemption using data provided by third-party administrators.
Product Royalty Revenues
Royalty revenues on commercial sales for JAKAVI and TABRECTA by Novartis are estimated based on
information provided by Novartis. Royalty revenues on commercial sales for OLUMIANT by Lilly are estimated based
on information provided by Lilly. We recognize royalty revenues in the period the sales occur. We exercise judgment in
determining whether the information provided is sufficiently reliable for us to base our royalty revenue recognition thereon.
If actual royalties vary from estimates, we may need to adjust the prior period, which would affect royalty revenue and
receivable in the period of adjustment. Historically, adjustments to these estimates to reflect actual royalty revenues have
not been material to our financial results and have been less than 1% of royalty revenues.
Milestone and Contract Revenues
At the inception of a contract, we determine the transaction price, in addition to any upfront payment, by
estimating the amount of variable consideration, including milestone payments, at the outset of the contract utilizing the
most likely amount method. Our contractual milestones typically relate to the achievement of pre-specified development,
regulatory and commercialization events outside of our control, such as regulatory approval of a compound, first patient
dosing or achievement of sales-based thresholds. We include milestones in the transaction price only to the extent that it
is probable that a significant reversal in the amount of cumulative revenue recognized will not occur when the uncertainty
associated with the milestone is subsequently resolved. Given the high level of uncertainty of achievement, variable
consideration associated with milestones are fully constrained until confirmation of the satisfaction or completion of the
milestone by the third-party. We review our estimate of the transaction price each period, and make revisions to such
estimates as necessary.
Stock Compensation. Share-based payment transactions with employees, which include stock options, restricted
stock units (RSUs) and performance shares (PSUs), are recognized as compensation expense over the requisite service
period based on their estimated fair values at the date of grant as well as expected forfeiture rates based on actual
experience. The stock compensation process requires significant judgment and the use of estimates, particularly
surrounding Black-Scholes assumptions such as stock price volatility over the option term and expected option lives, as
well as expected forfeiture rates and the probability of PSUs vesting. For the years ending December 31, 2021 and 2020,
our Black-Scholes assumptions have remained unchanged with a weighted-average stock price volatility of 39% to 40%,
average expected option life of approximately five years and an estimated annualized forfeiture rate of 5%.
The fair value of stock options, which are subject to graded vesting, are recognized as compensation expense over
the requisite service period using the accelerated attribution method. The fair value of RSUs that are subject to cliff vesting
are recognized as compensation expense over the requisite service period using the straight-line attribution method, and
the fair value of RSUs that are subject to graded vesting are recognized as compensation expense over the requisite service
70
period using the accelerated attribution method. The fair value of PSUs are recognized as compensation expense beginning
at the time in which the performance conditions are deemed probable of achievement. We assess the probability of
achievement of performance conditions, including projected product revenues and clinical development milestones, as of
the end of each reporting period. Once a performance condition is considered probable, we record compensation expense
based on the portion of the service period elapsed to date with respect to that award, with a cumulative catch-up, net of
estimated forfeitures, and recognize any remaining compensation expense, if any, over the remaining requisite service
period using the straight-line attribution method for PSUs that are subject to cliff vesting and using the accelerated
attribution method for PSUs that are subject to graded vesting. Compensation expense for PSUs with market performance
conditions is calculated using a Monte Carlo simulation model as of the date of grant and recorded over the requisite
service period.
Income Taxes. We account for income taxes using an asset and liability approach to financial accounting for
income taxes. Under this method, deferred tax assets and liabilities are determined based on the difference between the
financial statement carrying amounts and tax bases of assets and liabilities using enacted tax rates in effect for years in
which the basis differences are expected to reverse. We periodically assess the likelihood of the realization of deferred tax
assets, and reduce the carrying amount of these deferred tax assets to an amount that is considered to be more-likely-than-
not to be realizable. Our assessment considers recent cumulative earnings experience, projections of future taxable income
(losses) and ongoing prudent and feasible tax planning strategies. When performing our assessment on projections of
future taxable income (losses), we consider factors such as the likelihood of regulatory approval and commercial success
of products currently under development, among other factors. Significant judgment is required in making this assessment
and, to the extent that a reversal of any portion of our valuation allowance against our deferred tax assets is deemed
appropriate, a tax benefit will be recognized against our income tax provision in the period of such reversal.
We recognize the tax benefit from an uncertain tax position only if it is more-likely-than-not that the position will
be sustained upon examination by the taxing authorities, including resolutions of any related appeals or litigation processes,
based on the technical merits of the position. The tax benefit that is recorded for these positions is measured at the largest
amount of benefit that is greater than 50 percent likely of being realized upon ultimate settlement. We adjust the level of
the liability to reflect any subsequent changes in the relevant facts surrounding the uncertain positions. Any interest and
penalties on uncertain tax positions are included within the tax provision.
We record estimates and prepare and file tax returns in various jurisdictions across the United States, Canada,
Europe, and Asia based upon our interpretation of local tax laws and regulations. While we exercise significant judgment
when applying complex tax laws and regulations in these various taxing jurisdictions, many of our tax returns are open to
audit, and may be subject to future tax, interest, and penalty assessments.
We believe our estimates for the valuation allowances against certain deferred tax assets and the amount of
benefits associated with uncertain tax positions recognized in our financial statements are appropriate based upon our
assessment of the factors mentioned above. As a result of releasing the valuation allowance on the majority of our U.S.
deferred tax assets in 2021, we expect that our reported income tax expense (current plus deferred) for future periods will
be higher than that recorded for prior periods.
Acquisition-related contingent consideration. Acquisition-related contingent consideration, which consists of
our future royalty obligations to ARIAD/Takeda, was recorded on the acquisition date at the estimated fair value of the
obligation, in accordance with the acquisition method of accounting using an income approach based on projected future
net revenues of ICLUSIG in the European Union and other countries. The fair value of the acquisition-related contingent
consideration is remeasured each reporting period, with changes in fair value recorded in the consolidated statements of
operations. The assumptions used to determine the fair value of the acquisition-related contingent consideration include
projected future net revenues of ICLUSIG and a discount rate which, require significant judgement and are analyzed on a
quarterly basis. As the fair value measurement is based on significant inputs that are unobservable in the market, this
represents a Level 3 measurement.
The valuation inputs utilized to estimate the fair value of the contingent consideration as of December 31, 2021
and 2020 included a discount rate of 10% and updated projections of future net revenues of ICLUSIG in the European
Union and other countries for the approved third line treatment.
71
While we use the best available information to prepare our projections of future net revenues of ICLUSIG and
discount rate assumptions, actual ICLUSIG revenues and/or market conditions could differ significantly. Changes to one
or multiple inputs could have a material impact on the amount of acquisition-related contingent consideration expense
recorded during the reporting period.
Results of Operations
Years Ended December 31, 2021 and 2020
We recorded net income for the year ended December 31, 2021 of $948.6 million and net loss for the year ended
December 31, 2020 of $295.7 million. On a per share basis, basic net income was $4.30 and diluted net income was $4.27
for the year ended December 31, 2021. On a per share basis, basic and diluted net loss was $1.36 for the year ended
December 31, 2020. For the year ended December 31, 2021, we recorded a benefit from income taxes of $569.0 million
when we released the valuation allowance on the majority of our U.S. deferred tax assets. This benefit increased net income
by $2.58 per basic and $2.56 per diluted share for the year ended December 31, 2021.
Revenues
JAKAFI revenues, net
ICLUSIG revenues, net
PEMAZYRE revenues, net
MINJUVI revenues, net
OPZELURA revenues, net
Total product revenues, net
JAKAVI product royalty revenues
OLUMIANT product royalty revenues
TABRECTA product royalty revenues
Total product royalty revenues
Milestone and contract revenues
Total revenues
For the Year Ended,
December 31,
2021
2020
(in millions)
$
2,134.5
109.4
68.5
4.9
4.7
2,322.0
338.0
220.9
10.4
569.3
95.0
2,986.3 $
1,937.8
105.0
25.9
—
—
2,068.7
277.9
110.9
4.2
393.0
205.0
2,666.7
$
$
The increase in JAKAFI product revenues from 2020 to 2021 was comprised of a volume increase of
$110.1 million and a price increase of $86.6 million. Our product revenues may fluctuate from period to period due to our
customers’ purchasing patterns over the course of a year, including as a result of increased inventory building by customers
in advance of expected or announced price increases. Product revenues are recorded net of estimated product returns,
pricing discounts including rebates offered pursuant to mandatory federal and state government programs and chargebacks,
prompt pay discounts and distribution fees and co-pay assistance. Our revenue recognition policies require estimates of
the aforementioned sales allowances each period.
72
The following table provides a summary of activity with respect to our sales allowances and accruals (in
thousands):
Co-Pay
Discounts and Government
Distribution Rebates and
Assistance
and Other
Chargebacks Discounts
Product
Returns
Year Ended December 31, 2021
Balance at January 1, 2021
$
Allowances for current period sales
Allowances for prior period sales
Credits/payments for current period sales
Credits/payments for prior period sales
Balance at December 31, 2021
$
Fees
8,536 $
74,688
91
(62,250)
(6,387)
14,678 $
66,991 $
434,800
(889)
(359,936)
(41,662)
99,304 $
1,284 $
69,056
—
(45,859)
(407)
24,074 $
Total
78,379
1,568 $
583,284
4,740
(189)
609
(468,045)
—
(2,177)
(50,633)
4,740 $ 142,796
Government rebates and chargebacks are the most significant component of our sales allowances. Increases in
certain government reimbursement rates are limited to a measure of inflation, and when the price of a drug increases faster
than this measure of inflation it will result in a penalty adjustment factor that causes a larger sales allowance to those
government related entities. We expect government rebates and chargebacks as a percentage of our gross product sales
will continue to increase in connection with any future product price increases greater than the rate of inflation, and any
such increase in these government rebates and chargebacks will have a negative impact on our reported product revenues,
net. We adjust our estimates for government rebates and chargebacks based on new information regarding actual rebates
as it becomes available. Claims by third-party payors for rebates and chargebacks are frequently submitted after the period
in which the related sales occurred, which may result in adjustments to prior period accrual balances in the period in which
the new information becomes available. We also adjust our allowance for product returns based on new information
regarding actual returns as it becomes available.
We expect our sales allowances to fluctuate from quarter to quarter as a result of the Medicare Part D Coverage
Gap, the volume of purchases eligible for government mandated discounts and rebates as well as changes in discount
percentages which are impacted by potential future price increases, rate of inflation, and other factors.
Product royalty revenues on commercial sales of JAKAVI and TABRECTA by Novartis are based on net sales
of licensed products in licensed territories as provided by Novartis. Product royalty revenues on commercial sales of
OLUMIANT by Lilly are based on net sales of licensed products in licensed territories as provided by Lilly.
Our milestone and contract revenues were $95.0 million and $205.0 million for the years ended December 31,
2021 and 2020, respectively. During the year ended December 31, 2021, our milestone and contract revenues were derived
from a $50.0 million sales milestone under the Lilly license, development and commercialization agreement, a $10.0
million milestone under the Innovent research collaboration and licensing agreement and a $35.0 million upfront payment
under the InnoCare collaboration and license agreement. During the year ended December 31, 2020, our milestone and
contract revenues were derived from a $5.0 million milestone under the Innovent agreement, $170.0 million in milestones
under the Novartis agreement and $30.0 million in milestones under the Lilly agreement.
Cost of Product Revenues
Product costs
Salary and benefits related
Stock compensation
Royalty expense
Amortization of definite-lived intangible assets
Total cost of product revenues
73
For the Year Ended,
December 31,
2021
2020
(in millions)
$
21.0 $
7.2
1.7
99.6
21.5
$
151.0 $
15.3
3.6
1.0
89.9
21.5
131.3
Cost of product revenues includes all product related costs, employee personnel costs, including stock
compensation, for those employees dedicated to the production of our commercial products, low single-digit royalties to
Novartis on all sales of JAKAFI in the United States and amortization of our licensed intellectual property rights for
ICLUSIG using the straight-line method over the estimated useful life of 12.5 years. Cost of product revenues increased
from 2020 to 2021 due primarily to increased royalties to Novartis on all JAKAFI sales in the United States.
Operating Expenses
Research and development expenses
Salary and benefits related
Stock compensation
Clinical research and outside services
Occupancy and all other costs
Total research and development expenses
For the Years Ended,
December 31,
2021
2020
(in millions)
$
$
306.0 $
114.3
902.3
135.6
1,458.2 $
285.8
120.4
1,701.3
108.4
2,215.9
We account for research and development costs by natural expense line and not costs by project. Salary and
benefits related expense increased from 2020 to 2021 due primarily to increased development headcount to sustain our
development pipeline. Stock compensation expense may fluctuate from period to period based on the number of awards
granted, stock price volatility and expected award lives, as well as expected award forfeiture rates which are used to value
equity-based compensation.
The decrease in clinical research and outside services expense from 2020 to 2021 was primarily due to expense
related to the purchase of an FDA priority review voucher in the prior year that enabled OPZELURA to be the first JAK
inhibitor approved in a topical formulation and due to upfront consideration related to our collaborative agreements
recorded in the prior year. Research and development expenses include upfront and milestone expenses related to our
collaborative agreements of $149.0 million and $976.1 million for the years ended December 31, 2021 and 2020,
respectively. Research and development expenses for the years ended December 31, 2021 and 2020 were net of
$29.6 million and $8.5 million, respectively, of costs reimbursed by our collaborative partners.
In addition to one-time expenses resulting from upfront fees in connection with the entry into any new or amended
collaboration agreements and payment of milestones under those agreements, research and development expenses may
fluctuate from period to period depending upon the stage of certain projects and the level of pre-clinical and clinical trial
related activities. Many factors can affect the cost and timing of our clinical trials, including requests by regulatory agencies
for more information, inconclusive results requiring additional clinical trials, slow patient enrollment, adverse side effects
among patients, insufficient supplies for our clinical trials, timing of drug supply, including API, and real or perceived
lack of effectiveness or safety of our investigational drugs in our clinical trials. In addition, the development of all of our
products will be subject to extensive governmental regulation. These factors make it difficult for us to predict the timing
and costs of the further development and approval of our products.
74
Selling, general and administrative expenses
Salary and benefits related
Stock compensation
Other contract services and outside costs
Total selling, general and administrative expenses
For the Years Ended,
December 31,
2021
2020
(in millions)
$
$
222.4 $
67.0
450.2
739.6 $
158.2
56.6
302.1
516.9
Salary and benefits related expense increased from 2020 to 2021 due primarily to increased headcount. This
increased headcount was due primarily to the ongoing commercialization efforts related to JAKAFI for intermediate or
high-risk myelofibrosis, uncontrolled polycythemia vera and GVHD as well as increased headcount related to the
establishment of our dermatology commercial organization and activities to support the launch of OPZELURA for the
treatment of atopic dermatitis. Stock compensation expense may fluctuate from period to period based on the number of
awards granted, stock price volatility and expected award lives, as well as expected award forfeiture rates which are used
to value equity-based compensation. The increase in other contract services and outside costs was primarily due to the
establishment of our dermatology commercial organization, expenses related to activities to support the launch of
OPZELURA and expense recognized in connection with a legal settlement, as discussed in Note 15 of Notes to the
Consolidated Financial Statements.
Change in fair value of acquisition-related contingent consideration
Acquisition-related contingent consideration, which consists of our future royalty obligations to ARIAD/Takeda,
was recorded on the acquisition date, June 1, 2016, at the estimated fair value of the obligation, in accordance with the
acquisition method of accounting. The fair value of the acquisition-related contingent consideration is remeasured
quarterly. The change in fair value of the acquisition-related contingent consideration for the years ended December 31,
2021 and 2020 was expense of $14.7 million and $23.4 million, respectively, which is recorded in change in fair value of
acquisition-related contingent consideration on the consolidated statements of operations. The change in fair value of the
contingent consideration for the year ended December 31, 2021 was due primarily to the impact of updated projections of
future net revenues of ICLUSIG in the European Union and the passage of time. The change in fair value of the contingent
consideration for the year ended December 31, 2020 was due primarily to the passage of time as there were no other
significant changes in the key assumptions during the period.
Collaboration loss sharing
Under the collaboration and license agreement with MorphoSys, which was executed in March 2020, we and
MorphoSys are both responsible for the commercialization efforts of tafasitamab in the United States and will share equally
the profits and losses from the co-commercialization efforts. For the year ended December 31, 2021 and 2020, our 50%
share of the costs for tafasitamab was $37.0 million and $42.8 million, respectively, as recorded in collaboration loss
sharing on the consolidated statement of operations.
Other income (expense)
Other income (expense), net. Other income (expense), net, for the years ended December 31, 2021 and 2020 was
$10.6 million and $23.2 million, respectively. The decrease in other income (expense), net primarily relates to a decrease
in interest income earned from our investments in marketable securities and money market accounts.
Interest expense. Interest expense for the years ended December 31, 2021 and 2020, was $1.9 million and
$2.2 million, respectively. Included in interest expense for the years ended December 31, 2021 and 2020 was
approximately $1.3 million and $1.2 million, respectively, of interest expense on our finance lease liabilities. Also included
in interest expense for the year ended December 31, 2020 was $0.7 million of non-cash charges to amortize the discount
on our convertible senior notes that matured in November 2020.
75
Unrealized gain (loss) on long term investments. Unrealized gains and losses on long term investments will
fluctuate from period to period, based on the change in fair value of the securities we hold in our publicly held collaboration
partners. The following table provides a summary of those unrealized gains and (losses):
Agenus
Calithera
Merus
MorphoSys
Syndax
Syros
Total unrealized (loss) gain on long term investments
For the Years Ended,
December 31,
2021
2020
(in millions)
4.6 $
(7.3)
48.1
(68.7)
6.3
(7.1)
(24.1) $
(10.3)
(1.4)
11.0
7.4
—
3.7
10.4
$
$
(Benefit) provision for income taxes. The (benefit) provision for income taxes for the years ended December 31,
2021 and 2020 was a benefit of $378.1 million and a provision of $63.5 million, respectively. The benefit for income taxes
in 2021 is primarily driven by the release of the valuation allowance on the majority of our U.S. deferred tax assets in the
fourth quarter. This benefit is partially offset by higher tax expense from U.S. operations. Further information on the
release of the valuation allowance and significant judgments related to its release can be found in Note 12 of Notes to the
Consolidated Financial Statements.
Liquidity and Capital Resources
December 31:
Cash, cash equivalents, and marketable securities
Working capital
Year ended December 31:
Cash provided by (used in):
Operating activities
Investing activities
Financing activities
Capital expenditures (included in investing activities above)
Sources and Uses of Cash.
2021
2020
(in millions)
$
$
2,348.2 $
2,264.4 $
1,801.4
1,728.7
$
$
$
$
749.5 $
(207.7) $
6.2 $
(181.0) $
(124.6)
(269.0)
71.7
(187.4)
Due to historical net losses, we had an accumulated deficit of $0.8 billion as of December 31, 2021. We have
funded our research and development operations through cash received from customers, sales of equity securities, the
issuance of convertible notes, and collaborative arrangements. At December 31, 2021, we had available cash, cash
equivalents and marketable securities of $2.3 billion. Our cash and marketable securities balances are held in a variety of
interest-bearing instruments, including money market accounts and U.S. government debt securities. Available cash is
invested in accordance with our investment policy’s primary objectives of liquidity, safety of principal and diversity of
investments.
Cash provided by (used in) operating activities. The increase in cash provided by operating activities from 2020
to 2021 was due primarily to cash outflows in March 2020 related to our collaboration and license agreement with
MorphoSys and changes in working capital.
Cash used in investing activities. Our investing activities, other than purchases, sales and maturities of marketable
securities, have consisted predominantly of capital expenditures and purchases of long term investments. During 2021, net
cash used in investing activities was $207.7 million, which represents purchases of marketable securities of $235.2 million,
capital expenditures of $181.0 million and purchase of long term equity investments of $33.5 million, offset in part by the
76
sale and maturity of marketable securities of $231.5 million and the sale of long term investment of $10.5 million. During
2020, net cash used in investing activities was $269.0 million, which represents purchases of marketable securities of
$516.9 million, capital expenditures of $187.4 million and purchase of long term equity investments of $95.5 million,
offset in part by the sale and maturity of marketable securities of $513.5 million and the sale of long term investment of
$17.3 million.
Cash provided by financing activities. During 2021 and 2020, net cash provided by financing activities was
$6.2 million and $71.7 million, respectively, consisting primarily of proceeds from the issuance of common stock under
our stock plans net of tax withholdings, offset in part by cash paid to ARIAD/Takeda for contingent consideration.
