Vanda Pharmaceuticals Inc. Annual Report 2021

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FY2021 Annual Report · Vanda Pharmaceuticals Inc.

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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549

Form 10-K

☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the fiscal year ended December 31, 2021

☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF

1934

Commission File No. 001-34186

VANDA PHARMACEUTICALS INC.

(Exact name of registrant as specified in its charter)

Delaware
(State or other jurisdiction of
incorporation or organization)

03-0491827
(I.R.S. Employer
Identification No.)

2200 Pennsylvania Avenue NW, Suite 300 E
Washington, DC 20037
(Address of principal executive offices)

(202) 734-3400
(Registrant’s telephone number, including area code)

Securities registered pursuant to Section 12(b) of the Exchange Act:

Title of each class
Common Stock, par value $0.001 per share

Trading Symbol(s)
VNDA

Name of each exchange on which registered
The Nasdaq Global Market

Securities registered pursuant to Section 12(g) of the Exchange 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 Exchange 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

Non-accelerated filer

☒ 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. Yes ☒ No ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Securities Exchange Act of 1934). Yes ☐ No ☒

As of June 30, 2021, the last business day of the registrant’s last completed second quarter, the aggregate market value of the Common Stock held by non-
affiliates of the registrant was approximately $1,169.3 million based on the closing price of the registrant’s Common Stock, as reported by The Nasdaq
Global Market, on such date. Shares of Common Stock held by each executive officer and director have been excluded since such persons may be deemed
affiliates. This determination of affiliate status is not necessarily a conclusive determination for other purposes.

The number of shares of the registrant’s Common Stock, par value $0.001 per share, outstanding as of February 17, 2022 was 55,906,855.

The Exhibit Index as required by Item 601(a) of Regulation S-K is included in Item 15 of Part IV of this report.

DOCUMENTS INCORPORATED BY REFERENCE

Specified portions of the registrant’s proxy statement with respect to the registrant’s 2022 Annual Meeting of Stockholders, which is to be filed pursuant to
Regulation 14A within 120 days after the end of the registrant’s fiscal year ended December 31, 2021, are incorporated by reference into Part III of this
Form 10-K.

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Vanda Pharmaceuticals Inc.
Form 10-K

Table of Contents

Part I

Cautionary Note Regarding Forward-Looking Statements
Summary of Principal Risk Factors
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures

Part II

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
Qualitative and Quantitative Disclosures about Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Part III

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

Part IV

Item 1
Item 1A
Item 1B
Item 2
Item 3
Item 4

Item 5
Item 6
Item 7
Item 7A
Item 8
Item 9
Item 9A
Item 9B
Item 9C

Item 10
Item 11
Item 12
Item 13
Item 14

Exhibits and Financial Statement Schedules

Item 15
Signatures
Exhibit Index

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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

PART I

This annual report on Form 10-K (Annual Report) contains “forward-looking statements” within the meaning of Section 27A of the Securities Act
of 1933, as amended (Securities Act) and Section 21E of the Securities Exchange Act of 1934, as amended (Exchange Act). Words such as, but not limited
to, “believe,” “expect,” “anticipate,” “estimate,” “intend,” “plan,” “project,” “target,” “goal,” “likely,” “will,” “would,” and “could,” or the negative of
these terms and similar expressions or words, identify forward-looking statements. Forward-looking statements are based upon current expectations and
assumptions that involve risks, changes in circumstances and uncertainties. If the risks, changes in circumstances or uncertainties materialize or the
assumptions prove incorrect, the results of Vanda Pharmaceuticals Inc. (we, our, the Company or Vanda) may differ materially from those expressed or
implied by such forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking
statements. The forward-looking statements in this Annual Report may include, but are not limited to, statements about:

•

our ability to continue to commercialize HETLIOZ (tasimelteon) capsules for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24)
in the United States (U.S.) and Europe and HETLIOZ capsules and oral suspension (HETLIOZ LQ ) for the treatment of nighttime sleep
disturbances in Smith-Magenis Syndrome (SMS) in the U.S.;

our ability to increase market awareness of Non-24 and SMS and market acceptance of HETLIOZ ;
®

our ability to overcome the increased reimbursement and patient access challenges we face as a result of declining third-party payor coverage;

our ability to continue to generate U.S. sales of Fanapt (iloperidone) oral tablets for the treatment of schizophrenia;

our ability to obtain regulatory approval for tradipitant from the U.S. Food and Drug Administration (FDA);

the impact of the novel coronavirus (COVID-19) on our business and operations, including our revenue, our supply chain, our commercial
activities, our ongoing and planned clinical trial and our regulatory activities;

our dependence on third-party manufacturers to manufacture HETLIOZ , HETLIOZ LQ , and Fanapt in sufficient quantities and quality;

our ability to prepare, file, prosecute, defend and enforce any patent claims and other intellectual property rights;

our ability to maintain rights to develop and commercialize our products under our license agreements;

our ability to obtain and maintain regulatory approval of our products, and the labeling for any approved products;

our level of success in commercializing HETLIOZ and Fanapt in new markets;

our ability to obtain approval from the FDA for HETLIOZ for the treatment of jet lag disorder;

our expectations regarding the timing and success of preclinical studies and clinical trials;

the safety and efficacy of our products;

regulatory developments in the U.S., Europe and other jurisdictions;

limitations on our ability to utilize some or all of our prior net operating losses and orphan drug and research and development credits;

the size and growth of the potential markets for our products and our ability to serve those markets;

our expectations regarding trends with respect to our revenues, costs, expenses, liabilities and cash, cash equivalents and marketable
securities;

our ability to identify or obtain rights to new products;

our ability to attract and retain key scientific or management personnel;

the cost and effects of litigation;

our ability to obtain the capital necessary to fund our research and development or commercial activities;

potential losses incurred from product liability claims made against us; and

the use of our existing cash, cash equivalents and marketable securities.

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All written and verbal forward-looking statements attributable to us or any person acting on our behalf are expressly qualified in their entirety by the
cautionary statements contained throughout this report. We caution you not to rely too heavily on the forward-looking statements we make or that are made
on our behalf. Each forward-looking statement speaks only as of the date of this Annual Report, and we undertake no obligation, and specifically decline
any obligation, to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as
required by law.

We encourage you to read Part II, Item 7, Management’s Discussion and Analysis of Financial Condition and Results of Operations, and our

consolidated financial statements contained in this Annual Report. We also encourage you to read Summary of Principal Risk Factors below and Part I,
Item 1A of this Annual Report, entitled Risk Factors, which contains a more complete discussion of the risks and uncertainties associated with our
business. In addition to the risks described in this Annual Report, other unknown or unpredictable factors also could affect our results. Therefore, the
information in this report should be read together with other reports and documents that we file with the Securities and Exchange Commission from time to
time, including on Form 10-Q and Form 8-K, which may supplement, modify, supersede or update those risk factors. As a result of these factors, we cannot
assure you that the forward-looking statements in this report will prove to be accurate. Furthermore, if our forward-looking statements prove to be
inaccurate, the inaccuracy may be material. In light of the significant uncertainties in these forward-looking statements, you should not regard these
statements as a representation or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame, or at all.

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This summary briefly lists the principal risks and uncertainties facing our business, which are only a select portion of those risks. A more complete

discussion of those risks and uncertainties is set forth in Part I, Item 1A of this Annual Report, entitled Risk Factors. Additional risks not presently known
to us or that we currently deem immaterial may also affect us. If any of these risks occur, our business, financial condition or results of operations could be
materially and adversely affected.

SUMMARY OF PRINCIPAL RISK FACTORS

Our business is subject to the following principal risks and uncertainties:

Risks Related to our Business and Industry

• We are dependent on the commercial success of HETLIOZ and Fanapt .
®
®

•

Future performance of HETLIOZ and Fanapt
safety issues.

may be impacted by a number of factors including competing products or unanticipated

• We are subject to uncertainty relating to pricing and reimbursement policies in the U.S.
®
• We have experienced an increase in the rate at which third-party payors refuse to cover or reimburse prescriptions written for HETLIOZ .

•

The FDA may not accept our tradipitant New Drug Application (NDA) or supplemental New Drug Application (sNDA) filings for the
treatment of gastroparesis and motion sickness, or the FDA may determine that our clinical trial results for tradipitant for these indications do
not demonstrate adequate safety and substantial evidence of efficacy.
• Global economic conditions may have an adverse effect on our business.
• Global health crises and pandemics, such as the global outbreak of COVID-19, may adversely impact our business.

The FDA may not approve our sNDA for HETLIOZ for the treatment jet lag disorder.

•
• We may be unable to enter into third-party collaborations to develop and commercialize our products, or collaborations we enter into with any

such third party may not be commercially successful.

Even after we obtain regulatory approvals of a product, acceptance of the product in the marketplace is uncertain.

•
• We rely on, and will continue to rely on, outsourcing arrangements for many of our activities, including preclinical and clinical development

and supply of HETLIOZ , HETLIOZ LQ , Fanapt and our other products.

• We may experience disruptions to our HETLIOZ , HETLIOZ LQ or Fanapt supply chains.

• We may fail to comply with government regulations regarding the sale and marketing of our products.
• We may fail to comply with regulations and obligations related to the ongoing oversight of our products regarding, among other things,

development, manufacturing, labeling, recording keeping and reporting.

• We may not market or distribute our products in a manner compliant with federal or state healthcare fraud and abuse laws.
• We rely on a limited number of specialty pharmacies for distribution of HETLIOZ in the U.S., and the loss of one or more of these specialty

®
pharmacies or their failure to distribute HETLIOZ effectively would materially harm our business.

®
• Our revenues from Fanapt

are substantially dependent on sales through a limited number of wholesalers.

• We face substantial competition, which may result in others developing or commercializing products before or more successfully than we do.
•

FDA and foreign regulatory approval of our products is uncertain.

• Our products may cause undesirable side effects or have other properties that could delay, prevent or result in the revocation of their

regulatory approval or limit their marketability.

•

Clinical trials for our products are expensive and their outcomes are uncertain.

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• Our ability to use net operating loss carryforwards and tax credit carryforwards to offset future taxable income is dependent on generating

future taxable income and may be limited, including as a result of transactions involving our common stock.

• Our contract research organizations (CROs) may not successfully carry out their duties or we may lose our relationships with CROs.

• We rely on a limited number of third-party manufacturers to formulate and manufacture our products and these manufacturers may not able to

satisfy our demand and alternative sources may not be available.

• Materials necessary to manufacture our products may not be available on commercially reasonable terms, or at all.

• We may lose key scientists or management personnel or fail to recruit additional highly skilled personnel.
• We may be subject to product liability lawsuits.

•

European Union (E.U.) Member States tend to impose strict price controls, which may delay or prevent the further commercial launch or
impede the commercial success of HETLIOZ in Europe and adversely affect our future results of operations.

• We may not be able to effectively market and sell our future products, if approved, in the U.S.
• Healthcare legislative reform measures or developments arising from changes in political climate may have a material adverse effect on our

business and results of operations.

• We are subject to stringent laws, rules, regulations, policies, industry standards and contractual obligations regarding data privacy and security

in foreign jurisdictions which are subject to change and reinterpretation.

Risks Related to Intellectual Property and Other Legal Matters

• Our rights to develop and commercialize our products are subject in part to the terms and conditions of licenses or sublicenses granted to us

by other pharmaceutical companies.

• Our efforts to protect the proprietary nature of the intellectual property related to our products may not be adequate.

• We are, have been, and may continue to be, involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming

and unsuccessful, and third parties may challenge the validity or enforceability of our patents and they may be successful.

• We may not be able to obtain protection under the Hatch-Waxman Act and similar foreign legislation to extend our patents and to obtain

market exclusivity for our products.

• We may not be successful in the development of products for our own account.

•

Litigation or third-party claims of intellectual property infringement could require us to divert resources and may prevent or delay our drug
discovery and development efforts.

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ITEM 1.

BUSINESS

Overview

Vanda Pharmaceuticals Inc. (we, our, the Company or Vanda) is a leading global biopharmaceutical company focused on the development and

commercialization of innovative therapies to address high unmet medical needs and improve the lives of patients.

We strive to advance novel approaches to bring important, new medicines to market through responsible innovation. We are committed to the use

of technologies that support sound science, including genetics and genomics, in drug discovery, clinical trials and the commercial positioning of our
products.

Our commercial portfolio is currently comprised of two products, HETLIOZ for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24)
®
and nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) and Fanapt for the treatment of schizophrenia. HETLIOZ is the first treatment for
patients with Non-24 and SMS approved by the FDA. In addition, we have a number of drugs in development, including:

• HETLIOZ (tasimelteon) for the treatment of jet lag disorder, delayed sleep phase disorder (DSPD), symptoms of autism spectrum disorder

(ASD) and pediatric Non-24;

•

Fanapt (iloperidone) for the treatment of bipolar disorder and Parkinson’s disease psychosis and a long acting injectable (LAI) formulation
for the treatment of schizophrenia;

Tradipitant (VLY-686), a small molecule neurokinin-1 (NK-1) receptor antagonist, for the treatment of gastroparesis, motion sickness, atopic
dermatitis, and COVID-19 pneumonia;

• VTR-297, a small molecule histone deacetylase (HDAC) inhibitor for the treatment of hematologic malignancies and with potential use as a

treatment for several oncology indications;

•

Portfolio of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activators and inhibitors, including VSJ-110 for the treatment of
dry eye and ocular inflammation and BPO-27 for the treatment of secretory diarrhea disorders, including cholera;

• VQW-765, a small molecule nicotinic acetylcholine receptor partial agonist, with potential use for the treatment of psychiatric disorders; and

• VHX-896 (formerly P88), the active metabolite of iloperidone.

We were incorporated in 2002 and commenced operations in 2003. We are headquartered in Washington, D.C.

Our Strategy

Our goal is to further solidify our position as a leading global biopharmaceutical company focused on developing and commercializing innovative

therapies addressing high unmet medical needs through the application of our drug development expertise and our pharmacogenetics and
pharmacogenomics expertise. The key elements of our strategy to accomplish this goal are to:

• Maximize the commercial success of HETLIOZ and Fanapt ;
®

•

Enter into strategic partnerships to supplement our capabilities and to extend our commercial reach;

Pursue the clinical development and regulatory approval of our products, including tradipitant;

Apply our pharmacogenetics and pharmacogenomics expertise to differentiate our products;

Expand our product portfolio through the identification and acquisition of additional products; and

• Utilize novel and innovative approaches in pursuit of each of these strategies.

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Commercialized Products

Our commercial product portfolio consists of:

Product

Indication

Non-24 (capsules)

Nighttime sleep disturbances in
SMS (capsules and HETLIOZ
LQ oral suspension)

2021 Net Sales (in millions)
$173.5

Geography

United States

Europe (Non-24 in blind patients
only)

Schizophrenia (tablets)

$95.1

United States

Israel

HETLIOZ for Non-24 (capsules)

In January 2014, HETLIOZ capsules were approved in the U.S. for the treatment of adults with Non-24. Non-24 is a serious, rare and chronic

circadian rhythm sleep-wake disorder characterized by the inability to entrain (synchronize) the master body clock with the 24-hour day-night cycle.
HETLIOZ is the first FDA approved treatment for Non-24. HETLIOZ is a melatonin agonist of the human MT1 and MT2 receptors, with greater
specificity for MT2. These receptors are thought to be involved in the control of circadian rhythms. HETLIOZ is believed to reset the master body clock
in the suprachiasmatic nucleus, located in the hypothalamus, resulting in the entrainment and alignment of the body’s melatonin and cortisol rhythms to the
24-hour day-night cycle.

Most people have a master body clock that naturally runs longer than 24 hours and light is the primary environmental cue that resets it to 24 hours

each day. Individuals with Non-24 have a master body clock that is not reset, and continually delays, resulting in prolonged periods of misalignment
between their circadian rhythms and the 24-hour day-night cycle, including the timing of melatonin and cortisol secretion. As a result of this misalignment,
Non-24 is associated with significant disruption of the sleep-wake cycle and impairments in social and occupational functioning, and marked subjective
distress. Individuals with Non-24 cycle in and out of phase and suffer from disrupted nighttime sleep patterns and/or excessive daytime sleepiness.

HETLIOZ was launched commercially in the U.S. in April 2014. In addition, in July 2015, the European Commission (EC) granted centralized

marketing authorization with unified labeling for HETLIOZ for the treatment of Non-24 in totally blind adults and included post-marketing commitments
related to a pediatric investigation plan. This authorization was renewed in July 2020 for an unlimited duration, and is valid in the 27 countries that are
members of the European Union (E.U.), as well as European Economic Area members Iceland, Liechtenstein and Norway. HETLIOZ was launched
commercially in Germany in August 2016.

In January 2010, the FDA granted orphan drug designation status for HETLIOZ in Non-24 in blind individuals. The FDA grants orphan drug

designation to drugs that may provide significant therapeutic advantage over existing treatments and target conditions affecting 200,000 or fewer U.S.
patients per year. Orphan drug designation provides potential financial and regulatory incentives, including study design assistance, tax credits, waiver of
FDA user fees, and up to seven years of market exclusivity upon marketing approval. In February 2011, the European Medicines Agency (EMA)
designated HETLIOZ as an orphan medicinal product for the same indication.

Non-24 affects a majority of totally blind individuals, or approximately 80,000 people in the U.S. Blind individuals who develop Non-24 lack the

light sensitivity necessary to synchronize the master body clock in the brain with the 24-hour day-night cycle. Non-24 also can affect sighted individuals.
As with the totally blind, Non-24 in sighted individuals appears to be a comorbidity with certain other conditions. For example, a comorbidity has been
established between psychiatric mood disorders and Non-24. Hospitalized individuals with neurological and psychiatric disorders can become insensitive
to social cues, which

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may predispose them to the development of Non-24. This recognition of comorbidity led Vanda to an initiative to engage with the psychiatric community.
Patients diagnosed with traumatic brain injury, including concussions, frequently suffer from sleep disorders, some of which may be circadian rhythm
sleep-wake disorders, including Non-24.

While there are no FDA or EC approved treatments for Non-24 other than HETLIOZ , there are a number of drugs approved and prescribed for
patients with sleep disorders. The most commonly prescribed drugs are hypnotics. See Competition below for a discussion of commonly prescribed drugs
for patients with sleep disorders.

HETLIOZ for SMS (capsules and oral suspension)

In December 2020, HETLIOZ capsules and oral suspension (HETLIOZ LQ ) were approved in the U.S. for the treatment of adults and
®
children, respectively, with nighttime sleep disturbances in SMS. HETLIOZ capsules, for adults with SMS, were immediately available after approval and
the HETLIOZ LQ™ liquid formulation, for children with SMS, became available in the first quarter of 2021. SMS is a developmental disorder that is
caused by a small deletion of human chromosome 17p. In more rare cases, SMS is caused by a point mutation in the RAI1 gene, which resides in the
deleted region. HETLIOZ is the first FDA-approved medication for patients with SMS.

In April 2010, the FDA granted orphan drug designation status for HETLIOZ in the treatment of sleep disorder in SMS. SMS is estimated to

affect 1/15,000-25,000 births in the U.S. SMS is not usually inherited but rather is caused by a de-novo deletion. Patients with SMS present with a number
of physical, mental and behavioral problems. The most common symptom of SMS is a severe sleep disorder associated with significant disruption in the
lives of patients and their families.

While there are no FDA approved treatments for patients with SMS other than HETLIOZ , there are a number of drugs approved and prescribed
for patients with sleep disorders that may be used to treat patients with SMS. The most commonly prescribed drugs are hypnotics. See Competition below
for a discussion of commonly prescribed drugs for patients with sleep disorders.

Fanapt for schizophrenia (tablets)

Fanapt is a product approved for the treatment of schizophrenia. In May 2009, the FDA granted U.S. marketing approval of Fanapt for the acute

treatment of schizophrenia in adults. At that time, we had certain worldwide exclusive rights relating to Fanapt , which we obtained pursuant to a
sublicense agreement entered into with Novartis Pharma AG (Novartis) in June 2004. In October 2009, we amended and restated our sublicense agreement
with Novartis pursuant to which Novartis retained exclusive commercialization rights to all formulations of Fanapt in the U.S. and Canada. In January
2010, Novartis launched Fanapt in the U.S. On December 31, 2014, Novartis transferred all the U.S. and Canadian commercial rights to the Fanapt
®
franchise to us as part of a settlement agreement. Additionally, our distribution partners launched Fanapt in Israel in 2014. In May 2016, the FDA
approved a supplemental New Drug Application (sNDA) for Fanapt for the maintenance treatment of schizophrenia in adults.

Schizophrenia is a chronic, debilitating mental disorder characterized by hallucinations, delusions, racing thoughts and other psychotic symptoms

(collectively referred to as “positive symptoms”), as well as moodiness, anhedonia (inability to feel pleasure), loss of interest, eating disturbances and
withdrawal (collectively referred to as “negative symptoms”), and attention and memory deficits (collectively referred to as “cognitive symptoms”).
Schizophrenia develops in late adolescence or early adulthood in approximately 1% of the world’s population. Most schizophrenia patients today are
treated with drugs known as “atypical” antipsychotics, which were first approved in the U.S. in the late 1980s. These antipsychotics have been named
“atypical” for their ability to treat a broader range of negative symptoms than the first-generation “typical” antipsychotics, which were introduced in the
1950s and are now generic. Atypical antipsychotics are generally regarded as having improved side effect profiles and efficacy relative to typical
antipsychotics. See Competition below for a discussion of commonly prescribed atypical antipsychotics in addition to Fanapt .
®

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Research and Development

We have built a research and development organization that includes extensive expertise in the scientific disciplines of pharmacogenetics and
pharmacogenomics. We operate cross-functionally and are led by an experienced research and development management team. We use rigorous project
management techniques to assist us in making disciplined strategic research and development program decisions and to help limit the risk profile of our
product pipeline. We also access relevant market information and key opinion leaders in creating target product profiles and, when appropriate, as we
advance our programs towards commercialization. We engage third parties to conduct portions of our preclinical research. In addition, we utilize multiple
clinical sites to conduct our clinical trials; however, we are not substantially dependent upon any one of these sites for our clinical trials nor do any of them
conduct a major portion of our clinical trials.

Our product pipeline currently consists of the following products in clinical development or under regulatory review:

HETLIOZ for jet lag disorder

In March and May 2018, respectively, we announced the results of our JET8 and JET studies for the treatment of jet lag disorder. In the JET8

clinical study, HETLIOZ demonstrated significant and clinically meaningful benefits in nighttime and daytime symptoms of jet lag disorder, including
improvement in sleep time and benefits in measurements of next day alertness. The JET study showed effectiveness in treating travelers who traveled either
five or eight time zones from Washington, DC to London and San Francisco or Los Angeles to London, respectively. The results support the previously
reported pivotal JET5 and JET8 Phase III studies, which demonstrated improvements in patients who experienced circadian advances of five and eight
hours, respectively. Additionally, in September 2018, we announced results from a driving study, which demonstrated that tasimelteon did not impair
measures of driving performance.

The FDA accepted the filing of our sNDA for HETLIOZ for the treatment of jet lag disorder in December 2018. The FDA determined the action

target date under the Prescription Drug User Fee Act Amendments of 2017 (PDUFA) to be August 16, 2019, and on that date, we received a complete
response letter (CRL) from the FDA. The FDA asserted in the CRL that the measures demonstrating improved sleep were of unclear clinical significance.
We met with the FDA to discuss the CRL in a Post Action meeting and we are determining our next steps.

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Jet lag disorder is a common circadian disorder frequently observed in millions of travelers who cross multiple time zones. Jet lag disorder is

characterized by nighttime sleep disruption, a decrease in daytime alertness and impairment to social and occupational functioning. Jet lag disorder
symptoms are more severe during eastward travel. U.S. Department of Commerce, International Trade Administration reports state that more than 20
million U.S. residents make trips abroad each year to overseas destinations in Europe, the Middle East and Asia.

HETLIOZ for pediatric Non-24

We plan to develop HETLIOZ for the treatment of pediatric Non-24. A pharmacokinetic study of the HETLIOZ pediatric liquid formulation

was completed in the first quarter of 2018.

®
HETLIOZ for DSPD

A Phase III study of HETLIOZ in DSPD is ongoing. DSPD is a circadian rhythm disorder in which a person’s sleep is delayed beyond the

socially acceptable or conventional bedtime. This delay in falling asleep causes difficulty in waking up at the desired time and affects social and
occupational functioning. DSPD is likely the most prevalent circadian-rhythm sleep disorder, affecting approximately 1% of the population, and there is no
FDA approved treatment at this time.

®
HETLIOZ for ASD

A clinical program of HETLIOZ for the treatment of symptoms of ASD is ongoing. Sleep disturbances in ASD are a high unmet medical need in

people with ASD and have been characterized in the literature to include difficulties falling and staying asleep.

Fanapt for bipolar disorder

A Phase III study of Fanapt in bipolar disorder is ongoing. Bipolar disorders are brain disorders that cause changes in a person’s mood, energy

and ability to function. Bipolar disorder is a category that includes three different conditions - bipolar I, bipolar II and cyclothymic disorder.

People with bipolar disorders have extreme and intense emotional states that occur at distinct times, called mood episodes. These mood episodes

are categorized as manic, hypomanic or depressive. People with bipolar disorders generally have periods of normal mood as well.

Fanapt for schizophrenia (LAI)

In October 2018, we enrolled our first patient in a pharmacokinetic study of the LAI formulation of Fanapt . This pharmacokinetic study is
®

ongoing and will serve to inform the dosing for a later clinical study of Fanapt LAI for the treatment of schizophrenia.

Fanapt for Parkinson’s disease psychosis

A clinical program of Fanapt

in Parkinson’s disease psychosis is ongoing. Parkinson’s disease is a neurodegenerative disorder that affects

predominately dopaminergic neurons in a specific area of the brain called substantia nigra.

There are approximately one million adults in the U.S. with Parkinson’s disease. Between 20% and 40% of persons with Parkinson’s disease

experience a combination of hallucinations and delusions. The disease is associated with significant caregiver burden.

Tradipitant for gastroparesis

In December 2018, we announced results from a Phase II randomized clinical study (2301) of tradipitant as a monotherapy in the treatment of

gastroparesis. Several symptom severity scales were used to assess gastroparesis symptoms, including the Gastroparesis Symptom Index (GCSI), Patients
Assessment of Upper Gastrointestinal Disorders-Symptoms (PAGI-SYM), and Patient Global Impression of Change (PGI-C) as well as a Clinician Global
Impression of Severity (CGI-S). Tradipitant met the primary endpoint of the study of change in nausea score as measured by patient daily diaries and also
met the related endpoint of improvement in the number of nausea free days. Tradipitant also showed significant improvement in

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most of the secondary endpoints studied, including several key scales reflecting overall gastroparesis symptoms, specifically GCSI, PAGI-SYM, CGI-S,
and PGI-C.

In February 2022, we announced results from our Phase III clinical study, VP-VLY-686-3301, evaluating the efficacy and safety of tradipitant in
treating the symptoms of gastroparesis. The study did not meet its prespecified primary endpoint, which was the difference between drug and placebo on
the change of the severity of nausea from baseline at week 12 of treatment. Both treatment arms showed significant improvements from baseline on nausea
as well as the other core symptoms of gastroparesis. When restricting the analysis in the group of patients that used no rescue medications at baseline and
adjusting for poor compliance, we identified strong evidence of a drug effect across a number of symptoms and across the duration of the study, including a
significant and meaningful effect at the prespecified primary endpoint of nausea change at week 12. We plan to continue the analysis of the data of this
study and prepare the results for submission to peer review journals as well as prepare the data for submission to regulatory authorities. The FDA may not
view this data as constituting substantial evidence of efficacy for tradipitant in any indication for the treatment of gastroparesis or its symptoms, for any
length of treatment.

We believe that tradipitant has a well-established safety profile, as demonstrated by the results of extensive testing in animals and humans. Despite
these results, however, the FDA informed us in December 2018 that in order to treat patients beyond 12 weeks, we will have to conduct a nine-month non-
rodent chronic toxicity study. This currently limits our ability to collect safety data in humans for more than 12 weeks. The non-rodent study required by
the FDA necessitates the sacrifice of dozens of animals and we have disputed the necessity of a nine-month non-rodent chronic toxicity study. In February
2019, we filed a lawsuit in the U.S. District Court for the District of Columbia (DC District Court) challenging the FDA’s position, but we ultimately did
not prevail. Despite our disagreement with the FDA, the preclinical package has allowed us to continue to conduct all of the efficacy studies necessary for
New Drug Application (NDA) filing. Moreover, in July 2020, the FDA authorized tradipitant through an expanded access program (EAP) for a single
patient. An EAP allows a patient to request the use of tradipitant, prior to NDA approval, for up to six months with an option to request renewal. Since
then, certain patients who experienced a benefit in tradipitant studies have requested and received expanded access, while others have been denied
treatment under the EAP. The EAP is ongoing and a number of patients have initiated treatment. Although this EAP is not intended for data collection, we
will collect safety data from this cohort of expanded access patients and include this data in the NDA for tradipitant for the treatment of gastroparesis. The
FDA may disregard such safety data when reviewing the NDA. The lack of long-term (i.e., more than 12 weeks in humans) safety data would likely impact
the FDA’s willingness to approve tradipitant for a chronic indication. However, because long-term safety data is not normally a requirement for short-term
indications, and with a preclinical profile that has not precluded clinical development, we believe the package is complete for any NDA filing to treat
patients for 12 weeks or less. For example, the FDA has communicated to us that it is considering an indication for the short-term relief of nausea in
gastroparesis. While this short-term indication is not preferred, we would consider accepting this limited indication while continuing to pursue a chronic
indication. However, the FDA may not deem the safety information sufficient even for a short-term indication. Moreover, FDA authorization of an EAP is
not a guarantee of or a step in obtaining full FDA approval of an NDA.

Gastroparesis is a serious medical condition characterized by delayed gastric emptying associated with the symptoms of nausea, vomiting,
bloating, fullness after meals and abdominal pain, along with significant impairment of social and occupational functioning. A paper by Rey et al published
in the January 2012 Journal of Neurogastroenterology and Motility estimated the prevalence of gastroparesis in the U.S. to be approximately six million
patients, many of whom remain undiagnosed.