Our capital expenditures for construction activities and our non-operating contractual operating and finance lease
obligations are discussed in Note 7 of Notes to the Consolidated Financial Statements. In addition, in October 2019, we
entered into an agreement with Wilmington Friends School Inc., to purchase property for $50.0 million to expand our
global headquarters. Under that agreement, closing of the purchase is subject to certain standard closing conditions,
including an initial diligence period and a subsequent approval period.
In August 2021, we entered into a $500.0 million, three-year senior unsecured revolving credit facility. We may
increase the maximum revolving commitments or add one or more incremental term loan facilities, subject to obtaining
commitments from any participating lenders and certain other conditions, in an amount not to exceed $250.0 million plus
a contingent additional amount that is dependent on our pro forma consolidated leverage ratio. As of December 31, 2021,
we had no outstanding borrowings and were in compliance with all covenants under this facility.
We believe that our cash flow from operations, together with our cash, cash equivalents and marketable securities
and funds available under our revolving credit facility, will be adequate to satisfy our capital needs for the foreseeable
future. Our cash requirements depend on numerous factors, including our expenditures in connection with our drug
discovery and development programs and commercialization operations; expenditures in connection with litigation or other
legal proceedings; costs for future facility requirements; and expenditures for future strategic equity investments or
potential acquisitions. We have entered into and may in the future seek to license additional rights relating to technologies
or drug development candidates in connection with our drug discovery and development programs. Under these licenses,
we may be required to pay upfront fees, milestone payments, and royalties on sales of future products. These contingent
future payments are discussed in detail in Note 6 of Notes to the Consolidated Financial Statements.
To the extent we seek to augment our existing cash resources and cash flow from operations to satisfy our cash
requirements for future acquisitions or other strategic purposes, we expect that additional funding can be obtained through
equity or debt financings or from other sources. The sale of equity or convertible debt securities in the future may be
dilutive to our stockholders, and may provide for rights, preferences or privileges senior to those of our holders of common
stock. Debt financing arrangements may require us to pledge certain assets or enter into covenants that could restrict our
operations or our ability to incur further indebtedness.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk
Our investments in marketable securities, which are composed primarily of U.S. government securities, are
subject to default, changes in credit rating and changes in market value. These investments are also subject to interest rate
risk and will decrease in value if market interest rates increase. As of December 31, 2021, marketable securities were
$290.8 million. Due to the nature of these investments, if market interest rates were to increase immediately and uniformly
by 10% from levels as of December 31, 2021, the decline in fair value would not be material.
77
Item 8. Financial Statements and Supplementary Data
INDEX
Consolidated Financial Statements of Incyte Corporation
Report of Ernst & Young LLP, Independent Registered Public Accounting Firm (PCAOB ID: 42)
Consolidated Balance Sheets as of December 31, 2021 and 2020
Consolidated Statements of Operations for the years ended December 31, 2021, 2020 and 2019
Consolidated Statements of Comprehensive Income (Loss) for the years ended December 31, 2021, 2020 and
2019
Consolidated Statements of Stockholders’ Equity for the years ended December 31, 2021, 2020 and 2019
Consolidated Statements of Cash Flows for the years ended December 31, 2021, 2020 and 2019
Notes to the Consolidated Financial Statements
Page
79
82
83
84
85
86
87
78
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Incyte Corporation
Opinion on the Financial Statements
We have audited the accompanying consolidated balance sheets of Incyte Corporation (the Company) as of December 31,
2021 and 2020, the related consolidated statements of operations, comprehensive income (loss), stockholders’ equity and
cash flows for each of the three years in the period ended December 31, 2021, and the related notes (collectively referred
to as the “consolidated financial statements”). In our opinion, the consolidated financial statements present fairly, in all
material respects, the financial position of the Company at December 31, 2021 and 2020, and the results of its operations
and its cash flows for each of the three years in the period ended December 31, 2021, 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, 2021, 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 February 8, 2022 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 Matters
The critical audit matters communicated below are matters arising from the current period audit of the financial statements
that were communicated or required to be communicated to the audit committee and that: (1) relate to accounts or
disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex
judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated financial
statements, taken as a whole, and we are not, by communicating the critical audit matters below, providing separate
opinions on the critical audit matters or on the accounts or disclosures to which they relate.
Allowances for rebates and discounts owed to governmental entities
Description of the
Matter
As discussed in Note 1 to the consolidated financial statements, the Company recognizes revenues
for product received by its customers net of allowances for customer credits, including estimated
rebates, chargebacks, discounts, returns, distribution service fees, patient assistance programs, and
government rebates. Liabilities related to sales allowances are presented within accrued and other
current liabilities on the consolidated balance sheet and totaled $136.5 million as of December 31,
2021.
79
Auditing the allowances for rebates and discounts owed to governmental entities, including the
Medicaid Drug Rebate Program in the U.S. and Medicare Part D Coverage Gap, was complex and
highly judgmental due to the significant estimation uncertainty involved in management’s
assumptions, including the levels of expected utilization of these rebates and discounts based on
the amount of drugs sold to eligible patients, as well as the complexity of the government
mandated calculations. The allowances for rebates and discounts owed to governmental entities are
sensitive to these significant assumptions and calculations.
How We
Addressed the
Matter in Our
Audit
We obtained an understanding, evaluated the design and tested the operating effectiveness of
controls over management’s review of the allowances for rebates and discounts owed to
governmental entities. For example, we tested controls over management’s review of the
significant assumptions, such as the utilization of these rebates and discounts as well as controls
over management’s review of the application of the government mandated calculations.
To test the allowances for rebates and discounts owed to governmental entities, we performed
audit procedures that included, among others, evaluating the methodologies used and testing the
significant assumptions discussed above. We compared the significant assumptions used by
management to historical trends, evaluated the change in the accruals from prior periods, and
assessed the historical accuracy of management’s estimates against actual results. We also tested
the completeness and accuracy of the underlying data used in the Company’s calculations through
reconciliation to third-party invoices, claims data and actual cash payments. In addition, we
involved our governmental pricing specialists to assist in evaluating management’s methodology
and calculations used to measure certain estimated rebates and discounts.
Valuation of acquisition-related contingent consideration liability
Description of the
Matter
As discussed in Note 3 to the consolidated financial statements, the Company’s acquisition-related
contingent consideration liability, which consists of certain future royalty obligations on future net
revenues of ICLUSIG, is remeasured to its estimated fair value each reporting period, with
changes in fair value recorded in the consolidated statements of operations. As of December 31,
2021, the acquisition-related contingent consideration liability was $244.0 million.
Auditing the valuation of the acquisition-related contingent consideration liability was complex
and highly judgmental due to the significant estimation required in determining the fair value. In
particular, the fair value estimate was sensitive to significant assumptions such as the discount rate
and projected future net revenues of ICLUSIG, which are affected by expectations about future
industry, market or economic conditions, and are forward-looking and inherently uncertain.
How We
Addressed the
Matter in Our
Audit
We obtained an understanding, evaluated the design and tested the operating effectiveness of
controls over the Company’s valuation of the acquisition-related contingent consideration liability.
For example, we tested the Company's controls over management’s review of the valuation model,
including controls over the significant assumptions utilized in the calculation, such as the discount
rate and the projected future net revenues of ICLUSIG.
To test the estimated fair value of the acquisition-related contingent consideration liability, we
performed audit procedures that included, among others, assessing the terms of the arrangement,
evaluating the methodology used, and testing the significant assumptions discussed above used by
the Company in its analysis. We involved our valuation specialists to assist in the evaluation of the
significant assumptions and methodology used by the Company. We also compared the significant
assumptions to current industry, market and economic trends and to the Company's budgets and
forecasts. In addition, we assessed the historical accuracy of management’s estimates against
actual performance.
80
Realizability of deferred tax assets
Description of the
Matter
As discussed in Note 12 to the consolidated financial statements, at December 31, 2021, the
Company had deferred tax assets related to deductible temporary differences and tax credit
carryforwards of $507.9 million, net of a $408.2 million valuation allowance. Deferred tax assets
are reduced by a valuation allowance if, based on the weight of all available evidence, in
management’s judgment it is more likely than not that some portion, or all, of the deferred tax
assets will not be realized. During the fiscal year ended December 31, 2021, the Company
concluded that certain of its deferred tax assets were more likely than not to be realized in the
future and released the valuation allowance on a portion of its U.S. deferred tax assets resulting in
a tax benefit.
Auditing management’s assessment of the realizability of its deferred tax assets involved complex
auditor judgment because management’s estimate of future taxable income is highly judgmental
and based on significant assumptions that may be affected by future market or economic
conditions and the Company’s performance.
How We
Addressed the
Matter in Our
Audit
We obtained an understanding, evaluated the design and tested the operating effectiveness of
controls over the Company’s assessment of the realizability of deferred tax assets. For example,
we tested controls over management’s review of the significant assumptions used in estimating the
projections of future taxable income, exclusive of reversing temporary differences, as well as
controls over management’s review of the scheduling of the future reversals of existing temporary
differences.
To test the realizability of deferred tax assets, we performed audit procedures that included, among
others, evaluating the assumptions used by the Company to develop projections of future taxable
income, exclusive of reversing temporary differences, and tested the completeness and accuracy of
the underlying data used in its projections. For example, we compared the projections with the
actual results of prior periods, as well as management’s consideration of current industry and
economic trends. We also assessed the historical accuracy of management’s projections and
compared the projections with other forecasted financial information prepared by the Company.
Additionally, we performed sensitivity analyses over the forecasted financial information. We also
tested the scheduling of the future reversals of existing temporary differences.
/s/ Ernst & Young LLP
We have served as the Company's auditor since 1991.
Philadelphia, Pennsylvania
February 8, 2022
81
INCYTE CORPORATION
CONSOLIDATED BALANCE SHEETS
(in thousands, except number of shares and par value)
ASSETS
Current assets:
Cash and cash equivalents
Marketable securities—available-for-sale (amortized cost $291,871 and $288,199 as of
December 31, 2021 and 2020, respectively; allowance for credit losses $0 as of
December 31, 2021 and 2020)
Accounts receivable
Inventory
Prepaid expenses and other current assets
Total current assets
Restricted cash and investments
Long term investments
Inventory
Property and equipment, net
Finance lease right-of-use assets, net
Other intangible assets, net
Goodwill
Deferred income tax asset
Other assets, net
Total assets
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current liabilities:
Accounts payable
Accrued compensation
Accrued and other current liabilities
Finance lease liabilities
Acquisition-related contingent consideration
Total current liabilities
Acquisition-related contingent consideration
Finance lease liabilities
Other liabilities
Total liabilities
Commitments and contingencies (Note 15)
Stockholders’ equity:
December 31,
2021
2020
$ 2,057,440 $ 1,513,008
290,752
616,300
27,904
126,278
3,118,674
288,369
481,994
16,425
60,098
2,359,894
1,720
221,266
29,034
723,920
27,548
150,755
155,593
467,538
37,304
1,757
222,301
19,548
559,625
28,451
172,291
155,593
2,054
39,404
$ 4,933,352 $ 3,560,918
$
172,110 $
108,962
533,595
2,635
37,006
854,308
206,994
31,632
70,414
1,163,348
98,767
113,340
378,404
2,284
38,400
631,195
227,600
32,573
58,282
949,650
Preferred stock, $0.001 par value; 5,000,000 shares authorized; none issued or
outstanding as of December 31, 2021 and 2020
Common stock, $0.001 par value; 400,000,000 shares authorized; 221,084,433 and
219,489,329 shares issued and outstanding as of December 31, 2021 and 2020,
respectively
Additional paid-in capital
Accumulated other comprehensive loss
Accumulated deficit
Total stockholders’ equity
Total liabilities and stockholders’ equity
—
—
221
4,567,111
(19,454)
(777,874)
3,770,004
219
4,352,864
(15,360)
(1,726,455)
2,611,268
$ 4,933,352 $ 3,560,918
See accompanying notes.
82
INCYTE CORPORATION
CONSOLIDATED STATEMENTS OF OPERATIONS
(in thousands, except per share amounts)
Revenues:
Product revenues, net
Product royalty revenues
Milestone and contract revenues
Total revenues
Costs and expenses:
2021
Year Ended December 31,
2020
2019
$
2,322,012 $
569,255
95,000
2,068,736 $
392,966
205,000
1,774,922
306,337
77,500
2,986,267
2,666,702
2,158,759
Cost of product revenues (including definite-lived intangible
amortization)
Research and development
Selling, general and administrative
Change in fair value of acquisition-related contingent
consideration
Collaboration loss sharing
150,991
1,458,179
739,560
131,328
2,215,942
516,922
114,249
1,154,111
468,711
14,741
37,019
23,385
42,801
19,682
—
Total costs and expenses
2,400,490
2,930,378
1,756,753
Income (loss) from operations
Other income (expense), net
Interest expense
Unrealized (loss) gain on long term investments
585,777
10,647
(1,908)
(24,072)
(263,676)
23,206
(2,174)
10,426
402,006
52,182
(1,855)
34,458
Income (loss) before (benefit) provision for income taxes
570,444
(232,218)
486,791
(Benefit) provision for income taxes
(378,137)
63,479
39,885
Net income (loss)
$
948,581 $
(295,697) $
446,906
Net income (loss) per share:
Basic
Diluted
$
$
4.30 $
4.27 $
(1.36) $
(1.36) $
2.08
2.05
Shares used in computing net income (loss) per share:
Basic
Diluted
220,428
222,074
218,073
218,073
214,913
217,657
See accompanying notes.
83
INCYTE CORPORATION
CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
(in thousands)
Net income (loss)
Other comprehensive income (loss):
Foreign currency translation (loss) gain
Unrealized (loss) gain on marketable securities, net of tax
Defined benefit pension gain (loss), net of tax
Other comprehensive income (loss)
Year Ended December 31,
2020
2021
948,581 $ (295,697) $
2019
446,906
$
(2,959)
(1,289)
154
(4,094)
8,450
95
(8,363)
182
(192)
1,137
(6,322)
(5,377)
Comprehensive income (loss)
$
944,487 $ (295,515) $
441,529
See accompanying notes.
84
INCYTE CORPORATION
CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(in thousands, except number of shares)
Balances at December 31, 2018
Issuance of 2,657,892 shares of Common Stock upon
exercise of stock options and settlement of employee
restricted stock units and performance shares, net of
shares withheld for taxes, and 239,590 shares of
Common Stock under the ESPP
Issuance of 5,688 shares of Common Stock for
services rendered
Stock compensation
Other comprehensive loss
Adoption of ASU No. 2016-02
Net income
Balances at December 31, 2019
Issuance of 2,677,810 shares of Common Stock upon
exercise of stock options and settlement of employee
restricted stock units and performance shares, net of
shares withheld for taxes, and 258,453 shares of
Common Stock under the ESPP
Issuance of 6,350 shares of Common Stock for
services rendered
Issuance of 368,886 shares of Common Stock upon
conversion of Convertible Senior Notes due 2020
Stock compensation
Other comprehensive income
Net loss
Balances at December 31, 2020
Issuance of 1,324,926 shares of Common Stock upon
exercise of stock options and settlement of employee
restricted stock units and performance shares, net of
shares withheld for taxes, and 264,503 shares of
Common Stock under the ESPP
Issuance of 5,675 shares of Common Stock for
services rendered
Stock compensation
Other comprehensive loss
Net income
Balances at December 31, 2021
Common
Stock
Additional
Paid-in
Capital
$
213 $ 3,813,678 $
Accumulated
Other
Comprehensive Accumulated
Loss
(10,165) $ (1,877,759) $ 1,925,967
Deficit
Total
Stockholders’
Equity
3
63,296
—
—
63,299
—
—
—
—
—
216 $ 4,044,490 $
487
167,029
—
—
—
—
—
(5,377)
—
—
487
—
167,029
—
(5,377)
—
95
95
446,906
446,906
(15,542) $ (1,430,758) $ 2,598,406
$
3
110,302
—
—
—
—
—
546
18,999
178,527
—
—
$
219 $ 4,352,864 $
—
—
—
110,305
—
546
—
—
182
—
18,999
—
178,527
—
182
—
(295,697)
(295,697)
(15,360) $ (1,726,455) $ 2,611,268
2
28,684
—
—
28,686
—
—
—
—
434
185,129
—
—
$
221 $ 4,567,111 $
—
—
(4,094)
—
(19,454) $
434
—
185,129
—
(4,094)
—
948,581
948,581
(777,874) $ 3,770,004
See accompanying notes.
85
INCYTE CORPORATION
CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)
Cash flows from operating activities:
Net income (loss)
Adjustments to reconcile net income to net cash provided by operating
activities:
Depreciation and amortization
Stock-based compensation
Deferred income taxes (including benefit from valuation allowance
release)
Other, net
Unrealized loss (gain) on long term investments
Change in fair value of acquisition-related contingent consideration
Changes in operating assets and liabilities:
Accounts receivable
Prepaid expenses and other assets
Inventory
Accounts payable
Accrued and other liabilities
Net cash provided by (used in) operating activities
Cash flows from investing activities:
Purchase of long term investments
Sale of long term investments
Capital expenditures
Purchases of marketable securities
Sale and maturities of marketable securities
Net cash used in investing activities
Cash flows from financing activities:
Proceeds from issuance of common stock under stock plans
Tax withholdings related to restricted and performance share vesting
Payment of finance lease liabilities
Payment of contingent consideration
Net cash provided by financing activities
Year Ended December 31,
2020
2019
2021
$
948,581 $
(295,697) $
446,906
57,844
183,006
51,807
177,877
54,533
166,589
(465,604)
1,417
24,072
14,741
(134,306)
(64,080)
(20,965)
73,343
131,439
749,488
(33,510)
10,473
(181,006)
(235,167)
231,511
(207,699)
58,626
(29,940)
(2,417)
(20,093)
6,176
(350)
546
(10,426)
23,385
(173,185)
(8,050)
(19,468)
15,120
113,842
(124,599)
(377)
486
(34,458)
19,682
(1,211)
5,744
(6,100)
(20,180)
79,042
710,656
(95,468)
17,250
(187,379)
(516,874)
513,470
(269,001)
—
—
(78,064)
(374,809)
365,419
(87,454)
133,064
(22,759)
(836)
(37,760)
71,709
80,050
(16,751)
(822)
(16,766)
45,711
2,949
(3,570)
Effect of exchange rates on cash, cash equivalents, restricted cash and
investments
Net increase (decrease) in cash, cash equivalents, restricted cash and
investments
Cash, cash equivalents, restricted cash and investments at beginning of
period
1,164,986
Cash, cash equivalents, restricted cash and investments at end of period $ 2,059,160 $ 1,514,765 $ 1,833,707
Supplemental Schedule of Cash Flow Information
Interest paid
Income taxes paid
Reclassification to common stock and additional paid in capital in
connection with conversions of 1.25% convertible senior notes due 2020 $
$
Unpaid purchases of property and equipment
$
Leased assets obtained in exchange for new operating lease liabilities
$
Leased assets obtained in exchange for new finance lease liabilities
18,999 $
22,807 $
19,908 $
2,160 $
— $
27,098 $
14,416 $
1,513 $
—
12,732
7,607
29,889
396 $
67,731 $
194 $
70,712 $
239
33,553
(318,942)
1,833,707
1,514,765
544,395
668,721
$
$
(192)
See accompanying notes.
86
INCYTE CORPORATION
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
Note 1. Organization and Summary of Significant Accounting Policies
Organization and Business. Incyte Corporation (including its subsidiaries, “Incyte,” “we,” “us,” or “our”) is a
biopharmaceutical company focused on developing and commercializing proprietary therapeutics. Our portfolio includes
compounds in various stages, ranging from preclinical to late stage development, and commercialized products JAKAFI®
(ruxolitinib), ICLUSIG® (ponatinib), PEMAZYRE® (pemigatinib), OPZELURA™ (ruxolitinib cream), MINJUVI®
(tafasitamab) and MONJUVI® (tafasitamab-cxix), which is co-commercialized. Our operations are treated as one
operating segment.
Principles of Consolidation. The consolidated financial statements include the accounts of Incyte Corporation
and our wholly owned subsidiaries. All inter-company accounts, transactions, and profits have been eliminated in
consolidation.
Foreign Currency Translation. Operations in non-U.S. entities are recorded in the functional currency of each
entity. For financial reporting purposes, the functional currency of an entity is determined by a review of the source of an
entity's most predominant cash flows. The results of operations for any non-U.S. dollar functional currency entities are
translated from functional currencies into U.S. dollars using the average currency rate during each month. Assets and
liabilities are translated using currency rates at the end of the period. Adjustments resulting from translating the financial
statements of our foreign entities that use their local currency as the functional currency into U.S. dollars are reflected as
a component of other comprehensive income (loss). Transaction gains and losses are recorded in other income (expense),
net, in the consolidated statements of operations.
Use of Estimates. The preparation of financial statements in conformity with accounting principles generally
accepted in the United States requires management to make estimates and assumptions that affect the amounts reported in
the financial statements and accompanying notes. Actual results could differ from those estimates.
Concentrations of Credit Risk. Cash, cash equivalents, marketable securities, and trade receivables are financial
instruments which potentially subject us to concentrations of credit risk. The estimated fair value of financial instruments
approximates the carrying value based on available market information. By policy, we invest our excess available funds
primarily in U.S. government debt securities which are securities issued or guaranteed by the U.S. government and money
market funds that meet certain guidelines, which limits exposure to potential credit losses. Our receivables mainly relate
to our product sales and collaborative agreements with pharmaceutical companies. We have not experienced any significant
credit losses on cash, cash equivalents, marketable securities, or trade receivables to date and do not require collateral on
receivables.
Current Expected Credit Losses. Financial assets measured at amortized cost are assessed for future expected
credit losses under guidance within ASC 326, Financial Instruments – Credit Losses, to determine if application of an
expected credit losses reserve is necessary. On a quarterly basis, receivables that resulted from revenue transactions within
the scope of ASC 606, Revenue from Contracts with Customers, and recognized on an amortized cost basis are reviewed
on a customer-level basis to analyze expectations of future collections based upon past history of collections, payment,
aging of receivables and viability of the customer to continue payment, as well as estimates of future economic conditions.
Receivables generally consist of two types: receivables from collaborative agreements, including milestones,
reimbursements for agreed-upon activities and sales royalties; and receivables from customer product sales. Collaborative
agreement receivables are closely monitored relationships with select, reputable industry peers. Collection of receivables
is assessed within each collaborative partnership on a quarterly basis, including evaluation of each entity’s credit quality,
financial health and past history of payment. Customer product sales receivables are independently evaluated on a monthly
basis, on which unusual items or aged receivables are closely monitored for signs of credit deterioration, or indications of
payment refusal. Customer product sales are with specialty pharmaceutical distributors, wholesalers, and certain public
and private institutions, some of which whose financial obligations are funded by various government agencies.
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Cash and Cash Equivalents. Cash and cash equivalents are held in banks or in custodial accounts with banks.
Cash equivalents are defined as all liquid investments and money market funds with maturity from date of purchase of
90 days or less that are readily convertible into cash.
Marketable Securities—Available-for-Sale. Our marketable securities consist of investments in U.S. government
debt securities that are classified as available-for-sale. Available-for-sale securities are carried at fair value, based on
quoted market prices and observable inputs, with unrealized gains and losses, net of tax, reported as a separate component
of stockholders’ equity. We classify marketable securities that are available for use in current operations as current assets
on the consolidated balance sheets. Realized gains and losses and declines in value judged to be other than temporary for
available-for-sale securities are included in other income (expense), net on the consolidated statements of operations. The
cost of securities sold is based on the specific identification method.
Accounts Receivable. As of December 31, 2021 and 2020, we had no allowance for doubtful accounts. We
provide an allowance for doubtful accounts based on management’s assessment of the collectability of specific customer
accounts, which includes consideration of the credit worthiness and financial condition of those customers, aging of such
receivables, history of collectability with the customer and the general economic environment. We record an allowance to
reduce the receivables to the amount that is expected to be collected.
Inventory. Inventories are determined at the lower of cost and net realizable value with cost determined under
the specific identification method and may consist of raw materials, work in process and finished goods. We capitalize
inventory after FDA approval as the related costs are expected to be recoverable through the commercialization of the
product. Costs incurred prior to FDA approval are recorded as research and development expense in our statements of
operations.
Raw materials and work-in-process inventory are not subject to expiration and the shelf life of finished goods
inventory is approximately 36 months from the start of manufacturing of the finished goods. We evaluate for potential
excess inventory by analyzing current and future product demand relative to the remaining product shelf life. We build
demand forecasts by considering factors such as, but not limited to, overall market potential, market share, market
acceptance and patient usage. We classify inventory as current on the consolidated balance sheets when we expect
inventory to be consumed for commercial use within the next twelve months.
Variable Interest Entities. We perform an initial and ongoing evaluation of the entities with which we have
variable interests, such as equity ownership, in order to identify entities (i) that do not have sufficient equity investment at
risk to permit the entity to finance its activities without additional subordinated financial support or (ii) in which the equity
investors lack an essential characteristic of a controlling financial interest as variable interest entities (“VIE” or “VIEs”).
If an entity is identified as a VIE, we perform an assessment to determine whether we have both (i) the power to direct
activities that most significantly impact the VIE’s economic performance and (ii) have the obligation to absorb losses from
or the right to receive benefits of the VIE that could potentially be significant to the VIE. If both of these criteria are
satisfied, we are identified as the primary beneficiary of the VIE. As of December 31, 2021, there were no entities in which
we held a variable interest which we determined to be VIEs.
Long Term Investments. Our long term investments consist of equity investments in common stock of publicly-
held companies with whom we have entered into collaboration and license agreements. We classify all of our equity
investments in common stock of publicly-held companies as long term investments on the consolidated balance sheets.
Our equity investments are accounted for at fair value using readily determinable pricing available on a securities exchange
on the consolidated balance sheets. All changes in fair value are reported in the consolidated statements of operations as
an unrealized gain (loss) on long term investments.
In assessing whether we exercise significant influence over any of the companies in which we hold equity
investments, we consider the nature and magnitude of our investment, any voting and protective rights we hold, any
participation in the governance of the other company, and other relevant factors such as the presence of a collaboration or
other business relationship. Currently, none of our equity investments in publicly-held companies are considered
relationships in which we are able to assert control.
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Property and Equipment, net. Property and equipment, net is stated at cost, less accumulated depreciation and
amortization. Depreciation is recorded using the straight-line method over the estimated useful lives of the respective
assets. Leasehold improvements are amortized over the shorter of the estimated useful life of the assets or lease term.
Lease Accounting. All leases with a lease term greater than 12 months, regardless of lease type classification, are
recorded as an obligation on the balance sheet with a corresponding right-of-use asset. Both finance and operating leases
are reflected as liabilities on the commencement date of the lease based on the present value of the lease payments to be
made over the lease term. Current operating lease liabilities are reflected in accrued and other current liabilities and
noncurrent operating lease liabilities are reflected in other liabilities on the consolidated balance sheet. Right-of-use assets
are valued at the initial measurement of the lease liability, plus any initial direct costs or rent prepayments, minus lease
incentives and any deferred lease payments. Operating lease right-of-use assets are recorded in property and equipment,
net on the consolidated balance sheet and lease cost is recognized on a straight-line basis. For finance leases, expense is
recognized as separate amortization and interest expense, with higher interest expense in the earlier periods of a lease.
Leases with an initial term of 12 months or less are not recorded on the balance sheet and we recognize lease expense for
these leases on a straight-line basis over the term of the lease. In determining whether a contract contains a lease, asset and
service agreements are assessed at onset and upon modification for criteria of specifically identified assets, control and
economic benefit.
Other Intangible Assets, net. Other intangible assets, net consist of licensed intellectual property rights acquired
in business combinations, which are reported at acquisition date fair value, less accumulated amortization. Intangible assets
with finite lives are amortized over their estimated useful lives using the straight-line method.
Impairment of Long-Lived Assets. Long-lived assets with finite lives are tested for impairment whenever events
or changes in circumstances indicate that the carrying value of an asset may not be recoverable. If indicators of impairment
are present, the asset is tested for recoverability by comparing the carrying value of the asset to the related estimated
undiscounted future cash flows expected to be derived from the asset. If the expected cash flows are less than the carrying
value of the asset, then the asset is considered to be impaired and its carrying value is written down to fair value, based on
the related estimated discounted future cash flows.
Goodwill. Goodwill is calculated as the difference between the acquisition date fair value of the consideration
transferred and the values assigned to the assets acquired and liabilities assumed. Goodwill is not amortized but is tested
for impairment at the reporting unit level at least annually as of October 1 or when a triggering event occurs that could
indicate a potential impairment by assessing qualitative factors or performing a quantitative analysis in determining
whether it is more-likely-than-not that the fair value of net assets are below their carrying amounts. A reporting unit is the
same as, or one level below, an operating segment. Our operations are currently comprised of a single, entity wide reporting
unit. We completed our most recent annual impairment assessment as of October 1, 2021 and determined that the carrying
value of our goodwill was not impaired.
Income Taxes. We account for income taxes using the asset and liability approach which requires the recognition
of deferred tax assets and liabilities for the expected future tax consequences of temporary differences between the carrying
amount of assets and liabilities for financial reporting purposes and amounts reportable for income tax purposes. Deferred
tax assets are reduced by a valuation allowance when, in the opinion of management, it is more-likely-than-not that some
portion or all of the deferred tax assets will not be realized. The primary factors used to assess the likelihood of realization
are our recent history of cumulative earnings or losses, expected reversals of taxable temporary timing differences,
forecasts of future taxable income and available tax planning strategies that could be implemented to realize the deferred
tax assets. Upon evaluating and weighting both positive and negative evidence, we concluded that we should release the
valuation allowance on the majority of our U.S. deferred tax assets as of December 31, 2021.
We recognize the tax benefit from an uncertain tax position only if it is more-likely-than-not that the position will
be sustained upon examination by the taxing authorities, including resolutions of any related appeals or litigation processes,
based on the technical merits of the position. The tax benefit that is recorded for these positions is measured at the largest
amount of benefit that is greater than 50 percent likely of being realized upon ultimate settlement. We adjust the level of
the liability to reflect any subsequent changes in the relevant facts surrounding the uncertain positions. Any interest and
penalties on uncertain tax positions are included within the tax provision.
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The Coronavirus Aid, Relief, and Economic Security (CARES) Act was signed into law in March 2020 to provide
an estimated $2.2 trillion designed to stimulate the U.S. economy during the COVID-19 pandemic. The Act includes tax
relief, government loans, grants and investments for entities in affected industries, which has related accounting and
financial reporting impacts. Disclosure for certain income tax accounting measures are required in the period of enactment
and disclosure for government loans, investments, grants, and revenue recognition are required in future periods as federal
agencies establish rules and procedures to implement the CARES Act. During 2020, we delayed the payment of certain
employer payroll tax amounts to future periods as allowed under the Act. We do not expect the CARES Act to have a
material impact on our overall financial results, our income tax provision or our liquidity. We have further described the
impact and risks of the COVID-19 pandemic on our business in Item 1A. Risk Factors.
Net Income (Loss) Per Share. Our basic and diluted net income (loss) per share is calculated by dividing the net
income (loss) by the weighted average number of shares of common stock outstanding during all periods presented.
Options to purchase stock, restricted stock units and performance stock units are included in diluted earnings per share
calculations, unless the effects are anti-dilutive.
Accumulated Other Comprehensive Income (Loss). Accumulated other comprehensive income (loss) consists of
unrealized gains or losses on our marketable debt securities that are classified as available-for-sale, foreign currency
translation gains or losses and defined benefit pension obligations.
Revenue Recognition. Revenue-generating contracts are assessed under ASC 606, Revenue from contracts with
customers, to identify distinct performance obligations, determine the transaction price of the contract and allocate the
transaction price to each of the distinct performance obligations. Revenue is recognized when we have satisfied a
performance obligation through transferring control of the promised good or service to a customer. Control, in this instance,
may mean the ability to prevent other entities from directing the use of, and receiving benefit from, a good or service. We
apply the following five-step model in order to determine this amount: (i) identification of the promised goods or services
in the contract; (ii) determination of whether the promised goods or services are performance obligations, including
whether they are distinct in the context of the contract; (iii) measurement of the transaction price, including the constraint
on variable consideration; (iv) allocation of the transaction price to the performance obligations; and (v) recognition of
revenue when (or as) the Company satisfies each performance obligation, which for the Company is generally at a point
in time. We also assess collectability based primarily on the customer’s payment history and on the creditworthiness of
the customer.
Product Revenues
Our product revenues consist of sales of JAKAFI, OPZELURA and PEMAZYRE in the U.S., sales of MINJUVI,
PEMAZYRE and ICLUSIG in Europe, and sales of PEMAZYRE in Japan. Product revenues are recognized once we
satisfy the performance obligation at a point in time under the revenue recognition criteria as described above. We sell
JAKAFI, OPZELURA and PEMAZYRE to our customers in the U.S., which include specialty pharmacies, specialty
distributors and wholesalers. We sell MINJUVI, PEMAZYRE and ICLUSIG to our customers in the European Union and
certain other jurisdictions, which include retail pharmacies, hospital pharmacies and distributors. We sell PEMAZYRE in
Japan to an exclusive wholesaler.
We recognize revenues for product received by our customers net of allowances for customer credits, including
estimated rebates, chargebacks, discounts, returns, distribution service fees, patient assistance programs, and government
rebates, such as Medicare Part D coverage gap reimbursements in the U.S. Product shipping and handling costs are
included in cost of product revenues.
Customer Credits: Our customers are offered various forms of consideration, including allowances, service fees
and prompt payment discounts. We expect our customers will earn prompt payment discounts and, therefore, we deduct
the full amount of these discounts from total product sales when revenues are recognized. Service fees are also deducted
from total product sales as they are earned.
Rebates and Discounts: Allowances for rebates include mandated discounts under the Medicaid Drug Rebate
Program in the U.S. and mandated discounts in Europe in markets where government-sponsored healthcare systems are
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the primary payers for healthcare. Rebates are amounts owed after the final dispensing of the product to a benefit plan
participant and are based upon contractual agreements or legal requirements with public sector benefit providers. The
accrual for rebates is based on statutory discount rates and expected utilization as well as historical data we have
accumulated since product launches. Our estimates for expected utilization of rebates are based on data received from our
customers. Rebates are generally invoiced and paid in arrears so that the accrual balance consists of an estimate of the
amount expected to be incurred for the current quarter’s activity, plus an accrual balance for known prior quarters’ unpaid
rebates. If actual future rebates vary from estimates, we may need to adjust prior period accruals, which would affect
revenue in the period of adjustment.
Chargebacks: Chargebacks are discounts that occur when certain contracted customers, which currently consist
primarily of group purchasing organizations, Public Health Service institutions, non-profit clinics, and Federal government
entities purchasing via the Federal Supply Schedule, purchase directly from our wholesalers. Contracted customers
generally purchase the product at a discounted price. The wholesalers, in turn, charges back to us the difference between
the price initially paid by the wholesalers and the discounted price paid by the contracted customers. In addition to actual
chargebacks received we maintain an accrual for chargebacks based on the estimated contractual discounts on the inventory
levels on hand in our distribution channel. If actual future chargebacks vary from these estimates, we may need to adjust
prior period accruals, which would affect revenue in the period of adjustment.
Medicare Part D Coverage Gap: Medicare Part D prescription drug benefit mandates manufacturers to fund 70%
of the Medicare Part D insurance coverage gap for prescription drugs sold to eligible patients. Our estimates for the
expected Medicare Part D coverage gap are based on historical invoices received and in part from data received from our
customers. Funding of the coverage gap is generally invoiced and paid in arrears so that the accrual balance consists of an
estimate of the amount expected to be incurred for the current quarter’s activity, plus an accrual balance for known prior
quarters. If actual future funding varies from estimates, we may need to adjust prior period accruals, which would affect
revenue in the period of adjustment. Additionally, beginning in January 2020, the amount of spending required by eligible
patients in the Medicare Part D insurance coverage gap increased 30% due to the expiration of a provision in the Patient
Protection and Affordable Care Act, which now results in a change in the True Out of Pocket (TrOOP) calculation
methodology. The methodological change has resulted in an increase in required spending by patients and, in turn, an
increase in manufacturers’ contributions on behalf of patients in the Medicare Part D insurance coverage gap.
Co-payment Assistance: Patients who have commercial insurance and meet certain eligibility requirements may
receive co-payment assistance. We accrue a liability for co-payment assistance based on actual program participation and
estimates of program redemption using data provided by third-party administrators.
Product Royalty Revenues
Royalty revenues on commercial sales for ruxolitinib (marketed as JAKAVI® outside the United States) by
Novartis Pharmaceutical International Ltd. (“Novartis”) are based on net sales of licensed products in licensed territories
as provided by Novartis. Royalty revenues on commercial sales for baricitinib (marketed as OLUMIANT) by Eli Lilly and
Company (“Lilly”) are based on net sales of licensed products in licensed territories as provided by Lilly. Royalty revenues
on commercial sales for capmatinib (marketed as TABRECTA®) by Novartis are based on net sales of licensed products
in the licensed territories as provided by Novartis. We recognize royalty revenues in the period the sales occur.
Milestone and Contract Revenues
For each collaborative research, development and/or commercialization agreement that results in revenue under
the guidance of ASC 606 we identify all material performance obligations, which may include the license to intellectual
property and know-how, research and development activities and/or other activities. In order to determine the transaction
price, in addition to any upfront payment, we estimate the amount of variable consideration, including milestone payments,
at the outset of the contract utilizing the most likely amount method. The most likely amount method is used since the
milestone payments have a binary outcome (i.e., we receive all or none of the milestone payment). We constrain the
estimate of variable consideration such that it is probable that a significant reversal of previously recognized revenue will
not occur. When determining if variable consideration should be constrained, management considers whether there are
factors outside the Company’s control that could result in a significant reversal of revenue. In making these assessments,
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management considers the likelihood and magnitude of a potential reversal of revenue. These estimates are re-assessed
each reporting period as required. Once the estimated transaction price is established, amounts are allocated to the
performance obligations that have been identified. The transaction price is generally allocated to each separate performance
obligation on a relative standalone selling price basis.
Out-licensing arrangements contain the right to use functional intellectual property, which is the underlying
performance obligation of these collaborative arrangements. If the license of our intellectual property is determined to be
distinct from other performance obligations in the arrangement, the functional intellectual property that is transferred to
the collaborative partner at the onset of the arrangement is concluded to have significant standalone functionality and value
at the point in time at which the intellectual property is made available to the collaborative partner. For licenses that are
not distinct from other obligations identified in the arrangement, we utilize judgment to assess the nature of the combined
performance obligation to 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 apply an appropriate method of measuring progress
for purposes of recognizing revenue from nonrefundable, upfront license fees. We evaluate the measure of progress each
reporting period and, if necessary, adjust the measure of performance and related revenue recognition. For each of the
three years ended December 31, 2021, we had no revenues from intellectual property licenses recognized over time.
For milestone revenues related to sales-based achievements, we recognize the milestone revenues in the
corresponding period of the product sale, in accordance with the guidance of ASC 606-10-55-65 for contracts that include
a license to intellectual property and the license is the predominant item to which the product sale relates.
Subsequent to the transfer of the intellectual property, we may earn milestones through achievement of pre-
specified developmental or regulatory events and, as such, milestones are accounted for as variable consideration. We
include developmental or regulatory milestones in the transaction price only to the extent that it is probable that a
significant reversal in the amount of cumulative revenue recognized will not occur when the uncertainty associated with
the milestone is subsequently resolved. Under the agreements currently in place, we do not consider these events to be
within our control, but rather dependent upon the development activities of our collaborative partners and the decisions
made by regulatory agencies. Accordingly, these milestones are not included in the transaction price until the counterparty,
or third-party in the event of a regulatory submission, confirms the satisfaction or completion of the milestone triggering
event. Given the high level of uncertainty of achievement, variable consideration associated with milestones are fully
constrained until confirmation of the satisfaction or completion of the milestone by the third-party.
Generally, the milestone events contained in our collaboration agreements coincide with the progression of our
drugs from development, to regulatory approval and then to commercialization. The value of these milestones is dictated
within the contract and is fixed upon achievement and reflects the amount of consideration which we expect to be entitled
to in exchange for the satisfaction of that milestone. The process of successfully discovering a new development candidate,
having it approved and successfully commercialized is highly uncertain. As such, the milestone payments we may earn
from our partners involve a significant degree of risk to achieve and therefore, subsequent milestone payments due to
Incyte are recognized as revenue at the point in time when such milestones are achieved.
Our collaboration agreements may also include an option for the collaborative partner to elect to participate in
research and development activities, such as shared participation in additional clinical trials using the compound. The
presence of additional options for future participatory activities are assessed to determine if they represent material rights
offered by us to the collaborative partner. We also determine whether the reimbursement of research and development
expenses should be accounted for as collaborative revenues or an offset to research and development expenses in
accordance with the provisions of gross or net revenue presentation and recognize the corresponding revenues or records
the corresponding offset to research and development expenses as incurred.
Our collaborative agreements may also include provisions for additional future collaborative efforts, such as
options for shared commercialization staffing or licensing of additional molecules, involvement in joint committees, or
options for inclusion in negotiations of future supply rights, which at the time of each collaborative agreement’s inception,
are assessed to determine if these meet the definition of a performance obligation under ASC 606.