Tradipitant for motion sickness

In July 2019, we reported tradipitant was effective in treating motion sickness in a randomized double blind placebo controlled Phase II clinical

study conducted in the Pacific Ocean. The study had two primary endpoints: percentage of participants vomiting, and Motion Sickness Severity Scale
(MSSS) Worst score. In the overall population, a significantly higher percentage of participants experienced vomiting in the placebo arm as compared to
the tradipitant arm. The MSSS Worst score endpoint also favored tradipitant, but the difference did not reach statistical significance. The protocol for a
pivotal Phase III motion sickness study was discussed with the FDA at the end of Phase II meeting, and the FDA agreed with the adequacy of the program
design to support an NDA. In the fourth quarter of 2021, the boat trip portion of the Phase III study commenced as the lifting of local restrictions related to
the COVID-19 pandemic has allowed for boat trips to resume.

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Motion sickness is a disorder that arises often as a response to real or perceived movement, as occurring during vehicular travel. Vomiting is the
most disturbing symptom of motion sickness, although the disorder is often accompanied by a constellation of symptoms that includes nausea, sweating,
pallor, headache and anorexia. Motion sickness is one of the most prevalent episodic disorders in the world, whose prevalence has dramatically increased
with world population mobility over the last 100 years. It is reported that approximately 30% of the general population suffers from motion sickness under
ordinary travel conditions that include sea, air and land travel.

Tradipitant for atopic dermatitis

We announced results in September 2017 from a randomized Phase II clinical study of tradipitant as a monotherapy in the treatment of patients

with atopic dermatitis. Tradipitant was shown to improve the intensity of the worst itch patients experienced, as well as atopic dermatitis disease severity.
On the pre-specified primary endpoint of Average Itch Visual Analog Scale (VAS), tradipitant showed improvement over placebo, but this improvement
was not significant due to high placebo effect and the lack of sensitivity of this measure.

In June 2018, we initiated EPIONE, a Phase III study of tradipitant for pruritus in atopic dermatitis. In October 2019, we began enrolling patients
in EPIONE 2, a second Phase III clinical study of tradipitant in atopic dermatitis. We announced results of EPIONE in February 2020. The EPIONE study
did not meet its primary endpoint in reduction of pruritus across the overall study population. However, the antipruritic effect of tradipitant was robust in
the mild atopic dermatitis population. The EPIONE study continued to demonstrate that tradipitant is safe and well-tolerated. The EPIONE 2 study was
placed on hold due to the COVID-19 pandemic in 2020.

Atopic dermatitis is a chronic, relapsing inflammatory skin disorder characterized by the symptom of intense and persistent pruritus or itch. Other
clinical features include erythema, excoriation, edema, lichenification, oozing and xerosis. Atopic dermatitis is a common skin disorder affecting millions
of people worldwide. Currently, there are very few safe systemic treatments available for atopic dermatitis, representing a significant unmet medical need
in this population. A 2015 Decision Resources Group report estimated that 9.8 million individuals were diagnosed with atopic dermatitis in the U.S., of
which approximately 6.4 million were drug-treated atopic dermatitis patients.

Tradipitant for COVID-19 pneumonia

In April 2020, we announced the initiation of a Phase III clinical study, ODYSSEY VLY-686-3501, in hospitalized patients with COVID-19. We
received permission from the FDA to proceed with the study for the treatment and prevention of pneumonia associated with COVID-19. Enrollment in the
VLY-686-3501 study closed in August 2021 because the study met the pre-defined futility criteria, indicating that the study was unlikely to succeed in its
pre-specified primary endpoint. The study was designed to determine whether tradipitant plus standard of care is superior to placebo plus standard of care
in treating hospitalized patients with COVID-19 pneumonia who required supplemental oxygen support. An independent data and safety monitoring board
(DSMB) met to assess the planned interim analysis results and determined that the study is unlikely to show a significant difference between treatment
arms at the pre-specified primary endpoint and recommended termination of the study for futility. The DSMB also determined that there are no safety
concerns that contributed to its recommendation. Vanda will continue the genetics component of the study with the goal of identifying genetic susceptibility
factors contributing to the incidence of severe pneumonia among patients infected with COVID-19.

COVID-19 is associated with a lower respiratory tract inflammation that often progresses to acute respiratory distress syndrome requiring

mechanical ventilation. Tradipitant targets the neurokinin-1 receptor, which is coded by the TACR1 gene and is the main receptor for substance P, an 11
amino acid neuropeptide with a diverse set of functions. It has been shown that the substance P NK-1 receptor system is involved in the neuroinflammatory
processes that leads to significant lung injury following a number of insults, including viral challenges.

VTR-297

In the fourth quarter of 2018, we initiated a clinical study in patients with hematologic malignancies. Enrollment in the Phase I/II clinical study
(1101) of VTR-297 in hematologic malignancies is ongoing. VTR-297 is a small molecule HDAC inhibitor with potential use as a treatment for several
oncology indications.

Portfolio of CFTR activators and inhibitors

In October 2020, the FDA accepted the IND application to evaluate CFTR activator VSJ-110 and provided authorization to proceed with clinical

development. We are evaluating VSJ-110 for the treatment of allergic conjunctivitis.

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VSJ-110 is a small molecule nanomolar potency CFTR activator. VSJ-110 has shown efficacy in a dry eye model and exhibited anti-inflammatory
properties in both in vitro and in vivo assays.

In addition, an early stage CFTR inhibitor program is planned for BPO-27 for the treatment of secretory diarrhea disorders, including cholera. In

the fourth quarter of 2020, we initiated a study at a leading cholera lab at Harvard University.

Other products

VQW-765

In January 2020, the FDA accepted an IND application for VQW-765 and provided authorization to proceed with clinical development. We are

evaluating VQW-765 for the treatment of psychiatric disorders. We initiated a Phase II study of a single-dose treatment to alleviate social/performance
anxiety. VQW-765 is a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist that we licensed from Novartis on December 31, 2014 pursuant to a
settlement agreement.

VHX-896 (formerly P88)

In 2021, we initiated a bioequivalence study of Fanapt and VHX-896, the active metabolite of iloperidone. We believe that VHX-896 has the

potential to improve the clinical profile of Fanapt and create sustained, long-term value in the treatment of psychiatric disorders

For more detailed information regarding our clinical trial results and regulatory activities for our products please refer to our SEC filings and press
releases, which can be found on the SEC EDGAR website and on our website www.vandapharma.com. Information contained on those websites is not
incorporated by reference into this Annual Report or any other report or document that we file with the SEC.

License Agreements

Our rights to develop and commercialize our products are subject to the terms and conditions of licenses granted to us by other pharmaceutical

companies.

HETLIOZ
®

In February 2004, we entered into a license agreement with Bristol-Myers Squibb (BMS) under which we received an exclusive worldwide license

under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize HETLIOZ . We have paid BMS
$37.5 million in upfront fees and milestone obligations. We have no remaining milestone obligations to BMS. Additionally, we are obligated to make
royalty payments on HETLIOZ net sales to BMS. The royalty period in each territory where we commercialize HETLIOZ is 10 years following the first
commercial sale in the territory. In territories outside the U.S., the royalty is 5% on net sales. In the U.S., the current royalty on net sales is 10%. This
royalty will drop to 5% in December 2022 and will end in April 2024. We are also obligated under the license agreement to pay BMS a percentage of any
sublicense fees, upfront payments and milestone and other payments (excluding royalties) that we receive from a third party in connection with any
sublicensing arrangement, at a rate which is in the mid-twenties. We are obligated to use commercially reasonable efforts to develop and commercialize
®
HETLIOZ .

Either party may terminate the HETLIOZ license agreement under certain circumstances, including a material breach of the agreement by the

other. In the event we terminate our license, or if BMS terminates our license due to our breach, all rights licensed and developed by us under this
agreement will revert or otherwise be licensed back to BMS on an exclusive basis.

Fanapt
®

Pursuant to the terms of a settlement agreement with Novartis, Novartis transferred all U.S. and Canadian rights in the Fanapt franchise to us on

December 31, 2014. We paid directly to Sanofi S.A. (Sanofi) a fixed royalty of 3% of net sales through December 2019 related to manufacturing know-
how. No further royalties on manufacturing know-how are payable by us. We are also obligated to pay Sanofi a fixed royalty on Fanapt net sales equal up
to 6% on Sanofi know-how not related to manufacturing under certain conditions for a period of up to 10 years in markets where the NCE patent has
expired or was not issued. We are obligated to pay this 6% royalty on net sales in the U.S. through November 2026. No further royalties on know-how not
related to manufacturing will be payable by us for net sales in the U.S. after November 2026. We may lose our rights to develop and commercialize
Fanapt if we fail to comply with certain requirements in the Titan license agreement regarding

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our financial condition, or if we fail to comply with certain diligence obligations regarding our development or commercialization activities.

Tradipitant (VLY-686)

In April 2012, we entered into a license agreement with Eli Lilly and Company (Lilly) pursuant to which we acquired an exclusive worldwide

license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize an NK-1 receptor antagonist,
tradipitant, for all human indications. Lilly is eligible to receive future payments based upon achievement of specified development, regulatory approval
and commercialization milestones as well as tiered-royalties on net sales at percentage rates up to the low double digits. We have paid Lilly $3.0 million in
upfront fees and development milestones. As of December 31, 2021, remaining milestones include a $2.0 million development milestone due upon the
filing of the first marketing authorization for tradipitant in either the U.S. or the E.U, $10.0 million and $5.0 million for the first approval of a marketing
authorization for tradipitant in the U.S. and E.U., respectively, and up to $80.0 million for sales milestones. We are obligated to use commercially
reasonable efforts to develop and commercialize tradipitant.

Either party may terminate the agreement under certain circumstances, including a material breach of the agreement by the other. In the event that
we terminate the agreement, or if Lilly terminates the agreement due to our breach or for certain other reasons set forth in the agreement, all rights licensed
and developed by us under the agreement will revert or otherwise be licensed back to Lilly on an exclusive basis, subject to payment by Lilly to us of a
royalty on net sales of products that contain tradipitant.

Portfolio of CFTR activators and inhibitors

In March 2017, we entered into a license agreement with the University of California San Francisco (UCSF), under which we acquired an
exclusive worldwide license to develop and commercialize a portfolio of CFTR activators and inhibitors. Pursuant to the license agreement, we will
develop and commercialize the CFTR activators and inhibitors and are responsible for all development costs under the license agreement, including
current pre-investigational new drug development work. UCSF is eligible to receive future payments based upon achievement of specified development,
regulatory approval and commercialization milestones as well as single-digit tiered-royalties on net sales. We have paid UCSF $1.6 million in upfront fees
and development milestones. As of December 31, 2021, remaining milestones include $11.9 million for development milestones and $33.0 million for
future regulatory approval and sales milestones. Included in the $11.9 million in development milestones are $1.1 million of milestone obligations due
upon the conclusion of clinical studies for each licensed product, not to exceed $3.2 million in total for the CFTR portfolio.

Either party may terminate the agreement under certain circumstances. In the event that we terminate the agreement, or if UCSF terminates the

agreement due to our breach or for certain other reasons set forth in the agreement, all rights licensed and developed by us under the agreement will revert
or otherwise be licensed back to UCSF. Termination will not relieve us of our obligation to pay royalties or other payments owed, if any, to UCSF under the
terms of the agreement.

VQW-765

In connection with the settlement agreement with Novartis relating to Fanapt , we received an exclusive worldwide license under certain patents

and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7 nicotinic acetylcholine
receptor partial agonist. Pursuant to the license agreement, we are obligated to use commercially reasonable efforts to develop and commercialize VQW-
765 and are responsible for all development costs. We have no milestone obligations, but Novartis is eligible to receive tiered-royalties on net sales at
percentage rates up to the mid-teens.

Either party may terminate the agreement under certain circumstances, including a material breach of the agreement by the other. In the event that

we terminate the agreement, or if Novartis terminates the agreement due to our breach or for certain other reasons set forth in the agreement, all rights
licensed and developed by us under the agreement will revert or otherwise be licensed back to Novartis on an exclusive basis, subject to payment by
Novartis to us of a royalty on net sales of products that contain VQW-765.

Patents and Proprietary Rights; Hatch-Waxman Protection

We will be able to protect our products from unauthorized use by others only to the extent that our products are covered through regulatory

protections or by valid and enforceable patents, either licensed to us by others or generated through

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our activities internally, that give us sufficient proprietary rights. Accordingly, securing patents, regulatory data package protection, and other proprietary
rights is an essential element of our business strategies.

HETLIOZ , tradipitant and VQW-765 are covered by NCE and other patents and patent applications related to their respective medicinal uses. In
addition, NCE patent protection has been sought for VTR-297 and CFTR. Patent applications for these active ingredients remain pending. While the NCE
patents protecting Fanapt have expired, Fanapt remains protected by medicinal patents. For more on the license and sublicense arrangements related to
these active ingredients, see License Agreements above. In addition, we have filed for patents based on our own discoveries that seek to provide additional
protection for HETLIOZ and Fanapt .
®

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A comprehensive list of patents for our U.S. commercial products is available in the Approved Drug Products with Therapeutic Equivalence
Evaluations (Orange Book) for our commercial products and is also provided in the table below. Members of these patent families are also issued or
pending in a number of territories, such as Europe and Japan.

Product

HETLIOZ
®

HETLIOZ LQ

Fanapt
®

Number
US 5,856,529
US 9,060,995
US 9,539,234
US 9,549,913
US 9,730,910
US 9,855,241
US RE46604
US 10,071,977
US 10,149,829
US 10,179,119
US 10,376,487
US 10,449,176
US 10,610,510
US 10,610,511
US 10,829,465
US 10,945, 988
US 10,980,770
US 11,141,400
US 5,856,529
US 9,539,234
US 9,730,910
US 10,071,977
US 10,149,829
US 10,179,119
US 10,376,487
US 10,610,510
US 10,610,511
US 10,829,465
US 10,980,770
US 11,141,400
US 11,202,770
US 8,586,610
US 8,652,776
US 8,999,638
US 9,072,742
US 9,074,254
US 9,074,255
US 9,074,256
US 9,138,432
US 9,157,121

Type
New chemical entity
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Drug substance
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Drug substance
Method of treatment
Method of treatment
Method of treatment
New chemical entity
Method of treatment
Method of treatment
Drug substance
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Drug substance
Method of treatment
Method of treatment
Drug formulation
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment
Method of treatment

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HETLIOZ and HETLOZ LQ

Our rights to the NCE patent covering HETLIOZ capsules and oral suspension (HETLIOZ LQ ) and related intellectual property have been

acquired through a license with BMS. HETLIOZ and its formulations, genetic markers and uses are the subject of numerous patent filings for which
protection has been sought in selected countries worldwide. The NCE patent covering HETLIOZ expires in December 2022 in the U.S., which is inclusive
of a five-year extension granted under the Hatch-Waxman Act in October 2018. Corresponding NCE patent protection has expired in most other markets.
The U.S. Patent and Trademark Office has issued 15 method of treatment patents for HETLIOZ that will expire between 2033 and 2035 and two drug
TM
substance patents that will expire in 2035. Additionally, the U.S. Patent and Trademark Office has issued a drug formulation patent for HETLIOZ LQ
®
that will expire in 2040. We also have other pending patent applications covering methods of treatment and compositions of tasimelteon (HETLIOZ active
ingredient) oral suspensions.

In Europe, the law provides for 10 years of data exclusivity (with the potential for an additional year if a medicine is developed for a significant

new indication). In addition, Europe provides for 10 years of market exclusivity for orphan indications. As such, in Europe, data or market exclusivity will
provide protection for HETLIOZ for at least 10 years from approval. It is also possible that the protection through a basic patent (i.e., a patent that protects
a product as such, a process to obtain a product, or an application of a product) in Europe could be extended for up to five years by the issuance of a
supplementary protection certificate (SPC). A completed Pediatric Investigation Plan (PIP) could further extend SPC protection for an additional six
months or the market exclusivity in an orphan indication for two additional years. Thus, a PIP could provide a total of 12 years of market exclusivity for an
orphan indication. The European Patent Office has granted our patent application directed to the 20 mg/day dose. This patent will expire in 2027 and
provides the basis for an SPC. Other pending patent applications in Europe, if granted, may offer additional protection for HETLIOZ .
®

Outside the U.S. and Europe, data exclusivity will protect HETLIOZ from generic competition for varying numbers of years depending on the

country.

Additional patent applications directed to specific sleep disorders and to methods of treating patients with HETLIOZ , if issued, would provide

exclusivity for such indications and methods of treatment, potentially extending the effective patent protection period in the U.S., Europe, and other
markets.

Fanapt
®

The NCE patent for Fanapt , which expired in 2016 in the U.S. and in 2010 in other countries, was owned by Sanofi. Other patents and patent

applications relating to Fanapt are owned by Vanda.

Fanapt metabolites, formulations, genetic markers and uses are the subject of numerous patent filings in which protection has been sought in the

U.S., Europe, and other markets. In November 2013, a U.S. patent (U.S. 8,586,610) directed to a method of treating patients with Fanapt based on
genotype was issued to us by the U.S. Patent and Trademark Office. This patent, which was listed in the Orange Book in January 2015, is set to expire in
2027, potentially further extending the U.S. marketing exclusivity for Fanapt . Additional method of treatment patents have been issued in the U.S. and
®
listed in the Orange Book, with the latest expiration date in December 2031.

We have also filed and plan on filing additional patent applications covering the use of iloperidone (Fanapt active ingredient) LAI formulations.

Patents for the microsphere LAI formulation of Fanapt expire in 2024 in the U.S. and 2022 in some markets in Europe. Patents for the aqueous
microcrystals LAI formulation of Fanapt expire in 2023 in the U.S. and in some markets in Europe. We have pending patent applications covering the use
of iloperidone and plan on filing additional applications based on discoveries made throughout the development plan of this molecule.

In Europe, the law provides for 10 years of regulatory exclusivity (with the potential for an additional year if the drug is developed for a
significant new indication). No generic versions of Fanapt would be permitted to be marketed or sold during the applicable regulatory exclusivity period
in most European countries. Outside the U.S. and Europe, similar regulatory package protection periods may be available and could protect Fanapt from
generic competition for varying numbers of years depending upon the country.

Tradipitant

Lilly owns the NCE patent as well as patent applications directed to polymorphic forms of, and methods of making tradipitant. This patent
protection was sought in the U.S. and in other countries worldwide. These patents and patent applications have been licensed to us. The NCE patent
covering tradipitant expires in April 2023, except in the U.S., where it

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expires normally in June 2024, subject to any extension that may be received under the Hatch-Waxman Act. We have filed additional patent applications
based on discoveries made during recent studies with tradipitant.

VTR-297

VTR-297 is a small molecule HDAC inhibitor with potential use as a treatment for several oncology indications. We have pending patent

applications covering the use of VTR-297 and plan on filing additional applications based on discoveries made throughout the development plan of this
molecule.

Portfolio of CFTR activators and inhibitors

Our portfolio of CFTR activators and inhibitors may have broad applicability in addressing a number of high unmet medical needs, including
chronic dry eye, constipation, polycystic kidney disease, cholestasis and secretory diarrheas. We plan on filing applications based on discoveries made
throughout the development plan of these product candidates.

VQW-765

Novartis owns the NCE patent as well as patent applications directed to methods of using VQW-765, VQW-765 formulations, and combinations
of VQW-765 with other active pharmaceutical ingredients. In connection with the settlement agreement with Novartis relating to Fanapt , we received an
exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-
765, a Phase II alpha-7 nicotinic acetylcholine receptor partial agonist. The NCE patent expires normally in 2023 in the U.S., Europe, and other markets.

Other patents

Aside from the NCE patents and other in-licensed patents discussed above, we have obtained or filed numerous patents and patent applications,

most of which have been filed in key markets including the U.S., relating to our products and product candidates. In addition, we have filed numerous other
patent applications relating to drugs not presently in clinical studies. The claims in these various patents and patent applications are directed to
compositions of matter, including claims covering other products, pharmaceutical compositions and methods of use.

Proprietary know-how

For proprietary know-how that is not appropriate for patent protection, processes for which patents are difficult to enforce and any other elements

of our discovery process that involve proprietary know-how and technology that are not covered by patent applications, we generally rely on trade secret
protection and confidentiality agreements to protect our interests. We require all of our employees, relevant consultants and advisors to enter into
confidentiality agreements. Where it is necessary to share our proprietary information or data with outside parties, our policy is to make available only that
information and data required to accomplish the desired purpose and only pursuant to a duty of confidentiality on the part of those parties.

Marketing and Sales

HETLIOZ capsules were approved in the U.S. for the treatment of Non-24 in January 2014 and HETLIOZ capsules and oral suspension were

approved for the treatment of nighttime sleep disturbances in SMS in December 2020. We commercially launched HETLIOZ capsules in the U.S. in April
2014 and the oral suspension in March 2021. Additionally, HETLIOZ capsules were approved in the E.U. for the treatment of Non-24 in totally blind
adults in July 2015 and, in August 2016, we commercially launched HETLIOZ in Germany. Given the range of potential indications for HETLIOZ , we
®
may pursue one or more partnerships for the development and commercialization of HETLIOZ worldwide.

Fanapt oral tablets were approved in the U.S. for the treatment of schizophrenia in May 2009 and commercially launched in the U.S. in January

2010. We continue to explore the regulatory path and commercial opportunity for Fanapt oral formulation in other regions.

Major Customers

Our revenues are generated from product sales and are concentrated with specialty pharmacies, including OptumRx (a subsidiary of UnitedHealth

Group) and Accredo (a subsidiary of Express Scripts), and wholesalers, including Cardinal Health, Inc., AmerisourceBergen Drug Corporation, and
McKesson Corporation. These five major customers each accounted for more than 10% of total revenues for 2021 and, as a group, represented 91% of total
revenues for the year ended December 31, 2021.

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Competition

The pharmaceutical industry, in particular, is highly competitive and includes a number of established large and mid-sized companies with greater

financial, technical and personnel resources than we have and significantly greater commercial infrastructures than we have. Our market segment also
includes several smaller emerging companies whose activities are directly focused on our target markets and areas of expertise. Our products, once
approved for commercial use, will compete with numerous therapeutic treatments offered by these competitors. While we believe that our products will
have certain favorable features, existing and new treatments may also possess advantages. Additionally, the development of other drug technologies and
methods of disease prevention are occurring at a rapid pace. These developments may render our products or technologies obsolete or noncompetitive.

We believe the primary competitors for HETLIOZ and Fanapt are as follows:

•

For HETLIOZ in the treatment of Non-24 and nighttime sleep disturbances in SMS, there are no FDA approved direct competitors.
®
Sedative-Hypnotic treatments for certain sleep related disorders include, Ambien (zolpidem) by Sanofi (including Ambien CR ), Lunesta
(eszopiclone) by Sunovion Pharmaceuticals Inc., Sonata (zaleplon) by Pfizer Inc., Rozerem (ramelteon) by Takeda Pharmaceuticals
®
Company Limited, Silenor (doxepin) by Currax Pharmaceuticals LLC, Belsomra (suvorexant) by Merck & Co., Inc., Dayvigo
(lemborexant) by Eisai Inc., generic products such as zolpidem, trazodone and doxepin, and over-the-counter remedies such as Benadryl and
®
Tylenol PM . The class of melatonin agonists includes Rozerem (ramelteon) by Takeda Pharmaceuticals Company Limited, Valdoxan
(agomelatine) by Servier, Circadin (long-acting melatonin) by Neurim Pharmaceuticals Ltd. and the food supplement melatonin. Shift work
and excessive sleepiness disorder treatments include Nuvigil (armodafinil) and Provigil (modafinil) both by Teva Pharmaceutical Industries
Ltd.

For Fanapt in the treatment of schizophrenia, the atypical antipsychotics competitors are Risperdal (risperidone), including the LAI
formulation Risperdal Consta and Invega (paliperidone), including the LAI formulation Invega Sustenna , each by Ortho-McNeil-Janssen
Pharmaceuticals, Inc., Zyprexa (olanzapine), including the LAI formulation Zyprexa Relprevv , each by Lilly, Seroquel and Seroquel
XR (quetiapine) by AstraZeneca PLC, Abilify (aripiprazole) by Otsuka America Pharmaceutical Inc., Abilify Maintena (the LAI
formulation of Abilify ) by Lundbeck/Otsuka America Pharmaceutical Inc., Geodon (ziprasidone) by Pfizer Inc., Saphris (asenapine) by
AbbVie Inc., Latuda (lurasidone) by Sunovion Pharmaceuticals Inc., Rexulti (brexpiprazole) by Lundbeck/Otsuka America Pharmaceutical,
Inc., Aristada (aripiprazole lauroxil) extended-release injectable suspension by Alkermes, plc, Vraylar (cariprazine) by AbbVie Inc.,
Perseris (risperidone) extended-release injectable suspension by Indivior plc, Caplyta (lumapteperone) by Intra-Cellular Therapies, Lybalvi
(olanzapine and samidorphan) by Alkermes, Inc., and generic clozapine, as well as the typical antipsychotics haloperidol, chlorpromazine,
thioridazine, and sulpiride (all of which are generic).

Our ability to compete successfully will depend in part on our ability to utilize our pharmacogenetics and pharmacogenomics and drug

development expertise to identify, develop, secure rights to and obtain regulatory approvals for promising pharmaceutical products before others are able to
develop competitive products. Our ability to compete successfully will also depend on our ability to attract and retain skilled and experienced personnel.
Additionally, our ability to compete may be affected because insurers and other third-party payors in some cases seek to encourage the use of cheaper,
generic products, which could make our products less attractive.

Manufacturing

We currently utilize a virtual supply manufacturing and distribution chain, meaning that we do not have our own facilities to manufacture

commercial or clinical trial supplies of drugs, and we do not have our own distribution facilities. Instead, we contract with third parties to source critical
raw materials and for the manufacture, warehousing, order management, billing and collection and distribution of our products and product candidates.

We expect to continue to rely solely on third-party manufacturers to manufacture drug substance and final drug products for both clinical
development and commercial sale. However, there are numerous factors that could cause interruptions in the supply of our products, including regulatory
reviews, changes in our sources for manufacturing, disputes with a manufacturer, or financial instability of manufacturers, all of which could negatively
impact our operation and our financial results.

We have agreements in place with Patheon Pharmaceuticals Inc. and Patheon Inc. (collectively, Patheon), subsidiaries of Thermo Fisher Scientific,

for the manufacture of HETLIOZ capsules and Fanapt oral tablets.
®

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In January 2014, we entered into a manufacturing agreement with Patheon for the manufacture of commercial supplies of HETLIOZ 20 mg

capsules at Patheon’s Cincinnati, Ohio manufacturing site. Under the HETLIOZ manufacturing agreement, we are responsible for supplying the active
pharmaceutical ingredient (tasimelteon) for HETLIOZ to Patheon and have agreed to order from Patheon at least 80% of the total expected yearly
production of new units of HETLIOZ capsules. Patheon is responsible for manufacturing the HETLIOZ 20 mg capsules, conducting quality control and
stability testing, and packaging the HETLIOZ capsules. The HETLIOZ manufacturing agreement had an initial term of five years and automatically
renews after the initial term for successive terms of one year each, unless either party gives notice of its intention to terminate the agreement at least 12
months prior to the end of the then current term. Either party may terminate the HETLIOZ manufacturing agreement under certain circumstances upon
specified written notice to the other party.

As part of a settlement agreement in 2014, we assumed Novartis’ manufacturing agreement with Patheon for the manufacture of commercial

supplies of Fanapt . In May 2016, we entered into a new manufacturing agreement with Patheon for the manufacture of commercial supplies of Fanapt 1,
2, 4, 6, 8, 10 and 12 mg tablets at Patheon’s Mississauga, Ontario, Canada manufacturing site. Under the Fanapt manufacturing agreement, we are
responsible for sourcing the supply of the active pharmaceutical ingredient (iloperidone), and have agreed to order from Patheon at least 70% of the total
expected yearly production of new units of Fanapt tablets for the U.S. and other specified countries each year for the term of the agreement. Patheon is
responsible for manufacturing the Fanapt 1, 2, 4, 6, 8, 10 and 12 mg tablets, conducting quality control and stability testing, and packaging the Fanapt
®
tablets. The Fanapt manufacturing agreement has an initial term of five years and will automatically renew after the initial term for successive terms of
one year each, unless either party gives notice of its intention to terminate the agreement at least 12 months prior to the end of the then current term. Either
party may terminate the Fanapt manufacturing agreement under certain circumstances upon specified written notice to the other party.

In December 2020, we entered into a non-exclusive manufacturing agreement for the manufacture of commercial supplies of both 48 and 158 mL
HETLIOZ LQ bottles. The HETLIOZ LQ manufacturing agreement has an initial term of five years and automatically renews after the initial term for
successive terms of one year each, unless either party gives notice of its intention to terminate the agreement at least 12 months prior to the end of the then
current term.

Government Regulation

Government authorities in the U.S. at the federal, state and local levels and in other countries extensively regulate, among other things, the

research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution,
marketing and export and import of pharmaceutical products. A new drug must be approved by the FDA through the NDA process before it may be legally
marketed in the U.S. The process of obtaining regulatory approvals and the subsequent compliance with applicable federal, state, local and foreign laws and
regulations require the expenditure of substantial time and financial resources. Moreover, failure to comply with applicable requirements may result in,
among other things, warning letters, clinical holds, civil or criminal penalties, recall or seizure of products, injunction, disbarment, partial or total
suspension of production or withdrawal of the product from the market. Any judicial, administrative or other governmental enforcement action could have
a material adverse effect on our business.

U.S. government regulation

U.S. drug development and regulation

In the U.S., the FDA regulates drugs under the federal Food, Drug, and Cosmetic Act (FDCA) and related regulations. Drugs are also subject to

other federal, state and local statutes and regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate
federal, state and local statutes and regulations requires the expenditure of substantial time and financial resources. Failure to comply with the applicable
U.S. requirements at any time during the product development process, approval process or post-approval may subject an applicant to administrative or
judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning
letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts,
restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on our business.

Once a drug candidate is identified for development, it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of

product chemistry, toxicity and formulation, as well as animal studies. An IND application sponsor must submit the results of the preclinical tests, together
with manufacturing information and analytical data, to the FDA as part of the IND. The sponsor must also include a protocol detailing, among other things,
the objectives of the first phase of clinical trials, the parameters to be used in monitoring the safety of the trial, and the effectiveness criteria to be evaluated
should the first phase lend itself to an efficacy evaluation. Some preclinical testing may continue even after the IND is submitted. The IND

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automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, places the clinical trial on a clinical hold.
Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns about on-going or proposed clinical trials
or non-compliance with specific FDA requirements, and the trials may not begin or continue until the FDA notifies the sponsor that the hold has been
lifted.