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Cost of Product Revenues
Cost of product revenues includes all product related costs. In addition, cost of product revenues include low
single-digit royalties under our collaboration and license agreement to Novartis on all future sales of JAKAFI in the United
States and the amortization of our licensed intellectual property for ICLUSIG using the straight-line method over the
estimated useful life of 12.5 years from the date of acquisition on June 1, 2016 of all of the outstanding shares of ARIAD
Pharmaceuticals (Luxembourg) S.à.r.l. (since renamed Incyte Biosciences Luxembourg S.à.r.l.) from ARIAD
Pharmaceuticals, Inc. (“ARIAD”). Cost of product revenues also includes employee personnel costs, including stock
compensation, for those employees dedicated to the production of our commercial products.
Research and Development Costs. Our policy is to expense research and development costs as incurred, including
amounts funded by research and development collaborations. Research and development expenses are comprised of costs
we incur in performing research and development activities, including salary and benefits; stock-based compensation
expense; outsourced services and other direct expenses, including clinical trial and pharmaceutical development costs;
collaboration payments; expenses associated with drug supplies that are not being capitalized; and infrastructure costs,
including facilities costs and depreciation expense. If a collaboration is a cost-sharing arrangement in which both we and
our collaborator perform development work and share costs, we also recognize, as research and development expense in
the period when our collaborator incurs development expenses, our portion of the co-development expenses that we are
obligated to reimburse. Costs incurred under the collaboration arrangement that are reimbursable to us are recorded net
against the related research and development expenses.
We often contract with contract research organizations (“CROs”) to facilitate, coordinate and perform agreed
upon research and development of a new drug. To ensure that research and development costs are expensed as incurred,
we record monthly accruals for clinical trials and preclinical testing costs based on the work performed under the contract.
These CRO contracts typically call for the payment of fees for services at the initiation of the contract and/or upon the
achievement of certain clinical trial milestones. In the event that we prepay CRO fees, we record the prepayment as a
prepaid asset and amortize the asset into research and development expense over the period of time the contracted research
and development services are performed. Most professional fees, including project and clinical management, data
management, monitoring, and medical writing fees are incurred throughout the contract period. These professional fees
are expensed based on their percentage of completion at a particular date. Our CRO contracts generally include pass
through fees. Pass through fees include, but are not limited to, regulatory expenses, investigator fees, travel costs, and other
miscellaneous costs, including shipping and printing fees. We expense the costs of pass through fees under our CRO
contracts as they are incurred, based on the best information available to us at the time. The estimates of the pass through
fees incurred are based on the amount of work completed for the clinical trial and are monitored through correspondence
with the CROs, internal reviews and a review of contractual terms. The factors utilized to derive the estimates include the
number of patients enrolled, duration of the clinical trial, estimated patient attrition, screening rate and length of the dosing
regimen. CRO fees incurred to set up the clinical trial are expensed during the setup period. Under our clinical trial
collaboration agreements we may be reimbursed for certain development costs incurred. Such costs are recorded as a
reduction of research and development expense in the period in which the related expense is incurred.
Stock Compensation. Share-based payment transactions with employees, which include stock options, restricted
stock units (“RSUs”) and performance shares (“PSUs”), are recognized as compensation expense over the requisite service
period based on their estimated fair values as well as expected forfeiture rates. The stock compensation process requires
significant judgment and the use of estimates, particularly surrounding Black-Scholes assumptions such as stock price
volatility over the option term and expected option lives, as well as expected forfeiture rates and the probability of PSUs
vesting. The fair value of stock options, which are subject to graded vesting, are recognized as compensation expense over
the requisite service period using the accelerated attribution method. The fair value of RSUs that are subject to cliff vesting
are recognized as compensation expense over the requisite service period using the straight-line attribution method, and
the fair value of RSUs that are subject to graded vesting are recognized as compensation expense over the requisite service
period using the accelerated attribution method. The fair value of PSUs are recognized as compensation expense beginning
at the time in which the performance conditions are deemed probable of achievement, which we assess as of the end of
each reporting period. Once a performance condition is considered probable, we record compensation expense based on
the portion of the service period elapsed to date with respect to that award, with a cumulative catch-up, net of estimated
forfeitures, and recognize any remaining compensation expense, if any, over the remaining requisite service period using
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the straight-line attribution method for PSUs that are subject to cliff vesting and using the accelerated attribution method
for PSUs that are subject to graded vesting. Compensation expense for PSUs with market performance conditions is
calculated using a Monte Carlo simulation model as of the date of grant and recorded over the requisite service period.
Advertising Expenses. Advertising expenses, comprised primarily of television, radio, print media and Internet
advertising, are expensed as incurred and are included in selling, general, and administrative expenses. For the years ended
December 31, 2021, 2020, and 2019, advertising expenses were approximately $66.0 million, $28.9 million, and $15.3
million, respectively.
Long Term Incentive Plans. We have long term incentive plans which provide eligible employees with the
opportunity to receive performance and service-based incentive compensation, which may be comprised of cash, stock
options, restricted stock units and/or performance shares. The payment of cash and the grant or vesting of equity may be
contingent upon the achievement of pre-determined regulatory, sales and internal performance milestones.
Acquisition-Related Contingent Consideration. Acquisition-related contingent consideration consists of our
future royalty obligations on future net revenues of ICLUSIG owed to Takeda Pharmaceutical Company Limited, which
acquired ARIAD (“Takeda”). Acquisition-related contingent consideration was recorded on the acquisition date of June 1,
2016 at the estimated fair value of the obligation, in accordance with the acquisition method of accounting. The fair value
measurement is based on significant inputs that are unobservable in the market and thus represents a Level 3 measurement.
The fair value of the acquisition-related contingent consideration is remeasured each reporting period, with changes in fair
value recorded in the consolidated statements of operations.
Collaboration loss sharing. For the year ended December 31, 2021 and 2020, collaboration loss sharing
represents our 50% share of the United States loss for commercialization of MONJUVI (tafasitamab-cxix) under our
agreement with MorphoSys, which is described in Note 6 below.
Recent Accounting Pronouncements
In December 2019, the FASB issued ASU No. 2019-12, “Income Taxes (Topic 740): Simplifying the Accounting
for Income Taxes.” This guidance applies to all entities and aims to reduce the complexity of tax accounting standards
while enhancing reporting disclosures. This guidance is effective for fiscal years beginning after December 15, 2020 and
interim periods therein. We adopted this guidance for the period beginning January 1, 2021. Upon adoption, ASU
No. 2019-12 had an immaterial impact on the consolidated financial statements.
As of December 31, 2021, there were no other recently issued accounting standards that may have a material
impact on the Company's financial position, results of operations, or cash flows upon their adoption.
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Note 2. Revenues
As discussed in Note 1, revenues are recognized under guidance within ASC 606. The following table presents
our disaggregated revenue for the periods presented (in thousands):
JAKAFI revenues, net
ICLUSIG revenues, net
PEMAZYRE revenues, net
MINJUVI revenues, net
OPZELURA revenues, net
Total product revenues, net
JAKAVI product royalty revenues
OLUMIANT product royalty revenues
TABRECTA product royalty revenues
Total product royalty revenues
Milestone and contract revenues
Total revenues
For the Years Ended,
December 31,
2020
2021
$
$
2,134,508 $
109,395
68,531
4,910
4,668
2,322,012
337,991
220,875
10,389
569,255
95,000
2,986,267 $
1,937,850 $
105,002
25,884
—
—
2,068,736
277,902
110,920
4,144
392,966
205,000
2,666,702 $
2019
1,684,968
89,954
—
—
—
1,774,922
225,913
80,424
—
306,337
77,500
2,158,759
For further information on our revenue-generating contracts, refer to Note 6.
Note 3. Fair Value of Financial Instruments
The following is a summary of our marketable security portfolio for the periods presented (in thousands):
December 31, 2021
Debt securities (government)
December 31, 2020
Debt securities (government)
Amortized
Cost
Net
Unrealized
Gains
Net
Unrealized
Losses
Estimated
Fair Value
$
291,871 $
— $
(1,119) $
290,752
$
288,199 $
170 $
— $
288,369
Our available-for-sale debt securities generally have contractual maturity dates of between 12 to 18 months. Debt
security assets were assessed for risk of expected credit losses per our accounting policy as described in Note 1. As of
December 31, 2021 and 2020, the available-for-sale debt securities were held in U.S.-government backed securities and in
Treasury bonds and were assessed on an individual security basis to have a de minimis risk of credit loss.
Fair Value Measurements
FASB accounting guidance defines fair value as the price that would be received to sell an asset or paid to transfer
a liability (“the exit price”) in an orderly transaction between market participants at the measurement date. The standard
outlines a valuation framework and creates a fair value hierarchy in order to increase the consistency and comparability of
fair value measurements and the related disclosures. In determining fair value we use quoted prices and observable inputs.
Observable inputs are inputs that market participants would use in pricing the asset or liability based on market data
obtained from sources independent of us. The fair value hierarchy is broken down into three levels based on the source of
inputs as follows:
Level 1—Valuations based on unadjusted quoted prices in active markets for identical assets or liabilities.
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Level 2—Valuations based on observable inputs and quoted prices in active markets for similar assets and
liabilities.
Level 3—Valuations based on inputs that are unobservable and models that are significant to the overall fair value
measurement.
Recurring Fair Value Measurements
Our marketable securities consist of investments in U.S. government debt securities that are classified as
available-for-sale.
At December 31, 2021 and 2020, our Level 2 U.S. government debt securities were valued using readily available
pricing sources which utilize market observable inputs, including the current interest rate and other characteristics for
similar types of investments. Our long term investments classified as Level 1 were valued using their respective closing
stock prices on The Nasdaq Stock Market. We did not experience any transfers of financial instruments between the fair
value hierarchy levels during the years ended December 31, 2021 and 2020.
The following fair value hierarchy table presents information about each major category of our financial assets
measured at fair value on a recurring basis (in thousands):
Fair Value Measurement at Reporting Date Using:
Cash and cash equivalents
Debt securities (government)
Long term investments (Note 6)
Total assets
Cash and cash equivalents
Debt securities (government)
Long term investments (Note 6)
Total assets
Quoted Prices in Significant Other
Active Markets for
Identical Assets
(Level 1)
2,057,440 $
Observable
Inputs
(Level 2)
$
— $
—
221,266
2,278,706 $
290,752
—
290,752 $
$
Significant
Unobservable
Inputs
(Level 3)
Balance as of
December 31, 2021
2,057,440
290,752
221,266
2,569,458
— $
—
—
— $
Fair Value Measurement at Reporting Date Using:
Quoted Prices in Significant Other
Active Markets for
Identical Assets
(Level 1)
1,513,008 $
Observable
Inputs
(Level 2)
$
— $
—
222,301
1,735,309 $
288,369
—
288,369 $
$
Significant
Unobservable
Inputs
(Level 3)
Balance as of
December 31, 2020
1,513,008
288,369
222,301
2,023,678
— $
—
—
— $
The following fair value hierarchy table presents information about each major category of our financial liabilities
measured at fair value on a recurring basis (in thousands):
Fair Value Measurement at Reporting Date Using:
Significant Other
Observable
Inputs
(Level 2)
Quoted Prices in
Active Markets for
Identical Liabilities
(Level 1)
Significant
Unobservable
Inputs
(Level 3)
Balance as of
244,000 $
244,000 $
December 31, 2021
244,000
244,000
Acquisition-related contingent consideration
Total liabilities
$
$
— $
— $
— $
— $
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Fair Value Measurement at Reporting Date Using:
Significant Other
Observable
Inputs
(Level 2)
Quoted Prices in
Active Markets for
Identical Liabilities
(Level 1)
Significant
Unobservable
Inputs
(Level 3)
Balance as of
266,000 $
266,000 $
December 31, 2020
266,000
266,000
Acquisition-related contingent consideration
Total liabilities
$
$
— $
— $
— $
— $
The following is a roll forward of our Level 3 liabilities (in thousands):
Balance at January 1,
Contingent consideration earned during the period but not yet paid
Payments made during the period
Change in fair value of contingent consideration
Balance at December 31,
2021
266,000 $
(19,583)
(17,158)
14,741
244,000 $
2020
277,000
(9,595)
(24,790)
23,385
266,000
$
$
The fair value of the contingent consideration was determined on the date of acquisition, June 1, 2016, using an
income approach based on projected future net revenues of ICLUSIG in the European Union and other countries for the
approved third line treatment over 18 years, and discounted to present value at a rate of 10%. The fair value of the
contingent consideration is remeasured each reporting period, with changes in fair value recorded in the consolidated
statements of operations. The valuation inputs utilized to estimate the fair value of the contingent consideration as of
December 31, 2021 and 2020 included a discount rate of 10% and updated projections of future net revenues of ICLUSIG
in the European Union and other countries for the approved third line treatment. The change in fair value of the contingent
consideration during the year ended December 31, 2021 was due primarily to the impact of updated projections of future
net revenues of ICLUSIG in the European Union and the passage of time. The change in fair value of the contingent
consideration during the year ended December 31, 2020 was due primarily to the passage of time as there were no other
significant changes in the key assumptions.
We make payments to Takeda quarterly based on the royalties or any additional milestone payments earned in
the previous quarter. As of December 31, 2021 and 2020, contingent consideration earned but not yet paid was $19.6
million and $9.6 million, respectively, and was included in accrued and other current liabilities.
Non-Recurring Fair Value Measurements
During the years ended December 31, 2021 and 2020, there were no measurements required for any assets or
liabilities at fair value on a non-recurring basis.
Note 4. Concentrations of Credit Risk and Current Expected Credit Losses
In November 2009, we entered into a collaboration and license agreement with Novartis. In December 2009, we
entered into a license, development and commercialization agreement with Lilly. In December 2018, we entered into a
research collaboration and licensing agreement with Innovent Biologics, Inc. (“Innovent”). In July 2019, we entered into
a collaboration and license agreement with Zai Lab (Shanghai) Co., Ltd., a subsidiary of Zai Lab Limited (collectively,
“Zai Lab”). The above collaboration partners comprised, in aggregate, 36% and 42% of the accounts receivable balance
as of December 31, 2021 and 2020, respectively. For further information relating to these collaboration and license
agreements, refer to Note 6.
In November 2011, we began commercialization and distribution of JAKAFI, in April 2020, we began
commercialization and distribution of PEMAZYRE and in October 2021, we began commercialization and distribution of
OPZELURA to a number of customers. Our product revenues are concentrated in a number of these customers. The
concentration of credit risk related to our JAKAFI, PEMAZYRE and OPZELURA product revenues is as follows:
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Customer A
Customer B
Customer C
Customer D
Customer E
Percentage of Total Net
Product Revenues for the
Years Ended,
December 31,
2020
2019
2021
18 %
12 %
18 %
9 %
11 %
20 %
13 %
17 %
11 %
10 %
20 %
13 %
16 %
11 %
8 %
We are exposed to risks associated with extending credit to customers related to the sale of products. Customers
A, B, C, D and E comprised, in the aggregate, 31% and 33% of the accounts receivable balance as of December 31, 2021
and 2020, respectively. The concentration of credit risk relating to our other product revenues or accounts receivable is not
significant.
We assessed our collaborative and customer receivable assets as of December 31, 2021 according to our
accounting policy for applying reserves for expected credit losses, noting minimal history of uncollectible receivables and
the continued perceived creditworthiness of our third party sales relationships, upon which the expected credit losses were
considered de minimis.
Note 5. Inventory
Our inventory balance consists of the following (in thousands):
Raw materials
Work-in-process
Finished goods
Total inventory
December 31,
2021
1,275 $
39,895
15,768
56,938 $
2020
1,275
21,242
13,456
35,973
$
$
Inventories, stated at the lower of cost and net realizable value, consist of raw materials, work-in-process and
finished goods. At December 31, 2021, $27.9 million of inventory was classified as current on the consolidated balance
sheet as we expect this inventory to be consumed for commercial use within the next twelve months. At December 31,
2021, $29.0 million of inventory was classified as non-current on the consolidated balance sheet as we did not expect this
inventory to be consumed for commercial use within the next twelve months. We obtain some inventory components from
a limited number of suppliers due to technology, availability, price, quality or other considerations. The loss of a supplier,
the deterioration of our relationship with a supplier, or any unilateral violation of the contractual terms under which we are
supplied components by a supplier could adversely affect our total revenues and gross margins.
We capitalize inventory after FDA approval as the related costs are expected to be recoverable through the
commercialization of the product. Costs incurred prior to FDA approval are recorded as research and development expense
in our statements of operations. At December 31, 2021, inventory with approximately $71.9 million of product costs
incurred prior to FDA approval had not yet been sold. We expect to sell the pre commercialization inventory over the next
36 months and, as a result, cost of product revenues will reflect a lower average per unit cost of materials.
Note 6. License Agreements
Novartis
In November 2009, we entered into a Collaboration and License Agreement with Novartis. Under the terms of
the agreement, Novartis received exclusive development and commercialization rights outside of the United States to our
JAK inhibitor ruxolitinib and certain back-up compounds for hematologic and oncology indications, including all
hematological malignancies, solid tumors and myeloproliferative diseases. We retained exclusive development and
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commercialization rights to JAKAFI (ruxolitinib) in the United States and in certain other indications. Novartis also
received worldwide exclusive development and commercialization rights to our MET inhibitor compound capmatinib and
certain back-up compounds in all indications.
Under this agreement, we were initially eligible to receive up to $174.0 million for the achievement of
development milestones, up to $495.0 million for the achievement of regulatory milestones and up to $500.0 million for
the achievement of sales milestones. In addition, we are eligible to receive up to $75.0 million of additional potential
development and regulatory milestones relating to GVHD. We have recognized and received, in the aggregate, $157.0
million for the achievement of development milestones, $280.0 million for the achievement of regulatory milestones and
$200.0 million for the achievement of sales milestones through December 31, 2021.
We recognize development and regulatory milestones upon confirmation of achievement of the event, as
development and regulatory approvals are events not controllable by us but rather development activities of Novartis and
decisions made by regulatory agencies. We recognize sales milestones in the corresponding period of the product sale upon
confirmation of net sales milestone threshold achievement by Novartis.
In 2020, we recognized a $25.0 million development milestone and a $45.0 million regulatory milestone for the
FDA approval of capmatinib as TABRECTA for the treatment of adult patients with metastatic non-small cell lung cancer
(NSCLC) whose tumors have a mutation that leads to MET exon 14 skipping (METex14) as detected by an FDA-approved
test, a $20.0 million regulatory milestone for the Japanese Ministry of Health, Labour and Welfare approval of
TABRECTA for METex14 mutation-positive advanced and/or recurrent unresectable non-small cell lung cancer and a
$80.0 million sales milestone for Novartis achieving annual net sales of a JAK licensed product of $1.2 billion.
We also are eligible to receive tiered, double-digit royalties ranging from the upper-teens to the mid-twenties on
future JAKAVI net sales outside of the United States, and tiered, worldwide royalties on TABRECTA net sales that range
from 12% to 14%. We are obligated to pay to Novartis tiered royalties in the low single-digits on future JAKAFI net sales
within the United States. During the years ended December 31, 2021, 2020 and 2019, such royalties payable to Novartis
on net sales within the United States totaled $99.6 million, $89.9 million and $77.6 million, respectively, and were reflected
in cost of product revenues on the consolidated statements of operations. At December 31, 2021 and 2020, $148.1 million
and $96.4 million, respectively, of accrued royalties payable to Novartis were included in accrued and other current
liabilities on the consolidated balance sheets. Each company is responsible for costs relating to the development and
commercialization of ruxolitinib in its respective territories, with costs of collaborative studies shared equally. Novartis is
also responsible for all costs relating to the development and commercialization of capmatinib.
The Novartis agreement will continue on a program-by-program basis until Novartis has no royalty payment
obligations with respect to such program or, if earlier, the termination of the agreement or any program in accordance with
the terms of the agreement. Royalties are payable by Novartis on a product-by-product and country-by-country basis until
the latest to occur of (i) the expiration of the last valid claim of the licensed patent rights covering the licensed product in
the relevant country, (ii) the expiration of regulatory exclusivity for the licensed product in such country and (iii) a
specified period from first commercial sale in such country of the licensed product by Novartis or its affiliates or
sublicensees. The agreement may be terminated in its entirety or on a program-by-program basis by Novartis for
convenience. The agreement may also be terminated by either party under certain other circumstances, including material
breach.
Milestone and contract revenue under the Novartis agreement was $0.0 million, $170.0 million and $0.0 million
for the years ended December 31, 2021, 2020 and 2019, respectively. In addition, for the years ended December 31, 2021,
2020 and 2019, we recorded $338.0 million, $277.9 million and $225.9 million, respectively, of product royalty revenues
related to Novartis net sales of JAKAVI outside the United States. For the years ended December 31, 2021 and 2020 we
recorded $10.4 million and $4.1 million, respectively, of product royalty revenues related to Novartis net sales of
TABRECTA worldwide.
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Lilly - Baricitinib
In December 2009, we entered into a License, Development and Commercialization Agreement with Lilly. Under
the terms of the agreement, Lilly received exclusive worldwide development and commercialization rights to our JAK
inhibitor baricitinib, and certain back-up compounds for inflammatory and autoimmune diseases.
Under this agreement, we were initially eligible to receive up to $150.0 million for the achievement of
development milestones, up to $365.0 million for the achievement of regulatory milestones and up to $150.0 million for
the achievement of sales milestones. We have recognized and received, in aggregate, $149.0 million for the achievement
of development milestones, $265.0 million for the achievement of regulatory milestones and $50.0 million for the
achievement of sales milestones through December 31, 2021.
We recognize development and regulatory milestones upon confirmation of achievement of the event, as
development and regulatory approvals are events not controllable by us but rather development activities of Lilly and
decisions made by regulatory agencies. We recognize sales milestones in the corresponding period of the product sale upon
confirmation of net sales milestone threshold achievement by Lilly.
In 2021, we recognized a $50.0 million sales milestone for Lilly achieving annual net sales of a licensed product
of $1.0 billion. In 2020, we recognized a $20.0 million regulatory milestone for the European Commission approval of
OLUMIANT and a $10.0 million regulatory milestone for the MHLW approval of OLUMIANT for the treatment of
moderate-to-severe atopic dermatitis in adult patients who are candidates for systemic therapy.
In May 2020, we amended our agreement with Lilly to enable Lilly to develop and commercialize baricitinib for
the treatment of COVID-19. As part of the amended agreement, in addition to the royalties described above, we will be
entitled to receive additional royalty payments with rates in the low teens on global net sales of baricitinib for the treatment
of COVID-19 that exceed a specified aggregate global net sales threshold.
The Lilly agreement will continue until Lilly no longer has any royalty payment obligations or, if earlier, the
termination of the agreement in accordance with its terms. Royalties are payable by Lilly on a product-by-product and
country-by-country basis until the latest to occur of (i) the expiration of the last valid claim of the licensed patent rights
covering the licensed product in the relevant country, (ii) the expiration of regulatory exclusivity for the licensed product
in such country and (iii) a specified period from first commercial sale in such country of the licensed product by Lilly or
its affiliates or sublicensees. The agreement may be terminated by Lilly for convenience, and may also be terminated under
certain other circumstances, including material breach.
Milestone and contract revenue under the Lilly agreement was $50.0 million, $30.0 million and $0.0 million,
respectively, for the years ended December 31, 2021, 2020 and 2019. In addition, for the years ended December 31, 2021,
2020 and 2019, we recorded $220.9 million, $110.9 million and $80.4 million, respectively, of product royalty revenues
related to Lilly net sales of OLUMIANT outside the United States.
Lilly – Ruxolitinib
In March 2016, we entered into an amendment to the agreement with Lilly that amended the non-compete
provision of the agreement to allow us to engage in the development and commercialization of ruxolitinib in the GVHD
field. Lilly is eligible to receive up to $40.0 million in regulatory milestone payments relating to ruxolitinib in the GVHD
field. In May 2019, the approval of JAKAFI in steroid-refractory acute GVHD triggered a $20.0 million milestone payment
to Lilly.
Agenus
In January 2015, we entered into a License, Development and Commercialization Agreement with Agenus Inc.
and its wholly-owned subsidiary, 4-Antibody AG (now known as Agenus Switzerland Inc.), which we collectively refer
to as Agenus. Under this agreement, which was amended in February 2017, the parties have agreed to collaborate on the
discovery of novel immuno-therapeutics using Agenus’ antibody discovery platforms. Under the terms of the amended
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agreement, we received exclusive worldwide development and commercialization rights to four checkpoint modulators
directed against GITR, OX40, LAG-3 and TIM-3 as well as two undisclosed targets. Targets may be designated profit-
share programs, where all costs and profits are shared equally by us and Agenus, or royalty-bearing programs, where we
are responsible for all costs associated with discovery, preclinical, clinical development and commercialization activities.
There are currently no profit-share programs. For each royalty-bearing product other than GITR, OX40 and one
undisclosed target, Agenus will be eligible to receive tiered royalties on global net sales ranging from 6% to 12%. For
GITR, OX40 and one undisclosed target, Agenus will be eligible to receive 15% royalties on global net sales. The
agreement may be terminated by us for convenience upon 12 months’ notice and may also be terminated under certain
other circumstances, including material breach.
As of December 31, 2021, we have paid Agenus milestones totaling $30.0 million and Agenus is eligible to
receive up to an additional $500.0 million in future contingent development, regulatory and commercialization milestones
across all programs in the collaboration.
In addition, in 2017 we also agreed to purchase 10.0 million shares of Agenus common stock for an aggregate
purchase price of $60.0 million in cash, or $6.00 per share. The fair market value of our long term investment in Agenus
as of December 31, 2021 and 2020 was $38.9 million and $44.7 million, respectively. In 2020, we sold an aggregate of
approximately 3.7 million shares of Agenus common stock resulting in gross proceeds of approximately $17.2 million. In
2021, we sold an aggregate of approximately 2.0 million shares of Agenus common stock resulting in gross proceeds of
approximately $10.5 million. As of December 31, 2021, we owned less than 5% of the outstanding shares of Agenus
common stock.
We intend to hold the investment in Agenus for the foreseeable future and therefore, are accounting for our shares
held in Agenus at fair value whereby the investment is marked to market through earnings in each reporting period. Given
our intent to hold the investment for the foreseeable future, we have classified the investment within long term investments
on the accompanying consolidated balance sheets. For the years ended December 31, 2021, 2020 and 2019, we recorded
an unrealized gain of $4.6 million, an unrealized loss of $10.3 million and an unrealized gain of $30.0 million, respectively,
based on the change in fair value of Agenus Inc.’s common stock during the respective periods.
Merus
In December 2016, we entered into a Collaboration and License Agreement with Merus N.V. (“Merus”). Under
this agreement, the parties have agreed to collaborate with respect to the research, discovery and development of bispecific
antibodies utilizing Merus’ technology platform. The collaboration encompasses up to ten independent programs.
In January 2022, we decided to opt-out of the continued development of MCLA-145, a bispecific antibody
targeting PD-L1 and CD137. We continue to collaborate with Merus and leverage the Merus platform to develop a pipeline
of novel agents, as we continue to hold worldwide exclusive development and commercialization rights to up to ten
additional programs. Of these ten additional programs, Merus retained the option, subject to certain conditions, to co-fund
development of up to two such programs. If Merus exercises its co-funding option for a program, Merus would be
responsible for funding 35% of the associated future global development costs and, for certain of such programs, would
be responsible for reimbursing us for certain development costs incurred prior to the option exercise. Merus will also have
the right to participate in a specified proportion of detailing activities in the United States for one of those co-developed
programs. All costs related to the co-funded collaboration programs are subject to joint research and development plans
and overseen by a joint development committee, but we will have final determination as to such plans in cases of dispute.
We will be responsible for all research, development and commercialization costs relating to all other programs.
For each program as to which Merus does not have commercialization or development co-funding rights, Merus
is eligible to receive up to $100.0 million in future contingent development and regulatory milestones, and up to $250.0
million in commercialization milestones as well as tiered royalties ranging from 6% to 10% of global net sales. For each
program as to which Merus exercises its option to co-fund development, Merus is eligible to receive a 50% share of profits
(or sustain 50% of any losses) in the United States and be eligible to receive tiered royalties ranging from 6% to 10% of
net sales of products outside of the United States. If Merus opts to cease co-funding a program as to which it exercised its
co-development option, then Merus will no longer receive a share of profits in the United States but will be eligible to
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receive the same milestones from the co-funding termination date and the same tiered royalties described above with
respect to programs where Merus does not have a right to co-fund development and, depending on the stage at which
Merus chose to cease co-funding development costs, Merus will be eligible to receive additional royalties ranging up to
4% of net sales in the United States. As of December 31, 2021, we have paid Merus milestones totaling $2.0 million.
The Merus agreement will continue on a program-by-program basis until we have no royalty payment obligations
with respect to such program or, if earlier, the termination of the agreement or any program in accordance with the terms
of the agreement. The agreement may be terminated in its entirety or on a program-by-program basis by us for convenience.
The agreement may also be terminated by either party under certain other circumstances, including material breach, as set
forth in the agreement. If the agreement is terminated with respect to one or more programs, all rights in the terminated
programs revert to Merus, subject to payment to us of a reverse royalty of up to 4% on sales of future products, if Merus
elects to pursue development and commercialization of products arising from the terminated programs.
In addition, in 2016 we entered into a Share Subscription Agreement with Merus, pursuant to which we agreed
to purchase 3.2 million common shares of Merus for an aggregate purchase price of $80.0 million in cash, or $25.00 per
share. The fair market value of our total long term investment in Merus as of December 31, 2021 and 2020 was $112.9
million and $56.1 million, respectively. In January 2021, we purchased 350,000 common shares in Merus’ underwritten
public offering of 4,848,485 common shares at the public offering price of $24.75 per share, or an aggregate purchase
price of $8.7 million. As of December 31, 2021, we owned approximately 8% of the outstanding common shares of Merus.
We have concluded that we have the ability to exercise significant influence, but not control, over Merus based
primarily on our ownership interest, the level of intra-entity transactions between us and Merus related to development
expenses, as well as other qualitative factors. We have elected the fair value option to account for our long term investment
in Merus whereby the investment is marked to market through earnings in each reporting period. We believe the fair value
option to be the most appropriate accounting method to account for securities in publicly held collaborators for which we
have significant influence. For the years ended December 31, 2021, 2020 and 2019, we recorded an unrealized gain of
$48.1 million, $11.0 million, and $0.3 million, respectively, based on the change in fair value of Merus’ common shares
during the respective periods.
Calithera
In January 2017, we entered into a Collaboration and License Agreement with Calithera Biosciences, Inc.
(“Calithera”). Under this agreement, we received an exclusive, worldwide license to develop and commercialize small
molecule arginase inhibitors, including INCB01158. We have agreed to co-fund 70% of the global development costs for
the development of the licensed products for hematology and oncology indications. Calithera will have the right to conduct
certain clinical development under the collaboration, including combination studies of a licensed product with a proprietary
compound of Calithera. We will be entitled to 60% of the profits and losses from net sales of licensed product in the United
States, and Calithera will have the right to co-detail licensed products in the United States, and we have agreed to pay
Calithera tiered royalties ranging from the low to mid-double digits on net sales of licensed products outside the United
States.
As of December 31, 2021, we have paid Calithera milestones totaling $12.0 million. Calithera delivered notice of
its decision to opt out of its co-funding obligation, effective on September 30, 2020. As a result, the U.S. profit sharing
will no longer be in effect, we will be responsible for funding all of the development costs of INCB01158 and any other
licensed products, and the agreement provides that we will pay Calithera tiered royalties ranging from the low to mid-
double digits on net sales of licensed products both in the United States and outside the United States and additional
royalties to reimburse Calithera for previously incurred development costs. Calithera is eligible to receive $720.0 million
in potential future development, regulatory and sales milestone payments and will have no further rights to research,
develop or co-detail INCB001158. We will have the right to take over the conduct of all activities related to the research,
development and commercialization of INCB001158 for all indications in the hematology/oncology field.
The Calithera agreement will continue on a product-by-product and country-by-country basis for so long as we
are developing or commercializing products in the United States (if the parties are sharing profits in the United States) and
until we have no further royalty payment obligations, unless earlier terminated according to the terms of the agreement.
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The agreement may be terminated in its entirety or on a product-by-product and/or a country-by-country basis by us for
convenience. The agreement may also be terminated by us for Calithera’s uncured material breach, by Calithera for our
uncured material breach and by either party for bankruptcy or patent challenge. If the agreement is terminated early with
respect to one or more products or countries, all rights in the terminated products and countries revert to Calithera.
In addition, in 2017, we entered into a Stock Purchase Agreement with Calithera for the purchase of 1.7 million
common shares of Calithera for an aggregate purchase price of $8.0 million in cash, or $4.65 per share. The fair market
value of our long term investment in Calithera as of December 31, 2021 and 2020 was $1.1 million and $8.4 million,
respectively. As of December 31, 2021, we owned approximately 2% of the outstanding shares of Calithera common stock.
We intend to hold the investment in Calithera for the foreseeable future and therefore, are accounting for our
shares held in Calithera at fair value whereby the investment is marked to market through earnings in each reporting period.
Given our intent to hold the investment for the foreseeable future, we have classified the investment within long term
investments on the accompanying consolidated balance sheets. For the years ended December 31, 2021, 2020 and 2019,
we recorded an unrealized loss of $7.3 million, an unrealized loss of $1.4 million, and an unrealized gain of $2.9 million,
respectively, based on the change in fair value of Calithera’s common stock during the respective periods.
MacroGenics
In October 2017, we entered into a Global Collaboration and License Agreement with MacroGenics, Inc.
(“MacroGenics”). Under this agreement, we received exclusive development and commercialization rights worldwide to
MacroGenics’ INCMGA0012 (formerly MGA012), an investigational monoclonal antibody that inhibits PD-1. Except as
set forth in the succeeding sentence, we have sole authority over and bear all costs and expenses in connection with the
development and commercialization of INCMGA0012 in all indications, whether as a monotherapy or as part of a
combination regimen. MacroGenics has retained the right to develop and commercialize, at its cost and expense, its
pipeline assets in combination with INCMGA0012. In addition, MacroGenics has the right to manufacture a portion of
both companies’ global clinical and commercial supply needs of INCMGA0012.
As of December 31, 2021, we have paid MacroGenics developmental milestones totaling $70.0 million.
MacroGenics is eligible to receive up to an additional $350.0 million in future contingent development and regulatory
milestones, and up to $330.0 million in sales milestones as well as tiered royalties ranging from 15% to 24% of global net
sales.
The MacroGenics agreement will continue until we are no longer commercializing, developing or manufacturing
INCMGA0012 or, if earlier, the termination of the agreement in accordance with its terms. The agreement may be
terminated in its entirety or on a licensed product by licensed product basis by us for convenience. The agreement may
also be terminated by either party under certain other circumstances, including material breach, as set forth in the
agreement.
Research and development expenses for the years ended December 31, 2021, 2020 and 2019, also included $72.3
million, $59.0 million and $51.1 million, respectively, of additional development costs incurred pursuant to the
MacroGenics agreement. At December 31, 2021 and 2020, a total of $0.7 million and $0.1 million, respectively, of such
costs were included in accrued and other liabilities on the consolidated balance sheets.
Syros
In January 2018, we entered into a Target Discovery, Research Collaboration and Option Agreement with Syros
Pharmaceuticals, Inc. (“Syros”). Under this agreement, Syros will use its proprietary gene control platform to identify
novel therapeutic targets with a focus in myeloproliferative neoplasms and we have received options to obtain exclusive
worldwide rights to intellectual property resulting from the collaboration for up to seven validated targets. We will have
exclusive worldwide rights to develop and commercialize any therapies under the collaboration that modulate those
validated targets. We have agreed to pay Syros up to $54.0 million in target selection and option exercise fees should we
decide to exercise all of our options under the agreement. For products resulting from the collaboration against each of the
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seven selected and validated targets, we have agreed to pay up to $50.0 million in potential development and regulatory
milestones and up to $65.0 million in potential sales milestones. Syros is also eligible to receive low single-digit royalties
on net sales of products resulting from the collaboration.
In addition, in 2018, we entered into a Stock Purchase Agreement with Syros for the purchase of 0.8 million
shares of common stock of Syros for an aggregate purchase price of $10.0 million in cash, or $12.61 per share.
Subsequently in 2018, we entered into an Amended Stock Purchase Agreement with Syros for the purchase of an additional
0.1 million common shares of Syros for an aggregate purchase price of $1.4 million in cash, or $9.55 per share. The fair
market value of our long term investment in Syros as of December 31, 2021 and 2020 was $3.1 million and $10.2 million,
respectively. As of December 31, 2021, we owned approximately 2% of the outstanding shares of Syros common stock.
We intend to hold the investment in Syros for the foreseeable future and therefore, are accounting for our shares
held in Syros at fair value whereby the investment is marked to market through earnings in each reporting period. Given
our intent to hold the investment for the foreseeable future, we have classified the investment within long term investments
on the accompanying consolidated balance sheets. For the years ended December 31, 2021, 2020 and 2019, we recorded
an unrealized loss of $7.1 million, an unrealized gain of $3.7 million and an unrealized gain of $1.3 million, respectively,
based on the change in fair value of Syros’ common stock during the respective periods.
Innovent
In December 2018, we entered into a Research Collaboration and Licensing Agreement with Innovent. Under the
terms of this agreement, Innovent received exclusive development and commercialization rights to our clinical-stage
product candidates pemigatinib, itacitinib and parsaclisib in hematology and oncology in mainland China, Hong Kong,
Macau and Taiwan. In January 2019, we recognized an upfront payment under this agreement of $40.0 million upon our
transfer of the functional intellectual property related to the clinical-stage product candidates to Innovent, which was
recorded in milestone and contract revenues on the consolidated statement of operations for the year ended December 31,
2019. The upfront milestone was recognized as revenue at a point in time upon our transfer of the licenses to Innovent for
the right to use the functional intellectual property. In addition, we are eligible to receive up to an additional $94.0 million
in potential development and regulatory milestones.
We recognize development and regulatory milestones upon confirmation of achievement of the event, as
development and regulatory approvals are events not controllable by us but rather development activities of Innovent and
decisions made by regulatory agencies.
In 2021, we recognized a $10.0 million milestone for approval of PEMAZYRE (pemigatinib) in Taiwan. In 2020,
we recognized a $5.0 million milestone for the FDA approval of PEMAZYRE. In 2019, we recognized a $20.0 million
milestone for the first related IND filing in China.
In the event of commercialization of the licensed molecule, we are eligible to receive up to $202.5 million in
potential sales milestones from Innovent. We will recognize sales milestones in the corresponding period of the product
sale upon confirmation of net sales milestone threshold achievement by Innovent. We are also eligible to receive tiered
royalties from the high-teens to the low-twenties on future sales of products resulting from the collaboration. We retain an
option to assist in the promotion of the three product candidates in the Innovent territories.
Zai Lab
In July 2019, we entered into a Collaboration and License Agreement with Zai Lab. Under the terms of this
agreement, Zai Lab received development and exclusive commercialization rights to INCMGA0012 in hematology and
oncology in mainland China, Hong Kong, Macau and Taiwan. In 2019, we recognized an upfront payment under this
agreement of $17.5 million upon our transfer of the functional intellectual property related to the clinical-stage product
candidates to Zai Lab, which was recorded in milestone and contract revenues on the consolidated statement of operations
for the year ended December 31, 2019.
104
The agreement allows for Zai Lab to continue development of the licensed molecule and to submit the licensed
molecule to authorities for regulatory approval within the agreement territory, upon which we are eligible for up to $22.5
million in potential development and regulatory milestones. We recognize development and regulatory milestones upon
confirmation of achievement of the event, as development and regulatory approvals are events not controllable by us but
rather development activities of Zai Lab and decisions made by regulatory agencies.
In the event of commercialization of the licensed molecule, we are eligible to receive up to $37.5 million in
potential sales milestones from Zai Lab. We will recognize sales milestones in the corresponding period of the product
sale upon confirmation of net sales milestone threshold achievement by Zai Lab. We are also eligible to receive tiered
royalties from the low to mid-twenties on future product sales resulting from the collaboration. We also retain an option
to assist in the promotion of INCMGA0012 in Zai Lab’s licensed territories.
MorphoSys
In January 2020, we entered into a Collaboration and License Agreement with MorphoSys AG and MorphoSys
US Inc., a wholly-owned subsidiary of MorphoSys AG (together with MorphoSys AG, “MorphoSys”), covering the
worldwide development and commercialization of MOR208 (tafasitamab), an investigational Fc engineered monoclonal
antibody directed against the target molecule CD19 that is currently in clinical development by MorphoSys. MorphoSys
has exclusive worldwide development and commercialization rights to tafasitamab under a June 2010 collaboration and
license agreement with Xencor, Inc.
Under the terms of the agreement, we received exclusive commercialization rights outside of the United States,
and MorphoSys and we have co-commercialization rights in the United States, with respect to tafasitamab. MorphoSys is
responsible for leading the commercialization strategy and booking all revenue from sales of tafasitamab in the United
States, and we and MorphoSys are both responsible for commercialization efforts in the United States and will share
equally the profits and losses from the co-commercialization efforts. We will lead the commercialization strategy outside
of the United States, and will be responsible for commercialization efforts and book all revenue from sales of tafasitamab
outside of the United States, subject to our royalty payment obligations set forth below. We and MorphoSys have agreed
to co-develop tafasitamab and to share development costs associated with global and U.S.-specific clinical trials, with
Incyte responsible for 55% of such costs and MorphoSys responsible for 45% of such costs. Each company is responsible
for funding any independent development activities, and we are responsible for funding development activities specific to
territories outside of the United States. All development costs related to the collaboration are subject to a joint development
plan.