All clinical trials must be conducted under the supervision of one or more qualified investigators in accordance with FDA good clinical practice
(GCP) requirements, which include a requirement that all research subjects provide their informed consent in writing for their participation in any clinical
trial. Clinical trials must be conducted under protocols detailing the objectives of the trial, dosing procedures, subject selection and exclusion criteria and
the safety and/or effectiveness criteria to be evaluated. Each protocol must be submitted to the FDA as part of the IND, and timely safety reports must be
submitted to the FDA and the investigators for serious and unexpected adverse events. An Institutional Review Board (IRB) at each institution participating
in the clinical trial must review and approve each protocol before a clinical trial may commence at the institution and must also approve the information
regarding the trial as well as the consent form that must be provided to each trial subject or his or her legal representative, monitor the study until
completed and otherwise comply with all applicable IRB regulations.

Human clinical trials are typically conducted in three sequential phases that may overlap or be combined in certain cases:

•

Phase I: The compound is initially introduced into healthy human subjects and tested for safety, dosage tolerance, absorption, metabolism,
distribution and excretion and, if possible, to gain an early indication of its effectiveness. In most cases, initial Phase I clinical trials are
conducted with healthy volunteers. However, where the compound being evaluated is for the treatment of severe or life-threatening diseases,
such as cancer, and especially when the product may be too toxic to ethically administer to healthy volunteers, the initial human testing may
be conducted on patients with the target disease or condition. Sponsors sometimes subdivide their Phase I clinical trials into Phase Ia and
Phase Ib clinical trials. Phase Ib clinical trials are typically aimed at confirming dosage, pharmacokinetics and safety in a larger number of
patients. Some Phase Ib studies evaluate biomarkers or surrogate markers that may be associated with efficacy in patients with specific types
of diseases or conditions.

Phase II: This phase involves clinical trials in a limited patient population to identify possible adverse effects and safety risks, to preliminarily
evaluate the efficacy of the product for specific targeted diseases or conditions and to confirm dosage tolerance and appropriate dosage.

Phase III: Phase III clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety in an expanded patient population,
generally at geographically dispersed clinical study sites. These clinical trials, often referred to as “pivotal” clinical trials, are intended to
establish the overall risk-benefit ratio of the compound and provide, if appropriate, an adequate basis for product labeling.

The FDA or the sponsor may suspend a clinical trial at any time on various grounds, including any finding that the research subjects or patients are

being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is
not being conducted in accordance with the IRB’s requirements or if the drug has been associated with unexpected, serious harm to study subjects. In
addition, clinical trials may be overseen by a DSMB, an independent group of qualified experts organized by the sponsor. Depending on its charter, the
DSMB may determine whether a trial may move forward at designated check points based on access to certain data from the trial.

Post-approval trials may also be conducted after a drug receives initial marketing approval. These trials, often referred to as “Phase IV” trials, are

used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the
performance of such clinical trials as a condition of approval of an NDA.

During the development of a new drug, sponsors are given several opportunities to meet with the FDA. These meetings can provide an opportunity

for the sponsor to share information about the progress of the application or clinical trials, for the FDA to provide advice, and for the sponsor and the FDA
to reach agreement on the next phase of development. These meetings may occur prior to the submission of an IND, at the end of Phase II clinical trials, or
before an NDA is ultimately submitted. Sponsors typically use the meetings at the end of the Phase II trials to discuss Phase II clinical results and present
plans for the pivotal Phase III clinical trials that they believe will support approval of the new drug. Meetings at other times may be made upon request.

Concurrent with clinical trials, companies typically complete additional, animal or other non-clinical studies, develop additional information about

the chemistry and physical characteristics of the drug, and finalize a process for manufacturing the

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product in commercial quantities in accordance with the FDA’s current Good Manufacturing Practices (cGMP) requirements. The manufacturing process
must consistently produce quality batches of the drug and, among other things, the manufacturer must develop methods for testing the identity, strength,
quality and purity of the final drug. In addition, appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate
the effectiveness of the packaging and that the compound does not undergo unacceptable deterioration over its shelf life.

While the IND is active, progress reports summarizing the results of ongoing clinical trials and nonclinical studies performed since the last

progress report must be submitted on at least an annual basis to the FDA, and written IND safety reports must be submitted to the FDA and investigators
for serious and unexpected adverse events, findings from other studies suggesting a significant risk to humans exposed to the same or similar drugs,
findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important, increased incidence of a serious adverse
reaction compared to that listed in the protocol or investigator brochure.

There are also requirements governing the submission of certain clinical trials and completed trial results to public registries. Sponsors of certain

clinical trials of FDA-regulated products are required to register and disclose specified clinical trial registration and results information, which is made
publicly available at www.clinicaltrials.gov. Failure to properly report clinical trial results can result in civil monetary penalties. Disclosure of clinical trial
results can often be delayed until the new product or new indication being studied has been approved.

U.S. review and approval process

The results of product development, preclinical and other non-clinical studies and clinical trials, along with descriptions of the manufacturing

process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an
NDA. The submission of an NDA is subject to the payment of substantial user fees; a waiver of which may be obtained under certain limited
circumstances.

The FDA reviews NDAs to determine, among other things, whether the product is safe and effective for its intended use and whether it is
manufactured in a cGMP-compliant manner, which will assure and preserve the product’s identity, strength, quality and purity. Under PDUFA, the FDA has
a goal of 10 months from the date of “filing” of a standard, completed NDA for a new molecular entity to review and act on the submission. This review
typically takes 12 months from the date the NDA is submitted to the FDA because FDA has 60 days to make a “filing” decision after the application is
submitted. The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine
whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In
this event, the NDA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it
for filing.

The FDA may refer an application for a new drug to an advisory committee within the FDA. An advisory committee is a panel of independent

experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether and under what conditions
the application should be approved. The FDA is not bound by the recommendations of such an advisory committee, but it considers advisory committee
recommendations carefully when making decisions.

Before approving an NDA, the FDA will also inspect the facility where the product is manufactured. The FDA will not approve an application

unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and are adequate to assure consistent
production of the product within required specifications. Before approving an NDA, the FDA may also inspect one or more clinical trial sites to assure
compliance with GCP requirements.

After the FDA evaluates an NDA, it will issue an approval letter or a CRL. A CRL indicates that the review cycle of the application is complete,
and the application will not be approved in its present form. A CRL usually describes the specific deficiencies in the NDA identified by the FDA and may
require additional clinical data, such as an additional pivotal Phase III trial or other significant and time-consuming requirements related to clinical trials,
nonclinical studies or manufacturing. If a CRL is issued, the sponsor must resubmit the NDA, addressing all of the deficiencies identified in the letter, or
withdraw the application. Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval. An
approval letter authorizes commercial marketing of the drug with prescribing information for specific indications.

The Pediatric Research Equity Act (PREA) requires IND sponsors to conduct pediatric clinical trials for most drugs, for a new active ingredient,
new indication, new dosage form, new dosing regimen or new route of administration. Under the PREA, original NDAs and supplements must contain a
pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product
for the claimed indications in all

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relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The
sponsor or the FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several
reasons, including a finding that the drug is ready for approval for use in adults before pediatric clinical trials are complete or that additional safety or
effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to
submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

If a drug receives FDA approval, the approval may be limited to specific diseases and dosages, which could restrict the commercial value of the
product. In addition, the FDA may require testing and surveillance programs to monitor the safety of approved products that have been commercialized,
and may require a sponsor to conduct post-marketing clinical trials, which are designed to further assess a drug’s safety and effectiveness after NDA
approval. The FDA may also place other conditions on approval, including a requirement for a risk evaluation and mitigation strategy (REMS) to assure the
safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the
NDA without an approved REMS, if required. A REMS could include medication guides, physician communication plans or elements to assure safe use,
such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict
the commercial promotion, distribution, prescribing or dispensing of products. Marketing approval may be withdrawn for non-compliance with REMS or
other regulatory requirements, or if problems occur following initial marketing.

Post-approval requirements

Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory standards is not maintained or if problems occur

after the drug reaches the market. Later discovery of previously unknown problems with a drug may result in restrictions on the drug or even complete
withdrawal of the drug from the market. After approval, some types of changes to the approved drug, such as adding new indications, certain
manufacturing changes and additional labeling claims, are subject to further FDA review and approval. Manufacturers and other entities involved in the
manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to
periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP regulations and other laws and regulations.

Our approved products are, and any additional product manufactured or distributed by us following FDA approval will be, subject to continuing
regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the drug, providing the FDA
with updated safety and efficacy information, drug sampling and distribution requirements, complying with certain electronic records and signature
requirements, and complying with FDA promotion and advertising requirements. The FDA strictly regulates labeling, advertising, promotion and other
types of information regarding approved drugs that are placed on the market, and imposes requirements and restrictions on drug manufacturers, such as
those related to direct-to-consumer advertising, the prohibition on promoting products for uses or in patient populations that are not described in the
product’s approved labeling (known as “off-label use”), industry-sponsored scientific and educational activities, and promotional activities involving the
internet. Discovery of previously unknown problems or the failure to comply with the applicable regulatory requirements may result in restrictions on the
marketing of a product for a certain indication or withdrawal of the product from the market as well as possible civil or criminal sanctions. Failure to
comply with the applicable governmental requirements at any time during the product development process, approval process or after approval, may
subject an applicant or manufacturer to administrative or judicial civil or criminal sanctions and adverse publicity. FDA sanctions could include refusal to
approve pending applications, withdrawal of an approval, clinical holds on post-marketing clinical trials, enforcement letters, product recalls, product
seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, mandated corrective advertising or
communications with doctors, debarment, restitution, disgorgement of profits, or civil or criminal penalties, any of which could have a material adverse
effect on our business.

Orphan drug designation

Under the Orphan Drug Act, the FDA may grant orphan drug designation to drugs intended to treat a rare disease or condition, generally a disease

or condition that affects fewer than 200,000 individuals in the U.S or, if affects more than 200,000 individuals in the U.S., there is no reasonable
expectation that sales of the drug will be sufficient to offset the cost of developing and making the drug available in the U.S.. Orphan drug designation must
be requested before submitting an NDA. After the FDA grants Orphan drug designation, the generic identity of the drug and its potential orphan use are
disclosed publicly by the FDA. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval
process. The first NDA applicant to receive FDA approval for a particular active ingredient to treat a particular disease with FDA orphan drug designation
is entitled to a seven-year exclusive marketing period in the U.S. for that

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product, for that indication. During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug for the
same disease, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity. Orphan drug
exclusivity does not prevent FDA from approving a different drug for the same disease or condition, or the same drug for a different disease or condition.
Among the other benefits of orphan drug designation are tax credits for certain research and development expenses and a waiver of the NDA application
user fee.

Expedited development and review programs

The FDA has a fast track designation program that is intended to expedite or facilitate the process for reviewing new drug products that meet

certain criteria. Specifically, new drugs are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition
and demonstrate the potential to address unmet medical needs for the disease or condition. With regard to a fast track product, the FDA may consider for
review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the
sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user
fees upon submission of the first section of the NDA.

Any product submitted to the FDA for approval, including a product with a fast track designation, may also be eligible for other types of FDA

programs intended to expedite development and review, such as priority review and accelerated approval.

A product is eligible for priority review if it is intended to treat a serious condition, and if approved, would provide a significant improvement in

safety or efficacy compared to currently marketed products. The FDA will attempt to direct additional resources to the evaluation of an application for a
new drug designated for priority review in an effort to facilitate the review. The FDA endeavors to review applications with priority review designations
within six months of the filing date, as compared to 10 months for review of NDAs under its current PDUFA review goals.

In addition, a product may be eligible for accelerated approval. Drugs intended to treat serious or life-threatening diseases or conditions may be
eligible for accelerated approval upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict a clinical
benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on
irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack
of alternative treatments. As a condition of approval, the FDA may require that a sponsor of a drug receiving accelerated approval perform adequate and
well-controlled post-marketing clinical trials. Drugs receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails
to conduct the required post-marketing trials or if such trials fail to verify the predicted clinical benefit. In addition, the FDA currently requires as a
condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the
product.

The Food and Drug Administration Safety and Innovation Act established a category of drugs referred to as “breakthrough therapies” that may be

eligible to receive breakthrough therapy designation. A sponsor may seek FDA designation of a compound as a “breakthrough therapy” if the product is
intended, alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical
evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such
as substantial treatment effects observed early in clinical development. The designation includes all of the fast track program features, as well as more
intensive FDA interaction and guidance. The breakthrough therapy designation is a distinct status from both accelerated approval and priority review,
which can also be granted to the same drug if relevant criteria are met. If a product is designated as breakthrough therapy, the FDA will work to expedite
the development and review of such drug.
Fast track designation, priority review and breakthrough therapy designation do not change the standards for approval but may expedite the development or
approval process. However, even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the
conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Marketing exclusivity

The FDA provides periods of regulatory exclusivity, which provide the holder of an approved NDA limited protection from new competition in

the marketplace for the innovation represented by its approved drug for a period of three or five years following the FDA’s approval of the NDA. Five years
of exclusivity are available to NCEs. An NCE is a drug that contains no active moiety that has been approved by the FDA in any other NDA. An active
moiety is the molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt, including a salt with hydrogen or
coordination bonds, or other noncovalent, or not involving the sharing of electron pairs between atoms, derivatives, such as a complex (i.e., formed

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by the chemical interaction of two compounds), chelate (i.e., a chemical compound), or clathrate (i.e., a polymer framework that traps molecules), of the
molecule, responsible for the therapeutic activity of the drug substance. During the exclusivity period, the FDA may not accept for review or approve an
Abbreviated New Drug Application (ANDA) or a 505(b)(2) NDA submitted by another company that contains the previously approved active moiety. An
ANDA or 505(b)(2) application, however, may be submitted one year before NCE exclusivity expires if it includes a certification that the new product will
not infringe the already approved product’s listed patents, or that such patents are invalid. If a product is not eligible for the NCE exclusivity, it may be
eligible for three years of exclusivity. Three-year exclusivity is available to the holder of an NDA, including a 505(b)(2) NDA, for a particular condition of
approval, or change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical trials, other than
bioavailability or bioequivalence trials, was essential to the approval of the application and was conducted or sponsored by the applicant. This three-year
exclusivity period protects against FDA approval of ANDAs and 505(b)(2) NDAs for the condition of the new drug’s approval. As a general matter, three-
year exclusivity does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for generic versions of the original, unmodified drug product. Five-
year and three-year exclusivity will not delay the submission or approval of a full NDA; however, an applicant submitting a full NDA would be required to
conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and
efficacy.

Pediatric exclusivity is another type of marketing exclusivity available in the U.S. Pediatric exclusivity provides for an additional six months of

marketing exclusivity attached to another period of exclusivity if a sponsor conducts clinical trials in children in response to a written request from the
FDA. The issuance of a written request does not require the sponsor to undertake the described clinical trials. In addition, orphan drug designation, as
described above, may offer a seven-year period of marketing exclusivity, except in certain circumstances.

Orange Book listing, the Hatch-Waxman Act

In seeking approval for a drug through an NDA, applicants are required to list with the FDA each patent with claims that cover the applicant’s
drug. Upon approval of a drug, each of the patents listed in the application for the drug is then published in the FDA’s Orange Book. Drugs listed in the
Orange Book can, in turn be cited by potential competitors in support of approval of an ANDA. An ANDA provides for marketing of a drug that has the
same active ingredients in the same strengths and dosage form as the listed drug and has been shown through bioequivalence testing to be therapeutically
equivalent to the listed drug. ANDA applicants are not required to conduct or submit results of preclinical or clinical tests to prove the safety or
effectiveness of their drug, other than the requirement for bioequivalence testing. Drugs approved in this way are commonly referred to as “generic
equivalents” to the listed drug, and can often be substituted by pharmacists under prescriptions written for the original listed drug.

The ANDA applicant is required to certify to the FDA concerning any patents listed for the approved drug in the Orange Book. Specifically, the

applicant must certify that: (i) the required patent information has not been filed; (ii) the listed patent has expired; (iii) the listed patent has not expired, but
will expire on a particular date and approval is sought after patent expiration; or (iv) the listed patent is invalid or will not be infringed by the new drug. A
certification that the new drug will not infringe the already approved drug’s listed patents or that such patents are invalid is called a Paragraph IV
certification. If the applicant does not challenge the listed patents, the ANDA application will not be approved until all the listed patents claiming the
referenced drug have expired.

If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification

to the NDA and patent holders once the ANDA has been accepted for filing by the FDA. The NDA and patent holders may then initiate a patent
infringement lawsuit in response to the notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of
a Paragraph IV certification automatically prevents the FDA from approving the ANDA until the earlier of 30 months, expiration of the patent, settlement
of the lawsuit or a decision in the infringement case that is favorable to the ANDA applicant.

The ANDA application also will not be approved until any non-patent exclusivity, such as exclusivity for obtaining approval of a NCE, listed in

the Orange Book for the referenced drug has expired. The U.S. Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known
as the “Hatch-Waxman Act,” provides a period of five years following approval of a drug containing no previously approved active ingredients, during
which ANDAs for generic versions of those drugs cannot be submitted unless the submission contains a Paragraph IV challenge to a listed patent, in which
case the submission may be made four years following the original drug approval. Federal law provides for a period of three years of exclusivity following
approval of a listed drug that contains previously approved active ingredients but is approved in a new dosage form, route of administration or combination,
or for a new use, the approval of which was required to be supported by new clinical trials conducted by or for the sponsor, during which FDA cannot grant
effective approval of an ANDA based on that listed drug.

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Fraud and abuse laws and other U.S. regulatory matters

Pharmaceutical companies are subject to broadly applicable fraud and abuse and other healthcare laws and regulations, in addition to the FDCA,

that may constrain the business or financial arrangements and relationships through which these companies market, sell and distribute the products for
which they obtain marketing approval. Some of the laws and regulations that may affect the ability of pharmaceutical companies to operate are described
below.

Anti-kickback laws

The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting, or receiving remuneration,

directly or indirectly, in cash or in kind, to induce or reward the purchasing, leasing, ordering or arranging for or recommending the purchase, lease, or
order of any health care item or service reimbursable under federal healthcare programs such as Medicare and Medicaid. The term “remuneration” has been
broadly interpreted to include anything of value, and the government can establish a violation of the Anti-Kickback Statute without proving that a person or
entity had actual knowledge of the law or specific intent to violate it. This statute has been interpreted to apply to arrangements between pharmaceutical
manufacturers on the one hand and prescribers, purchasers, patients, and formulary managers on the other. There are a number of statutory exceptions and
regulatory safe harbors protecting certain common activities from prosecution or other regulatory sanctions, however, the exceptions and safe harbors are
drawn narrowly. Failure to meet all of the requirements of a particular statutory exception or regulatory safe harbor does not make the conduct per se illegal
under the Anti-Kickback Statute, but the legality of the arrangement will be evaluated on a case-by-case basis based on the totality of the facts and
circumstances. Violations of the Anti-Kickback Statute are punishable by imprisonment, criminal fines, civil monetary penalties and exclusion from the
participation in federal healthcare programs, such as Medicare and Medicaid. A number of states also have anti-kickback laws that establish similar
prohibitions that may apply to items or services reimbursed by government programs, as well as any third-party payors, including commercial payors,
known as "all-payor" laws.

Prescription Drug Marketing Act

As part of the sales and marketing process, pharmaceutical companies frequently provide healthcare providers with samples of approved drugs.

The Prescription Drug Marketing Act (PDMA) imposes requirements and limitations upon the distribution of drugs and drug samples, and prohibits states
from licensing distributors of prescription drugs unless the state licensing program meets certain federal guidelines that include minimum standards for
storage and handling, as well as record keeping and other requirements. Violations of the PDMA may result in criminal and civil penalties. In addition, the
Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively known as the
Affordable Care Act or ACA), discussed in more detail in Pharmaceutical Coverage, Pricing and Reimbursement and Healthcare Reform below, imposes
annual reporting requirements related to sample distribution.

False Claims Act

The False Claims Act prohibits, among other things, knowingly presenting, or causing to be presented false or fraudulent claims for payment of
government funds and knowingly making, or causing to be made or used, a false record or statement to get a false claim paid. Certain marketing practices
may implicate the False Claims Act, including promotion of pharmaceutical products for unapproved uses, providing free product to customers with the
expectation that customers would bill federal programs for the product, or inflating prices reported to private price publication services used to set drug
reimbursement rates under federal healthcare programs. In addition, the ACA amended the Social Security Act to provide that a claim including items or
services resulting from a violation of the Anti-Kickback Statute constitutes a false claim for purposes of the False Claims Act. Actions under the False
Claims Act may be brought by the government or as a qui tam action by private individuals who may receive financial awards if their claims are successful.
False Claims Act liability is potentially significant in the healthcare industry because the statute provides for treble damages and monetary penalties of
$5,500 to $11,000 per false claim or statement, adjusted for inflation as applicable, with respect to violations occurring after November 2, 2015. Violations
of the False Claims Act are also punishable by exclusion from participation in federal healthcare programs, such as Medicare and Medicaid.
Pharmaceutical and other life sciences companies often resolve allegations without admissions of liability for significant and sometimes material amounts
to avoid the uncertainty of treble damages and per claim penalties that may be awarded in litigation. These companies may be required, however, to enter
into corporate integrity agreements with the government, which may impose substantial costs on companies to ensure compliance.

HIPAA

The Health Insurance Portability and Accountability Act of 1996 (HIPAA), includes federal criminal statutory provisions that prohibit among
other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-
party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a
healthcare offense, and knowingly and willfully

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falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or
payment for healthcare benefits, items or services.

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and their implementing regulations,

impose certain requirements and restrictions on certain types of individuals and entities relating to the privacy and security of individually identifiable
health information. Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable not only to covered entities (e.g.,
health care providers and health plans), but also to business associates (i.e., independent contractors or agents of covered entities that create, receive,
maintain or transmit protected health information in connection with providing a service for or on behalf of a covered entity). HITECH also created four
new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state
attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees
and costs associated with pursuing federal civil actions.

Physician Payment Sunshine Act

The Physician Payment Sunshine Act requires manufacturers of drugs, devices, biologics and medical supplies for which payment is available
under Medicare, Medicaid or the Children’s Health Insurance Program to report annually (with certain exceptions) to Centers for Medicare & Medicaid
Services (CMS) information related to payments or other “transfers of value” made to physicians and teaching hospitals, and requires applicable
manufacturers and group purchasing organizations to report annually to CMS ownership and investment interests held by physicians and their immediate
family members and payments or other “transfers of value” to such physician owners. Failure to report relevant data may result in civil fines and/or
penalties.

Foreign Corrupt Practices Act

The Foreign Corrupt Practices Act (FCPA), prohibits U.S. corporations and their representatives and intermediaries from offering, promising,

authorizing or making payments to any foreign government official, government staff member, political party or political candidate in an attempt to obtain
or retain business abroad. The scope of the FCPA includes interactions with certain healthcare professionals in many countries. Violation of the FCPA
could result in substantial civil and criminal penalties and remedies, including fines, disgorgement, and/or imprisonment.

Analogous state laws

Analogous state fraud and abuse laws and regulations, such as state anti-kickback and false claims laws, can apply to the business practices of
pharmaceutical companies, including but not limited to research, distribution, sales or marketing arrangements and claims involving healthcare items or
services reimbursed by non-governmental third-party payors and are generally broad and are enforced by many different federal and state agencies as well
as through private actions. In addition to requiring reporting transfers of value, some states have imposed price reporting requirements. These state laws
apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor. In addition, a number
of states require pharmaceutical companies to report expenses relating to the marketing and promotion of pharmaceutical products and to report gifts and
payments to individual physicians in the states. Other states restrict when pharmaceutical companies may provide meals to prescribers or engage in other
marketing related activities or require pharmaceutical companies to implement compliance programs or marketing codes of conduct, and file periodic
reports or disclosures with states. Compliance with these laws requires significant resources and companies that do not comply may face civil penalties or
other consequences.

Many state laws govern the privacy and security of personal information in specified circumstances. For example, the California Consumer

Privacy Act (CCPA), which became effective on January 1, 2020, established a new legal framework governing covered businesses’ collection and use of
personal information of California residents by, among other things, creating an expanded definition of covered personal information, establishing new
privacy rights for California residents, imposing an opt-in standard for certain disclosures of personal information about minors, and creating a new and
potentially severe statutory damages framework for businesses subject to certain data breaches resulting from the failure to implement and maintain
reasonable security procedures and practices. While properly collected clinical trial data and all protected health information governed by HIPAA are
exempt from the current version of the CCPA, other personal information may be applicable and possible changes to the CCPA may broaden its scope.

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Foreign regulation

Foreign drug development, review and approval processes

Regardless of whether we obtain FDA approval for a product, we must obtain approval by the comparable regulatory authorities of foreign

countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country, and
the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials, product licensing, pricing
and reimbursement also vary greatly from country to country. Although governed by the applicable country, clinical trials conducted outside of the U.S.
typically are administered with the three-Phase sequential process that is discussed above under U.S. drug development and regulation. However, the
foreign equivalent of an IND is not a prerequisite to performing pilot studies or Phase I clinical trials.

Under E.U. regulatory systems, we may submit Marketing Authorization Applications either under a centralized or decentralized procedure. The
centralized procedure, which is available for drugs produced by biotechnology or which are highly innovative, provides for the grant of a single marketing
authorization that is valid for all E.U. member states. This authorization is a marketing authorization approval. The decentralized procedure provides for
mutual recognition of national approval decisions. Under this procedure, the holder of a national marketing authorization may submit an application to the
remaining member states. Within 90 days of receiving the applications and assessment report, each member state must decide whether to recognize
approval. This procedure is referred to as the mutual recognition procedure. In addition, regulatory approval of prices is required in most countries other
than the U.S. We face the risk that the resulting prices would be insufficient to generate an acceptable return to us.

Foreign fraud and abuse laws and other regulatory matters

Outside the U.S., we are subject to similar regulations in those countries where we market and sell products, including with respect to

transparency, bribery and other laws mentioned above. In some foreign countries, including major markets in the E.U. and Japan, the pricing of prescription
pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can take nine to 12 months or
longer after the receipt of regulatory marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may be required
to conduct a clinical trial that compares the cost-effectiveness of our product to other available therapies, which can be costly and time-consuming.

The collection and processing of personal data in the E.U. is governed by the General Data Protection Regulation (GDPR), which became
applicable in May 2018. The GDPR implements stringent operational requirements for processors and controllers of personal data, including, for example,
expanded disclosure requirements about how personal information is to be used, strengthened individual data subject rights, limitations on retention of
personal data, increased requirements pertaining to health data and pseudonymised (i.e., key-coded) data, shortened mandatory data breach notification
timelines and higher standards for controllers to demonstrate they have obtained valid consent for certain data processing activities. The GDPR provides
that E.U. member states may make their own additional laws and regulations in relation to the processing of genetic, biometric or health data, which could
result in differences between member states, limit our ability to use and share personal data or cause our costs to increase, and harm our business and
financial condition. Further, the U.K.’s exit from the E.U., often referred to as Brexit, has created uncertainty with regard to data protection regulation in
the U.K. While the transition period has now concluded, decisions are still to be made on how data transfers to and from the U.K. will be regulated. We are
also subject to evolving and strict rules on the transfer of personal data out of the E.U. Failure to comply with E.U. data protection laws may result in
significant fines, including GDPR fines of up to the higher of €20,000,000 or 4% of our total worldwide annual revenue of the preceding financial year, and
other administrative penalties, which may be onerous and adversely affect our business, financial condition, results of operations and prospects.

Pharmaceutical Coverage, Pricing and Reimbursement and Healthcare Reform

Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities.

Sales of products will depend, in part, on the extent to which the costs of the products will be covered by third-party payors, including government health
programs in the U.S. such as Medicare and Medicaid, commercial health insurers and managed care organizations. The process for determining whether a
payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the
product once coverage is approved. Third-party payors are increasingly challenging the prices charged, examining the medical necessity, and reviewing the
cost-effectiveness of medical products and services and imposing controls to manage costs. Third-party payors may also limit coverage to specific products
on an approved list, or formulary, which might not include all of the approved products for a particular indication.

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In order to secure coverage and reimbursement for any product that might be approved for sale, a company may need to conduct expensive

pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the product, in addition to the costs required to obtain
FDA or other comparable regulatory approvals. A payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement
rate will be approved. Third party reimbursement may not be sufficient to maintain price levels high enough to realize an appropriate return on investment
in product development.

A primary trend in the U.S. healthcare industry and elsewhere is cost containment. There have been a number of federal and state proposals during

the last several years regarding the pricing of pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for drugs and other
medical products, government control and other changes to the healthcare system in the U.S. By way of example, in March 2010, the ACA was passed,
ushering in significant changes to the coverage and payment for products under government health care programs. Among the provisions of the ACA of
importance to pharmaceutical companies are:

•

an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned
among these entities according to their market share in certain government healthcare programs, although this fee does not apply to sales of
certain products approved exclusively for orphan indications;

expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain
individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate
liability;

expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded and
generic drugs and revising the definition of “average manufacturer price,” for calculating and reporting Medicaid drug rebates on outpatient
prescription drug prices and extending rebate liability to prescriptions for individuals enrolled in Medicaid managed care plans;

addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs
that are inhaled, infused, instilled, implanted or injected;

expanded the types of entities eligible for the 340B drug discount program;

established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50% point‑of‑sale‑discount off the
negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’
outpatient drugs to be covered under Medicare Part D. The Bipartisan Budget Act of 2018 increased the manufacturer discount from 50% to
70% effective in 2019;

established a new Patient‑Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical
effectiveness research, along with funding for such research;

added a requirement to annually report product samples that manufacturers and distributors provide to physicians;

expanded healthcare fraud and abuse laws, including the False Claims Act and the federal Anti-Kickback Statute, and enhanced penalties for
noncompliance; and

established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lower
Medicare and Medicaid spending, potentially including prescription drug spending.

Some of the provisions of the ACA have yet to be fully implemented, however, while others have been subject to judicial and Congressional

At the federal level, the former Trump administration supported legislative proposals and issued certain Executive Orders seeking to reduce drug

prices, increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs. The
Department of Health and Human Services (HHS), has solicited feedback on some of these measures and implemented others under its existing authority.
The FDA also released a final rule in

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September 2020 providing guidance for states to build and submit importation plans for drugs from Canada. Further, in November 2020, HHS finalized a
regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Medicare Part D, either directly
or through pharmacy benefit managers, unless the price reduction is required by law. The rule also creates a new safe harbor for price reductions reflected
at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers. These modifications
to the safe harbors are being challenged in court and HHS has delayed their implementation until January 1, 2023; however, the rule may be repealed
through legislative action before such time. In July 2021, President Biden issued an executive order pertaining to drug pricing, which expressed support for
legislation allowing direct negotiation in Medicare Part D and inflationary rebates and directed various executive branch agencies to take actions to lower
drug prices and promote generic competition. In response to President Biden’s executive order, in September 2021, HHS issued a Comprehensive Plan for
Addressing High Drug Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make
drug prices more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation.
Several pending or proposed legislative efforts incorporate these drug pricing reforms in addition to inflationary rebates on Part B and Part D drugs that
would be payable on commercial and governmental program utilization, policies aimed at redesigning the Medicare Part D benefit and adopting drug price
transparency measures. Drug manufacturers who are unwilling to negotiate with Medicare would be subject to additional excise taxes. Additionally, the
plan would impose tax penalties on drug manufacturers that increase the prices of drug products faster than the rate of inflation. If elements of these
prescription drug pricing plans become law, our pricing strategy and commercial prospects may be adversely affected.

Additionally, in December 2020, CMS issued a final rule that materially modifies current Medicaid Drug Rebate Program regulations by, among
other things, broadening the definitions for “line extension” and “new formulation”, the key term within the line extension definition. A “line extension”
drug may be subject to a higher Medicaid rebate, thereby reducing the amount the manufacturer is paid with respect to such product. These new definitions
became effective on January 1, 2022.

Other legislative changes have been proposed and adopted since the ACA was enacted. These changes include the Budget Control Act of 2011,
which, among other things, led to aggregate reductions to Medicare payments to providers of up to 2% per fiscal year that started in 2013 and will stay in
effect through 2024 unless additional congressional action is taken, the American Taxpayer Relief Act of 2012, which, among other things, reduced
Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers
from three to five years and the American Rescue Plan Act of 2021, which will eliminate the statutory Medicaid drug rebate cap, currently set at 100% of a
drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024. These new laws may result in
additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which
we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used. Further, there have been several recent
U.S. congressional inquiries and proposed state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the
relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement
methodologies for drug products.

In the coming years, additional legislative and regulatory changes could be made to governmental health programs that could significantly impact
pharmaceutical companies and the success of our product candidates. At the state level, legislatures have increasingly passed legislation and implemented
regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions
on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other
countries and bulk purchasing. In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine
what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs. These measures could reduce
the ultimate demand for our products, once approved, or put pressure on our product pricing. The ACA, as well as other federal, state and foreign
healthcare reform measures that have been and may be adopted in the future, could have a material adverse effect on our business. Further, it is also
possible that additional governmental action is taken in response to the COVID-19 pandemic as it continues into 2022.

These healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in
Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price for
any approved product and/or the level of reimbursement physicians receive for administering any approved product. Reductions in reimbursement levels
may negatively impact the prices we can charge or the frequency with which products are prescribed or administered. Any reduction in reimbursement
from Medicare or other government programs may result in a similar reduction in payments from private payors.

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Similarly, pricing and reimbursement and the containment of healthcare costs has become a priority in a number of foreign jurisdictions. In the
E.U., pricing and reimbursement schemes vary widely from country to country. Some countries provide that drug products may be marketed only after a
reimbursement price has been agreed. Some countries may require the completion of additional studies that compare the cost-effectiveness of a particular
drug candidate to currently available therapies, or so-called health technology assessments, in order to obtain reimbursement or pricing approval. For
example, the E.U. provides options for its member states to restrict the range of drug products for which their national health insurance systems provide
reimbursement and to control the prices of medicinal products for human use. E.U. member states may approve a specific price for a drug product or may
instead adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market. Other member states allow
companies to fix their own prices for drug products but monitor and control company profits. The downward pressure on health care costs in general,
particularly prescription drugs, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. In addition, in
some countries, cross-border imports from low-priced markets exert competitive pressure that may reduce pricing within a country. Any country that has
price controls or reimbursement limitations for drug products may not provide favorable reimbursement and pricing arrangements.

Human Capital

We had 278 full-time employees as of December 31, 2021, compared with 292 employees as of December 31, 2020. None of our employees are
represented by a labor union. We have not experienced any work stoppages and consider our employee relations to be good. Our human capital objectives
include attracting, training and retaining employees in a manner that supports innovation across our business.

Corporate Information

We were incorporated in Delaware in 2002. Our principal executive offices are located at 2200 Pennsylvania Avenue NW, Suite 300E,
Washington, D.C. 20037, and our telephone number is (202) 734-3400. Our website address is www.vandapharma.com, and the information contained in,
or that can be accessed through, our website is not incorporated by reference in this Annual Report and should not be considered a part of this Annual
Report.

Available Information

We file annual, quarterly, and current reports, proxy statements, and other documents with the Securities and Exchange Commission (SEC) under

the Securities Exchange Act of 1934 (Exchange Act). The SEC maintains a website at www.sec.gov that contains reports, proxy and information
statements, and other information regarding issuers, including us, that file electronically with the SEC.

We also make available free of charge on our Internet website at www.vandapharma.com our annual reports on Form 10-K, quarterly reports on

Form 10-Q, current reports on Form 8-K, and, if applicable, amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the
Exchange Act as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.

Our code of business conduct and ethics, other corporate policies and procedures, and the charters of our Audit Committee, Compensation

Committee and Nominating/Corporate Governance Committee are available at our corporate website at www.vandapharma.com. To access these
documents from the main page of our website, click on “Investor” at the top of the page, then click on “Learn More” under “Corporate Governance” and
then click on the desired document. We intend to satisfy the disclosure requirements under Item 5.05 of Form 8‑K regarding amendments to, or waivers
from, provisions of our code of business conduct and ethics by posting such information on the website address and location specified above.

None of the information contained on our website or www.sec.gov is incorporated by reference into this Annual Report or any other report or

document filed with the SEC unless expressly stated otherwise therein.

ITEM 1A.

RISK FACTORS

Our business, financial condition and operating results can be affected by a number of factors, whether currently known or unknown, including
but not limited to those described below, any one or more of which could, directly or indirectly, cause our actual operating results and financial condition
to vary materially from past, or anticipated future, operating results and financial condition. Any of these factors, in whole or in part, could materially and
adversely affect our business, financial condition, operating results and the price of our common stock.

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The following discussion of risk factors contains forward-looking statements. These risk factors may be important to understanding any statement
in this annual report on Form 10-K (Annual Report) or elsewhere. The following information should be read in conjunction with the consolidated financial
statements and related notes in Part II, Item 8, Financial Statements and Supplementary Data and Part II, Item 7, Management’s Discussion and Analysis
of Financial Condition and Results of Operations.

Because of the following risk factors, as well as other risk factors affecting our financial condition and operating results, past financial
performance should not be considered to be a reliable indicator of future performance, and investors should not use historical trends to anticipate results
or trends in future periods.

Risks Related to our Business and Industry

We are dependent on the commercial success of HETLIOZ and Fanapt .
®

We are substantially dependent upon the commercial success of HETLIOZ capsules for the treatment of Non-24-Hour Sleep-Wake Disorder

(Non-24) and HETLIOZ capsules and oral suspension (HETLIOZ LQ ) for the treatment of nighttime sleep disturbances in Smith-Magenis Syndrome
and Fanapt oral tablets for the treatment of schizophrenia.

In January 2014, the U.S. Food and Drug Administration (FDA) approved our New Drug Application (NDA) for HETLIOZ for the treatment of
Non-24 and in April 2014, we commenced the U.S. commercial launch of HETLIOZ . In July 2015, the European Commission (EC) granted centralized
marketing authorization with unified labeling for HETLIOZ for the treatment of Non-24 in totally blind adults, and in August 2016 we commenced the
commercial launch of HETLIOZ in Germany. This authorization, which was renewed in July 2020 for an unlimited duration, is valid in the 27 countries
that are members of the European Union (E.U.), as well as European Economic Area members Iceland, Liechtenstein and Norway. In December 2020, the
FDA approved our NDA and supplemental New Drug Application (sNDA) for HETLIOZ for the treatment of nighttime sleep disturbances in SMS in
adults and children, respectively. HETLIOZ capsules, for adults with SMS, were immediately available after approval and the HETLIOZ LQ liquid
formulation, for children with SMS, became available in March 2021.

In the fourth quarter of 2014, we acquired the U.S. commercial rights to Fanapt , and began selling, marketing and distributing Fanapt in the U.S.

Our ability to generate significant product revenue from sales of HETLIOZ and Fanapt , both in the U.S. and abroad, in the near term will

depend on, among other things, our ability to:

•

properly price and obtain adequate coverage and reimbursement of these products by governmental authorities, private health insurers,
managed care organizations and other third-party payors;

gain broad acceptance of our products from physicians, health care payors, patients, pharmacists and the medical community;

defend our patents and intellectual property from generic competition;

• minimize the impact of disruptions caused by the COVID-19 pandemic;

• maintain commercial manufacturing arrangements with third-party manufacturers;

•

produce, through a validated process, sufficiently large quantities of inventory of our products to meet demand;

continue to maintain and grow a wide variety of internal sales, distribution and marketing capabilities sufficient to sustain sales trajectories of
our products;

• maintain compliance with ongoing labeling, packaging, storage, advertising, promotion, recordkeeping, safety and other post-market

requirements;

•

obtain regulatory approval to expand the labeling of our approved products for additional indications;

obtain regulatory approval for HETLIOZ or Fanapt in additional countries;

• maintain our existing regulatory approval for HETLIOZ in Europe;

•

adequately protect against and effectively respond to any claims by holders of patents and other intellectual property rights that our products
infringe their rights; and

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•

adequately protect against and effectively respond to any unanticipated adverse effects or unfavorable publicity that develops in respect to our
products, as well as the emergence of new or existing competitive products, which may be proven to be more clinically effective and cost-
effective.

We expect to continue to incur significant expenses and to utilize a substantial portion of our cash resources as we continue the commercialization
®

of HETLIOZ and Fanapt , evaluate foreign market opportunities for HETLIOZ and Fanapt and continue to grow our operational capabilities, both
domestically and abroad. This activity represents a significant investment in the commercial success of HETLIOZ and Fanapt , which is uncertain.

If our continued commercial efforts are not successful with respect to HETLIOZ and Fanapt in the U.S., Europe or other jurisdictions in which

these products may be approved for sale, our ability to generate increased product sales revenue may be adversely affected.

The cost of growing and maintaining a sales, marketing and distribution organization may exceed its cost effectiveness. If we fail to continue to

develop sales, marketing and distribution capabilities, if sales efforts are not effective or if costs of developing sales, marketing and distribution capabilities
exceed their cost effectiveness, our business, results of operations and financial condition could be materially adversely affected.

Future performance of HETLIOZ and Fanapt may be impacted by a number of factors including competing products or unanticipated safety issues.
If either HETLIOZ or Fanapt is not successful in gaining broad commercial acceptance, our business would be harmed.

Future performance of HETLIOZ and Fanapt sales will be dependent on several factors, including our ability to educate physicians and to

increase physician awareness of the benefits of our products relative to competing products. The degree of further market acceptance of any of our
products, including with respect to new indications, or market acceptance of approved product candidates among physicians, patients, health care payors
and the medical community will depend on a number of factors, including but not limited to:

•

acceptable evidence of safety and efficacy;

relative convenience and ease of administration;

the prevalence and severity of any adverse side effects;

availability of alternative treatments;

• market awareness of the condition to be treated; and

•

pricing and cost effectiveness.

In addition, HETLIOZ and Fanapt are subject to continual review by the FDA, and we cannot assure that newly discovered or reported safety

issues will not arise. With the use of any newly marketed drug by a wider patient population, serious adverse events may occur from time to time that
initially do not appear to relate to the drug itself. Any safety issues could cause us to suspend or cease marketing of our approved products, cause us to
modify how we market our approved products, subject us to substantial liabilities and adversely affect our revenues and financial condition. In the event of
a withdrawal of either HETLIOZ or Fanapt from the market, our revenues would decline significantly and our business would be seriously harmed.

We are subject to uncertainty relating to pricing and reimbursement policies in the U.S. which, if not favorable for our products, could hinder or
prevent our products’ commercial success.

Our ability to commercialize our products successfully depends in part on the coverage and reimbursement levels with governmental authorities,

private health insurers and other third-party payors. In determining whether to reimburse our products and at what level, third-party payors consider factors
that include the efficacy, cost effectiveness and safety of our products, as well as the availability of other treatments including generic prescription drugs
and over-the-counter alternatives. We expect to continue to face increasing pressure to make unfavorable pricing modifications, such as discounts or
rebates. Negotiating favorable reimbursement can be a time consuming and expensive process, and there is no guarantee that we will be able to reach
pricing terms with third-party payors at levels that are profitable to us. Certain third-party payors also have reimbursement or coverage processes that we
believe are difficult to navigate and require prior authorization for, or even refuse to provide, reimbursement for our products, and others may do so in the
future. Our business may be materially adversely affected if our patients are not able to receive approval for reimbursement of our products from third-
party payors on a broad, timely or satisfactory basis; if reimbursement is subject to difficult reimbursement or coverage processes or prior authorization

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requirements; or if reimbursement is not maintained at satisfactory levels. In addition, our business could be adversely affected if third-party payors limit or
reduce the indications for or conditions under which, or the patient populations for whom, our products may be reimbursed. Moreover, as discussed further
below and above in in Part I, Item 1 under the heading Pharmaceutical Coverage, Pricing and Reimbursement and Healthcare Reform, changes in
insurance coverage or reimbursement levels by third-party payors, or in the type of such coverage held by patients, as well as the impacts to healthcare
access or administration (including, for example, limitations on medications or procedures deemed “non-essential,” reduced interaction between patients
and physicians, and increased unemployment), due to the COVID-19 pandemic may materially harm our business and commercialization efforts.

We expect to experience pricing pressures in connection with the sale of our current and future products due to the healthcare reforms discussed

below and above in in Part I, Item 1 under the heading Pharmaceutical Coverage, Pricing and Reimbursement and Healthcare Reform, as well as the trend
toward initiatives aimed at reducing healthcare costs, the increasing influence of managed care, the scrutiny of pharmaceutical pricing, the ongoing debates
on reducing government spending and additional legislative proposals. There has been significant scrutiny of pharmaceutical pricing and the resulting costs
of pharmaceutical products that could cause significant operational and reimbursement changes for the pharmaceutical industry. There have been a number
of federal and state efforts to address drug costs, which generally have focused on increasing transparency around drug costs or limiting drug prices, price
increases or other related costs. For example, the Bipartisan Budget Act of 2018 contained various provisions that affect coverage and reimbursement of
drugs, including an increase, which began in 2019, in the discount that manufacturers of Medicare Part D brand name drugs must provide to Medicare Part
D beneficiaries during the coverage gap from 50% to 70%.

Healthcare reform efforts or any future legislation or regulatory actions aimed at controlling and reducing healthcare costs, including through
measures designed to limit reimbursement, restrict access or impose unfavorable pricing modifications on pharmaceutical products, could impact our
ability to obtain or maintain reimbursement for our products at satisfactory levels, or at all, which could materially harm our business and financial results.

We have experienced both an increase in the rate at which third-party payors refuse to cover or reimburse prescriptions written for HETLIOZ and in
the number of patients who are unable to navigate the coverage or reimbursement processes established by these third-party payors. If this trend
continues, the commercial success of HETLIOZ may be limited, and our business and results of operations may be materially harmed.

®
We have recently experienced an increase in the rate at which third-party payors refuse to cover or reimburse prescriptions written for HETLIOZ .

Additionally, we are aware of an increasing number of patients who are experiencing difficulties navigating coverage processes established by third-party
payors, making it difficult for them to fill a prescription for HETLIOZ . Although currently there are no other FDA-approved products for the treatment of
Non-24, the rate at which third-party payors have refused to allow patients access to HETLIOZ has continued to increase. As a result, the revenue that we
receive from HETLIOZ is significantly less than it would be if third-party payors were to remove or lessen these reimbursement challenges and hurdles
®
and approve a greater percentage of the prescriptions written for HETLIOZ . Our business may be materially adversely affected if this trend continues and
large numbers of patients cannot fill their HETLIOZ prescriptions due to coverage or reimbursement challenges.

If the FDA does not accept our tradipitant NDA or sNDA filings for the treatment of gastroparesis and motion sickness; if the FDA determines that our
clinical trial results for tradipitant for the treatment of gastroparesis or for the treatment of motion sickness do not demonstrate adequate safety and
substantial evidence of efficacy; or the FDA does not approve an applicable PDUFA date, continued development of tradipitant will be significantly
delayed or terminated, our business will be significantly harmed, and the market price of our stock could decline.

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results or perceived adverse developments or results with respect to our regulatory submission or the tradipitant clinical programs in any or all indications
will significantly harm our business and could cause the market price of our stock to decline. Examples of such adverse developments include, but are not
limited to:

•

the FDA determining that they believe additional clinical studies are required with respect to tradipitant for the treatment of gastroparesis or
for the treatment of motion sickness;

safety, efficacy or other concerns arising from clinical or non-clinical studies in these programs; or

the FDA determining that the tradipitant clinical trial programs raise safety concerns or do not demonstrate substantial evidence of efficacy.

We believe that tradipitant has a well-established safety profile, as demonstrated by the results of extensive testing in animals and humans. Despite
these results, however, the FDA informed us in December 2018 that in order to treat patients beyond 12 weeks, we will have to conduct a nine-month non-
rodent chronic toxicity study. This currently limits our ability to collect safety data in humans for more than 12 weeks. The non-rodent study required by
the FDA necessitates the sacrifice of dozens of animals and we have disputed the necessity of a nine-month non-rodent chronic toxicity study. In February
2019, we filed a lawsuit in the U.S. District Court for the District of Columbia (DC District Court) challenging the FDA’s position, but we ultimately did
not prevail. Despite our disagreement with the FDA, the preclinical package has allowed us to continue to conduct all of the efficacy studies necessary for
NDA filing. Moreover, in July 2020, the FDA authorized tradipitant through an expanded access program (EAP) for a single patient. An EAP allows a
patient to request the use of tradipitant, prior to NDA approval, for up to six months with an option to request renewal. Since then, certain patients who
experienced a benefit in tradipitant studies have requested and received expanded access, while others have been denied treatment under the EAP. The EAP
is ongoing and a number of patients have initiated treatment. Although this EAP is not intended for data collection, we will collect safety data from this
cohort of expanded access patients and include this data in the NDA for tradipitant for the treatment of gastroparesis. The FDA may disregard such safety
data when reviewing the NDA. The lack of long-term (i.e., more than 12 weeks in humans) safety data would likely impact the FDA’s willingness to
approve tradipitant for a chronic indication. However, because long-term safety data is not normally a requirement for short-term indications, and with a
preclinical profile that has not precluded clinical development, we believe the package is complete for any NDA filing to treat patients for 12 weeks or less.
For example, the FDA has communicated to us that it is considering an indication for the short-term relief of nausea in gastroparesis. While this short-term
indication is not preferred, we would consider accepting this limited indication while continuing to pursue a chronic indication. However, the FDA may not
deem the safety information sufficient even for a short-term indication. Moreover, FDA authorization of an EAP is not a guarantee of or a step in obtaining
full FDA approval of an NDA. Our business will be materially adversely impacted if we are not able to agree with the FDA on a regulatory path to
approval for tradipitant, we experience any delay in filing, or the FDA delays or denies approval of NDA or sNDA filings for the treatment of gastroparesis
or motion sickness.

Global economic conditions may have an adverse effect on our business.

Financial instability or a general decline in economic conditions in the U.S. and other countries where we sell our products, including as a result of

the COVID-19 pandemic, could adversely affect our operations. Economic conditions, and uncertainty as to the general direction of the macroeconomic
environment, are beyond our control and may make any necessary debt or equity financing more difficult, costly and dilutive. While we believe we have
adequate capital resources to meet current working capital and capital expenditure requirements, an economic downturn or significant increase in our
expenses could require additional financing on less than attractive rates or on terms that are excessively dilutive to existing stockholders. Failure to secure
any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our stock price and could require us to delay or
abandon clinical development plans.

As discussed in the risk factor entitled "We are subject to uncertainty relating to pricing and reimbursement policies in the U.S. which, if not

favorable for our products, could hinder or prevent our products’ commercial success", sales of our products are dependent, in large part, on
reimbursement from government health administration authorities, private health insurers, distribution partners and other organizations. In the event of
economic decline, these organizations may be unable to satisfy their reimbursement obligations or may delay payment. In addition, federal and state health
authorities may further reduce Medicare and Medicaid reimbursements, and private insurers may further increase their scrutiny of claims. A reduction in
the availability or extent of reimbursement could negatively affect our product sales and revenue.

In addition, we rely on third parties for several important aspects of our business. For example, we use third parties for sales, distribution, medical

affairs and clinical research, and we rely upon several single source providers of raw materials and contract manufacturers for the manufacture of our
products. During challenging and uncertain economic times and in tight credit markets, there may be a disruption or delay in the performance of our third-
party contractors, suppliers or partners. If

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such third parties are unable to satisfy their commitments to us, our business and results of operations would be adversely affected.

Global health crises and pandemics, such as the global outbreak of COVID-19, may adversely impact our business.

The current global pandemic caused by the spread of the novel coronavirus (COVID-19) has led to the implementation of various responses,

including government-imposed quarantines, travel restrictions and other public health safety measures. The extent to which the effects of shelter-in-place
orders and our work-from-home policies may negatively impact productivity and disrupt our business will depend, in part, on the length and severity of the
restrictions, the extent of which new strains of the virus, such as the Delta and Omicron variants, continue to develop and spread, and other limitations on
our ability to conduct our business in the ordinary course. Additionally, the COVID-19 pandemic has caused global supply chain disruptions that may have
lasting impacts and consequences that are difficult to predict.

Our sales force has had physical access to healthcare providers curtailed, which may have a negative impact on our revenues. While we have
implemented marketing and sales strategies aimed at overcoming the disruptions caused by the pandemic, we cannot ensure that these methods will be
effective. Additionally, patients who might be currently using our products, or might otherwise be eligible to use our products, may be unable to meet with
their healthcare providers, which may reduce the number of prescription refills or new patient starts, thereby adversely affecting our revenues.

The COVID-19 pandemic has impacted clinical research globally, including delays in our development programs. While our clinical trials have

since resumed patient enrollment, we may continue to experience disruptions that could adversely impact our supply chain, our ongoing and planned
clinical trials, and other regulatory activities, including:

•

interruption of, or delays in receiving, supplies of the active pharmaceutical ingredients that our contract manufacturing organizations use to
manufacture our products and any related interruption of, or delays in receiving, supplies of our products from these organizations, due to
staffing shortages, production slowdowns or stoppages and disruptions in delivery systems;

delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;

diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites
and hospital staff supporting the conduct of our clinical trials;

delays or difficulties in enrolling patients in our clinical trials;

interruption of key clinical trial activities, such as clinical trial site data monitoring, due to limitations on travel imposed or recommended by
federal or state governments, employers and others or interruption of clinical trial subject visits and study procedures (such as procedures that
are deemed non-essential), which may impact the integrity of subject data and clinical study endpoints;

limitations on our employee resources or those of third-party clinical research organizations towards the development of our products,
including because of sickness of employees or their families or the desire of employees to avoid contact with large groups of people; and

interruption or delays in the operations of regulatory agencies, which may impact review and approval timelines.

In addition, the trading prices for our common stock and other biopharmaceutical companies have been highly volatile as a result of the COVID-

19 pandemic. As a result, we may face difficulties raising capital through sales of our common stock or such sales may be on unfavorable terms.

The COVID-19 pandemic continues to rapidly evolve. The extent to which the pandemic may continue to impact our business, financial condition
and results of operations will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration and
severity of the pandemic, the emergence of new variant strains of the virus, travel restrictions and social distancing practices, business closures or business
disruptions and the effectiveness of actions taken in the U.S. and other countries to contain and treat the disease.

If the FDA does not approve our sNDA for HETLIOZ for the treatment of jet lag disorder or continued development of tasimelteon for the treatment
of jet lag disorder is significantly delayed or terminated, our business will be significantly harmed, and the market price of our stock could decline.

In December 2018, we announced that the FDA had accepted the HETLIOZ sNDA for the treatment of jet lag disorder. We received a complete

response letter (CRL) in August 2019 in which the FDA asserted that the measures of the

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study were of unclear clinical significance and declined to approve our sNDA. We met with the FDA to discuss the CRL in a Post Action meeting and we
are determining our next steps.

Any additional adverse developments or results or perceived adverse developments or results with respect to our regulatory submission for jet lag
disorder will significantly harm our business and could cause the market price of our stock to decline. Examples of such adverse developments include, but
are not limited to:

•

the FDA determining that additional clinical studies are required with respect to the jet lag disorder program;

safety, efficacy or other concerns arising from clinical or non-clinical studies in the jet lag disorder program, or the manufacturing processes
or facilities used for the jet lag disorder program; or

the FDA determining that the jet lag disorder program raises safety concerns or does not demonstrate substantial evidence of efficacy.

We may enter into third-party collaborations from time to time in order to develop and commercialize our products. If we are unable to identify or enter
into an agreement with any material third-party collaborator, if our collaborations with any such third party are not commercially successful or if our
agreement with any such third party is terminated or allowed to expire, we could be adversely affected financially or our business reputation could be
harmed.

Our business strategy includes entering into collaborations with corporate collaborators for the commercialization of HETLIOZ , Fanapt and our
other products. While we are not currently party to any material commercial collaborative arrangements, areas in which we may potentially enter into third-
party collaboration arrangements include joint sales and marketing arrangements for sales and marketing in certain E.U. countries and elsewhere outside of
the U.S., and future product development arrangements. If we are unable to identify or enter into an agreement with any material third-party collaborator,
our business, results of operations or financial condition could be adversely affected. Any arrangements we do enter into may not be scientifically or
commercially successful. The termination of any of these arrangements might adversely affect our ability to develop, commercialize and market our
products.

The success of our collaboration arrangements will depend heavily on the efforts and activities of our collaborators. Our collaborators will have
significant discretion in determining the efforts and resources that they will apply to these collaborations. We expect that the risks we face in connection
with these future collaborations will include the following:

•

our collaboration agreements are expected to be for fixed terms and subject to termination under various circumstances, including, in many
cases, on short notice without cause;

our collaborators may develop and commercialize, either alone or with others, products and services that are similar to or competitive with
our products that are the subject of their collaboration with us; and

our collaborators may change the focus of their commercialization efforts.

In recent years there have been a significant number of mergers and consolidations in the pharmaceutical and biotechnology industries, some of
which have resulted in the participant companies reevaluating and shifting the focus of their business following the completion of these transactions. The
ability of our products to reach their potential could be limited if any of our future collaborators decreases or fails to increase spending relating to such
products.

Collaborations with pharmaceutical companies and other third parties often are terminated or allowed to expire by the other party. Any such

termination or expiration with respect to our future collaborations could adversely affect us financially as well as harm our business reputation.

Even after we obtain regulatory approvals of a product, acceptance of the product in the marketplace is uncertain and failure to achieve commercial
acceptance will prevent or delay our ability to generate significant revenue from such product.

Even after obtaining regulatory approvals for the sale of our products, the commercial success of these products will depend, among other things,
on their acceptance by physicians, patients, third-party payors and other members of the medical community as therapeutic and cost-effective alternatives
to competing products and treatments. The degree of market acceptance of any product will depend on a number of factors, including the demonstration of
its safety and efficacy, its cost-effectiveness, its potential advantages over other therapies, the reimbursement policies of government and third-party payors
with respect to such product, our ability to attract and maintain corporate partners, including pharmaceutical companies, to assist in commercializing our
products, receipt of regulatory clearance of marketing claims for the uses that we are developing and the effectiveness of our marketing and distribution
capabilities. If our approved products fail to gain market acceptance or

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do not become widely accepted by physicians, patients, third-party payors and other members of the medical community, it is unlikely that we will ever
become profitable on a sustained basis or achieve significant revenues.

We rely on, and will continue to rely on, outsourcing arrangements for many of our activities, including preclinical and clinical development and
supply of HETLIOZ , HETLIOZ LQ , Fanapt and our other products.

We rely on outsourcing arrangements for a significant portion of our activities, including distribution, preclinical and clinical research and

development, data collection and analysis and manufacturing. We have limited control over these third parties and we cannot guarantee that they will
perform their obligations in an effective and timely manner.

Disruptions to our HETLIOZ , HETLIOZ LQ or Fanapt supply chains could materially affect our level of success in commercializing these
products, thereby reducing our future earnings and prospects.

A loss or disruption with any one of our manufacturers or suppliers could disrupt the supply of HETLIOZ , HETLIOZ LQ or Fanapt , possibly

for a significant time period, and we may not have sufficient inventories to maintain supply before the manufacturer or supplier could be replaced or the
disruption is resolved. In addition, marketed drugs and their contract manufacturing organizations are subject to continual review, including review and
approval by regulatory authorities of their manufacturing facilities and the manufacturing processes, which can result in delays in the regulatory approval
process and/or commercialization. Introducing a replacement or backup manufacturer or supplier for HETLIOZ , HETLIOZ LQ or Fanapt requires a
lengthy regulatory and commercial process, including FDA approval of chemistry, manufacturing and controls (CMC) changes, and there can be no
guarantee that we could obtain necessary regulatory approvals in a timely fashion or at all. In addition, it is difficult to identify and select qualified
suppliers and manufacturers with the necessary technical capabilities, and establishing new supply and manufacturing sources involves a lengthy and
technical engineering process.

Failure to comply with government regulations regarding the sale and marketing of our products could harm our business.

In U.S. markets, our ability to commercialize our products successfully, and to attract commercialization partners for our products, should we

choose to do so, depends in significant part on the availability of adequate financial coverage and reimbursement from third-party payors, including, in the
U.S., governmental payors such as the Medicare and Medicaid programs, managed care organizations, and private health insurers.