In 2020, we paid MorphoSys an upfront non-refundable payment of $750.0 million. MorphoSys is eligible to
receive up to $740.0 million in future contingent development and regulatory milestones and up to $315.0 million in
commercialization milestones as well as tiered royalties ranging from the mid-teens to mid-twenties of net sales outside of
the United States. MorphoSys’ right to receive royalties in any particular country will expire upon the last to occur of
(a) the expiration of patent rights in that particular country, (b) a specified period of time after the first post-marketing
authorization sale of a licensed product comprising tafasitamab in that country, and (c) the expiration of any regulatory
exclusivity for that licensed product in that country.
In addition, under the terms of the agreement and pursuant to a related purchase agreement, we agreed to purchase
American Depositary Shares (“ADSs”), each representing 0.25 of an ordinary share of MorphoSys AG, for an aggregate
purchase price of $150.0 million or $41.33 per ADS (such ADSs to be purchased, the “New ADSs”). The fair market value
of our long term investment in MorphoSys as of December 31, 2021 and 2020 was $34.2 million and $102.9 million,
respectively. As of December 31, 2021, we owned approximately 3% of the outstanding shares of MorphoSys common
stock.
We intend to hold the investment in MorphoSys for the foreseeable future and therefore, are accounting for our
shares held in MorphoSys at fair value whereby the investment is marked to market through earnings in each reporting
period. Given our intent to hold the investment for the foreseeable future, we have classified the investment within long
term investments on the accompanying consolidated balance sheets. For the year ended December 31, 2021 and 2020, we
105
recorded an unrealized loss of $68.7 million and an unrealized gain of $7.4 million, respectively, based on the change in
fair value of MorphoSys’ common stock during the respective periods.
Our 50% share of the United States loss for the commercialization of tafasitamab for the years ended
December 31, 2021 and 2020 was $37.0 million and $42.8 million, respectively, and is recorded as collaboration loss
sharing on the consolidated statement of operations. Research and development expenses for the year ended December 31,
2021 and 2020, included $77.0 million and $88.2 million, respectively, related to our 55% share of the co-development
costs for tafasitamab. At December 31, 2021 and 2020, $21.5 million and $54.2 million, respectively, was included in
accrued and other liabilities on the consolidated balance sheet for amounts due to MorphoSys under the agreement.
Nimble
In September 2020, we entered into a Collaboration and License Agreement with Nimble Therapeutics, Inc.
(“Nimble”). Under the terms of this agreement, Nimble will utilize their peptide synthesis, screening and optimization
platform for discovery and validation of peptides against specified targets. Under the agreement, Nimble is eligible to
receive up to $8.0 million in future contingent discovery milestones and up to $127.0 million in future contingent
development and regulatory milestones. Additionally, in the event of successful commercialization, Nimble is eligible to
receive up to $130.0 million in future contingent sales milestones and tiered royalties on net sales in the low single digits.
InnoCare
In August 2021, we entered into a Collaboration and License Agreement with Sunny Investments Limited, a
wholly-owned subsidiary of InnoCare Pharma Limited (“InnoCare”). InnoCare received development and exclusive
commercialization rights to tafasitamab in hematology and oncology in mainland China, Hong Kong, Macau and Taiwan.
In September 2021, we recognized an upfront payment under this agreement of $35.0 million upon our transfer of
technology related to the licensed product candidate to InnoCare, which was recorded in milestone and contract revenues
on the consolidated statement of operations for the year ended December 31, 2021. Under the terms of this agreement, we
are eligible to receive up to an additional $45.0 million in potential development and regulatory milestones. We recognize
development and regulatory milestones upon confirmation of achievement of the event, as development and regulatory
approvals are events not controllable by us but rather development activities of InnoCare and decisions made by regulatory
agencies. In the event of commercialization, we are eligible to receive up to $37.5 million in potential sales milestones
from InnoCare. We will recognize sales milestones in the corresponding period of the product sale upon confirmation of
net sales milestone threshold achievement by InnoCare. We are also eligible to receive tiered royalties from the low to
mid-twenties on future product sales resulting from the collaboration.
Syndax
In September 2021, we entered into a Collaboration and License Agreement with Syndax Pharmaceuticals, Inc.
(“Syndax”), covering the worldwide development and commercialization of SNDX-6352 (“axatilimab”). Axatilimab,
currently in clinical development by Syndax, is a monoclonal antibody that blocks the colony stimulating factor-1 (CSF-1)
receptor. Syndax has exclusive worldwide development and commercialization rights to axatilimab under a June 2016
license agreement with UCB Biopharma Sprl. The agreement became effective in December 2021 with the expiration of
the initial waiting period under the Hart-Scott-Rodino Antitrust Improvements Act.
Under the terms of the agreement, we received exclusive commercialization rights outside of the United States,
and Syndax and we have co-commercialization rights in the United States, with respect to axatilimab. We will be
responsible for leading the commercialization strategy and booking all revenue from sales of tafasitamab globally, and
Syndax will have the option to co-commercialization axatilimab with Incyte in the United States. Incyte and Syndax will
share equally the profits and losses from the co-commercialization efforts in the United States. Sales of axatilimab outside
the United States will be subject to our royalty payment obligations to Syndax, as set forth below. We and Syndax have
agreed to co-develop axatilimab and to share development costs associated with global and U.S.-specific clinical trials,
with Incyte responsible for 55% of such costs and Syndax responsible for 45% of such costs. Each company is responsible
for funding any independent development activities. All development costs related to the collaboration are subject to a
106
joint development plan.
In December 2021, we paid Syndax an upfront, non-refundable (except in the event of termination of the
agreement as described below) payment of $117.0 million, which was recorded in research and development expense on
the consolidated statement of operations for the year ended December 31, 2021. Syndax is eligible to receive up to $220.0
million in future contingent development and regulatory milestones and up to $230.0 million in sales milestones as well
as tiered royalties ranging in the mid-teens on net sales in Europe and Japan and low double digit percentage on net sales
in the rest of the world outside of the United States. Syndax’ right to receive royalties in any particular country will expire
upon the last to occur of (a) the expiration of patent rights in that particular country, (b) a specified period of time after the
first post-marketing authorization sale of a licensed product comprising tafasitamab in that country, and (c) the expiration
of any regulatory exclusivity for that licensed product in that country.
We have the sole right to terminate the agreement beginning March 23, 2022 in the event of any formal action by
a relevant governmental authority to challenge the transactions under this agreement that occurs prior to that date. If
triggered, our right to terminate will expire on September 23, 2022. Exercise of this termination right would require Syndax
to refund all payments under the agreement, including the $117.0 million upfront payment and any payments for
development costs.
In addition, under the terms of the agreement and pursuant to a related stock purchase agreement, we agreed to
purchase approximately 1.4 million shares of common stock of Syndax for an aggregate purchase price of $35.0 million,
or $24.62 per share. We agreed, subject to limited exceptions, not to sell or otherwise transfer any of the shares for a six
month period after the closing date of the sale. We completed the purchase of the shares on December 9, 2021 when the
closing price on The Nasdaq Stock Market was $17.48 per share. Of the $35.0 million aggregate purchase price paid, $24.8
million was allocated to our stock purchase and was recorded within long term investments and $10.2 million, representing
premium paid on the purchase, was allocated to research and development expense on the consolidated statement of
operations for the year ended December 31, 2021. The fair market value of our long term investment in Syndax as of
December 31, 2021 was $31.1 million. As of December 31, 2021, we owned approximately 3% of the outstanding shares
of Syndax common stock.
We intend to hold the investment in Syndax for the foreseeable future and therefore, are accounting for our shares
held in Syndax at fair value whereby the investment is marked to market through earnings in each reporting period. Given
our intent to hold the investment for the foreseeable future, we have classified the investment within long term investments
on the accompanying consolidated balance sheets. For the year ended December 31, 2021, we recorded an unrealized gain
of $6.3 million based on the change in fair value of Syndax’s common stock during the period.
Note 7. Property and Equipment, net
Property and equipment, net consists of the following (in thousands):
Office equipment
Laboratory equipment
Computer equipment
Land
Building and leasehold improvements
Operating lease right-of-use assets
Construction in progress
Less accumulated depreciation and amortization
Property and equipment, net
December 31,
2021
22,554 $
105,040
79,871
10,494
434,321
27,308
220,052
899,640
(175,720)
723,920 $
2020
17,880
86,021
66,640
10,671
238,042
26,816
257,929
703,999
(144,374)
559,625
$
$
Depreciation expense, including amortization expense of leasehold improvements, was $36.3 million,
$29.6 million and $32.1 million for the years ended December 31, 2021, 2020 and 2019, respectively.
107
In March 2017, we acquired additional adjacent buildings to our global headquarters in Wilmington, Delaware
and in 2019, began demolition of these buildings and construction of a new laboratory and office building totaling
approximately 200,000 square feet. The certificate of occupancy was received in December 2021 and we capitalized
approximately $158.2 million in building and office equipment that was previously included in construction in progress as
of December 31, 2021.
In February 2018, we signed an agreement to rent a building in Morges, Switzerland for an initial term of 15 years
plus one year of free rent, with multiple options to extend for an additional 20 years. The building serves as our new
European headquarters and consists of approximately 100,000 square feet of office space. This building allowed for
consolidation of our European operations that were located in Geneva and Lausanne, Switzerland. In June 2019, we
obtained control of the Morges building to begin our construction activity, which was completed in 2020. At that time, we
determined the lease to be a finance lease and recorded a lease liability of $31.1 million and a finance lease right-of-use
asset of $29.1 million, net of a lease incentive from our landlord of $2.0 million. We have capitalized approximately $19.5
million in leasehold improvements as of December 31, 2021 relating to Morges.
In July 2018, we signed an agreement to purchase land located in Yverdon, Switzerland. The land was purchased,
in cash, for approximately $4.8 million. Upon this parcel, we are constructing a large molecule production facility.
Construction activity commenced in July 2018, and as of December 31, 2021, we have capitalized approximately $197.4
million in costs for construction, ground preparation and architectural and engineering studies. We currently expect the
facility will be operational in the second half of 2022.
We are the lessee of several contracts, including those to secure fleet vehicles, buildings and equipment. Our lease
agreements do not contain any material residual value guarantees or restrictive covenants. Some of our building leases
include options to renew and the exercise of these options is at our discretion.
Our current operating lease liabilities are reflected in accrued and other current liabilities and our noncurrent
operating lease liabilities are reflected in other liabilities on the consolidated balance sheets and are as follows (in
thousands):
Current
Operating lease liabilities
Finance lease liabilities
Noncurrent
Operating lease liabilities
Finance lease liabilities
Total lease liabilities
The maturity of our lease liabilities are as follows (in thousands):
2022
2023
2024
2025
2026
After 2026
Total lease cash payments
Less: discount
Present value of lease liabilities
December 31,
2021
2020
$
10,554 $
2,635
12,674
2,284
15,608
31,632
60,429 $
14,188
32,573
61,719
Operating
Finance
11,887 $
8,664
4,599
1,418
953
5,814
33,335 $
7,173
26,162 $
4,020
3,908
3,291
3,020
2,828
26,492
43,559
9,292
34,267
$
$
$
$
108
The cash paid for amounts included in the measurement of our operating lease liabilities for the years ended
December 31, 2021 and 2020 was $14.3 million and $12.1 million, respectively, in operating cash flows. The cash paid
for amounts included in the measurement of our finance lease liabilities for the years ended December 31, 2021 and 2020
was $2.4 million and $0.8 million, respectively, in financing cash flows.
As of December 31, 2021, our finance and operating leases had a weighted average lease term of approximately
13.4 and 4.9 years, respectively. The discount rate of our leases is an approximation of an estimated incremental borrowing
rate and is dependent upon the term and economics of each agreement. The weighted average discount rate of our finance
and operating leases is approximately 4.1% and 4.8%, respectively. As of December 31, 2020, our finance and operating
leases had a weighted average lease term of approximately 14.2 and 4.7 years, respectively. The weighted average discount
rate of our finance and operating leases is approximately 3.7% and 4.7%, respectively.
For the year ended December 31, 2021, we incurred approximately $14.2 million of expense related to our
operating leases, approximately $2.7 million of amortization on our finance lease right-of-use assets and approximately
$1.3 million of interest expense on our finance lease liabilities. For the year ended December 31, 2020, we incurred
approximately $12.5 million of expense related to our operating leases, approximately $2.6 million of amortization on our
finance lease right-of-use assets and approximately $1.2 million of interest expense on our finance lease liabilities. For the
years ended December 31, 2021 and 2020, the cost of our short term leases with a term less than 12 months was
approximately $0.8 million and $1.9 million, respectively.
Note 8. Intangible Assets and Goodwill
Intangible Assets, Net
The components of intangible assets were as follows (in thousands, except for useful life):
Balance at December 31, 2021
Balance at December 31, 2020
Weighted-
Gross
Average Useful
Carrying
Lives (Years) Amount
Net
Accumulated
Carrying
Amortization Amount
Gross
Carrying
Amount
Accumulated
Amortization
Net
Carrying
Amount
Finite-lived intangible assets:
Licensed IP
12.5
$ 271,000 $ 120,245 $ 150,755 $ 271,000 $ 98,709 $ 172,291
Amortization expense was $21.5 million for the years ended December 31, 2021, 2020 and 2019 and is recorded
in cost of product revenues on the consolidated statement of operations. Estimated aggregate amortization expense based
on the current carrying value of amortizable intangible assets will be as follows for the years ending December 31 (in
thousands):
Amortization expense
Goodwill
2022
21,536 $
2023
21,536 $
2024
21,536 $
2025
21,536 $
2026
21,536 $
Thereafter
43,075
$
There were no changes to the carrying amount of goodwill for the years ended December 31, 2021 and 2020.
109
Note 9. Accrued and Other Current Liabilities
Accrued and other current liabilities consisted of the following (in thousands):
Royalties
Clinical related costs
Sales allowances
Sales and marketing
Construction in progress
Operating lease liabilities
Other current liabilities
Total accrued and other current liabilities
Note 10. Stockholders’ Equity
December 31,
2021
168,412 $
109,486
136,541
35,750
27,098
10,554
45,754
533,595 $
2020
106,011
115,897
73,204
12,699
22,807
12,674
35,112
378,404
$
$
Preferred Stock. We are authorized to issue 5,000,000 shares of preferred stock, none of which was outstanding
as of December 31, 2021 and 2020. The Board of Directors may determine the rights, preferences and privileges of any
preferred stock issued in the future.
Common Stock. We are authorized to issue 400,000,000 shares of common stock.
Stock Compensation Plans. As of December 31, 2021, we had a total of 10,794,273 shares of our common stock
available for future issuance related to our stock plans as described below.
2010 Stock Incentive Plan. In May 2010 the Board of Directors adopted the 2010 Stock Incentive Plan (the “2010
Stock Plan”), which was most recently amended and restated in May 2021, for issuance of common stock to employees,
non-employee directors, consultants, and scientific advisors. Options are granted to employees, consultants, and scientific
advisors under the 2010 Stock Plan, pursuant to a formula determined by our Board of Directors. All options are exercisable
at the fair market value of the stock on the date of grant. Non-employee director options expire after ten years.
In May 2021, our stockholders approved an increase in the number of shares of common stock reserved for
issuance under the 2010 Stock Plan from 44,453,475 to 53,953,475.
Option activity under the 2010 Stock Plan was as follows:
Shares Subject to
Outstanding Options
Balance at December 31, 2020
Options granted
Options exercised
Options cancelled
Balance at December 31, 2021
Weighted Average
Exercise Price
Shares
12,115,288 $
2,540,313 $
(622,944) $
(1,269,197) $
12,763,460 $
88.31
84.92
66.44
91.44
88.39
In July 2016, we revised the terms of our annual stock option grants to provide that new option grants would
generally have a 10-year term and vest over four years, with 25% vesting after one year and the remainder vesting in 36
equal monthly installments. Previously, our option grants generally had 7-year terms and vested over three years, with
33% vesting after one year and the remainder vesting in 24 equal monthly installments.
Options to purchase a total of 8,024,951, 6,732,942 and 6,896,492 shares as of December 31, 2021, 2020 and
2019, respectively, were exercisable. The aggregate intrinsic value of options exercised for the years ended December 31,
110
2021, 2020 and 2019 were $12.7 million, $87.5 million and $113.8 million, respectively. At December 31, 2021, the
aggregate intrinsic value of options outstanding and vested options are $13.5 million and $13.4 million, respectively.
The following table summarizes information about stock options outstanding as of December 31, 2021 under the
2010 Stock Plan:
Range of Exercise Prices
$22.05 - $68.62
$68.82 - $69.35
$72.27 - $72.27
$72.58 - $80.50
$80.56 - $83.58
$83.83 - $85.01
$85.34 - $94.63
$95.34 - $101.79
$102.65 - $113.64
$115.19 - $138.52
Options Outstanding
Weighted Average
Remaining
Contractual Life
(in years)
Weighted
Average
Exercise
Price
6.05 $
8.35
6.88
5.77
9.26
6.14
7.63
3.88
6.11
4.93
64.71
69.15
72.27
77.49
83.34
84.52
91.18
96.28
109.99
128.71
Number
Outstanding
1,304,595
89,030
1,470,150
1,614,398
1,338,974
1,371,805
1,655,056
1,293,897
1,853,430
772,125
12,763,460
Options Exercisable
Weighted
Average
Exercise
Price
64.04
68.95
72.27
76.77
81.68
84.42
92.12
96.33
111.21
128.71
Number
Exercisable
1,048,050 $
31,252
770,726
1,131,015
72,885
1,008,722
927,332
876,609
1,386,235
772,125
8,024,951
Restricted Stock Units and Performance Shares
In 2014, we began granting restricted stock units (“RSUs”) and performance shares (“PSUs”) to our employees
at the share price on the date of grant. Each RSU represents the right to acquire one share of our common stock. Each RSU
granted in connection with our annual equity awards will vest 25% annually over four years, while each RSU granted as
outstanding merit awards or as part of retention award programs will vest in a single installment at the end of four years.
We grant PSUs with performance and/or service-based milestones with graded and/or cliff vesting over three to
four years. The shares of our common stock into which each PSU may convert is subject to a multiplier based on the level
at which the financial, developmental and market performance conditions are achieved over the service period.
Compensation expense for PSUs with financial and developmental performance conditions is recorded over the estimated
service period for each milestone when the performance conditions are deemed probable of achievement. For PSUs
containing performance conditions which were not deemed probable of achievement, no stock compensation expense is
recorded. Compensation expense for PSUs with market performance conditions is calculated using a Monte Carlo
simulation model as of the date of grant and recorded over the requisite service period. For the years ended December 31,
2021, 2020 and 2019, we recorded $8.3 million, $13.9 million and $9.9 million, respectively, of stock compensation
expense for PSUs on our consolidated statements of operations.
RSU and PSU award activity under the 2010 Stock Plan was as follows:
Shares Subject to
Outstanding Awards
Balance at December 31, 2020
RSUs granted
PSUs granted
RSUs released
PSUs released
RSUs cancelled
PSUs cancelled
Balance at December 31, 2021
111
Shares
3,284,583 $
2,102,386 $
214,449 $
(857,367) $
(200,353) $
(409,333) $
(167,477) $
3,966,888 $
Grant Date Value
87.42
82.39
74.26
87.82
68.08
89.17
72.48
84.91
The following table summarizes our shares available for grant under the 2010 Plan. Each RSU and PSU grant
reduces the available share pool by 2 shares.
Balance at December 31, 2020
Additional authorization
Options, RSUs and PSUs granted
Options, RSUs and PSUs cancelled
Balance at December 31, 2021
Shares Available
for Grant
5,515,182
9,500,000
(7,174,371)
2,272,487
10,113,298
Employee Stock Purchase Plan. On May 21, 1997, our stockholders adopted the 1997 Employee Stock Purchase
Plan, which was most recently amended in April 2020 (the “ESPP”). Each regular full-time and part-time employee
working 20 hours or more per week is eligible to participate after one month of employment. We issued 264,503, 258,453
and 239,590 shares under the ESPP in 2021, 2020 and 2019, respectively. For the years ended December 31, 2021, 2020
and 2019, we recorded stock compensation expense of $4.6 million, $4.6 million and $3.4 million, respectively, as the
ESPP is considered compensatory under the FASB stock compensation rules. As of December 31, 2021, 680,975 shares
remain available for issuance under the ESPP.