We participate in the Medicaid Drug Rebate Program. Under the Medicaid Drug Rebate Program, we are required to pay a rebate to each state

Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition of
having our drugs eligible for coverage under Medicaid and Medicare Part B. Those rebates are based on pricing data that are reported by us on a monthly
and quarterly basis to the Centers for Medicare & Medicaid Services (CMS). Federal law requires that any company that participates in the Medicaid Drug
Rebate Program also participate in the Public Health Service Act’s 340B drug pricing discount program (340B program), in order for the manufacturer’s
drugs to be eligible for coverage under Medicaid and Medicare Part B. The 340B program requires participating manufacturers to agree to charge
statutorily defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered outpatient drugs. The ceiling price can represent a
significant discount and is based on the pricing data reporting to the Medicaid Drug Rebate Program.

The Patient Protection and Affordable Care Act (ACA) expanded the 340B program to include additional entity types: certain free-standing cancer
hospitals, critical access hospitals, rural referral centers and sole community hospitals, each as defined by ACA. The ACA exempts drugs designated under
section 526 of the Federal Food, Drug and Cosmetic Act (FDC Act) as “orphan drugs” from the ceiling price requirements for these newly eligible entities.
The ACA also obligates the Health Resources and Services Administration to create regulations and processes to improve the integrity of the 340B
program and to update the agreement that manufacturers must sign to participate in the 340B program. A final regulation regarding the calculation of the
340B ceiling price and the imposition of civil monetary penalties on manufacturers that knowingly and intentionally overcharge covered entities became
effective on January 1, 2019.

Federal law also requires that for a drug manufacturer’s products to be eligible for coverage under the Medicaid and Medicare Part B programs

and to be purchased by certain federal agencies and grantees, the manufacturer must participate in the Department of Veterans Affairs Federal Supply
Schedule (FSS), pricing program, established by Section 603 of the Veterans Health Care Act of 1992. Manufacturers that participate in the FSS pricing
program must list their covered (innovator and authorized generic) drugs on an FSS contract and charge no more than Federal Ceiling Price (FCP), to the
Department of Veterans Affairs, Department of Defense, Public Health Service, and Coast Guard when those agencies purchase from the FSS contract or a
depot contract. FCP is calculated based on non-federal average manufacturer price data, which manufacturers must

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submit quarterly and annually. In addition, because our products are available in the retail and specialty pharmacy setting, we are required to provide
rebates to the Department of Defense for prescriptions dispensed to Tricare beneficiaries from Tricare retail network pharmacies under the Tricare Retail
Refund Program. To the extent we continue to choose to participate in these government healthcare programs for our current and future products, these and
other requirements may affect our ability to profitably sell any product for which we obtain marketing approval.

Pricing and rebate calculations vary among products and programs. The calculations are complex and will often be subject to interpretation by us,

governmental or regulatory agencies and the courts. If we become aware that our reporting of pricing data for a prior quarter was incorrect, we will be
obligated to resubmit the corrected data. For the Medicaid Drug Rebate Program, corrected data must be submitted for a period not to exceed 12 quarters
from the quarter in which the data originally were due. Such restatements and recalculations increase our costs for complying with the laws and regulations
governing the Medicaid Drug Rebate Program and other governmental pricing programs. We may be liable for errors associated with our submission of
pricing data. If we are found to have knowingly submitted false pricing data to the Medicaid program or the FSS pricing program, we may be liable for
civil monetary penalties in the amount of up to $100,000 per item of false information, adjusted for inflation as applicable. Our failure to submit pricing
data to the Medicaid program or the FSS pricing program on a timely basis could result in a civil monetary penalty of $10,000 per day for each day the
information is late, adjusted for inflation as applicable. Such failure also could be grounds for CMS to terminate our Medicaid drug rebate agreement,
which is the agreement under which we would participate in the Medicaid Drug Rebate Program. In the event that CMS terminates our rebate agreement,
our products may no longer be eligible for coverage under Medicaid or Medicare Part B. There can be no assurance that our submissions will not be found
to be incomplete or incorrect.

Efforts to ensure that our business arrangements with third parties, and our business generally, will comply with applicable healthcare laws and

regulations may involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current
or future statutes, regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations
are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal
and administrative penalties, damages, fines, imprisonment, exclusion from government funded healthcare programs, such as Medicare and Medicaid, and
the curtailment or restructuring of our operations.

We are subject to ongoing regulatory obligations and oversight of our products, and any failure by us to maintain compliance with applicable
regulations may result in adverse consequences including the suspension of the manufacturing, marketing and sale of our respective products, the
incurrence of significant additional expense and other limitations on our ability to commercialize our respective products.

We are subject to ongoing regulatory requirements and review, including periodic audits pertaining to the development, manufacture, labeling,
packaging, adverse event reporting, distribution, storage, marketing, promotion, record keeping and export of our products. Failure to comply with such
regulatory requirements or the later discovery of previously unknown problems with the manufacture, distributions and storage of our products, or our
third-party contract manufacturing facilities or processes by which we manufacture our products may result in restrictions on our ability to develop,
manufacture, market, distribute or sell our products, including potential withdrawal of our products from the market. Any such restriction could slow or
stop production development or result in decreased sales, damage to our reputation or the initiation of lawsuits against us or our third-party contract
manufacturers. We may also be subject to additional sanctions, including, but not limited, to the following:

• Warning letters, public warnings and untitled letters;

•

Court-ordered seizures or injunctions;

Civil or criminal penalties, or criminal prosecutions;

• Variation, suspension or withdrawal of regulatory approvals for our products;

•

Changes to the package insert of our products, such as additional warnings regarding potential side effects or potential limitations on the
current dosage or administration;

Requirements to communicate with physicians and other customers about concerns related to actual or potential safety, efficacy, or other
issues involving our products;

Implementation of risk mitigation programs and post-approval obligations;

Restrictions on our continued manufacturing, marketing, distribution or sale of our products;

Temporary or permanent closing of the facilities of our third-party contract manufacturers;

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•

Interruption or suspension of clinical trials; and

Refusal by regulators to consider or approve applications for additional indications.

Any of the above sanctions could have a material adverse impact on our revenues or our reputation, and cause us to incur significant additional

expenses.

In addition, if our products face any safety or efficacy issues, including drug interaction problems, under the federal FDC Act, the FDA has broad

authority to force us to take any number of actions, including, but not limited to, the following:

•

Requiring us to conduct post-approval clinical studies to assess product efficacy or known risks or new signals of serious risks, or to evaluate
unexpected serious risks;

• Mandating changes to a product’s label;

•

Requiring us to implement a risk evaluation and mitigation strategy (REMS) where necessary to assure safe use of the drug; or

Removing an already approved product from the market.

Further, our partners, including our licensors, are subject to similar requirements and obligations as well as the attendant risks and uncertainties. If
our partners, including our licensors, suffer material and adverse effects from such risks and uncertainties, our rights and benefits for our licensed products
could be negatively impacted, which could have a material adverse effect on our business.

If our products are marketed or distributed in a manner that violates federal or state healthcare fraud and abuse laws, marketing disclosure laws or
other federal or state laws and regulations, we may be subject to civil or criminal penalties.

In addition to FDA and related regulatory requirements, our general operations, and the research, development, manufacture, sale and marketing

of our products, are subject to extensive additional federal and state healthcare regulation, including the federal Anti-Kickback Statute, the Prescription
Drug Marketing Act, and the federal False Claims Act (FCA), the federal Health Insurance Portability and Accountability Act of 1996, the federal
Physician Payment Sunshine Act and the Foreign Corrupt Practices Act (and their state analogues), as discussed above in Part I, Item 1 under the heading
Government Regulation - Fraud and abuse laws and other U.S. regulatory matters. If we or our partners, such as licensors, fail to comply with any federal
and state laws or regulations governing our industry, we could be subject to administrative, criminal and civil penalties and a range of regulatory actions
that could adversely affect our ability to commercialize our products, harm or prevent sales of our products, or substantially increase the costs and expenses
of commercializing and marketing our products, all of which could have a material adverse effect on our business, financial condition and results of
operations. In recent years, CMS has been actively proposing and implementing changes to the list of business practices that are protected by safe harbors.
There is inherent risk and uncertainty in any changing regulatory environment as companies work to transition business practices to conform with new
regulations.

Our activities relating to the sale and marketing of our products may be subject to scrutiny under these laws, and private individuals have been

active in bringing so-called “whistleblower” lawsuits on behalf of the government (as Relators) under the FCA and similar regulations in other countries. In
addition, incentives exist under applicable U.S. law that encourage employees and physicians to report violations of rules governing promotional activities
for pharmaceutical products. These incentives have led to, and could continue to lead to, FCA lawsuits, which attempt to recoup moneys paid by
government agencies and extract penalties from manufacturers. For example, federal enforcement agencies have recently pursued enforcement actions
against pharmaceutical companies’ product and patient assistance programs, including relationships with specialty pharmacies, and support for charitable
foundations providing patients with co-pay assistance. In addition, Relators have filed lawsuits involving manufacturer reimbursement support services as
well as promotion of pharmaceutical products beyond labeled claims. Some FCA lawsuits have resulted in government enforcement authorities obtaining
significant civil and criminal settlements. Such lawsuits, whether with or without merit, are typically time-consuming and costly to defend. Such suits may
also result in related shareholder lawsuits, which are also time-consuming and costly to defend. (See Note 16, Legal Matters, to the consolidated financial
statements in Part II, Item 8 of this Annual Report, which is incorporated herein by reference, for information regarding ongoing litigation related to similar
matters.)

Further, the FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products. A product

may not be promoted for uses that are not approved by the FDA as reflected in the product’s approved labeling. The FDA also regulates the content of
promotional material, including, among other things, the presentation of efficacy information, the types of comparative claims that can be made to
distinguish products from those with similar

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indications, and the balance of risk information provided. For drug products that are approved by the FDA under the FDA’s accelerated approval
regulations, unless otherwise informed by the FDA, the sponsor must submit promotional materials at least 30 days prior to the intended time of initial
dissemination of the promotional materials, which delays and may negatively impact a company’s ability to implement changes to its marketing materials,
thereby negatively impacting revenues. For other products, the FDA does not review promotional materials prior to dissemination but does issue “Untitled
Letters” or “Warning Letters” if it objects to content that has been used promotionally. The FDA may also withdraw approval of drug products under
certain conditions. In particular, the FDA may withdraw approval of a drug if, among other things, the promotional materials are false or misleading, or
other evidence demonstrates that the drug is not shown to be safe or effective under its conditions of use.

In recent years, in addition to federal legislation related to transparency reporting of transfers of value to healthcare providers and healthcare

organizations, several states have enacted legislation requiring pharmaceutical companies to file periodic reports. Several states have adopted legislation to
require pharmaceutical companies to establish marketing and promotional compliance programs or codes of conduct or to file periodic reports with the
state or make periodic public disclosures on sales, marketing, pricing, clinical trials, and other activities. Several states have also adopted laws that prohibit
certain marketing-related activities, including the provision of gifts, meals or other items to certain healthcare providers.

We have developed and implemented a corporate compliance program based on what we believe are current best practices in the pharmaceutical

industry; however, relevant compliance laws are broad in scope and there may not be regulations, guidance or court decisions that definitively interpret
these laws in the context of particular industry practices. We cannot guarantee that we, our employees, our partners, our consultants or our contractors are
or will be in compliance with all federal and state regulations. If we, our partners, or our representatives fail to comply with any of these laws or
regulations, a range of fines, penalties or other sanctions and regulatory actions could be imposed on us, including, but not limited to, restrictions on how
we market and sell our products, significant fines, exclusions from government healthcare programs, including Medicare and Medicaid, litigation, or other
sanctions. Even if it is not determined that we have violated these laws, government investigations into these issues typically require the expenditure of
significant resources and generate negative publicity, which could also have a material adverse effect on our business, financial condition and results of
operations. Such investigations or suits have resulted in, and may continue to result in, related shareholder lawsuits, which can also have a material adverse
effect on our business.

Our partners, including our licensors, are subject to similar requirements and obligations as well as the attendant risks and uncertainties. If our
partners, including our licensors, suffer material and adverse effects from such risks and uncertainties, our rights and benefits for our licensed products
could be negatively impacted, which could have a material adverse effect on our business.

We rely on a limited number of specialty pharmacies for distribution of HETLIOZ in the U.S., and the loss of one or more of these specialty
pharmacies or their failure to distribute HETLIOZ effectively would materially harm our business.

HETLIOZ is available for distribution through a limited number of specialty pharmacies in the U.S. A specialty pharmacy is a pharmacy that

specializes in the dispensing of medications for complex or chronic conditions that often require a high level of patient education and ongoing
management. The use of specialty pharmacies involves certain risks, including, but not limited to, risks that these specialty pharmacies will:

•

not provide us accurate or timely information regarding their inventories, the number of patients who are using HETLIOZ or complaints
about HETLIOZ ;
®

reduce their efforts or discontinue to sell or support or otherwise not effectively sell or support HETLIOZ ;
®

not devote the resources necessary to sell HETLIOZ in the volumes and within the time frames that we expect;

be unable to satisfy financial obligations to us or others; or

cease operations.

In addition, if one or more of our specialty pharmacies do not fulfill their contractual obligations to us, or refuse or fail to adequately serve

patients, or their agreements are terminated without adequate notice, shipments of HETLIOZ , and associated revenues, would be adversely affected. We
expect that it would take a significant amount of time if we were required to replace one or more of our specialty pharmacies.

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Our revenues from Fanapt are substantially dependent on sales through a limited number of wholesalers, and such revenues may fluctuate from
quarter to quarter.

We sell Fanapt primarily through a limited number of pharmaceutical wholesalers in the U.S. The use of pharmaceutical wholesalers involves

certain risks, including, but not limited to, risks that these pharmaceutical wholesalers will:

•

not provide us accurate or timely information regarding their inventories, demand from wholesaler customers buying Fanapt or complaints
about Fanapt ;
®

reduce their efforts or discontinue to sell or support or otherwise not effectively sell or support Fanapt ;
®

not devote the resources necessary to sell Fanapt in the volumes and within the time frames that we expect;

be unable to satisfy financial obligations to us or others; or

cease operations.

Additionally, our reliance on a small number of wholesalers could cause revenues to fluctuate from quarter to quarter based on the buying patterns

of these wholesalers. In addition, if any of these wholesalers fails to pay on a timely basis or at all, our business, financial condition and results of
operations could be materially adversely affected.

We face substantial competition, which may result in others developing or commercializing products before or more successfully than we do.

Our future success will depend on our ability to demonstrate and maintain a competitive advantage with respect to our products and our ability to

identify and develop additional products. Large, fully integrated pharmaceutical companies, either alone or together with collaborative partners, have
substantially greater financial resources and have significantly greater experience than we do in:

•

developing products;

undertaking preclinical testing and clinical trials;

obtaining FDA and other regulatory approvals of products; and

• manufacturing, marketing and selling products.

These companies may invest heavily and quickly to discover and develop novel products that could make our products obsolete. Accordingly, our

competitors may succeed in obtaining patent protection, receiving FDA or foreign regulatory approval or commercializing superior products or other
competing products before we do. Technological developments or the approval by the FDA or foreign regulators of new therapeutic indications for existing
products may make our products obsolete or may make them more difficult to market successfully, any of which could have a material adverse effect on
our business, results of operations and financial condition.

Our products, if successfully developed and approved for commercial sale, will compete with a number of drugs and therapies currently

manufactured and marketed by other biotechnology companies, including major pharmaceutical companies. Our products may also compete with new
products currently under development by others or with products that may cost less than our products. Physicians, patients, third-party payors and the
medical community may not accept or utilize any of our products that may be approved. If HETLIOZ , Fanapt and our other products, if and when
approved, do not achieve significant market acceptance, our business, results of operations and financial condition would be materially adversely affected.
(See Part I, Item 1, Competition, for a discussion of the primary competitors for HETLIOZ and Fanapt

Additionally, we may face competition from newly developed generic products. Under the Hatch-Waxman Act, newly approved drugs and

indications may benefit from a statutory period of non-patent marketing exclusivity. The Hatch-Waxman Act seeks to stimulate competition by providing
incentives to generic pharmaceutical manufacturers to introduce non-infringing forms of patented pharmaceutical products and to challenge patents on
branded pharmaceutical products. If we are unsuccessful at challenging an ANDA filed pursuant to the Hatch-Waxman Act, cheaper generic versions of our
products, which may be favored by insurers and third-party payors, may be launched commercially, which would significantly harm our business.

To obtain an ANDA approval for a generic drug, the generic company needs to show, among other things, that its version of the product is

bioequivalent to the Reference Listed Drug (RLD). This usually requires the generic company to conduct bioequivalence studies comparing its product to
the RLD, and to retain sufficient samples of the RLD used in testing

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after a study is complete. In recent years, U.S. federal lawmakers and the FDA have considered proposals and enacted legislation to facilitate the generic
drug company’s access to samples and foster the generic competition. For example, the Creating and Restoring Equal Access to Equivalent Samples Act
(CREATES Act) allows a biosimilar or generic product developer to bring a civil action against a brand drug manufacturer for failing to provide samples of
the brand product for comparative testing “on commercially reasonable, market-based terms.” The developer could receive injunctive relief and a monetary
award “sufficient to deter the license holder from failing to provide other eligible product developers with sufficient quantities of a covered product on
commercially reasonable, market-based terms” in certain cases. While the full impact of the CREATES Act is unclear at this time, its provisions do have
the potential to facilitate the development and future approval of generic versions of our products, introducing generic competition that could have a
material adverse effect on our business, results of operations and financial condition.

Certain states have also taken similar actions. For example, in 2018, Maine passed a new law that requires brand drug manufacturers to make
samples of drugs distributed in the state available for sale in Maine at a price no greater than wholesale acquisition cost and without any restriction that
would block or delay a biosimilar and generic drug application in a manner inconsistent with federal law. The state may seek injunctive relief and
attorney’s fees from a drug manufacturer who fails to comply with this requirement.

FDA and foreign regulatory approval of our products is uncertain.

The research, testing, manufacturing and marketing of products such as those that we have developed or that we are developing are subject to

extensive regulation by federal, state and local government authorities, including the FDA, as well as foreign regulatory authorities in jurisdictions in which
we seek approval. To obtain regulatory approval of such products, we must demonstrate to the satisfaction of the applicable regulatory agency that, among
other things, the product is safe and effective for its intended use. In addition, we must show that the manufacturing facilities used to produce such products
are in compliance with current good manufacturing practices (cGMPs).

The process of obtaining FDA and other required regulatory approvals and clearances can take many years and will require us to expend
substantial time and capital. Despite the time and expense expended, regulatory approval is never guaranteed. The number of preclinical and clinical trials
that will be required for FDA or foreign regulatory approval varies depending on the product, the disease or condition that the product is in development
for, and the requirements applicable to that particular product. The FDA or applicable foreign regulatory agency can delay, limit or deny approval of a
product for many reasons, including that:

•

a product may not be shown to be safe or effective;

the FDA or foreign agency may interpret data from preclinical and clinical trials in different ways than we do;

the FDA or foreign agency may not approve our or our partners’ manufacturing processes or facilities;

a product may not be approved for all the indications we request;

the FDA or foreign agency may change its approval policies or adopt new regulations;

the FDA or foreign agency may not meet, or may extend, the PDUFA date or its foreign equivalent with respect to a particular NDA or
foreign application; and

the FDA or foreign agency may not agree with our regulatory approval strategies or components of the regulatory filings, such as clinical trial
designs.

For example, if certain of our methods for analyzing trial data are not accepted by the FDA or the applicable foreign agency, we may fail to obtain

regulatory approval for our products.

Additionally, the approval procedure varies among countries and jurisdictions and can involve additional trials, and the time required to obtain

approval may differ from that required to obtain FDA approval. Approval by the FDA does not ensure approval by regulatory authorities in other countries
or jurisdictions, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or
jurisdictions or by the FDA.

Any delay or failure to obtain regulatory approvals for our products will result in increased costs, could diminish competitive advantages that we
may attain and would adversely affect the marketing and sale of our products. Other than HETLIOZ and HETLIOZ LQ in the U.S. and HETLIOZ in
the countries in Europe covered by the centralized marketing authorization by the EC, and Fanapt in the U.S., Mexico and Israel, we have not received,
and may never receive, regulatory approval to market any of our products in any jurisdiction.

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Even following regulatory approval of our products, the FDA or the applicable foreign agency may impose limitations on the indicated uses for

which such products may be marketed, subsequently withdraw approval or take other actions against us, or such products that are adverse to our business.
The FDA and foreign agencies generally approve drugs for use in specific indications. An approval for a more limited indication reduces the size of the
potential market for the product. Product approvals, once granted, may be withdrawn or modified if problems occur after initial marketing.

We and our partners also are subject to numerous federal, state, local and foreign laws, regulations and recommendations relating to safe working
conditions, laboratory and manufacturing practices, the environment and the use and disposal of hazardous substances used in connection with discovery,
research and development work. In addition, we cannot predict the extent to which new governmental regulations might significantly impede the discovery,
development, production and marketing of our products. We or our partners may be required to incur significant costs to comply with current or future laws
or regulations, and we may be adversely affected by the cost of such compliance or the inability to comply with such laws or regulations.

Our products may cause undesirable side effects or have other properties that could delay, prevent or result in the revocation of their regulatory
approval or limit their marketability.

Undesirable side effects caused by our products could interrupt, delay or halt clinical trials and could result in the denial of regulatory approval by
the FDA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing or continuing the commercialization
of such products and generating revenues from their sale. We will continue to assess the side effect profile of our products in ongoing clinical development
programs. However, we cannot predict whether the commercial use of our approved products (or our products in development, if and when they are
approved for commercial use) will produce undesirable or unintended side effects that have not been evident in the use of, or in clinical trials conducted for,
such products to date. For example, despite the positive results of our completed trials for HETLIOZ and Fanapt , as well as the FDA’s approval of the
NDA for HETLIOZ for the treatment of Non-24 in January 2014, the NDA for Fanapt for the treatment of schizophrenia in May 2009, the EC’s grant of
the centralized marketing authorization for HETLIOZ for the treatment of Non-24 in totally blind adults in July 2015, and the FDA’s approval of the
sNDA and NDA for HETLIOZ capsule and liquid formulation for the treatment of adults and children, respectively, with nighttime sleep disturbances in
SMS in December 2020, we are uncertain whether either of these products will ultimately prove to be effective and safe in humans long term and in all
uses. Frequently, products that have shown promising results in clinical trials have suffered significant setbacks in later clinical trials or even long after they
are approved for commercial sale. Additionally, incidents of product misuse may occur. These events, among others, could result in product recalls, product
liability actions or withdrawals or additional regulatory controls, any of which could have a material adverse effect on our business, results of operations
and financial condition.

In addition, if after receiving marketing approval of a product, we or others identify undesirable side effects caused by such product, we could face

one or more of the following:

•

regulatory authorities may require us to implement a REMS, such as the addition of labeling statements (e.g., “black box” warning or a
contraindication);

regulatory authorities may withdraw their approval of the product;

• we may be required to change the way the product is administered, conduct additional clinical trials or change the labeling of the product; and

•

our or the product’s reputation may suffer.

Any of these events could prevent us from achieving or maintaining market acceptance of the affected product or could substantially increase the

costs and expenses of commercializing the product, which in turn could delay or prevent us from generating significant revenues from its sale.

Clinical trials for our products are expensive and their outcomes are uncertain. Any failure or delay in completing clinical trials for our products could
severely harm our business.

Preclinical studies and clinical trials required to demonstrate the safety and efficacy of our products are time-consuming and expensive and
together take several years to complete. Before obtaining regulatory approvals for the commercial sale of any of our products, we must demonstrate
through preclinical testing and clinical trials that such product is safe and effective for use in humans. We have incurred, and we will continue to incur,
substantial expense for, and devote a significant amount of time to, preclinical testing and clinical trials.

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Historically, the results from preclinical testing and early clinical trials often have not predicted results of later clinical trials. A number of new

drugs have shown promising results in clinical trials, but subsequently failed to establish sufficient safety and efficacy data to obtain necessary regulatory
approvals. Clinical trials conducted by us or by third parties on our behalf may not demonstrate sufficient safety and efficacy to obtain the requisite
regulatory approvals for our products. Regulatory authorities may not permit us to undertake any additional clinical trials for our products, may force us to
stop any ongoing clinical trials and it may be difficult to design efficacy studies for our products in new indications.

Clinical development efforts performed by us may not be successfully completed or completed in a timely manner. Completion of clinical trials
may take several years or more. The length of time can vary substantially with the type, complexity, novelty and intended use of the products and the size
of the prospective patient population. Our ability to enroll patients in, and the commencement and rate of completion of, clinical trials for our products may
be affected by many factors, including:

•

the impact of global health crises, including the COVID-19 pandemic;

the size and nature of the patient population;

the design of the trial protocol for our clinical trials;

the eligibility and exclusion criteria for the trial in question;

the availability of competing therapies and competing clinical trials, and physician and patient perception of our product candidates and our
other product candidates being studied in relation to these other potential options;

the availability of raw materials and the possibility of raw materials expiring prior to their use;

difficulty in maintaining contact with patients after treatment, resulting in incomplete data;

poor effectiveness of our products during clinical trials;

unforeseen safety issues or side effects;

the number and location of clinical sites in our clinical trials;

the proximity and availability of clinical trial sites for prospective patients;

the availability of time and resources at the institutions where clinical trials are and will be conducted;

the availability of adequate financing to fund ongoing clinical trial expenses;

the study endpoints that rely on subjective patient reported outcomes; and

governmental or regulatory delays and changes in regulatory requirements and guidelines.

If we fail to complete successfully, or have difficulty enrolling a sufficient number of patients for, our clinical trials, we or they may not receive

the regulatory approvals needed to market that product. Any such failure or difficulty could have a material adverse effect on our business.

We may not be able to achieve sustained profitability.

We have been engaged in identifying and developing drug products since March 2003, which has required, and will continue to require, significant
research and development expenditures. The continued commercialization of HETLIOZ and Fanapt will also require substantial additional expenditures.

As of December 31, 2021, we had an accumulated deficit of $164.2 million and we cannot estimate with precision the extent of our future income

or loss. We may not succeed in gaining additional market acceptance of HETLIOZ and Fanapt in the U.S. and we may not succeed in commercializing
HETLIOZ or Fanapt outside of the U.S. We may be unable to fully develop, obtain regulatory approval for, commercialize, manufacture, market, sell and
derive revenue from our products in the timeframes we project, if at all, and our inability to do so would materially and adversely impact the market price
of our common stock and our ability to raise capital and continue operations.

There can be no assurance that we will achieve sustained profitability, which depends on many factors, including but not limited to, our ability to
obtain regulatory approval for our products and achieve success in commercializing them in the U.S., Europe and our other target jurisdictions, as well as
other factors described in this Annual Report.

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In addition, the amount we spend on developing, obtaining and maintaining regulatory approval for and commercializing our products, among

other expenditures described in this Annual Report, will impact our profitability.

Our ability to use net operating loss carryforwards and tax credit carryforwards to offset future taxable income is dependent on generating future
taxable income and may be limited, including as a result of transactions involving our common stock.

We have recorded deferred tax assets based on our assessment that we will be able to realize the benefits of our net operating losses and other

favorable tax attributes. Realization of deferred tax assets involve significant judgments and estimates, which are subject to change and ultimately depends
on generating sufficient taxable income of the appropriate character during the appropriate periods. Changes in circumstances may affect the likelihood of
such realization, which in turn may trigger the need for additional valuation allowance against our deferred tax assets and adversely affect our net income
and financial condition. In addition, we are potentially subject to ongoing and periodic tax examinations and audits in various jurisdictions, including with
respect to the amount of our net operating losses and any limitation thereon. An adjustment to such net operating loss carryforwards, including an
adjustment from a taxing authority, could result in higher tax costs, penalties and interest, thereby adversely impacting our financial condition.

In general, under Section 382 of the Internal Revenue Code of 1986, as amended (IRC), a corporation that undergoes an “ownership change” is
subject to limitations on its ability to utilize its pre-change net operating losses (NOLs) and certain other tax assets (tax attributes) to offset future taxable
income. In general, an ownership change occurs if the aggregate stock ownership of certain stockholders increases by more than 50 percentage points over
such stockholders’ lowest percentage ownership during the testing period (generally three years). Transactions involving our common stock, even those
outside our control, such as purchases or sales by investors, within the testing period could result in an ownership change. A limitation on our ability to
utilize some or all of our NOLs or credits could have a material adverse effect on our results of operations and cash flows. Ownership changes occurred in
the years ended December 31, 2014 and 2008. We believe that the ownership changes in 2014 and 2008 will not impact our ability to utilize NOL and
credit carryforwards; however, future ownership changes may cause our existing tax attributes to have additional limitations.

If we fail to adequately fund our research and development activities and commercialization efforts, we may be unable to continue operations or we
may be forced to share our rights to commercialize our products with third parties on terms that may not be attractive to us.

Our activities will necessitate significant uses of working capital throughout 2022 and beyond. It is uncertain whether cash provided by our
operating activities, together with our existing funds, will be sufficient to meet our long-term operating needs. As of December 31, 2021, our total cash and
cash equivalents and marketable securities were $432.8 million. Our long-term capital requirements are expected to depend on many factors, including,
among others:

•

our level of success in commercializing HETLIOZ and Fanapt , as well as other products that may be approved, globally;

outcomes of ongoing and potential patent litigation;

costs of developing and maintaining sales, marketing and distribution channels and our ability to sell our products;

• market acceptance of our products;

•

costs involved in establishing and maintaining manufacturing capabilities for commercial quantities of our products;

the number of potential formulations and products in development;

progress with preclinical studies and clinical trials;

time and costs involved in obtaining regulatory (including FDA) approval;

costs involved in preparing, filing, prosecuting, maintaining and enforcing patent, trademark and other intellectual property claims;

cost of evaluating and acquiring new products from third parties;

competing technological and market developments;

costs for recruiting and retaining employees and consultants;

costs for training physicians; and

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•

legal, accounting, insurance and other professional and business-related costs.

As a result, we may need to raise additional capital to fund our anticipated operating expenses and execute on our business plans. In our capital-

raising efforts, we may seek to sell debt securities or additional equity securities, obtain a bank credit facility, or enter into partnerships or other
collaboration agreements. The sale of additional equity or debt securities, if convertible, could result in dilution to our stockholders and may also result in a
lower price for our common stock. The incurrence of indebtedness would result in increased fixed obligations and could also result in covenants that could
restrict our operations. However, we may not be able to raise additional funds on acceptable terms, or at all. If additional financing is not available when
required or is not available on acceptable terms, we may be unable to fund our operations and planned growth, develop or enhance our technologies or
products, take advantage of business opportunities or respond to competitive market pressures, any of which would materially harm our business, financial
condition and results of operations.

If our contract research organizations (CROs) do not successfully carry out their duties or if we lose our relationships with CROs, our drug
development efforts could be delayed.

Our arrangements with CROs are critical to our success in bringing our products to the market. We are dependent on CROs, third-party vendors
and investigators for preclinical testing and clinical trials related to our drug discovery and development efforts and we will likely continue to depend on
them to assist in our future discovery and development efforts. These parties are not our employees and we cannot control the amount or timing of
resources that they devote to our programs. As such, they may not complete activities on schedule or may not conduct our clinical trials in accordance with
regulatory requirements or our stated protocols. The parties with which we contract for execution of our clinical trials play a significant role in the conduct
of the trials and the subsequent collection and analysis of data. If they fail to devote sufficient time and resources to our drug development programs or if
their performance is substandard, it will delay the development, approval and commercialization of our products. Moreover, these parties may also have
relationships with other commercial entities, some of which may compete with us. If they assist our competitors, it could harm our competitive position.

Our CROs could merge with or be acquired by other companies or experience financial or other setbacks unrelated to our collaboration that could,

nevertheless, materially adversely affect our business, results of operations and financial condition.

If we lose our relationship with any one or more of these parties, we could experience a significant delay in both identifying another comparable

provider and then contracting for its services. We may be unable to retain an alternative provider on reasonable terms, if at all. Even if we locate an
alternative provider, it is likely that this provider may need additional time to respond to our needs and may not provide the same type or level of service as
the original provider. In addition, any provider that we retain will be subject to current Good Laboratory Practices as set forth in 21 Code of Federal
Regulations (C.F.R.) Part 58 and Good Clinical Practices as set forth in 21 C.F.R. Part 50, 54, and 312, and similar international standards and we do not
have control over compliance with these regulations by these providers. Consequently, if these practices and standards are not adhered to by these
providers, the development and commercialization of our products could be delayed.

We rely on a limited number of third-party manufacturers to formulate and manufacture our products, and our business will be seriously harmed if
these manufacturers are not able to satisfy our demand and alternative sources are not available.

We do not have an in-house manufacturing capability and depend completely on a small number of third-party manufacturers and active
pharmaceutical ingredient formulators for the manufacture of our products. Therefore, we are dependent on third parties for our formulation development
and manufacturing of our products. This may expose us to the risk of not being able to directly oversee the production and quality of the manufacturing
process and provide ample commercial supplies to successfully launch and maintain the marketing of our products. Furthermore, these third-party
contractors, whether foreign or domestic, may experience regulatory compliance difficulty, mechanical shut downs, employee strikes, or other
unforeseeable events that may delay or limit production. Our inability to adequately establish, supervise and conduct (either ourselves or through third
parties) all aspects of the formulation and manufacturing processes would have a material adverse effect on our ability to develop and commercialize our
products.

We have agreements in place with Patheon Pharmaceuticals Inc. and Patheon Inc. (collectively, Patheon), subsidiaries of Thermo Fisher Scientific,

for the manufacture of HETLIOZ and Fanapt . In January 2014, we entered into a manufacturing agreement with Patheon for the manufacture of
commercial supplies of HETLIOZ 20 mg capsules at Patheon’s Cincinnati, Ohio manufacturing site. In May 2016, we entered into a manufacturing
agreement with Patheon for the manufacture of commercial supplies of Fanapt tablets at Patheon’s Mississauga, Ontario, Canada manufacturing site.
Additionally, in December 2020, we entered into a non-exclusive third-party manufacturing agreement for the manufacture of commercial

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supplies of HETLIOZ LQ . We do not have exclusive long-term agreements with any other third-party manufacturers of our products. If our current
manufacturers, or any other third-party manufacturer, is unable or unwilling to perform its obligations under our manufacturing agreements for any reason,
we may not be able to locate alternative acceptable manufacturers or formulators or enter into favorable agreements with them. Any inability to acquire
sufficient quantities of our products in a timely manner from these third parties could adversely affect sales of our products, delay clinical trials and prevent
us from developing our products in a cost-effective manner or on a timely basis. In addition, manufacturers of our products are subject to cGMP and similar
foreign standards and we do not have control over compliance with these regulations by our manufacturers. If one of our contract manufacturers fails to
maintain compliance, the production of our products could be interrupted, resulting in delays and additional costs. Moreover, if the facilities of such
manufacturers do not pass a pre-approval or post-approval plant inspection, the FDA will not grant approval for our products and may institute restrictions
on the marketing or sale of our products. Similarly, if we change contract manufacturers, the FDA must approve these contract manufacturers or any other
CMC changes before our products can be manufactured.

Our manufacturing strategy presents the following additional risks:

•

because most of our third-party manufacturers and formulators are located outside of the U.S., there may be difficulties in importing our
products or their components into the U.S. as a result of, among other things, FDA import inspections, incomplete or inaccurate import
documentation or defective packaging; and

because of the complex nature of our products, our manufacturers may not be able to successfully manufacture our products in a cost-effective
and/or timely manner.

Materials necessary to manufacture our products may not be available on commercially reasonable terms, or at all, which may delay the development,
regulatory approval and commercialization of our products.

We rely on manufacturers to purchase from third-party suppliers the materials necessary to produce our products for clinical trials and
commercialization. Suppliers may not sell these materials to such manufacturers at the times we need them or on commercially reasonable terms. We do
not have any control over the process or timing of the acquisition of these materials by these manufacturers. Moreover, we currently do not have any
agreements for the commercial production of these materials. If the manufacturers are unable to obtain these materials for our clinical trials, including due
to supply chain issues caused by the COVID-19 pandemic, product testing, potential regulatory approval of our products and commercial scale
manufacturing could be delayed, significantly affecting our ability to further develop and commercialize our products. If we or our manufacturers are
unable to purchase these materials for our products, there would be a shortage in supply or the commercial launch of such products would be delayed,
which would materially and adversely affect our ability to generate revenues from the sale of such products.

If we cannot identify, or enter into licensing arrangements for, new products, our ability to develop a diverse product portfolio will be limited.

A component of our business strategy is acquiring rights to develop and commercialize products discovered or developed by other pharmaceutical

and biotechnology companies for which we may find effective uses and markets through our unique pharmacogenetics and pharmacogenomics expertise.
Competition for the acquisition of these products is intense. If we are not able to identify opportunities to acquire rights to commercialize additional
products, we may not be able to develop a diverse portfolio of products. Additionally, it may take substantial human and financial resources to secure
commercial rights to promising products. Moreover, if other firms develop pharmacogenetics and pharmacogenomics capabilities, we may face increased
competition in identifying and acquiring additional products.

If we lose key scientists or management personnel, or if we fail to recruit additional highly skilled personnel, our ability to identify, develop, and
commercialize new products will be impaired.

We are highly dependent on principal members of our management team and scientific staff, including our Chief Executive Officer, Mihael H.

Polymeropoulos, M.D. These executives each have significant pharmaceutical industry experience. The loss of any such executives, including
Dr. Polymeropoulos, or any other principal member of our management team or scientific staff, would impair our ability to identify, develop and market
new products. Our management and other employees may voluntarily terminate their employment with us at any time. The loss of the services of these or
other key personnel, or the inability to attract and retain additional qualified personnel, could result in delays to development or approval, loss of sales and
diversion of management resources. In addition, we depend on our ability to attract and retain other highly skilled personnel, including research scientists.
Competition for qualified personnel is intense, and the process of hiring and integrating such qualified personnel is often lengthy. We may be unable to
recruit such personnel on a timely basis, if at all, which would negatively impact our development and commercialization programs.

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Additionally, we do not currently maintain “key person” life insurance on the lives of our executives or any of our employees. This lack of

insurance means that we may not have adequate compensation for the loss of the services of these individuals.

Product liability lawsuits could divert our resources, result in substantial liabilities and reduce the commercial potential of our products.

The risk that we may be sued on product liability claims is inherent in the development and sale of pharmaceutical products. For example, we face

a risk of product liability exposure related to the testing of our products in clinical trials and will face even greater risks upon commercialization of our
products. We believe that we may be at a greater risk of product liability claims relative to other pharmaceutical companies because certain of our products
are intended to treat central nervous system disorders, among others, and it is possible that we may be held liable for the behavior and actions of patients
who use our products. These lawsuits may divert our management from pursuing our business strategy and may be costly to defend. In addition, if we are
held liable in any of these lawsuits, we may incur substantial liabilities and we may be forced to limit or forego further commercialization of one or more of
our products. Although we maintain product liability insurance, our aggregate coverage limit under this insurance is $30.0 million, and while we believe
this amount of insurance is sufficient to cover our product liability exposure, these limits may not be high enough to fully cover potential liabilities. As our
development activities and commercialization efforts progress and we sell our products, this coverage may be inadequate, we may be unable to obtain
adequate coverage at an acceptable cost or we may be unable to get adequate coverage at all or our insurer may disclaim coverage as to a future claim. This
could prevent the commercialization or limit the commercial potential of our products. Even if we are able to maintain insurance that we believe is
adequate, our results of operations and financial condition may be materially adversely affected by a product liability claim. Uncertainties resulting from
the initiation and continuation of products liability litigation or other proceedings could have a material adverse effect on our ability to compete in the
marketplace. Product liability litigation and other related proceedings may also require significant management time.

E.U. Member States tend to impose strict price controls, which may delay or prevent the further commercial launch or impede the commercial success
of HETLIOZ in Europe and adversely affect our future results of operations.

In the E.U., prescription drug pricing and reimbursement are subject to governmental control and reimbursement mechanisms used by private and

public health insurers in the E.U. vary by Member State. For the public systems, reimbursement is determined by law and/or by guidelines established by
the responsible national authority. As elsewhere, inclusion in reimbursement catalogues focuses on the medical usefulness, need, quality and economic
benefits to patients and the health care system. Acceptance for reimbursement comes with cost, use and often volume restrictions, which can vary by
Member State. Although we have received marketing authorization for HETLIOZ capsules from the EC, pricing negotiations with governmental
authorities may take a considerable amount of time in those Member States that impose price controls. For example, we launched HETLIOZ
®
commercially in Germany in August 2016, and concluded our pricing negotiations with German authorities in October 2017. In addition, to obtain
reimbursement or pricing approval for HETLIOZ in some Member States, we may be required to conduct an additional clinical trial that compares the
cost-effectiveness of HETLIOZ , to other available therapies.

Some Member States require approval of the sale price of a drug before it can be marketed. In others, the pricing review period begins after

marketing or product licensing approval is granted. In some Member States, prescription pharmaceutical pricing remains subject to continuing
governmental control even after initial approval is granted. As a result, we may be subject to lengthy price regulations that delay or prevent the commercial
launch of HETLIOZ in a particular Member State and negatively impact the revenues that are generated from the sale of HETLIOZ in that country. If
reimbursement of HETLIOZ is unavailable or limited in scope or amount, or if pricing for HETLIOZ is set at unsatisfactory levels or takes too long to
establish, or if there is competition from lower priced cross-border sales, our results of operations will be negatively affected.

We may not be able to effectively market and sell our future products, if approved, in the U.S.

We plan to continue to build our sales and marketing capabilities in the U.S. to commercialize future products, if approved. Our current sales and
marketing capabilities in the U.S. may not be adequate to support the commercialization of future products and we would expect to build such capabilities
by investing significant amounts of financial and management resources. Furthermore, the cost of establishing and maintaining marketing and sales
capabilities may not be justifiable in light of the revenues generated by any future products.

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If we are unable to establish and maintain adequate sales and marketing capabilities for future products or are unable to do so in a timely manner,

we may not be able to generate product revenues from these products, which may prevent us from reaching or maintaining profitability.

Healthcare legislative reform measures or developments arising from changes in the political climate may have a material adverse effect on our
business and results of operations.

In the U.S., there have been and continue to be a number of legislative initiatives to contain healthcare costs. For example, in March 2010, the

ACA was passed, which substantially changes the way healthcare is financed by both governmental and private insurers, and significantly impacts the U.S.
pharmaceutical industry. The ACA, among other things, increases the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate
Program and extends the rebate program to individuals enrolled in Medicaid managed care organizations, establishes annual fees and taxes on
manufacturers of certain branded prescription drugs, and creates a new Medicare Part D coverage gap discount program, in which manufacturers must
agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a
condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D.

Some of the provisions of the ACA have yet to be fully implemented, while certain provisions have been subject to judicial and Congressional

challenges, as well as efforts by the former Trump administration to repeal or replace certain aspects of the ACA. While Congress has not passed
comprehensive repeal legislation, it has enacted laws that modify certain provisions of the ACA such as removing or delaying penalties, starting January 1,
2019, for not complying with the ACA’s individual mandate to carry health insurance, delaying the implementation of certain ACA-mandated fees, and
increasing the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D. Further, in December 2018, a Texas
District Court judge ruled that the ACA is unconstitutional in its entirety because the individual mandate was repealed by Congress. In July 2021, the U.S
Supreme Court ruled that the states and individuals that brought the lawsuit did not have standing to challenge the ACA, and therefore, the Court did not
reach the merits of the lawsuit. Accordingly, we continue to evaluate the effect that the ACA has on our business. At the federal level, the former Trump
administration supported legislative proposals and issued certain Executive Orders seeking to reduce drug prices, increase competition, lower out-of-pocket
drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs. The Department of Health and Human Services (HHS), has
solicited feedback on some of these measures and implemented others under its existing authority. The FDA also released a final rule in September 2020
providing guidance for states to build and submit importation plans for drugs from Canada. Further, in November 2020, HHS finalized a regulation
removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Medicare Part D, either directly or through
pharmacy benefit managers, unless the price reduction is required by law. The rule also creates a new safe harbor for price reductions reflected at the point-
of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers. These modifications to the safe
harbors are being challenged in court and HHS has delayed their implementation until January 1, 2023; however, the rule may be repealed through
legislative action before such time. In July 2021, President Biden issued an executive order pertaining to drug pricing, which expressed support for
legislation allowing direct negotiation in Medicare Part D and inflationary rebates and directed various executive branch agencies to take actions to lower
drug prices and promote generic competition. In response to President Biden’s executive order, in September 2021, HHS issued a Comprehensive Plan for
Addressing High Drug Prices that identified potential legislative policies and administrative tools that Congress and the agency can pursue in order to make
drug prices more affordable and equitable, improve and promote competition throughout the prescription drug industry, and foster scientific innovation.
Several pending or proposed legislative efforts incorporate these drug pricing reforms in addition to inflationary rebates on Part B and Part D drugs that
would be payable on commercial and governmental program utilization, policies aimed at redesigning the Medicare Part D benefit and adopting drug price
transparency measures. Drug manufacturers who are unwilling to negotiate with Medicare would be subject to additional excise taxes. Additionally, the
plan would impose tax penalties on drug manufacturers that increase the prices of drug products faster than the rate of inflation. If elements of these
prescription drug pricing plans become law, our pricing strategy and commercial prospects may be adversely affected.

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and increased the statute of limitations period for the government to recover overpayments to providers from three to five years and the American Rescue
Plan Act of 2021, which will eliminate the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single
source and innovator multiple source drugs, beginning January 1, 2024. These new laws may result in additional reductions in Medicare and other
healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for which we may obtain regulatory approval or the
frequency with which any such product candidate is prescribed or used. Further, there have been several recent U.S. congressional inquiries and proposed
state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and
manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug
products.

Additionally, there has been increasing legislative and enforcement interest in the U.S. with respect to specialty drug pricing practices.
Specifically, there have been several recent U.S. Congressional inquiries and proposed and enacted federal and state legislation designed to, among other
things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and
manufacturer patient programs, and reform government program reimbursement methodologies for drugs. We expect that additional state and federal
healthcare reform measures will be adopted in the future, any of which could result in more rigorous coverage criteria and/or limit the amounts that federal
and state governments will pay for healthcare products and services, which could result in reduced demand for our products and additional downward
pricing pressures. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from
private third-party payors.

These healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in
Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price for
any approved product and/or the level of reimbursement physicians receive for administering any approved product which could affect our business
strategy or commercial prospects. Reductions in reimbursement levels may negatively impact the prices we can charge or the frequency with which
products are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in
payments from private payors.

Changes in U.S. social, political, regulatory and economic conditions or in laws and policies governing foreign trade, manufacturing, development

and investment, and any negative sentiments towards the U.S. as a result of such changes, could also adversely affect our business.

We are subject to stringent laws, rules, regulations, policies, industry standards and contractual obligations regarding data privacy and security in
foreign jurisdictions and may be subject to additional related laws and regulations in other jurisdictions into which we expand. Many of these laws and
regulations are subject to change and reinterpretation and could result in claims, changes to our business practices, monetary penalties, increased cost
of operations or other harm to our business.

The regulatory framework for privacy and personal information security issues worldwide is rapidly evolving and is likely to remain uncertain for

the foreseeable future. Various foreign government bodies and agencies have adopted or are considering adopting laws, rules, regulations and standards
limiting, or laws, rules, regulations and standards regarding, the collection, distribution, use, disclosure, storage, security and other processing of personal
information.

Outside of the U.S., legal requirements relating to the collection, storage, processing and transfer of personal data continue to evolve. For example,
the collection and use of health data and other personal data is governed in the European Union by the General Data Protection Regulation (GDPR), which
became applicable in May 2018. The GDPR implements stringent operational requirements for processors and controllers of personal data, including, for
example, expanded disclosure requirements about how personal information is to be used, strengthened individual data subject rights, limitations on
retention of personal data, increased requirements pertaining to health data and pseudonymised (i.e., key-coded) data, shortened mandatory data breach
notification timelines and higher standards for controllers to demonstrate they have obtained valid consent for certain data processing activities. The GDPR
provides that E.U. member states may make their own additional laws and regulations in relation to the processing of genetic, biometric or health data,
which could result in differences between member states, limit our ability to use and share personal data. Failure to comply with the GDPR may result in
fines up to €20,000,000 or 4% of the total worldwide annual revenue of the preceding financial year, whichever is higher, and other administrative
penalties. The GDPR may increase our responsibility and liability in relation to personal data that we may process, and we may be required to implement
additional measures in an effort to comply with the GDPR and with other laws, rules, regulations and standards in the E.U., including those of E.U.
Member States, relating to privacy and data protection. This may be onerous and if our efforts to comply with GDPR or other applicable E.U. laws, rules,
regulations and standards are not successful, or are perceived to be unsuccessful, it could adversely affect our business. In July 2020, the European Court of

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Justice (ECJ) invalidated the E.U.-U.S. Privacy Shield, which had enabled the transfer of personal data from the E.U. to the U.S. for companies that had
self-certified to the Privacy Shield. While we do not rely on the Privacy Shield, the ECJ decision also raised questions about the continued validity of the
European Commission’s Standard Contractual Clauses, on which we rely. E.U. regulators have issued additional guidance regarding considerations and
requirements that we and other companies must consider and undertake when using the Standard Contractual Clauses. Although the European Commission
has presented a new set of Standard Contractual Clauses, which are required to be implemented, there are few, if any, viable alternatives to the Standard
Contractual Clauses and it remains to be seen whether additional means for lawful data transfers will become available. The ECJ’s decision and other
regulatory guidance or developments may impose additional obligations with respect to the transfer of personal data from the E.U. to the U.S, all of which
could restrict our activities in those jurisdictions, limit our ability to provide our products and services in those jurisdictions, require us to modify our
policies and practices, and to engage in additional contractual negotiations, or increase our costs and obligations and impose limitations upon our ability to
efficiently transfer personal data from the E.U. to the U.S.

Risks related to intellectual property and other legal matters

Our rights to develop and commercialize our products are subject in part to the terms and conditions of licenses or sublicenses granted to us by other
pharmaceutical companies.

Our rights to our product portfolio are based in part on patents and other intellectual property licensed from third parties. These third parties may

generally terminate the license agreements under certain circumstances, including a material breach of the agreement by the other. In the event we
terminate our license, or if the third party terminates our license due to our breach, rights to the intellectual property revert back to the licensor. Any
termination or reversion of our rights to develop or commercialize our products would have a material adverse effect on our business.

If our efforts to protect the proprietary nature of the intellectual property related to our products are not adequate, we may not be able to compete
effectively in our markets.

Method of treatment patents protect the use of a product for the method specified in the patent claims. This type of patent does not prevent a

competitor from making and marketing a product that is identical to our product for a use that is outside the scope of the patented method. Moreover, even
if competitors do not actively promote their product for our patented methods, physicians may prescribe these products “off-label.” Although off-label
prescriptions may infringe or contribute to the infringement of method of treatment patents, such infringement may be difficult to prevent.

Our patents and patent applications may be challenged or fail to result in issued patents and our existing or future patents may be too narrow to

prevent third parties from developing or designing around these patents. In addition, we generally rely on trade secret protection and confidentiality
agreements to protect certain proprietary know-how that is not patentable, for processes for which patents are difficult to enforce and for any other elements
of our drug development processes that involve proprietary know-how, information and technology that is not covered by patent applications. While we
require all of our employees, consultants, advisors and any third parties who have access to our proprietary know-how, information and technology to enter
into confidentiality agreements, we cannot be certain that this know-how, information and technology will not be disclosed or that competitors will not
otherwise gain access to our trade secrets or independently develop substantially equivalent information and techniques. Further, the laws of some foreign
countries do not protect proprietary rights to the same extent as the laws of the U.S. As a result, we may encounter significant problems in protecting and
defending our intellectual property both in the U.S. and abroad. If we are unable to protect or defend the intellectual property related to our technologies,
we will not be able to establish or maintain a competitive advantage in our market.

Even if our patent applications issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent

competitors from competing with us or otherwise provide us with any competitive advantage. Our competitors may be able to circumvent our owned or
licensed patents by developing similar or alternative technologies or products in a non-infringing manner. Our competitors may seek to market generic
versions of any approved products by submitting ANDAs to the FDA in which they claim that patents owned or licensed by us are invalid, unenforceable
and/or not infringed. Alternatively, our competitors may seek approval to market their own products similar to or otherwise competitive with our products.
In these circumstances, we may need to defend and/or assert our patents, including by filing lawsuits alleging patent infringement. In any of these types of
proceedings, a court or other agency with jurisdiction may find our patents invalid and/or unenforceable. Even if we have valid and enforceable patents,
these patents still may not provide protection against competing products or processes sufficient to achieve our business objectives.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be

challenged in the courts or patent offices in the U.S. and abroad. Such challenges may result in loss of

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exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to
stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and
products. In addition, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting
such candidates might expire before or shortly after such candidates are commercialized.

We are, have been, and may continue to be, involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming and
unsuccessful, and third parties may challenge the validity or enforceability of our patents and they may be successful.

Even where laws provide protection or we are able to obtain patents, costly and time-consuming litigation may be necessary to enforce and

determine the scope of our proprietary rights, and the outcome of such litigation would be uncertain. Moreover, any actions we may bring to enforce our
intellectual property rights against our competitors could provoke them to bring counterclaims against us, and some of our competitors have substantially
greater intellectual property portfolios than we have. To counter infringement or unauthorized use of any patents we may obtain, we may be required to file
infringement claims, which can be expensive and time-consuming to litigate. In addition, if we or one of our future collaborators were to initiate legal
proceedings against a third party to enforce a patent covering one of our products, current product candidates, or one of our future products, the defendant
could counterclaim that the patent is invalid or unenforceable. In patent litigation in the U.S., defendant counterclaims alleging invalidity or
unenforceability are commonplace and challenges to validity of patents in certain foreign jurisdictions are common as well. Grounds for a validity
challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, non-enablement or lack of
statutory subject matter. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld
relevant material information from the U.S. Patent and Trademark Office, or made a materially misleading statement, during prosecution. We may assert
the patents in Hatch-Waxman litigation against the party filing the ANDA to keep the competing product off of the market until the patents expire but there
is a risk that we will not succeed. The party filing the ANDA may also counterclaim in the litigation that our patents are not valid or unenforceable, and the
court may find one or more claims of our patents invalid or unenforceable. If this occurs, a competing generic product could be marketed prior to expiration
of our patents listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the “Orange Book,” which
would harm our business.

We have been and continue to be involved in number of lawsuits with a variety of generic drug manufacturers who have filed ANDAs relating to

certain of our patents. We have been successful in asserting that these third parties have infringed certain of our patents, but we may not be successful in
such lawsuits in the future. Please see Note 16, Legal Matters, to the consolidated financial statements in Part II, Item 8 of this Annual Report, which is
incorporated herein by reference, for additional information.

If we do not obtain protection under the Hatch-Waxman Act and similar foreign legislation to extend our patents and to obtain market exclusivity for
our products, our business will be harmed.

The Hatch-Waxman Act provides for an extension of patent term for drugs for a period of up to five years to compensate for time spent in

development. The HETLIOZ U.S. new chemical entity (NCE) patent (the primary patent covering the product as a new composition of matter) received
the full five-year patent term extension under the Hatch-Waxman Act and so, assuming that we continue to have rights under our license agreement with
respect to this product, this patent in the U.S. will expire in December 2022. We also own HETLIOZ U.S. method of treatment patents (directed to the
approved method of treatment as described in the HETLIOZ label approved by the FDA), which expire normally between 2033 and 2035, and two drug
substance patents that expire in 2035. Additionally, the U.S. Patent and Trademark Office has issued a drug formulation patent for HETLIOZ LQ that
will expire in 2040. The Fanapt U.S. NCE patent received the full five-year patent term extension under the Hatch-Waxman Act and so this patent in the
U.S. expired in November 2016. In November 2013, a patent directed to a method of treating patients with Fanapt based on genotype was issued to us by
the U.S. Patent and Trademark Office. This patent, which was listed in the Orange Book in January 2015, is set to expire in 2027. Please see the risk factor
entitled “We are, have been, and may continue to be, involved in lawsuits to protect or enforce our patents, which could be expensive, time-consuming and
unsuccessful, and third parties may challenge the validity or enforceability of our patents and they may be successful,” and Note 16, Legal Matters, to the
consolidated financial statements in Part II, Item 8 of this Annual Report, which is incorporated herein by reference, for additional information. Eight
additional U.S. patents directed to methods of treating patients with Fanapt , which are set to expire between 2025 and 2031, were issued to us in 2015.
®

The E.U. provides that companies that receive regulatory approval for a new medicinal product will have a 10-year period of regulatory data

protection and market protection for that product (with the possibility of a further one-year extension

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under certain conditions), beginning on the date of such European regulatory approval, regardless of when the European NCE patent covering such product
expires. A generic version of the approved drug that refers to the approved drug’s regulatory data may not be marketed or sold in Europe during such
market protection period. This legislation is of material importance with respect to Fanapt , since the European NCE patent for Fanapt has expired.

Assuming we gain a five-year patent term restoration for tradipitant, and that we continue to have rights under our license agreement with respect

to this product, we would have exclusive rights to tradipitant’s U.S. NCE patent until 2029. Assuming we gain a five-year patent term restoration for VQW-
765, and that we continue to have rights under our license agreement with respect to this product, we would have exclusive rights to VQW-765’s U.S. NCE
patent until 2028.

However, there is no assurance that we will receive the extensions of our patents or other exclusive rights available under the Hatch-Waxman Act
or similar foreign legislation. Such extensions may not be granted because of, for example, the failure to exercise due diligence during the testing phase or
regulatory review process, the failure to apply within applicable deadlines, the failure to apply prior to expiration of relevant patents, or any other failure to
satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we fail to
receive such extensions or exclusive rights, our ability to prevent competitors from manufacturing, marketing and selling generic versions of our products
will be materially impaired.

We may not be successful in the development of products for our own account.

In addition to our business strategy of acquiring rights to develop and commercialize products, we may develop products for our own account by
applying our technologies to off-patent drugs as well as developing our own proprietary molecules. Because we will be funding the development of such
programs, there is a risk that we may not be able to continue to fund all such programs to completion or to provide the support necessary to perform the
clinical trials, obtain regulatory approvals or market any approved products. We expect the development of products for our own account to consume
substantial resources. If we are able to develop commercial products on our own, the risks associated with these programs may be greater than those
associated with our programs with collaborative partners.

Litigation or third-party claims of intellectual property infringement could require us to divert resources and may prevent or delay our drug discovery
and development efforts.

Our commercial success depends in part on our not infringing the patents and proprietary rights of third parties. Third parties may assert that we

are employing their proprietary technology without authorization. In addition, third parties may obtain patents in the future and claim that use of our
technologies infringes upon these patents.

Furthermore, parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to develop

and commercialize one or more of our products. Defense of these claims, regardless of their merit, would divert substantial financial and employee
resources from our business. In the event of a successful claim of infringement against us, we may have to pay substantial damages, obtain one or more
licenses from third parties or pay royalties. In addition, even in the absence of litigation, we may need to obtain additional licenses from third parties to
advance our research or allow commercialization of our products. We may fail to obtain any of these licenses at a reasonable cost or on reasonable terms, if
at all. In that event, we would be unable to develop and commercialize further one or more of our products.

In addition, in the future we could be required to initiate litigation to enforce our proprietary rights against infringement by third parties.
Prosecution of these claims to enforce our rights against others could divert substantial financial and employee resources from our business. If we fail to
enforce our proprietary rights against others, our business will be harmed.

As described elsewhere in these risk factors and in Note 16, Legal Matters, to the consolidated financial statements in Part II, Item 8 of this

Annual Report, incorporated herein by reference, we have initiated lawsuits to enforce our patent rights against certain generic pharmaceutical companies.

General Risk Factors

Our stock price has been highly volatile and may be volatile in the future, and purchasers of our common stock could incur substantial losses.

The realization of any of the risks described in these risk factors or other unforeseen risks could have a dramatic and adverse effect on the market

price of our common stock. Between January 1, 2021 and December 31, 2021, the high and low

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sale prices of our common stock as reported on The Nasdaq Global Market varied between $13.14 and $21.86. Additionally, market prices for securities of
biotechnology and pharmaceutical companies, including ours, have historically been very volatile. The market for these securities has from time to time
experienced significant price and volume fluctuations for reasons that were unrelated to the operating performance of any one company.