Note 11. Stock Compensation
We recorded $183.0 million, $177.9 million and $166.6 million, respectively, of stock compensation expense for
the years ended December 31, 2021, 2020 and 2019. Stock compensation expense within the consolidated statements of
operations included research and development expense for the years ended December 31, 2021, 2020 and 2019 of $114.3
million, $120.4 million and $114.0 million, respectively. Stock compensation expense within the consolidated statements
of operations also included selling, general and administrative expense for the years ended December 31, 2021, 2020 and
2019 of $67.0 million, $56.6 million and $51.9 million, respectively. Stock compensation expense within the consolidated
statements of operations also included cost of product revenues for the years ended December 31, 2021, 2020 and 2019 of
$1.7 million, $1.0 million and $0.7 million, respectively. For the years ended December 31, 2021, 2020 and 2019, we
capitalized $2.1 million, $0.6 million and $0.4 million, respectively, of stock compensation expense as part of the cost of
assets.
We utilized the Black-Scholes valuation model for estimating the fair value of the stock options granted, with the
following weighted-average assumptions:
Employee Stock Options
For the year ended December 31,
2021
2020
2019
Employee Stock Purchase Plan
For the year ended December 31,
2020
2019
2021
Average risk-free interest rates
Average expected life (in years)
Volatility
Weighted-average fair value (in dollars)
0.62 % 0.80 % 2.27 % 0.40 % 0.17 % 1.82 %
5.01
0.50
0.50
5.27
0.50
4.98
39 %
40 %
45 %
33 %
45 %
31 %
29.03
32.65
32.38
18.02
19.13
14.04
The risk-free interest rate is derived from the U.S. Federal Reserve rate in effect at the time of grant. The expected
life calculation is based on the observed and expected time to the exercise of options by our employees based on historical
exercise patterns for similar type options. Expected volatility is based on the historical volatility of our common stock over
the period commensurate with the expected life of the options. A dividend yield of zero is assumed based on the fact that
we have never paid cash dividends and have no present intention to pay cash dividends. Nonemployee awards are measured
on the grant date by estimating the fair value of the equity instruments to be issued using the expected term, similar to our
employee awards.
Based on our historical experience of employee turnover, we have assumed an annualized forfeiture rate of 5%
for our options, PSUs and RSUs. Under the true-up provisions of the stock compensation guidance, we will record
additional expense as the awards vest if the actual forfeiture rate is lower than we estimated, and will record a recovery of
112
prior expense if the actual forfeiture is higher than we estimated.
Total compensation cost of options granted but not yet vested as of December 31, 2021, was $62.2 million, which
is expected to be recognized over the weighted average period of 1.1 years. Total compensation cost of RSUs granted but
not yet vested, as of December 31, 2021, was $162.9 million, which is expected to be recognized over the weighted average
period of 1.9 years. Total compensation cost of PSUs granted but not yet vested, as of December 31, 2021, was $24.3
million, which is expected to be recognized over the weighted average period of 1.9 years, should the underlying
performance conditions be deemed probable of achievement.
Note 12. Income Taxes
We are subject to U.S. federal, state and foreign corporate income taxes. The (benefit) provision for income taxes
is based on income (loss) before (benefit) provision for income taxes as follows (in thousands):
U.S.
Non-U.S.
Income (loss) before (benefit) provision for income taxes
2021
991,873 $
(421,429)
570,444 $
Year Ended December 31,
2020
(16,609) $
(215,609)
(232,218) $
2019
712,486
(225,695)
486,791
$
$
On a periodic basis, we reassess the valuation allowance on our deferred income tax assets. Valuation allowances
require an assessment of both positive and negative evidence when determining whether it is more likely than not that
deferred tax assets are recoverable. Such assessment is required on a jurisdiction-by-jurisdiction basis. The ultimate
realization of deferred tax assets is dependent upon the generation of future taxable income during the periods in which
those temporary differences become deductible.
In the fourth quarter of 2021, we assessed the valuation allowance and considered positive evidence, including
significant cumulative consolidated and U.S. income over the three years ended December 31, 2021, consistent growth in
product revenues, and expectations regarding future profitability. We also assessed negative evidence, including the
potential impact of competition, clinical failures and patent expirations on our projections. After assessing both the positive
evidence and negative evidence, we determined it was more likely than not that the majority of our U.S. deferred tax assets
would be realized in the future and released the associated valuation allowance as of December 31, 2021. This resulted in
a benefit of $569.0 million. As of December 31, 2021, we maintained a valuation allowance of $408.2 million against a
portion of our remaining U.S. deferred tax assets as well as select state and foreign deferred tax assets.
Our (benefit) provision for income taxes consists of the following (in thousands):
Current:
Federal
State
Foreign
Deferred:
Federal
State
Foreign
$
Total (benefit) provision for income taxes
$
2021
Year Ended December 31,
2020
2019
50,565 $
32,505
4,397
87,467
(407,852)
(57,677)
(75)
(465,604)
(378,137) $
43,595 $
18,881
1,353
63,829
—
—
(350)
(350)
63,479 $
23,526
11,553
5,183
40,262
—
(205)
(172)
(377)
39,885
113
A reconciliation of income taxes at the U.S. federal statutory rate to the (benefit) provision for income taxes is as
follows (in thousands):
Provision (benefit) at U.S. federal statutory rate
State and local income taxes
Foreign tax rate differential
Income tax credits
Change in valuation allowance
Foreign-derived intangible income
Stock based compensation
Other
(Benefit) provision for income taxes
$
2021
119,793 $
34,461
55,171
(55,139)
(523,279)
(28,259)
15,497
3,618
Year Ended December 31,
2020
(48,766) $
(21,637)
30,839
(38,221)
158,815
(22,830)
2,802
2,477
63,479 $
2019
102,226
15,109
57,351
(60,072)
(70,264)
(9,153)
(414)
5,102
39,885
$ (378,137) $
The foreign tax rate differential in the table above reflects the impact of operations in jurisdictions with tax rates
that differ from the U.S. federal statutory rate of 21%.
Significant components of our deferred tax assets and liabilities are as follows (in thousands):
Deferred tax assets:
Net operating loss carry forwards
Federal and state research credits
Capitalized research and development
Deferred revenue and accruals
Non-cash compensation
Acquisition-related contingent consideration
Intangibles, net
Long term investments
Other
Total gross deferred tax assets
Less valuation allowance for deferred tax assets
Net deferred tax assets
Deferred tax liabilities:
Property and equipment
Other
Total gross deferred tax liabilities
Net deferred tax assets
December 31,
2021
2020
137,935 $
206,184
59,247
42,326
83,002
31,450
305,228
34,733
15,991
916,096
(408,180)
507,916 $
128,088
305,099
43,806
27,467
75,867
32,658
289,848
25,968
26,422
955,223
(930,209)
25,014
(33,259) $
(7,119)
(40,378)
467,538 $
(19,880)
(3,080)
(22,960)
2,054
$
$
$
$
The valuation allowance for deferred tax assets decreased by approximately $522.0 million during the year ended
December 31, 2021, increased by approximately $159.7 million during the year ended December 31, 2020 and decreased
by approximately $66.5 million during the year ended December 31, 2019. The net valuation allowance decrease during
2021 was primarily due to the valuation allowance release on the majority of our U.S. deferred tax assets mentioned above.
114
As of December 31, 2021, we had net operating loss (“NOL”) carryforwards, research and development credit
carryforwards and orphan drug tax credit carryforwards as follows (in thousands):
Net operating loss carryforwards
State
Foreign
Research and development credit carryforwards
Federal
State
Orphan drug tax credit carryforwards
Amount
Expiring if not utilized
$
296,112
1,422,407
2022 through 2041; indefinite
2022 through 2028
114,595
21,062
121,389
2037 through 2041
2021 through 2040; indefinite
2036 through 2041
The financial statement recognition of the benefit for a tax position is dependent upon the benefit being more
likely than not to be sustainable upon audit by the applicable taxing authority. If this threshold is met, the tax benefit is
then measured and recognized at the largest amount that is greater than 50% likely of being realized upon ultimate
settlement. If such unrecognized tax benefits were realized, we would recognize a tax benefit of $50.1 million. The
following table summarizes the gross amounts of unrecognized tax benefits (in thousands):
Balance at beginning of year
Additions related to prior periods tax positions
Reductions related to prior periods tax positions
Additions related to current period tax positions
Settlements
Reductions due to lapse of applicable statute of limitations
Currency translation adjustment
Balance at end of year
Year Ended December 31,
2021
31,597 $
28,488
(311)
3,042
(95)
(288)
(74)
62,359 $
2020
24,251
3,953
(216)
4,119
(201)
(397)
88
31,597
$
$
Our policy is to recognize interest and penalties related to uncertain tax positions, if any, as a component of
income tax expense. During the year ending December 31, 2021, we recorded interest and penalties as a component of
income tax expense of $0.6 million and during the year ended December 31, 2020, we recorded a negligible reduction to
interest and penalties as a component of income tax expense. We do not anticipate any significant changes to our
unrecognized tax benefits during the next twelve months.
We file U.S. federal, state and local income tax returns and income tax returns in various foreign jurisdictions,
with statutes of limitation generally ranging from three to five years during which such tax returns may be audited by the
relevant tax authorities. Those statutes could be extended due to NOL or tax credit carryforwards generated during these
periods that are subsequently utilized in open tax periods. In general, tax authorities have the ability to adjust the NOL
carryforward or tax credits for three years after utilization of that year’s tax attribute carryforward.
Note 13. Net Income (Loss) Per Share
Our basic net income (loss) per share is computed by dividing the net income (loss) by the number of weighted
average common shares outstanding during the period. Our diluted net income (loss) per share is computed by dividing
net income (loss) by the weighted average common shares outstanding during the period assuming potentially dilutive
common shares of stock options, RSUs, PSUs and common shares issuable upon conversion of the 1.25% convertible
senior notes that matured in November 2020 (the “2020 Notes”) using the if-converted method. Common shares issuable
upon conversion of the 2020 Notes were excluded from the diluted net income (loss) per share computation for 2019 as
their share effect was anti-dilutive.
115
Net income (loss) per share was calculated as follows for the periods indicated below:
(in thousands, except per share data)
Basic Net Income (Loss) Per Share
Basic net income (loss)
Weighted average common shares outstanding
Year Ended December 31,
2020
2021
2019
$
948,581 $ (295,697) $
220,428
218,073
446,906
214,913
Basic net income (loss) per share
$
4.30 $
(1.36) $
2.08
Diluted Net Income (Loss) Per Share
Diluted net income (loss)
Weighted average common shares outstanding
$
948,581 $ (295,697) $
220,428
218,073
446,906
214,913
Dilutive stock options and awards
1,646
—
2,744
Weighted average shares used to compute diluted net income (loss) per
share
222,074
218,073
217,657
Diluted net income (loss) per share
$
4.27 $
(1.36) $
2.05
The potential common shares that were excluded from the diluted net income (loss) per share computation are as
follows:
Outstanding stock options and awards
Common shares issuable upon conversion of the 1.25% Convertible
Senior Notes due 2020
Total potential common shares excluded from diluted net income
(loss) per share computation
2021
10,106,837
2020
15,274,871
2019
9,349,889
—
—
368,939
10,106,837
15,274,871
9,718,828
Note 14. Employee Benefit Plans
Defined Contribution Plans
We have a defined contribution plan qualified under Section 401(k) of the Internal Revenue Code covering all
U.S. employees and defined contribution plans for other Incyte employees in Europe and Japan. Employees may contribute
a portion of their compensation, which is then matched by us, subject to certain limitations. Defined contribution expense
was $16.7 million, $13.4 million and $11.7 million for the years ended December 31, 2021, 2020 and 2019, respectively.
Included in the 2021, 2020 and 2019 defined contribution expense was $2.4 million, $1.7 million and $1.6 million,
respectively, of expense related to matching contributions under the non-U.S. defined contribution plans.
Defined Benefit Pension Plans
We have defined benefit pension plans for our employees in Europe which provide benefits to employees upon
retirement, death or disability. The assets of the pension plans are held in collective investment accounts represented by
the cash surrender value of an insurance policy and are classified as Level 2 within the fair value hierarchy.
The pension plans assumptions reflect the expected investment return and discount rate on plan assets and
disability rate probabilities. The benefit obligation at December 31, 2021 for the plans was determined using a discount
rate of 0.20% and rate of compensation increase of 2.00%. The 2021 net periodic benefit cost for the plans was determined
using discount rates of 0.10%, rates of compensation increase of 2.00% and long-term expected return on plan assets of
0.10%. The benefit obligation at December 31, 2020 for the plans was determined using a discount rate of 0.10% and rate
of compensation increase of 2.00%. The 2020 net periodic benefit cost for the plans was determined using discount rates
of 0.30%, rates of compensation increase of 2.25% and long-term expected return on plan assets of 0.30%.
116
Summarized information regarding changes in the obligations and plan assets, the funded status and the amounts
recorded were as follows (in thousands):
Benefit obligation, beginning of year
Employer service cost
Interest cost
Plan participants' contributions
Actuarial loss
Plan change
Transfer of benefits net of payments from fund
Expenses paid from assets
Translation (gain) loss
Benefit obligation, end of year
Fair value of plan assets, beginning of year
Actual return on plan assets
Employer contributions
Plan participants' contributions
Transfer of benefits net of payments from fund
Expenses paid from assets
Translation gain
Fair value of plan assets, end of year
$
Year Ended December 31,
2020
2021
97,959 $
7,977
92
2,795
7,618
5,595
12,834
(117)
(2,787)
131,966
61,265
12,396
6,858
2,795
12,834
(117)
(2,036)
93,995
62,770
6,047
193
2,237
9,372
—
11,057
(88)
6,371
97,959
38,662
260
5,413
2,237
11,057
(88)
3,724
61,265
Unfunded liability, end of year
$
37,971 $
36,694
The unfunded liability is reported in other liabilities on the consolidated balance sheets as of December 31, 2021
and 2020. The accumulated benefit obligation is $120.9 million and $83.2 million as of December 31, 2021 and 2020,
respectively.
The net periodic benefit cost was as follows (in thousands):
Service cost
Interest cost
Expected return on plan assets
Amortization of prior service cost
Amortization of actuarial losses
Net periodic benefit cost
2021
Year Ended December 31,
2020
2019
7,977 $
92
(60)
217
1,154
9,380 $
6,047 $
193
(126)
216
667
6,997 $
5,195
345
(241)
214
247
5,760
$
$
The components of net periodic benefit cost other than the service cost component are included in other income
(expense), net on the consolidated statements of operations.
117
Other changes in the plans assets and the benefit obligation that is recognized in accumulated other comprehensive
loss were as follows, net of tax (in thousands):
Pension liability, beginning of year
Plan amendment
Net prior service costs
Net (gain) loss
Pension liability, end of year
$
$
Year Ended December 31,
2020
15,468 $
—
(216)
8,579
2021
23,831 $
6,017
(217)
(5,954)
23,677 $
23,831 $
2019
9,146
—
(214)
6,536
15,468
We expect to contribute a total of $6.4 million to the pension plans in 2022. The following benefit payments,
which reflect expected future service, as appropriate, are expected to be paid (in thousands):
2022
2023
2024
2025
2026
2027-2031
Total
Note 15. Commitments and Contingencies
Commitments
$
$
4,582
4,688
4,760
5,308
5,107
33,815
58,260
In August 2021, we entered into a revolving credit and guaranty agreement (the “Credit Agreement”) among the
Incyte Corporation, as borrower, subsidiary Incyte Holdings Corporation, as a guarantor, a group of lenders (the
“Lenders”), and J.P. Morgan Chase Bank, N.A. as administrative agent. Under the Credit Agreement, the Lenders have
committed to provide an unsecured three-year revolving credit facility in an aggregate principal amount of up to $500.0
million. We may increase the maximum revolving commitments or add one or more incremental term loan facilities to the
Credit Agreement, subject to obtaining commitments from any participating lenders and certain other conditions, in an
amount not to exceed (1) $250.0 million plus (2) an additional amount, so long as after giving effect to the incurrence of
such additional amount, the Company’s pro forma consolidated leverage ratio would not exceed 0.25 above its consolidated
leverage ratio in effect immediately prior to giving effect to such increase.
Loans under the Credit Agreement will bear interest, at our option, at a per annum rate equal to either (a) a base
rate plus an applicable rate per annum varying from 0.125% to 0.875% depending on the consolidated leverage ratio or
(b) a Eurodollar rate plus an applicable rate per annum varying from 1.125% to 1.875% depending on the consolidated
leverage ratio. Commitment fees payable on the undrawn amount range from 0.150% per annum to 0.225% per annum,
based on our consolidated leverage ratio.
As of December 31, 2021, we are in compliance with all financial and operational covenants under the terms of
the Credit Agreement and there were no outstanding borrowings or letters of credit outstanding. We capitalized
approximately $1.3 million in debt issuance costs related to the execution of the Credit Agreement. The debt issuance costs
are being amortized over the term of the facility.
Contingencies
In December 2018, we received a civil investigative demand from the U.S. Department of Justice (“DOJ”) for
documents and information relating to our speaker programs and patient assistance programs, including our support of
non-profit organizations that provide financial assistance to eligible patients. In November 2019, the qui tam complaint
underlying the DOJ inquiry was unsealed (“Complaint”), at which time we learned that a former employee whom we had
terminated had made certain allegations relating to the programs described above. We filed an Answer to the Complaint
118
on January 22, 2020 and on November 12, 2020 we filed a Motion for Summary Judgment (“Motion”). All briefing on
the Motion was completed on December 22, 2020. While we deny that any improper claims were submitted to government
payers, we agreed on May 4, 2021 to settle the matter with the DOJ Civil Division for $12.6 million, plus certain statutory
fees, which was recorded in selling, general and administrative expense during the year ended December 31, 2021.
In the ordinary course of our business, we may become involved in lawsuits, proceedings, and other disputes,
including commercial, intellectual property, regulatory, employment, and other matters. We record a reserve for these
matters when it is both probable that a liability has been incurred and the amount of the loss can be reasonably estimated.
We have entered into the collaboration agreements described in Note 6, as well as various other collaboration
agreements that are not individually, or in the aggregate, significant to our operating results or financial condition at this
time. We may in the future seek to license additional rights relating to technologies or drug development candidates in
connection with our drug discovery and development programs. Under these agreements, we may be required to pay
upfront fees, milestone payments, and royalties on sales of future products.
Note 16. Segment Information
We currently operate in one operating business segment focused on the global discovery, development and
commercialization of proprietary therapeutics. Our determination that we operate as a single segment is consistent with
the financial information regularly reviewed by the chief operating decision maker for purposes of evaluating performance,
allocating resources, setting incentive compensation targets, and planning and forecasting for future periods. We do not
operate in any material separate lines of business or separate business entities with respect to our products or product
development.
During the year ended December 31, 2021, total revenues generated by subsidiaries in the United States was
approximately $2.9 billion and total revenues generated from subsidiaries in Europe was approximately $124.1 million.
During the year ended December 31, 2020, total revenues generated by subsidiaries in the United States was approximately
$2.6 billion and total revenues generated from subsidiaries in Europe was approximately $105.0 million. During the year
ended December 31, 2019, total revenues generated by subsidiaries in the United States was approximately $2.1 billion
and total revenues generated from subsidiaries in Europe was approximately $90.0 million.
As of December 31, 2021, property and equipment, net was approximately $434.2 million in the United States,
approximately $286.8 million in Europe and approximately $2.9 million in Japan. As of December 31, 2020, property and
equipment, net was approximately $336.9 million in the United States and approximately $218.0 million in Europe and
approximately $4.7 million in Japan.
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Not applicable.
Item 9A. Controls and Procedures
Evaluation of disclosure controls and procedures. We maintain “disclosure controls and procedures,” as such
term is defined in Rule 13a-15(e) under the Securities Exchange Act of 1934 (the “Exchange Act”), that are designed to
ensure that information required to be disclosed by us in reports that we file or submit under the Exchange Act is recorded,
processed, summarized, and reported within the time periods specified in Securities and Exchange Commission rules and
forms, and that such information is accumulated and communicated to our management, including our Chief Executive
Officer and Chief Financial Officer, as appropriate, to allow timely decisions regarding required disclosure. In designing
and evaluating our disclosure controls and procedures, management recognized that disclosure controls and procedures,
no matter how well conceived and operated, can provide only reasonable, not absolute, assurance that the objectives of the
disclosure controls and procedures are met. Our disclosure controls and procedures have been designed to meet reasonable
assurance standards. Additionally, in designing disclosure controls and procedures, our management necessarily was
required to apply its judgment in evaluating the cost-benefit relationship of possible disclosure controls and procedures.
The design of any disclosure controls and procedures also is based in part upon certain assumptions about the likelihood
119
of future events, and there can be no assurance that any design will succeed in achieving its stated goals under all potential
future conditions.
Based on their evaluation as of the end of the period covered by this Annual Report on Form 10-K, our Chief
Executive Officer and Chief Financial Officer concluded that, as of such date, our disclosure controls and procedures were
effective at the reasonable assurance level.