The following factors, in addition to the other risk factors described in this section, may also have a significant impact on the market price of our

common stock:

•

our level of success in commercializing our products;

our level of success in executing our commercialization strategies;

publicity regarding actual or potential testing or trial results relating to products under development by us or our competitors;

the outcome of regulatory review relating to products under development by us or our competitors;

regulatory developments in the U.S. and foreign countries;

newly enacted healthcare legislation or changes to existing legislation;

developments concerning any collaboration or other strategic transaction we may undertake;

publicity regarding actual or potential litigation involving us;

announcements of patent issuances or denials, technological innovations or new commercial products by us or our competitors;

safety issues with our products or those of our competitors;

announcements of technological innovations or new therapeutic products or methods by us or others;

actual or anticipated variations in our quarterly operating results;

changes in estimates of our financial results or recommendations by securities analysts or failure to meet such financial expectations;

changes in government regulations or policies;

changes in patent legislation or patent decisions or adverse changes to patent law;

additions or departures of key personnel or members of our board of directors;

the publication of negative research or articles about our company, our business or our products by industry analysts or others;

• market rumors or press reports;

•

publicity regarding actual or potential transactions involving us; and

economic, political and other external factors beyond our control.

We have been and may in the future be subject to litigation, which could harm our stock price, business, results of operations and financial condition.

We have been the subject of litigation in the past and may be subject to litigation in the future. In the past, following periods of volatility in the

market price of their stock, many companies, including us, have been the subjects of securities class action litigation. Any such litigation can result in
substantial costs and diversion of management’s attention and resources and could harm our stock price, business results of operations and financial
condition. As a result of these factors, holders of our common stock might be unable to sell their shares at or above the price they paid for such shares.

If there are substantial sales of our common stock, our stock price could decline.

A small number of institutional investors and private equity funds hold a significant number of shares of our common stock. Sales by these

stockholders of a substantial number of shares, or the expectation of such sales, could cause a significant reduction in the market price of our common
stock.

In addition to our outstanding common stock, as of December 31, 2021, there were a total of 5,485,888 shares of our common stock that we have

registered and are obligated to issue upon the exercise of currently outstanding options and

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settlement of restricted stock unit awards granted under our 2006 and 2016 Equity Incentive Plans. Upon the exercise of these options or settlement of the
shares underlying these restricted stock units, as the case may be, in accordance with their respective terms, these shares may be resold freely, subject to
restrictions imposed on our affiliates under Rule 144. If significant sales of these shares occur in short periods of time, these sales could reduce the market
price of our common stock. Any reduction in the trading price of our common stock could impede our ability to raise capital on attractive terms, if at all.

If securities or industry analysts do not publish research or reports or publish unfavorable research about our business, our stock price and trading
volume could decline.

The trading market for our common stock will depend in part on the research and reports that securities or industry analysts publish about us or

our business. We currently have research coverage by securities and industry analysts. If one or more of the analysts who covers us downgrades our stock,
our stock price would likely decline. If one or more of these analysts ceases coverage of our company or fails to regularly publish reports on us, interest in
the purchase of our stock could decrease, which could cause our stock price or trading volume to decline.

Our common stock may experience future dilution as a result of future equity offerings.

In order to raise additional capital, we may in the future offer additional shares of our common stock or other securities convertible into or
exchangeable for our common stock at prices that may not be the same as the price per share in previous offerings. We may sell shares or other securities in
any other offering at a price per share that is less than the price per share paid by investors in previous offerings, and investors purchasing shares or other
securities in the future could have rights superior to existing stockholders. The price per share at which we sell additional shares of our common stock, or
securities convertible or exchangeable into common stock, in future transactions may be higher or lower than the price per share paid by investors.

Our business could be negatively affected as a result of the actions of activist stockholders.

Proxy contests have been waged against many companies in the biopharmaceutical industry, including us, over the last several years. If faced with

a proxy contest or other type of shareholder activism, we may not be able to respond successfully to the contest or dispute, which would be disruptive to
our business. Even if we are successful, our business could be adversely affected by a proxy contest or shareholder dispute involving us for several reasons,
including, among others:

•

responding to proxy contests and other actions by activist stockholders can be costly and time-consuming, disrupting operations and diverting
the attention of management and employees;

perceived uncertainties as to future direction may result in the loss of potential acquisitions, collaborations or in-licensing opportunities, and
may make it more difficult to attract and retain qualified personnel and business partners; and

if individuals are elected to our board of directors with a specific agenda, it may adversely affect our ability to effectively and timely
implement our strategic plan and create additional value for our stockholders.

These actions could cause our stock price to experience periods of volatility.

Anti-takeover provisions in our charter and bylaws and under Delaware law, and the adoption of a rights plan, could prevent or delay a change in
control of our company.

We are a Delaware corporation and the anti-takeover provisions of Section 203 of the Delaware General Corporation Law may discourage, delay

or prevent a change in control by prohibiting us from engaging in a business combination with an interested stockholder for a period of three years after the
person becomes an interested stockholder, even if a change of control would be beneficial to our existing stockholders. In addition, our amended and
restated certificate of incorporation and bylaws may discourage, delay or prevent a change in our management or control over us that stockholders may
consider favorable. Our amended and restated certificate of incorporation and bylaws:

•

authorize the issuance of “blank check” preferred stock that could be issued by our board of directors to thwart a takeover attempt;

do not provide for cumulative voting in the election of directors, which would allow holders of less than a majority of the stock to elect some
directors;

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•

establish a classified board of directors, as a result of which the successors to the directors whose terms have expired will be elected to serve
from the time of election and qualification until the third annual meeting following their election;

require that directors only be removed from office for cause;

provide that vacancies on the board of directors, including newly created directorships, may be filled only by a majority vote of directors then
in office;

limit who may call special meetings of stockholders;

prohibit stockholder action by written consent, requiring all actions to be taken at a meeting of the stockholders; and

establish advance notice requirements for nominating candidates for election to the board of directors or for proposing matters that can be
acted upon by stockholders at stockholder meetings.

Our board of directors previously adopted a rights agreement, the provisions of which could have had the effect of discouraging, delaying or

preventing a change in or management or control over us. While there is no plan to do so at this time, our board of directors may choose to adopt a new
rights plan in the future.

Changes to tax regulations to which we are subject could adversely affect us.

We are subject to tax laws, treaties and regulations in the countries in which we operate, and these laws and treaties are subject to interpretation.
New legislation or regulation that could affect our tax burden could be enacted by any governmental authority. We cannot predict the timing or extent of
such tax-related developments which could have a negative impact on our financial results. We have taken, and will continue to take, tax positions based on
our interpretation of such tax laws. However, a challenge by a taxing authority, our ability to utilize tax benefits such as carryforwards or tax credits, or a
deviation from other tax-related assumptions may cause our actual financial results to deviate from previous estimates.

Future transactions may harm our business or the market price of our stock.

We regularly review potential transactions related to technologies, products or product rights and businesses complementary to our business.

These transactions could include:

• mergers;

•

acquisitions;

strategic alliances;

licensing agreements; and

co-promotion and similar agreements.

We may choose to enter into one or more of these transactions at any time, which may cause substantial fluctuations in the market price of our

stock. Moreover, depending upon the nature of any transaction, we may experience a charge to earnings, which could also materially adversely affect our
results of operations and could harm the market price of our stock.

We may undertake strategic acquisitions in the future, and difficulties integrating such acquisitions could damage our ability to achieve or sustain
profitability.

Although we have no experience in acquiring businesses, we may acquire businesses or assets that complement or augment our existing business.
If we acquire businesses with promising products or technologies, we may not be able to realize the benefit of acquiring such businesses if we are unable to
move one or more products through preclinical and/or clinical development to regulatory approval and commercialization. Integrating any newly acquired
businesses or technologies could be expensive and time-consuming, resulting in the diversion of resources from our current business. We may not be able
to integrate any acquired business successfully. We cannot assure that, following an acquisition, we will achieve revenues, specific net income or loss levels
that justify the acquisition or that the acquisition will result in increased earnings, or reduced losses, for the combined company in any future period.
Moreover, we may need to raise additional funds through public or private debt or equity financing to acquire any businesses, which would result in
dilution for stockholders or the incurrence of indebtedness and may not be available on terms which would otherwise be acceptable to us. We may not be
able to operate acquired businesses profitably or otherwise implement our growth strategy successfully.

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Our operating results may fluctuate significantly due to a number of factors which make our future results difficult to predict and could cause our
operating results to fall below expectations or our guidance.

Our operating results will continue to be subject to fluctuations and are affected by numerous factors, including:

•

product sales;

cost of product sales;

the rate at which third-party payors approve coverage for our products;

• marketing and other expenses;

• manufacturing or supply issues;

•

the timing and amount of royalties or milestone payments;

our addition or termination of development programs;

variations in the level of expenses related to our products or future development programs;

regulatory developments affecting our products or those of our competitors;

our execution of collaborative, licensing or other arrangements, and the timing of payments we may make or receive under these
arrangements;

any intellectual property infringement or other lawsuit in which we may become involved; and

the timing and recognition of stock-based compensation expense.

If our operating results fall below the expectations of investors or securities analysts or below any guidance we may provide, the price of our
common stock could decline substantially. Furthermore, any fluctuations in our operating results may, in turn, cause the price of our stock to fluctuate
substantially. We believe that comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our
future performance.

We are increasingly dependent on information technology systems, infrastructure and data. Cybersecurity breaches could expose us to liability, damage
our reputation, compromise our confidential information or otherwise adversely affect our business.

We are increasingly dependent upon information technology systems, infrastructure and data. Our computer systems may be vulnerable to service

interruption or destruction, malicious intrusion and random attack. Security breaches pose a risk that sensitive data, including intellectual property, trade
secrets or personal information may be exposed to unauthorized persons or to the public. Cyber-attacks are increasing in their frequency, sophistication and
intensity, and have become increasingly difficult to detect. Cyber-attacks could include the deployment of harmful malware, denial-of service, social
engineering and other means to affect service reliability and threaten data confidentiality, integrity and availability. Our key business partners face similar
risks, and a security breach of their systems could adversely affect our security posture. While we continue to invest in data protection and information
technology, there can be no assurance that our efforts will prevent service interruptions, or identify breaches in our systems, that could adversely affect our
business and operations and/or result in the loss of critical or sensitive information, which could result in financial, legal, business or reputational harm.

Our internal computer systems, or those of our collaborators, CROs or other contractors or consultants, may fail or suffer security breaches, which
could result in a material disruption of development programs for our product candidates.

Despite the implementation of security measures, our internal computer systems and those of our collaborators, CROs, and other contractors and
consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical
failures. Information security risks have significantly increased in recent years in part due to the proliferation of new technologies and the increased
sophistication and activities of organized crime, hackers, terrorists and other external parties, including foreign state actors. As cyber threats continue to
evolve, we may be required to expend significant additional resources to continue to modify or enhance our protective measures or to investigate and
remediate any information security breaches.

While we have not experienced any such system failure, accident or security breach to date, if such an event were to occur and cause interruptions

in our operations, it could result in a material disruption of our independent drug development programs. For example, the loss of clinical trial data from
ongoing or future clinical trials for any of our product candidates could result in delays in regulatory approval efforts and significantly increase costs to
recover or reproduce the data. Our

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information security systems are also subject to laws and regulations requiring that we take measures to protect the privacy and security of certain
information we gather and use in our business. For example, HIPAA and its implementing regulations impose, among other requirements, certain
regulatory and contractual requirements regarding the privacy and security of personal health information. In addition to HIPAA, numerous other federal
and state laws, including, without limitation, state security breach notification laws, state health information privacy laws and federal and state consumer
protection laws, govern the collection, use, disclosure and storage of personal information. To the extent that any disruption or security breach were to
result in a loss of or damage to data or applications, or inappropriate disclosure of confidential or proprietary information or personal health information,
we could incur substantial liability, our reputation would be damaged, and the further development of our product candidates could be delayed.

ITEM 1B.

UNRESOLVED STAFF COMMENTS

Not applicable.

ITEM 2.

PROPERTIES

Our headquarters office consists of a total of 43,462 square feet of office space located at 2200 Pennsylvania Avenue, N.W. in Washington, D.C.

under operating leases and subleases that expire between 2026 and 2028 and are subject to renewal options. In addition, we have 2,880 square feet of office
space in London, England under an operating lease that has a lease term ending in 2023 and is subject to a renewal option, and other short-term leases. We
believe that these facilities are suitable and adequate to meet our anticipated near-term needs. We anticipate that following the expiration of the leases,
additional or alternative space will be available at commercially reasonable terms.

ITEM 3.

LEGAL PROCEEDINGS

Information with respect is item may be found in Note 16, Legal Matters, to the consolidated financial statements in Part II, Item 8 of this annual

report on Form 10-K, which is incorporated herein by reference.

ITEM 4.

MINE SAFETY DISCLOSURES

Not applicable.

PART II

ITEM 5.

MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES
OF EQUITY SECURITIES

Our common stock is quoted on The Nasdaq Global Market under the symbol “VNDA.” As of February 17, 2022, there were eight holders of

record of our common stock. The number of holders of record of our common stock does not reflect the number of beneficial holders whose shares are held
by depositors, brokers or other nominees.

Market Price of and Dividends on the Registrant’s Common Equity and Related Stockholder Matters

The following graph shows the cumulative five-year total return on our common stock relative to the cumulative total returns of the Nasdaq
Composite Index and the Nasdaq Biotechnology Index. An investment of $100 (with reinvestment of dividends) is assumed to have been made in our
common stock and in each of the indexes on December 31, 2016 and its relative performance is tracked through December 31, 2021. The comparisons in
the table are required by the Securities and Exchange Commission (SEC) and are not intended to forecast or be indicative of possible future performance of
our common stock. We have never paid cash dividends to our stockholders and do not plan to pay dividends in the foreseeable future. The following graph
and related information is being furnished solely to accompany this annual report on Form 10-K pursuant to Item 201(e) of Regulation S-K and shall not be
deemed “soliciting materials” or to be “filed” with the SEC (other than as provided in Item 201), nor shall such information be incorporated by reference
into any of our filings under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, whether made before or after the
date hereof, and irrespective of any general incorporation language in any such filing.

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Securities Authorized for Issuance under Equity Incentive Plans

Information regarding securities authorized for issuance under equity incentive plans will be contained in our Proxy Statement for the 2022

Annual Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year ended December 31, 2021 and is incorporated
herein by reference pursuant to General Instruction G(3) to Form 10-K.

ITEM 6.

RESERVED

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ITEM 7.

MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

You should read the following discussion and analysis of our financial condition and results of operations together with our consolidated financial

statements and related notes appearing in this annual report on Form 10-K (Annual Report). This discussion and analysis generally addresses 2021 and
2020 items and year-to-year comparisons between 2021 and 2020. Discussions of 2019 items and year-to-year comparisons between 2020 and 2019 that
are not included in this Annual Report can be found in Part II, Item 7, Management’s Discussion and Analysis of Financial Condition and Results of
Operations, in our Annual Report on Form 10-K for the fiscal year ended December 31, 2020. Some of the information contained in this discussion and
analysis or set forth elsewhere in this Annual Report include historical information and other information with respect to our plans and strategy for our
business and contain forward-looking statements that involve risks, uncertainties and assumptions. Our actual results may differ materially from those
anticipated in these forward-looking statements as a result of certain factors, including but not limited to those set forth under Part I, Item 1A, Risk
Factors, and elsewhere in this Annual Report.

Overview

Vanda Pharmaceuticals Inc. (we, our or Vanda) is a leading global biopharmaceutical company focused on the development and commercialization

of innovative therapies to address high unmet medical needs and improve the lives of patients.

We strive to advance novel approaches to bring important, new medicines to market through responsible innovation. We are committed to the use

of technologies that support sound science, including genetics and genomics, in drug discovery, clinical trials and the commercial positioning of our
products.

Our commercial portfolio is currently comprised of two products, HETLIOZ for the treatment of Non-24-Hour Sleep-Wake Disorder (Non-24)
®

and nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) and Fanapt for the treatment of schizophrenia. HETLIOZ is the first product
approved by the U.S. Food and Drug Administration (FDA) for patients with Non-24 and patients with SMS. In addition, we have a number of drugs in
development, including:

• HETLIOZ (tasimelteon) for the treatment of jet lag disorder, delayed sleep phase disorder (DSPD), symptoms of autism spectrum disorder

(ASD) and pediatric Non-24;

•

Fanapt (iloperidone) for the treatment of bipolar disorder and Parkinson’s disease psychosis and a long acting injectable (LAI) formulation for
the treatment of schizophrenia;

Tradipitant (VLY-686), a small molecule neurokinin-1 (NK-1) receptor antagonist, for the treatment of gastroparesis, motion sickness, atopic
dermatitis, and COVID-19 pneumonia;

• VTR-297, a small molecule histone deacetylase (HDAC) inhibitor for the treatment of hematologic malignancies and with potential use as a

treatment for several oncology indications;

•

Portfolio of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) activators and inhibitors, including VSJ-110 for the treatment of dry
eye and ocular inflammation and BPO-27 for the treatment of secretory diarrhea disorders, including cholera;

• VQW-765, a small molecule nicotinic acetylcholine receptor partial agonist, with potential use for the treatment of psychiatric disorders; and

• VHX-896 (formerly P88), the active metabolite of iloperidone.

Operational Highlights

HETLIOZ (tasimelteon)

•

In January 2022, we announced we have settled our HETLIOZ patent litigation against MSN Pharmaceuticals Inc. and MSN Laboratories Private
Limited. The litigation remains pending against the other defendants.

In November 2021, a HETLIOZ patient filed a federal lawsuit challenging the unlawfulness of Colorado Medicaid’s prior authorization criteria,
which limited HETLIOZ coverage to totally blind patients. In response to the lawsuit, Colorado changed its criteria to cover HETLIOZ for all
Non-24 patients and to no longer restrict HETLIOZ coverage on the basis of vision status. Since then, 10 additional states have revised their
criteria to eliminate the restriction of HETLIOZ coverage to totally blind patients.

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Tradipitant

•

In February 2022, we reported the results from the Phase III study (VP-VLY-686-3301) of tradipitant in gastroparesis. The study did not meet its
prespecified primary endpoint, but significant treatment effects were observed when adjusting for confounding factors. We plan to complete the
analysis of the data of this study and prepare for submission to regulatory authorities and scientific journals.

Fanapt (iloperidone)

• A Phase III clinical study of Fanapt in acute manic episodes in patients with bipolar disorder is now more than 50% enrolled and expected to

complete enrollment by the end of 2022.

Since we began operations, we have devoted substantially all of our resources to the in-licensing, clinical development and commercialization of

our products. Our ability to generate meaningful product sales and achieve profitability largely depends on our level of success in commercializing
HETLIOZ and Fanapt in the U.S. and Europe, on our ability, alone or with others, to complete the development of our products, and to obtain the
regulatory approvals for and to manufacture, market and sell our products. The results of our operations will vary significantly from year-to-year and
quarter-to-quarter and depend on a number of factors, including risks related to our business, risks related to our industry, and other risks that are detailed in
Part I, Item 1A, Risk Factors, of this Annual Report.

Critical Accounting Policies and Estimates

The preparation of our consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets

and liabilities and the disclosure of contingent assets and liabilities at the date of our financial statements, as well as the reported revenues and expenses
during the reported periods. We base our estimates on historical experience and on various other factors that we believe are reasonable under the
circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not apparent from other
sources. Actual results may differ from these estimates under different assumptions or conditions.

A summary of our significant accounting policies appears in the notes to our audited consolidated financial statements for the year ended

December 31, 2021 included in this Annual Report. However, we believe that the following accounting policies are important to understanding and
evaluating our reported financial results as they involve the most significant judgments and estimates used in the preparation of our consolidated financial
statements, and we have accordingly included them in this discussion.

Revenue from net product sales. We account for a contract when it has approval and commitment from both parties, the rights of the parties are

identified, payment terms are identified, the contract has commercial substance and collectability of consideration is probable. We recognize revenue when
control of the product is transferred to the customer in an amount that reflects the consideration we expect to be entitled to in exchange for those product
sales, which is typically once the product physically arrives at the customer.

HETLIOZ is available in the U.S. for distribution through a limited number of specialty pharmacies, and is not available in retail pharmacies.

Fanapt is available in the U.S. for distribution through a limited number of wholesalers and is available in retail pharmacies. We invoice and record
revenue when customers, specialty pharmacies and wholesalers, receive product from the third-party logistics warehouse, which is the point at which
®
control is transferred to the customer. Revenues and accounts receivable are concentrated with these customers. Outside the U.S., we sell HETLIOZ in
Germany and have a distribution agreement with Megapharm Ltd. for the commercialization of Fanapt in Israel. Receivables are carried at transaction
price net of allowance for credit losses. Allowance for credit losses is measured using historical loss rates based on the aging of receivables and
incorporating current conditions and forward-looking estimates.

The transaction price is determined based upon the consideration to which we will be entitled in exchange for transferring product to the customer.
Our product sales are recorded net of applicable product revenue allowances for which reserves are established and include discounts, rebates, chargebacks,
service fees, co-pay assistance and product returns that are applicable for various government and commercial payors. Where appropriate, our estimates of
variable consideration included in the transaction price consider a range of possible outcomes. Allowances for rebates, chargebacks and co-pay assistance
are based upon the insurance benefits of the end customer, which are estimated using historical activity and, where available, actual and pending
prescriptions for which we have validated the insurance benefits. Variable consideration is included in the transaction price if, in our judgment, it is
probable that a significant future reversal of cumulative revenue under the contract will not occur. Overall, these reserves reflect our best estimates of the
amount of consideration to which we are entitled based

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on the terms of the respective underlying contracts. If actual results in the future vary from our estimates, we adjust our estimate in the period identified,
which would affect net product sales in the period such variances become known.

Reserves for variable consideration are classified as product revenue allowances on the Consolidated Balance Sheets, with the exception of

prompt-pay discounts which are classified as reductions of accounts receivable. The reserve for product returns for which the product may not be returned
for a period of greater than one year from the balance sheet date is included as a component of other non-current liabilities in the Consolidated Balance
Sheets. Uncertainties related to variable consideration are generally resolved in the quarter subsequent to period end, with the exception of Medicaid
rebates, which are dependent upon the timing of when states submit reimbursement claims, and product returns that are resolved during the product expiry
period specified in the customer contract. We currently record sales allowances for the following:

•

Prompt-pay: Specialty pharmacies and wholesalers are offered discounts for prompt payment. We expect that the specialty pharmacies and
wholesalers will earn prompt payment discounts and, therefore, deduct the full amount of these discounts from total product sales when
revenues are recognized.

Rebates: Allowances for rebates include mandated discounts under the Medicaid Drug Rebate Program as well as contracted rebate programs
with other payors. Rebate amounts owed after the final dispensing of the product to a benefit plan participant are based upon contractual
agreements or legal requirements with public sector benefit providers, such as Medicaid. The allowance for rebates is based on statutory or
contracted discount rates and estimated patient utilization.

Chargebacks: Chargebacks are discounts that occur when contracted indirect customers purchase directly from specialty pharmacies and
wholesalers. Contracted indirect customers, which currently consist primarily of Public Health Service institutions and federal government
entities purchasing via the Federal Supply Schedule, generally purchase the product at a discounted price. The specialty pharmacy or
wholesaler, in turn, charges back the difference between the price initially paid by the specialty pharmacy or wholesaler and the discounted
price paid to the specialty pharmacy or wholesaler by the contracted customer.

• Medicare Part D coverage gap: The Medicare Part D prescription drug benefit requires manufacturers to fund approximately 70% of the

Medicare Part D insurance coverage gap for prescription drugs sold to eligible patients for applicable drugs. We account for the Medicare Part
D coverage gap using a point of sale model. Estimates for expected Medicare Part D coverage gap are based in part on historical activity and,
where available, actual and pending prescriptions when we have validated the insurance benefits.

•

Service fees: We receive sales order management, data and distribution services from certain customers, for which we are assessed fees. These
fees are based on contracted terms and are known amounts. We accrue service fees at the time of revenue recognition, resulting in a reduction
of product sales and the recognition of an accrued liability, unless it is a payment for a distinct good or service from the customer in which
case the fair value of those distinct goods or services are recorded as selling, general and administrative expense.

Co-payment assistance: Patients who have commercial insurance and meet certain eligibility requirements may receive co-payment
assistance. Co-pay assistance utilization is based on information provided by our third-party administrator.

Product returns: We generally offer direct customers a limited right to return as contractually defined with our customers. We consider several
factors in the estimation process, including expiration dates of product shipped to customers, inventory levels within the distribution channel,
product shelf life, historical return activity, including activity for product sold for which the return period has past, prescription trends and
other relevant factors. We do not expect returned goods to be resalable. There was no right of return asset as of December 31, 2021 or 2020.

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The following table summarizes sales discounts and allowance activity as of and for the years ended December 31, 2021, 2020 and 2019:

(in thousands)
Balances at December 31, 2018
Provision related to current period sales
Adjustments for prior period sales
Credits/payments made
Balances at December 31, 2019
Provision related to current period sales
Adjustments for prior period sales
Credits/payments made
Balances at December 31, 2020
Provision related to current period sales
Adjustments for prior period sales
Credits/payments made

Balances at December 31, 2021

Rebates &
Chargebacks

Discounts,
Returns
and Other

Total

22,134
59,358
(350)
(58,750)
22,392
70,563
(480)
(65,605)
26,870
83,965
(853)
(78,128)
31,854 $

9,700
26,872
(399)
(26,022)
10,151
27,952
1,327
(30,557)
8,873
31,176
193
(30,641)

9,601 $

31,834
86,230
(749)
(84,772)
32,543
98,515
847
(96,162)
35,743
115,141
(660)
(108,769)
41,455

The provision for rebates and chargebacks of $84.0 million and $70.6 million for the years ended December 31, 2021 and 2020, respectively, and
their ending balances at December 31, 2021 and 2020, primarily represent Medicaid rebates applicable to sales of Fanapt and, to a lesser extent, Medicaid
rebates applicable to sales of HETLIOZ . The provision for discounts, returns and other of $31.2 million and $28.0 million for the years ended
December 31, 2021 and 2020, primarily represents wholesaler distribution fees applicable to sales of Fanapt and, to a lesser extent, estimated product
returns of Fanapt , and co-pay assistance costs and prompt pay discounts applicable to the sales of both HETLIOZ and Fanapt . The ending balances of
discounts, returns and other as of December 31, 2021 and 2020 primarily represent estimated product returns of Fanapt and wholesaler distribution fees
applicable to sales of Fanapt .
®

Stock-based compensation. Compensation costs for all stock-based awards to employees and directors are measured based on the grant date fair
value of those awards and recognized over the period during which the employee or director is required to perform service in exchange for the award. We
use the Black-Scholes-Merton option pricing model to determine the fair value of stock options. The determination of the fair value of stock options on the
date of grant using an option pricing model is affected by our stock price as well as assumptions regarding a number of complex and subjective variables.
These variables include the expected stock price volatility over the expected term of the awards, actual and projected employee stock option exercise
behaviors, risk-free interest rate and expected dividends. Expected volatility rates are based on the historical volatility of our publicly traded common stock
and other factors. The risk-free interest rates are based on the U.S. Treasury yield for a period consistent with the expected term of the option in effect at the
time of the grant. We have never paid cash dividends to our stockholders and do not plan to pay dividends in the foreseeable future. As stock-based
compensation expense recognized in the Consolidated Statements of Operations is based on awards ultimately expected to vest, it has been reduced for
estimated forfeitures. Forfeitures are estimated at the time of grant and revised, if necessary, in subsequent periods if actual forfeitures differ from those
estimates.

Research and development expenses. Research and development expenses consist primarily of fees for services provided by third parties in
connection with the clinical trials, costs of contract manufacturing services for clinical trial use, milestone payments made under licensing agreements prior
to regulatory approval, costs of materials used in clinical trials and research and development, costs for regulatory consultants and filings, depreciation of
capital resources used to develop products, related facilities costs, and salaries, other employee-related costs and stock-based compensation for research and
development personnel. We expense research and development costs as they are incurred for products in the development stage, including manufacturing
costs and milestone payments made under license agreements prior to FDA approval. Upon and subsequent to FDA approval, manufacturing and milestone
payments made under license agreements are capitalized. Milestone payments are accrued when it is deemed probable that the milestone event will be
achieved. Costs related to the acquisition of intellectual property are expensed as incurred if the underlying technology is developed in connection with our
research and development efforts and has no alternative future use.

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Clinical trials are inherently complex, often involve multiple service providers, and can include payments made to investigator physicians at study

sites. Because billing for services often lags delivery of service by a substantial amount of time, we often are required to estimate a significant portion of
our accrued clinical expenses. Our assessments include, but are not limited to: (i) an evaluation by the project manager of the work that has been completed
during the period, (ii) measurement of progress prepared internally and/or provided by the third-party service provider, (iii) analyses of data that justify the
progress, and (iv) management’s judgment. In the event that we do not identify certain costs that have begun to be incurred or we under- or over-estimate
the level of services performed or the costs of such services, our reported expenses for such period would be too low or too high.

Intangible assets. Our intangible assets consist of capitalized license costs for products approved by the FDA. We amortize our intangible assets

on a straight-line basis over the estimated useful economic life of the related product patents. We assess the impairment of intangible assets whenever
events or changes in circumstances indicate that the carrying value may not be recoverable. Factors we consider important that could trigger an impairment
review include significant underperformance relative to expected historical or projected future operating results, a significant adverse change in legal or
regulatory factors that could affect the value or patent life including our ability to defend and enforce patent claims and other intellectual property rights
and significant negative industry or economic trends. When we determine that the carrying value of our intangible assets may not be recoverable based
upon the existence of one or more of the indicators of impairment, we measure any impairment based on the amount that carrying value exceeds fair value.
No impairments have been recognized on our intangible assets.

Income taxes. We assess the need for a valuation allowance against our deferred tax asset each quarter through the review of all available positive

and negative evidence. Deferred tax assets are reduced by a tax valuation allowance when, in the opinion of management, it is more likely than not that
some portion of the deferred tax assets will not be realized. The analysis is highly dependent upon historical and projected taxable income. Projected
taxable income includes significant assumptions related to revenue, commercial expenses and research and development activities. Tax benefits are
recognized from an uncertain tax position only if it is more likely than not that the tax position will be sustained on examination by the taxing authorities
based on the technical merits of the position. The tax benefit recognized in the financial statements for a particular tax position is based on the largest
benefit that is more likely than not to be realized upon settlement.

Recent Accounting Pronouncements

See Note 2, Summary of Significant Accounting Policies, to the consolidated financial statements included in Part II, Item 8 of this Annual Report

for information on recent accounting pronouncements.

Results of Operations

We anticipate that our results of operations will fluctuate for the foreseeable future due to several factors, including our and our partners’ ability to
continue to successfully commercialize our products, any possible payments made or received pursuant to license agreements, progress of our research and
development efforts, the timing and outcome of clinical trials and related possible regulatory approvals, and the impact of the COVID-19 pandemic.