Changes in internal control over financial reporting. There were no changes in our internal control over financial
reporting (as defined in Rule 13a-15(f) under the Exchange Act) for the quarter ended December 31, 2021, that have
materially affected or are reasonably likely to materially affect our internal control over financial reporting.
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
Rule 13a-15(f). Because of its inherent limitations, internal control over financial reporting may not prevent or detect
misstatements. Projections of any evaluation of the 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. Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, 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, 2021. The
effectiveness of our internal control over financial reporting as of December 31, 2021 has been audited by Ernst &
Young LLP, an independent registered public accounting firm, as stated in their report which is included herein.
120
Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of Incyte Corporation
Opinion on Internal Control over Financial Reporting
We have audited Incyte Corporation’s internal control over financial reporting as of December 31, 2021, 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, Incyte Corporation (the Company)
maintained, in all material respects, effective internal control over financial reporting as of December 31, 2021, 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 consolidated balance sheets of Incyte Corporation as of December 31, 2021 and 2020, the related
consolidated statements of operations, comprehensive income (loss), stockholders’ equity and cash flows for each of the
three years in the period ended December 31, 2021, and the related notes and our report dated February 8, 2022 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
Philadelphia, Pennsylvania
February 8, 2022
121
Item 9B. Other Information
None.
Item 10. Directors, Executive Officers and Corporate Governance
PART III
The information required by this item (with respect to Directors) is incorporated by reference from the information
under the caption “Election of Directors” contained in our Proxy Statement to be filed with the Securities and Exchange
Commission in connection with the solicitation of proxies for our 2022 Annual Meeting of Stockholders to be held on
June 15, 2022 (the “Proxy Statement”). Certain information required by this item concerning executive officers is set forth
in Part I of this Report under the caption “Information about our Executive Officers” and is incorporated herein by
reference.
Item 405 of Regulation S-K calls for disclosure of any known late filing or failure by an insider to file a report
required by Section 16(a) of the Exchange Act. To the extent disclosure for delinquent reports is being made, it can be
found under the caption “Section 16(a) Beneficial Ownership Reporting Compliance” in the Proxy Statement and is
incorporated herein by reference.
We have adopted a Code of Business Conduct and Ethics that applies to all of our officers and employees,
including our Chief Executive Officer, Chief Financial Officer, Principal Accounting Officer, Corporate Controller and
other employees who perform financial or accounting functions. The Code of Business Conduct and Ethics sets forth the
basic principles that guide the business conduct of our employees. We have also adopted a Senior Financial Officers’ Code
of Ethics that specifically applies to our Chief Executive Officer, Chief Financial Officer, Principal Accounting Officer,
Corporate Controller, and others providing similar functions. Stockholders may request a free copy of our Code of Business
Conduct and Ethics and our Senior Financial Officers’ Code of Ethics by contacting Incyte Corporation, Attention: Investor
Relations, 1801 Augustine Cut-Off, Wilmington, DE 19803 or by visiting the Corporate Governance section of our website
at investor.incyte.com/corporate-governance. Our website address listed in the prior sentence and below is intended to be
an inactive, textual reference only. None of the materials on, or accessible through, our website is part of this report or is
incorporated by reference herein.
To date, there have been no waivers under our Code of Business Conduct and Ethics or Senior Financial Officers’
Code of Ethics. We intend to disclose future amendments to certain provisions of our Code of Business Conduct and Ethics
or Senior Financial Officers’ Code of Ethics or any waivers, if and when granted, of our Code of Business Conduct and
Ethics or Senior Financial Officers’ Code of Ethics on our website at www.incyte.com within four business days following
the date of such amendment or waiver.
Our Board of Directors has appointed an Audit and Finance Committee of three directors, currently comprised of
Mr. Paul J. Clancy, as Chairman, Dr. Wendy L. Dixon and Dr. Jacqualyn A. Fouse. The Board of Directors has also
determined that Mr. Clancy and Dr. Fouse are each qualified as an Audit Committee Financial Expert under the definition
outlined by the Securities and Exchange Commission. In addition, each of the members of the Audit Committee qualifies
as an “independent director” under the applicable standards of The Nasdaq Stock Market.
Item 11. Executive Compensation
The information required by this item is incorporated by reference from the information under the captions
“Compensation of Directors” and “Executive Compensation” contained in the Proxy Statement.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The information required by this item is incorporated by reference from the information under the captions
“Equity Compensation Plan Information” and “Security Ownership of Certain Beneficial Owners and Management”
contained in the Proxy Statement.
122
Item 13. Certain Relationships and Related Transactions, and Director Independence
The information required by this item is incorporated by reference from the information under the captions
“Corporate Governance—Certain Relationships and Related Transactions” and “Corporate Governance—Director
Independence” contained in the Proxy Statement.
Item 14. Principal Accountant Fees and Services
The information required by this item is incorporated by reference from the information under the caption
“Ratification of Independent Registered Public Accounting Firm” contained in the Proxy Statement.
PART IV
Item 15. Exhibits, Financial Statement Schedules
(a)
Documents filed as part of this report:
(1)
Financial Statements
Reference is made to the Index to Consolidated Financial Statements of Incyte Corporation under Item 8
of Part II hereof.
(2)
Financial Statement Schedules
All financial statement schedules have been omitted because they are not applicable or not required or
because the information is included elsewhere in the Consolidated Financial Statements or the Notes
thereto.
(3)
Exhibits
See Item 15(b) below. Each management contract or compensatory plan or arrangement required to be
filed has been identified.
(b)
Exhibits
Exhibit
Number
3(i)
Description of Document
Integrated copy of the Restated Certificate of Incorporation, as amended, of the Company (incorporated
by reference to Exhibit 3(i) to the Company’s Annual Report on Form 10-K for the year ended
December 31, 2009).
3(ii)
Bylaws of the Company, as amended as of February 18, 2021 (incorporated by reference to Exhibit 3.1
to the Company’s Current Report on Form 8-K filed February 19, 2021).
4.1
Form of Common Stock Certificate (incorporated by reference to the Exhibit 4.1 to the Company’s
Annual Report on Form 10-K for the year ended December 31, 2002).
4.2
Description of Registrant’s Securities Registered under Section 12 of the Securities Exchange Act of
10.1#
1934 (incorporated by reference to Exhibit 4.3 to the Company’s Annual Report on Form 10-K for the
year ended December 31, 2019).
Incyte Corporation Amended and Restated 2010 Stock Incentive Plan, as amended and restated
May 13, 2021 (incorporated by reference to Exhibit 10.1 to the Company’s Current Report on
Form 8-K filed May 27, 2021).
10.2#
Form of Global Stock Option Agreement for Executive Officers under the Incyte Corporation
Amended and Restated 2010 Stock Incentive Plan (incorporated by reference to Exhibit 10.1 to the
Company's Quarterly Report on Form 10-Q for the quarter ended September 30, 2020).
123
Exhibit
Number
10.3#
10.4#
Description of Document
Form of Global Restricted Stock Unit Award Agreement under the Incyte Corporation Amended and
Restated 2010 Stock Incentive Plan (incorporated by reference to Exhibit 10.2 to the Company's
Quarterly Report on Form 10-Q for the quarter ended September 30, 2020).
Form of Performance Share Award Agreement under the Incyte Corporation Amended and Restated
2010 Stock Incentive Plan (incorporated by reference to Exhibit 10.3 to the Company's Quarterly
Report on Form 10-Q for the quarter ended September 30, 2020).
10.5#
Form of Nonstatutory Stock Option Agreement for Outside Directors under the Incyte Corporation
10.6#
Amended and Restated 2010 Stock Incentive Plan (incorporated by reference to Exhibit 10.24 to the
Company’s Annual Report on Form 10-K for the year ended December 31, 2013).
Form of Restricted Stock Unit Award Agreement for Outside Directors under the Incyte Corporation
Amended and Restated 2010 Stock Incentive Plan (incorporated by reference to Exhibit 10.1 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2019).
10.7#
Form of Indemnity Agreement between the Company and its directors and officers (incorporated by
10.8#
reference to Exhibit 10.5 to the Company’s Registration Statement on Form S-1 (File No. 33 68138)).
1997 Employee Stock Purchase Plan of Incyte Corporation, as amended and restated effective
November 17, 2020 (incorporated by reference to Exhibit 10.8 to the Company’s Annual Report on
Form 10-K for the year ended December 31, 2020).
10.9#
Form of Employment Agreement between the Company and Barry P. Flannelly (effective as of
August 11, 2014), Christiana Stamoulis (effective as of February 11, 2019), Steven H. Stein (effective
as of March 2, 2015), Vijay K. Iyengar (effective as of May 9, 2016), Maria E. Pasquale (effective as of
April 9, 2018) and Dashyant Dhanak (effective as of December 10, 2018) (incorporated by reference to
Exhibit 10.14 to the Company’s Annual Report on Form 10-K for the year ended December 31, 2012).
Form of Amended and Restated Employment Agreement, effective as of April 18, 2012, between the
Company and Paula J. Swain (incorporated by reference to Exhibit 10.14 to the Company’s Quarterly
Report on Form 10-Q for the quarter ended March 31, 2012).
Offer of Employment Letter, dated December 14, 2018, from the Company to Christiana Stamoulis
(incorporated by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q for the
quarter ended March 31, 2019).
Amended and Restated Employment Agreement between the Company and Hervé Hoppenot, dated as
of October 25, 2019 (incorporated by reference to Exhibit 10.3 to the Company’s Quarterly Report on
Form 10-Q for the quarter ended September 30, 2019).
10.10#
10.11#
10.12#
10.13†
Collaboration and License Agreement entered into as of November 24, 2009, by and between the
10.13.1†
Company and Novartis International Pharmaceutical Ltd. (incorporated by reference to Exhibit 10.1 to
the Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019).
Amendment, dated as of April 5, 2016, to Collaboration and License Agreement entered into as of
November 24, 2009, by and between the Company and Novartis International Pharmaceutical Ltd.
(incorporated by reference to Exhibit 10.1.1 to the Company’s Quarterly Report on Form 10-Q for the
quarter ended September 30, 2019).
10.13.2†† Amendment, dated as of March 20, 2020, to the Collaboration and License Agreement entered into as
of November 24, 2009, by and between the Company and Novartis International Pharmaceutical Ltd.
(incorporated by reference to Exhibit 10.2 to the Company’s Quarterly Report on Form 10-Q for the
quarter ended March 31, 2020).
10.14†
License, Development and Commercialization Agreement, entered into as of December 18, 2009, by
10.14.1†
and between the Company and Eli Lilly and Company (incorporated by reference to Exhibit 10.2 to the
Company’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2019).
Amendment, dated June 22, 2010, to License, Development and Commercialization Agreement entered
into as of December 18, 2009, by and between the Company and Eli Lilly and Company (incorporated
by reference to Exhibit 10.2.1 to the Company’s Quarterly Report on Form 10-Q for the quarter ended
September 30, 2019).
10.14.2†
Third Amendment, entered into effective March 31, 2016, to License, Development and
Commercialization Agreement entered into as of December 18, 2009, by and between the Company
and Eli Lilly and Company (incorporated by reference to Exhibit 10.2.2 to the Company’s Quarterly
Report on Form 10-Q for the quarter ended September 30, 2019).
124
Exhibit
Number
10.14.3†
Fourth Amendment, entered into effective December 13, 2016, to License, Development and
Commercialization Agreement entered into as of December 18, 2009, by and between the Company
and Eli Lilly and Company (incorporated by reference to Exhibit 10.21.4 to Amendment No. 2 on
Form 10-K/A to the Company’s Annual Report on Form 10-K for the year ended December 31, 2016).
Description of Document
10.14.4†† Letter Agreement, dated May 13, 2020, between the Company and Eli Lilly and Company, together
with related Letter of Understanding, dated March 5, 2020, between the Company and Eli Lilly and
Company, each relating to License, Development and Commercialization Agreement entered into as of
December 18, 2009 by and between the Company and Eli Lilly and Company (incorporated by
reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for the quarter ended
June 30, 2020).
10.15†
10.15.1†
License, Development and Commercialization Agreement, dated as of January 9, 2015, by and among
the Company, Incyte Europe S.à.r.l. (a wholly owned subsidiary of the Company), Agenus Inc. and
4-Antibody AG (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on
Form 10-Q for the quarter ended March 31, 2015).
First Amendment, dated as of February 14, 2017, to License, Development and Commercialization
Agreement entered into as of January 9, 2015, by and among the Company, Incyte Europe S.à.r.l. (a
wholly owned subsidiary of the Company), Agenus Inc. and Agenus Switzerland Inc. (f/k/a 4-Antibody
AG) (incorporated by reference to Exhibit 10.1 to the Company's Quarterly Report on Form 10-Q for
the quarter ended March 31, 2017).
10.16†
Amended and Restated Buy-In License Agreement, dated as of June 1, 2016, between ARIAD
Pharmaceuticals, Inc., ARIAD Pharmaceuticals (Europe) S.à.r.l. and the Company, as guarantor
(incorporated by reference to Exhibit 10.3 to Amendment No. 1 on Form 10-Q/A to the Company’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2016).
10.17†
Collaboration and License Agreement, dated December 20, 2016, by and between the Company and
Merus N.V. (incorporated by reference to Exhibit 10.27 to Amendment No. 2 on Form 10-K/A to the
Company’s Annual Report on Form 10-K for the year ended December 31, 2016).
10.18†
Global Collaboration and License Agreement, dated October 24, 2017, by and between the Company
10.18.1†
10.19††
10.19.1††
and MacroGenics, Inc. (incorporated by reference to Exhibit 10.23 to the Company's Annual Report on
Form 10-K for the year ended December 31, 2017).
Amendment No. 1, dated as of March 15, 2018, to Global Collaboration and License Agreement, dated
October 24, 2017, by and between the Company and MacroGenics, Inc. (incorporated by reference to
Exhibit 10.1 to the Company's Quarterly Report on Form 10-Q for the quarter ended March 31, 2018).
Collaboration and License Agreement entered into as of January 12, 2020 by and among the Company,
MorphoSys AG and MorphoSys US Inc. (incorporated by reference to Exhibit 10.1 to the Company’s
Quarterly Report on Form 10-Q for the quarter ended March 31, 2020).
First Amendment, dated as of July 17, 2020, to Collaboration and License Agreement entered into as of
January 12, 2020 by and among the Company, MorphoSys AG and MorphoSys US Inc. (incorporated
by reference to Exhibit 10.19.1 to the Company’s Annual Report on Form 10-K for the year ended
December 31, 2020).
10.19.2
Second Amendment, dated as of January 8, 2021, to Collaboration and License Agreement entered into
10.20
as of January 12, 2020 by and among the Company, MorphoSys AG and MorphoSys US Inc.
(incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for the
quarter ended March 31, 2021).
Registration Rights Agreement, dated as of February 12, 2016, between the Company and 667, L.P.,
Baker Brothers Life Sciences, L.P. and 14159, L.P. (incorporated by reference to Exhibit 10.28 to the
Company’s Annual Report on Form 10-K for the year ended December 31, 2015).
10.21
Revolving Credit and Guaranty Agreement, dated as of August 18, 2021, among the Company, the
guarantors party thereto, the lenders party thereto, and JPMorgan Chase Bank, N.A., as Administrative
Agent (incorporated by reference to Exhibit 10.1 to the Company’s Quarterly Report on Form 10-Q for
the quarter ended September 30, 2021).
21.1*
23.1*
24.1*
Subsidiaries of the Company.
Consent of Ernst & Young LLP, Independent Registered Public Accounting Firm.
Power of Attorney (included on the signature page to this Annual Report on Form 10-K).
125
Exhibit
Number
31.1*
31.2*
32.1**
Rule 13a 14(a) Certification of the Chief Executive Officer.
Rule 13a 14(a) Certification of the Chief Financial Officer.
Statement of the Chief Executive Officer under Section 906 of the Sarbanes Oxley Act of 2002 (18
U.S.C Section 1350).
Description of Document
32.2**
Statement of the Chief Financial Officer under Section 906 of the Sarbanes Oxley Act of 2002 (18
U.S.C Section 1350).
101
XBRL Instance – the instance document does not appear in the Interactive Data File because its XBRL
tags are embedded within the Inline XBRL document
XBRL Instance Document
101.INS*
101.SCH*
XBRL Taxonomy Extension Schema Document
101.CAL* XBRL Taxonomy Extension Calculation Linkbase Document
101.LAB* XBRL Taxonomy Extension Label Linkbase Document
101.PRE*
101.DEF*
104
XBRL Taxonomy Presentation Linkbase Document
XBRL Taxonomy Definition Linkbase Document
Cover Page Interactive Data File (embedded within the Inline XBRL document).
*
**
†
††
#
Filed herewith.
In accordance with Item 601(b)(32)(ii) of Regulation S-K and SEC Release Nos. 33-8238 and 34-47986, Final
Rule: Management’s Reports on Internal Control Over Financial Reporting and Certification of Disclosure in
Exchange Act Periodic Reports, the certifications furnished in Exhibits 32.1 and 32.2 hereto are deemed to
accompany this Form 10-K and will not be deemed “filed” for purpose of Section 18 of the Exchange Act. Such
certifications will not be deemed to be incorporated by reference into any filing under the Securities Act or the
Exchange Act, except to the extent that the registrant specifically incorporates it by reference.
Confidential treatment has been granted with respect to certain portions of these agreements.
Portions of this exhibit have been omitted pursuant to Item 601(b)(10)(iv) of Regulation S-K.
Indicates management contract or compensatory plan or arrangement.
Copies of above exhibits not contained herein are available to any stockholder upon written request to: Investor
Relations, Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE 19803.
(c)
Financial Statements and Schedules
Reference is made to Item 15(a)(2) above.
Item 16. Form 10-K Summary.
Not applicable.
126
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has
duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
SIGNATURES
INCYTE CORPORATION
By:/s/ HERVÉ HOPPENOT
Hervé Hoppenot
Chairman, President, and Chief Executive
Officer
Date: February 8, 2022
127
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes
and appoints Hervé Hoppenot, Christiana Stamoulis, and Maria E. Pasquale, and each of them, his true and lawful
attorneys-in-fact, each with full power of substitution, for him or her in any and all capacities, to sign any amendments to
this report on Form 10-K and to file the same, with exhibits thereto and other documents in connection therewith, with the
Securities and Exchange Commission, hereby ratifying and confirming all that each of said attorneys-in-fact or their
substitute or substitutes may do or cause to be done by virtue hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the
following persons on behalf of the registrant and in the capacities and on the dates indicated.
Signature
Title
Chairman, President, and Chief Executive Officer
(Principal Executive Officer) and Director
Date
February 8, 2022
/s/ HERVÉ HOPPENOT
Hervé Hoppenot
/s/ CHRISTIANA STAMOULIS
Christiana Stamoulis
/s/ PAUL TROWER
Paul Trower
Chief Financial Officer (Principal Financial Officer)
February 8, 2022
Division VP, Finance (Principal Accounting Officer)
February 8, 2022
February 8, 2022
February 8, 2022
February 8, 2022
February 8, 2022
February 8, 2022
February 8, 2022
February 8, 2022
February 8, 2022
/s/ JULIAN C. BAKER
Julian C. Baker
Director
/s/ JEAN-JACQUES BIENAIMÉ
Jean-Jacques Bienaimé
Director
/s/ OTIS W. BRAWLEY
Otis W. Brawley
/s/ PAUL J. CLANCY
Paul J. Clancy
/s/ WENDY L. DIXON
Wendy L. Dixon
/s/ JACQUALYN A. FOUSE
Jacqualyn A. Fouse
/s/ EDMUND P. HARRIGAN
Edmund P. Harrigan
/s/ KATHERINE A. HIGH
Katherine A. High
Director
Director
Director
Director
Director
Director
128
STOCK PRICE PERFORMANCE GRAPH
The following graph illustrates a comparison of the cumulative total stockholder return (change in stock price
plus reinvested dividends) of the Company’s Common Stock, the Total Return Index for the Nasdaq U.S. Stocks (the
“Nasdaq Composite Index”), and the Total Return Index for the Nasdaq Biotechnology Stocks (the “Nasdaq Biotechnology
Index”) assuming an investment of $100 in each on December 31, 2016. The Company’s Common Stock is traded on The
Nasdaq Global Select Market. The graph is required by the Securities and Exchange Commission and is not intended to
forecast or be indicative of possible future performance of the Company’s Common Stock.
COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN*
Among Incyte Corporation, the NASDAQ Composite Index
and the NASDAQ Biotechnology Index
$350
$300
$250
$200
$150
$100
$50
$0
12/16
12/17
12/18
12/19
12/20
12/21
Incyte Corporation
NASDAQ Composite
NASDAQ Biotechnology
*$100 invested on 12/31/16 in stock or index, including reinvestment of dividends.
Fiscal year ending December 31.
129