Year ended December 31, 2021 compared to year ended December 31, 2020

Revenues. Total revenues increased by $20.5 million, or 8%, to $268.7 million for the year ended December 31, 2021 compared to $248.2 million

for the year ended December 31, 2020. Revenues were as follows:

(in thousands)
HETLIOZ net product sales
Fanapt net product sales
Total net product sales

2021

173,536 $
95,146
268,682 $

Year Ended December 31,
Net
Change

2020

160,686 $
87,482
248,168 $

12,850
7,664
20,514

Percent

8 %
9 %
8 %

HETLIOZ net product sales increased by $12.9 million, or 8%, to $173.5 million for the year ended December 31, 2021 compared to $160.7

million for the year ended December 31, 2020. The increase to net product sales was attributable to an increase in price net of deductions partially offset by
a decrease in volume. We have experienced an increase in the rate at which third-party payors refuse to cover or reimburse prescriptions written for
HETLIOZ , which has contributed to the decrease in volume.

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Fanapt net product sales increased by $7.7 million, or 9%, to $95.1 million for the year ended December 31, 2021 compared to $87.5 million for
the year ended December 31, 2020. The increase to net product sales was attributable to an increase in price net of deductions partially offset by a decrease
in volume.

Cost of goods sold. Cost of goods sold increased by $2.3 million, or 10%, to $25.6 million for the year ended December 31, 2021 compared to

$23.4 million for the year ended December 31, 2020. Cost of goods sold includes third-party manufacturing costs of product sold, third-party royalty costs
and distribution and other costs. Third-party royalty costs were 10% and 5% of HETLIOZ net product sales in the U.S. and Germany, respectively. Third-
party royalty costs on HETLIOZ net product sales in the U.S. will decrease to 5% in December 2022. Third-party royalty costs on Fanapt net product
sales decreased from 9% to 6% beginning January 2020.

In addition to third-party royalty costs, HETLIOZ and Fanapt cost of goods sold as a percentage of revenue depends upon our cost to
manufacture inventory at normalized production levels with our third-party manufacturers. We expect that, in the future, total HETLIOZ manufacturing
costs included in cost of goods sold will continue to be less than 2% of HETLIOZ net product sales. We expect that, in the future, total
Fanapt manufacturing costs included in cost of goods sold will continue to be less than 3% of Fanapt net product sales.

Research and development expenses. Research and development expenses increased by $19.8 million, or 36%, to $75.4 million for the year ended

December 31, 2021 compared to $55.6 million for the year ended December 31, 2020. The increase was primarily due to an increase in clinical trial
expenses associated with our HETLIOZ and Fanapt development programs. The COVID-19 pandemic has impacted clinical research globally, including
delays in our development programs. While our clinical trials have since resumed patient enrollment, we may continue to experience disruptions that could
adversely impact our supply chain, our ongoing and planned clinical trials, and other regulatory activities.

The following table summarizes the costs of our product development initiatives for the years ended December 31, 2021 and 2020.

(in thousands)
Direct project costs (1)

HETLIOZ
®
Fanapt
®
Tradipitant
VTR-297
CFTR
VQW-765
Other

Total direct project costs
Indirect project costs (1)

Stock-based compensation
Other indirect overhead

Total indirect project costs
Total research and development expense

Year Ended December 31,

2021

2020

11,450 $
22,284
23,460
1,928
3,180
2,548
3,067
67,917

3,955
3,491
7,446
75,363 $

9,518
7,669
23,540
1,487
3,938
1,111
1,100
48,363

3,804
3,410
7,214
55,577

(1) We record direct costs, including personnel costs and related benefits, on a project-by-project basis. Many of our research and development costs

are not attributable to any individual project because we share resources across several development projects. We record indirect costs that support
a number of our research and development activities in the aggregate, including stock-based compensation.

We expect to incur significant research and development expenses as we continue to develop our products. In addition, we expect to incur

licensing costs in the future that could be substantial, as we continue our efforts to expand our product pipeline.

Selling, general and administrative expenses. Selling, general and administrative expenses decreased by $16.5 million, or 12%, to $124.0 million

for the year ended December 31, 2021 compared to $140.5 million for the year ended December 31,

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2020. The decrease was primarily the result of a decrease in spending on marketing activities for our commercial products, partially offset by increased
spending on legal activities.

Intangible asset amortization. Intangible asset amortization was $1.5 million for each of the years ended December 31, 2021 and 2020.

Other income. Other income was $0.2 million for the year ended December 31, 2021 compared to $4.4 million for the year ended December 31,

2020. Other income primarily consists of investment income on our marketable securities, which decreased beginning in the second half of 2020 as a result
of lower yields on our marketable securities.

Provision for income taxes. A provision for income taxes of $9.2 million and $8.3 million was recorded for the years ended December 31, 2021

and 2020, respectively. Our income tax expense or benefit is determined by applying the statutory tax rates in jurisdictions where we operate to each
period’s income before income taxes. Adjustments are made for permanent differences in taxability or deductibility of pretax items as well as for other
items, such as tax credits that are generated on our research and development activities. See Note 14, Income Taxes, to the consolidated financial statements
in Part II, Item 8 of this Annual Report for additional information.

Liquidity and Capital Resources

As of December 31, 2021, our total cash and cash equivalents and marketable securities were $432.8 million compared to $367.7 million at
December 31, 2020. Our cash and cash equivalents are deposits in operating accounts and highly liquid investments with an original maturity of 90 days or
less at date of purchase and consist of investments in money market funds with commercial banks and financial institutions, and commercial paper of high-
quality corporate issuers. Our marketable securities consist of investments in government sponsored and corporate enterprises and commercial paper.

Our liquidity resources as of December 31, 2021 and 2020 are summarized as follows:

(in thousands)
Cash and cash equivalents
Marketable securities:

U.S. Treasury and government agencies
Corporate debt

Total marketable securities
Total cash, cash equivalents and marketable securities

December 31, 2021

December 31, 2020

52,071 $

61,031

194,719
186,023
380,742
432,813 $

166,092
140,617
306,709
367,740

As of December 31, 2021, we maintained all of our cash, cash equivalents and marketable securities in two financial institutions. Deposits held
with these institutions may exceed the amount of insurance provided on such deposits, but we do not anticipate any losses with respect to such deposits.

In the normal course of our business, we regularly enter into agreements with third-party vendors under fee service arrangements which generally

may be terminated on 90 days’ notice without incurring additional charges, other than charges for work completed or materials procured but not paid for
through the effective date of termination and other costs incurred by our contractors in closing out work in progress as of the effective date of termination.
Our non-cancellable purchase commitments for agreements longer than one year primarily relate to commitments for data services and are not material.
Various other long-term agreements entered into for services with other third-party vendors, such as inventory purchase arrangements, are cancellable in
nature or contain variable commitment terms within the agreement that are within our control.

We also have long-term contractual obligations related to our operating leases and license agreements. Refer to Note 7, Leases, and Note 10,

Commitments and Contingencies, respectively, to the consolidated financial statements in Part II, Item 8 of this Annual Report for more information about
these commitments.

We do not have any off-balance sheet arrangements.

Based on our current operating plans, which include costs and expenses in connection with our continued clinical development of tradipitant and

our other products, U.S. commercial activities for HETLIOZ and Fanapt , pursuit of market approval of HETLIOZ and Fanapt in other regions, and
payments due upon achievement of milestones under our license agreements, we believe that our cash, cash equivalents and marketable securities and cash
received from product sales will be

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sufficient for at least the next 12 months. Our future cash requirements and the adequacy of our available funds will depend on many factors, primarily
including our ability to generate revenue, the scope and costs of our commercial, manufacturing and process development activities, the magnitude of our
discovery, preclinical and clinical development programs, and potential costs to acquire or license the rights to additional products.

We may need or desire to obtain additional capital to finance our operations through debt, equity or alternative financing arrangements. We may
also seek capital through collaborations or partnerships with other companies. The issuance of debt could require us to grant liens on certain of our assets
that may limit our flexibility and debt securities may be convertible into common stock. If we raise additional capital by issuing equity securities, the terms
and prices for these financings may be much more favorable to the new investors than the terms obtained by our existing stockholders. These financings
also may significantly dilute the ownership of our existing stockholders. If we are unable to obtain additional financing, we may be required to reduce the
scope of our future activities which could harm our business, financial condition and operating results. There can be no assurance that any additional
financing required in the future will be available on acceptable terms, if at all.

Cash Flow

The following table summarizes our net cash flows from operating, investing and financing activities for the years ended December 31, 2021 and

2020:

(in thousands)
Net cash provided by (used in):
Operating activities:
Net income
Non-cash charges
Net change in operating assets and liabilities

Operating activities

Investing activities:

Purchases of property and equipment
Net purchases, sales and maturities of marketable securities

Investing activities

Financing activities:

Proceeds from the exercise of stock options

Financing activities

Effect of exchange rate changes on cash, cash equivalents and restricted cash
Net change in cash, cash equivalents and restricted cash

2021

Year Ended December 31,
2020

Net Change

33,152 $
28,325
2,737
64,214

(552)
(76,144)
(76,696)

3,550
3,550
(91)
(9,023) $

23,337 $
24,121
4,317
51,775

(1,795)
(39,704)
(41,499)

5,634
5,634
53
15,963 $

9,815
4,204
(1,580)
12,439

1,243
(36,440)
(35,197)

(2,084)
(2,084)
(144)
(24,986)

Operating Activities. Cash flows provided by operating activities during the year ended December 31, 2021 were $64.2 million, an increase of

$12.4 million compared to $51.8 million during the year ended December 31, 2020. The increase reflects an increase of $9.8 million in net income and an
increase of $4.2 million in non-cash charges primarily due to increased stock-based compensation expense, partially offset by a decrease of $1.6 million
from the net change in operating assets and liabilities.

Investing Activities. Cash flows used in investing activities during the year ended December 31, 2021 were $76.7 million, an increase of $35.2

million compared to cash used in investing activities of $41.5 million during the year ended December 31, 2020. Investing activities reflect continued net
reinvestment of available cash and cash equivalents in our portfolio of marketable securities.

Financing Activities. Cash flows provided by financing activities during the year ended December 31, 2021 were $3.6 million, a decrease of $2.1

million compared to $5.6 million during the year ended December 31, 2020. Financing activities include proceeds from exercises of stock options.

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ITEM 7A.

QUALITATIVE AND QUANTITATIVE DISCLOSURES ABOUT MARKET RISK

Our exposure to market risk is currently confined to our cash and cash equivalents, marketable securities and restricted cash. We currently do not

hedge interest rate exposure. We have not used derivative financial instruments for speculation or trading purposes.

We deposit our cash with financial institutions that we consider to be of high credit quality and purchase marketable securities that are generally

investment grade, liquid, short-term fixed income securities and money-market instruments denominated in U.S. dollars. Our marketable securities consist
of commercial paper, corporate notes and U.S. government agency notes and have maturities of less than two years. We do not believe that an increase in
market rates would have any significant impact on the realized value of our cash equivalents and marketable securities.

We are also exposed to risks related to changes in foreign currency exchange rates relating to our foreign operations. The functional currency of

our international subsidiaries is the local currency. We are exposed to foreign currency risk to the extent that we enter into transactions denominated in
currencies other than our subsidiaries’ respective functional currencies. We are also exposed to unfavorable fluctuations of the U.S. dollar, which is our
reporting currency, against the currencies of our operating subsidiaries when their respective financial statements are translated into U.S. dollars for
inclusion in our consolidated financial statements. We do not currently hedge our foreign currency exchange rate risk. Foreign currency has not had a
material impact on our results of operations.

ITEM 8.

FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA

The consolidated financial statements and related financial statement schedules required to be filed are listed in the Index to Consolidated

Financial Statements and are incorporated in Part IV, Item 15 of this annual report on Form 10-K.

ITEM 9.

CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE

None.

ITEM 9A.

CONTROLS AND PROCEDURES

Conclusion Regarding the Effectiveness of Disclosure Controls and Procedures

Under the supervision and with the participation of our management, including the Chief Executive Officer and Chief Financial Officer, we

evaluated the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the
Securities Exchange Act of 1934 (Exchange Act)) as of December 31, 2021. Based upon that evaluation, our Chief Executive Officer and Chief Financial
Officer concluded that our disclosure controls and procedures are effective as of December 31, 2021, the end of the period covered by this annual report on
Form 10- K (Annual Report), to ensure that the information required to be disclosed by us in the reports that we file or submit under the Exchange Act is
recorded, processed, summarized and reported within the time periods specified in the SEC’s 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 disclosures.

Management’s Report on Internal Control over Financial Reporting

Our management is responsible for establishing and maintaining an adequate system of internal control over financial reporting, as defined in the

Exchange Act Rule 13a-15(f). Management conducted an assessment of our internal control over financial reporting based on the original framework
established in 2013 by the Committee of Sponsoring Organizations of the Treadway Commission in Internal Control — Integrated Framework. Based on
the assessment, management concluded that, as of December 31, 2021, our internal control over financial reporting was effective. The effectiveness of our
internal control over financial reporting as of December 31, 2021 has been audited by PricewaterhouseCoopers LLP, an independent registered public
accounting firm, as stated in their report included in this Annual Report.

Changes in Internal Control over Financial Reporting

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There has been no change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act)

during the fourth quarter of 2021 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.

ITEM 9B.

OTHER INFORMATION

None.

ITEM 9C.

DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS

Not applicable.

ITEM 10.

DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE

Information required under this item will be contained in our Proxy Statement for the 2022 Annual Meeting of Stockholders to be filed with the

SEC within 120 days after the end of the fiscal year ended December 31, 2021 and is incorporated herein by reference pursuant to General Instruction G(3)
to Form 10-K.

PART III

ITEM 11.

EXECUTIVE COMPENSATION

Information required under this item will be contained in our Proxy Statement for the 2022 Annual Meeting of Stockholders to be filed with the

SEC within 120 days after the end of the fiscal year ended December 31, 2021 and is incorporated herein by reference pursuant to General Instruction G(3)
to Form 10-K, except that information required by Item 407(e)(5) of Regulation S-K will be deemed furnished in this Form 10-K and will not be deemed
incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, except to the
extent that we specifically incorporate it by reference into such filing.

ITEM 12.

SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER
MATTERS

Information required under this item will be contained in our Proxy Statement for the 2022 Annual Meeting of Stockholders to be filed with the

SEC within 120 days after the end of the fiscal year ended December 31, 2021 and is incorporated herein by reference pursuant to General Instruction G(3)
to Form 10-K.

ITEM 13.

CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE

Information required under this item will be contained in our Proxy Statement for the 2022 Annual Meeting of Stockholders to be filed with the

SEC within 120 days after the end of the fiscal year ended December 31, 2021 and is incorporated herein by reference pursuant to General Instruction G(3)
to Form 10-K.

ITEM 14.

PRINCIPAL ACCOUNTANT FEES AND SERVICES

Information required under this item will be contained in our Proxy Statement for the 2022 Annual Meeting of Stockholders to be filed with the

SEC within 120 days after the end of the fiscal year ended December 31, 2021 and is incorporated herein by reference pursuant to General Instruction G (3)
to Form 10-K.

ITEM 15.

EXHIBITS AND FINANCIAL STATEMENT SCHEDULES

PART IV

The consolidated financial statements filed as part of this annual report on Form 10-K are listed in the Index to Consolidated Financial Statements.
Certain schedules are omitted because they are not applicable, or not required, or because the required information is included in the consolidated financial
statements or notes thereto. The Exhibits are listed in the Exhibit Index.

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Signatures

Pursuant to the requirements of Section 13 and 15(d) of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this

annual report on Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized.

February 24, 2022

Vanda Pharmaceuticals Inc.

By:

/s/ Mihael H. Polymeropoulos, M.D.
Mihael H. Polymeropoulos, M.D.
President, Chief Executive Officer and Chairman
of the Board of Directors

Pursuant to the requirements of the Securities Act of 1934, this annual report on Form 10-K has been signed below by the following persons on

behalf of the registrant and in the capacities and on the dates indicated.

Name

Title

Date

/s/ Mihael H. Polymeropoulos, M.D.
Mihael H. Polymeropoulos, M.D.

President, Chief Executive Officer and Chairman
of the Board of Directors (Principal Executive
Officer)

February 24, 2022

/s/ Kevin Moran
Kevin Moran

Chief Financial Officer (Principal Financial
Officer and Principal Accounting Officer)

February 24, 2022

/s/ H. Thomas Watkins
H. Thomas Watkins

/s/ Anne Sempowski Ward
Anne Sempowski Ward

/s/ Phaedra Chrousos
Phaedra Chrousos

/s/ Richard W. Dugan
Richard W. Dugan

/s/ Stephen Ray Mitchell
Stephen Ray Mitchell

Lead Independent Director

February 24, 2022

Director

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Vanda Pharmaceuticals Inc.

Index to Consolidated Financial Statements

Report of Independent Registered Public Accounting Firm (PCAOB ID 238)
Consolidated Balance Sheets at December 31, 2021 and 2020
Consolidated Statements of Operations for the years ended December 31, 2021, 2020 and 2019
Consolidated Statements of Comprehensive Income for the years ended December 31, 2021, 2020 and 2019
Consolidated Statements of Changes in 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
72
74
75
76
77
78
79

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Report of Independent Registered Public Accounting Firm

To the Board of Directors and Stockholders of Vanda Pharmaceuticals Inc.

Opinions on the Financial Statements and Internal Control over Financial Reporting

We have audited the accompanying consolidated balance sheets of Vanda Pharmaceuticals Inc. and its subsidiaries (the “Company”) as of December 31,
2021 and 2020, and the related consolidated statements of operations, of comprehensive income, of changes in stockholders’ equity and of cash flows for
each of the three years in the period ended December 31, 2021, including the related notes (collectively referred to as the “consolidated financial
statements”). We also have audited the Company’s internal control over financial reporting as of December 31, 2021, based on criteria established in
Internal Control - Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission (COSO).

In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of the Company as of
December 31, 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 accounting principles generally accepted in the United States of America. Also in our opinion, the Company maintained, in all material
respects, effective internal control over financial reporting as of December 31, 2021, based on criteria established in Internal Control - Integrated
Framework (2013) issued by the COSO.

Basis for Opinions

The Company’s management is responsible for these consolidated financial statements, for maintaining effective internal control over financial reporting,
and for its assessment of the effectiveness of internal control over financial reporting, included in Management’s Report on Internal Control over Financial
Reporting appearing under Item 9A. Our responsibility is to express opinions on the Company’s consolidated financial statements and on the Company’s
internal control over financial reporting based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight
Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the
applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable
assurance about whether the consolidated financial statements are free of material misstatement, whether due to error or fraud, and whether effective
internal control over financial reporting was maintained in all material respects.

Our audits of the consolidated financial statements included performing procedures to assess the risks of material misstatement of the consolidated financial
statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis,
evidence regarding the amounts and disclosures in the consolidated financial statements. Our audits also included evaluating the accounting principles used
and significant estimates made by management, as well as evaluating the overall presentation of the consolidated financial statements. Our audit of internal
control over financial reporting included obtaining an understanding of internal control over financial reporting, assessing the risk that a material weakness
exists, and testing and evaluating the design and operating effectiveness of internal control based on the assessed risk. Our audits also included performing
such other procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for our opinions.

Definition and Limitations of Internal Control over Financial Reporting

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting
and the preparation of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control
over financial reporting includes those policies and procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly
reflect the transactions and dispositions of the assets of the company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit
preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the company are
being made only in accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding
prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect on the financial
statements.

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Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also, projections of any evaluation of
effectiveness to future periods are subject to the risk that controls may become inadequate because of changes in conditions, or that the degree of
compliance with the policies or procedures may deteriorate.

Critical Audit Matters

The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial statements that was
communicated or required to be communicated to the audit committee and that (i) relates to accounts or disclosures that are material to the consolidated
financial statements and (ii) involved our especially challenging, subjective, or complex judgments. The communication of critical audit matters does not
alter in any way our opinion on the consolidated financial statements, taken as a whole, and we are not, by communicating the critical audit matter below,
providing a separate opinion on the critical audit matter or on the accounts or disclosures to which it relates.

®
Medicaid Rebates for Fanapt

As described in Note 2 to the consolidated financial statements, the allowances for rebates include mandated discounts under the Medicaid Drug Rebate
Program as well as contracted rebate programs with other payors. Rebate amounts owed after the final dispensing of the product to a benefit plan
participant are based upon contractual agreements or legal requirements with public sector benefit providers, such as Medicaid. The allowance for rebates
is based on statutory or contracted discount rates and estimated patient utilization. The Company has recorded product revenue allowances of $40.0 million
®
as of December 31, 2021, of which a significant amount relates to allowances for Medicaid Rebates for Fanapt .

The principal considerations for our determination that performing procedures relating to Medicaid Rebates for Fanapt is a critical audit matter are the
significant judgment by management due to the significant measurement uncertainty involved in developing the allowances, as these allowances are based
on assumptions developed for estimated patient utilization, primarily payor mix and invoice lag; this in turn led to a high degree of auditor judgment,
subjectivity and effort in performing procedures and evaluating audit evidence related to the estimated patient utilization assumption.

Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated
financial statements. These procedures included testing the effectiveness of controls relating to the allowances for Medicaid Rebates for Fanapt , including
controls over the assumptions used to estimate these rebates. These procedures also included, among others, (i) developing an independent estimate of the
Medicaid Rebates for Fanapt by utilizing third-party information related to patient utilization, as well as the historical trends of the invoice lag; and (ii)
comparing the independent estimate to management’s estimate. Developing the independent estimate involved (i) testing the completeness and accuracy of
the patient utilization data from third-party reports, and (ii) testing rebate claims processed by the Company, including evaluating those claims for
consistency with the contractual and mandated terms of the Medicaid Drug Rebate Program.

/s/ PricewaterhouseCoopers LLP

Baltimore, Maryland
February 24, 2022

We have served as the Company’s auditor since 2003.

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VANDA PHARMACEUTICALS INC.
CONSOLIDATED BALANCE SHEETS

(in thousands, except for share and per share amounts)
ASSETS

Current assets:

Cash and cash equivalents
Marketable securities
Accounts receivable, net
Inventory
Prepaid expenses and other current assets

Total current assets

Property and equipment, net
Operating lease right-of-use assets
Intangible assets, net
Deferred tax assets
Non-current inventory and other
Total assets

LIABILITIES AND STOCKHOLDERS’ EQUITY

Current liabilities:

Accounts payable and accrued liabilities
Product revenue allowances
Total current liabilities

Operating lease non-current liabilities
Other non-current liabilities
Total liabilities

Commitments and contingencies (Notes 10 and 16)
Stockholders’ equity:

Preferred stock, $0.001 par value; 20,000,000 shares authorized, and no shares issued or outstanding at
December 31, 2021 and 2020, respectively
Common stock, $0.001 par value; 150,000,000 shares authorized; 55,900,855 and 54,865,092 shares
issued and outstanding at December 31, 2021 and 2020, respectively
Additional paid-in capital
Accumulated other comprehensive income (loss)
Accumulated deficit

Total stockholders’ equity
Total liabilities and stockholders’ equity

December 31, 2021

December 31, 2020

52,071 $
380,742
32,467
1,025
11,996
478,301
3,113
9,272
20,081
74,878
8,147
593,792 $

34,438 $
39,981
74,419
10,055
4,390
88,864

61,031
306,709
30,036
1,280
10,089
409,145
4,136
10,459
21,559
81,516
6,641
533,456

31,509
34,427
65,936
11,497
2,757
80,190

—

56
669,223
(175)
(164,176)
504,928
593,792 $

55
650,300
239
(197,328)
453,266
533,456

The accompanying notes are an integral part of these consolidated financial statements.

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(in thousands, except for share and per share amounts)
Revenues:

Net product sales

Total revenues

Operating expenses:

Cost of goods sold excluding amortization
Research and development
Selling, general and administrative
Intangible asset amortization
Total operating expenses

Income from operations
Other income

Income before income taxes

Provision (benefit) for income taxes

Net income
Net income per share:

Basic
Diluted

Weighted average shares outstanding:

Basic
Diluted

VANDA PHARMACEUTICALS INC.
CONSOLIDATED STATEMENTS OF OPERATIONS

2021

Year Ended December 31,
2020

2019

268,682 $
268,682

25,629
75,363
124,047
1,478
226,517
42,165
199
42,364
9,212
33,152 $

0.60 $

0.58 $

248,168 $
248,168

23,364
55,577
140,510
1,478
220,929
27,239
4,416
31,655
8,318
23,337 $

0.43 $

0.42 $

227,188
227,188

24,488
48,649
129,736
1,505
204,378
22,810
6,218
29,028
(86,525)
115,553

2.17

2.11

55,548,122

56,921,836

54,427,683

55,190,802

53,137,562

54,847,060

The accompanying notes are an integral part of these consolidated financial statements.

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VANDA PHARMACEUTICALS INC.
CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME

(in thousands)
Net income
Other comprehensive income (loss):

Net foreign currency translation gain (loss)
Change in net unrealized gain (loss) on marketable securities
Tax benefit (provision) on other comprehensive income (loss)

Other comprehensive income (loss), net of tax
Comprehensive income

2021

Year Ended December 31,
2020

2019

33,152 $

23,337 $

115,553

(49)
(472)
107
(414)
32,738 $

68
(102)
24
(10)
23,327 $

6
313
(71)
248
115,801

The accompanying notes are an integral part of these consolidated financial statements.

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VANDA PHARMACEUTICALS INC.
CONSOLIDATED STATEMENTS OF CHANGES IN STOCKHOLDERS’ EQUITY

(in thousands, except for share amounts)
Balances at December 31, 2018
Issuance of common stock from the exercise

of stock options and settlement of
restricted stock units

Stock-based compensation expense
Net income
Other comprehensive income, net of tax
Balances at December 31, 2019
Issuance of common stock from the exercise

of stock options and settlement of
restricted stock units

Stock-based compensation expense
Net income
Other comprehensive loss, net of tax
Balances at December 31, 2020
Issuance of common stock from the exercise

of stock options and settlement of
restricted stock units

Stock-based compensation expense
Net income
Other comprehensive loss, net of tax

Balances at December 31, 2021

Common Stock

Shares
52,477,593 $

Par Value

Additional
Paid-in Capital

Accumulated Other
Comprehensive
Income (Loss)

Accumulated
Deficit

Total

52 $

611,587 $

1 $

(336,218) $

275,422

1,072,019
—
—
—
53,549,612

1,315,480
—
—
—
54,865,092

2
—
—
—
54

1
—
—
—
55

6,262
13,458
—
—
631,307

5,633
13,360
—
—
650,300

—
—
—
248
249

—
—
—
(10)
239

—
—
115,553
—
(220,665)

—
—
23,337
—
(197,328)

1,035,763
—
—
—

55,900,855 $

1
—
—
—
56 $

3,549
15,374
—
—
669,223 $

—
—
—
(414)
(175) $

—
—
33,152
—

(164,176) $

6,264
13,458
115,553
248
410,945

5,634
13,360
23,337
(10)
453,266

3,550
15,374
33,152
(414)
504,928

The accompanying notes are an integral part of these consolidated financial statements.

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VANDA PHARMACEUTICALS INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS

(in thousands)
Cash flows from operating activities
Net income
Adjustments to reconcile net income to net cash provided by operating activities:

Depreciation of property and equipment
Stock-based compensation
Amortization of premiums and accretion of discounts on marketable securities
Gain on sale of marketable securities
Intangible asset amortization

Deferred income taxes
Other non-cash adjustments, net

Changes in operating assets and liabilities:

Accounts receivable
Prepaid expenses and other assets
Inventory
Accounts payable and other liabilities
Product revenue allowances

Net cash provided by operating activities

Cash flows from investing activities
Purchases of property and equipment
Purchases of marketable securities
Sales and maturities of marketable securities
Net cash used in investing activities

Cash flows from financing activities
Proceeds from exercise of stock options

Net cash provided by financing activities

Effect of exchange rate changes on cash, cash equivalents and restricted cash
Net change in cash, cash equivalents and restricted cash
Cash, cash equivalents and restricted cash
Beginning of year
End of year

2021

Year Ended December 31,
2020

2019

33,152 $

23,337 $

115,553

1,363
15,374
1,649
(12)
1,478
6,745
1,728

(2,469)
(1,247)
(2,233)
3,040
5,646
64,214

(552)
(420,461)
344,317
(76,696)

3,550
3,550
(91)
(9,023)

1,386
13,360
179
(229)
1,478
6,189
1,758

(3,767)
4,068
(2,876)
3,759
3,133
51,775

(1,795)
(346,622)
306,918
(41,499)

5,634
5,634
53
15,963

61,613
52,590 $

45,650
61,613 $

1,387
13,458
(3,099)
—
1,505
(87,767)
1,785

2,342
(2,764)
(722)
3,508
761
45,947

(1,019)
(394,517)
327,227
(68,309)

6,264
6,264
(1)
(16,099)

61,749
45,650

The accompanying notes are an integral part of these consolidated financial statements.

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1. Business Organization and Presentation

Business Organization

VANDA PHARMACEUTICALS INC.

NOTES TO CONSOLIDATED FINANCIAL STATEMENTS

Vanda Pharmaceuticals Inc. (the Company) is a global biopharmaceutical company focused on the development and commercialization of
innovative therapies to address high unmet medical needs and improve the lives of patients. The Company commenced its operations in 2003 and operates
in one reporting segment.

The Company’s commercial portfolio is currently comprised of two products, HETLIOZ for the treatment of Non-24-Hour Sleep-Wake Disorder

(Non-24) and nighttime sleep disturbances in Smith-Magenis Syndrome (SMS) and Fanapt for the treatment of schizophrenia. HETLIOZ is the first
product approved by the United States Food and Drug Administration (FDA) for patients with Non-24 and patients with SMS. In addition, the Company
has a number of drugs in development, including:

• HETLIOZ (tasimelteon) for the treatment of jet lag disorder, delayed sleep phase disorder (DSPD), symptoms of autism spectrum disorder

•

(ASD) and pediatric Non-24;
Fanapt (iloperidone) for the treatment of bipolar disorder and Parkinson’s disease psychosis and a long acting injectable (LAI) formulation
for the treatment of schizophrenia;
Tradipitant (VLY-686), a small molecule neurokinin-1 (NK-1) receptor antagonist, for the treatment of gastroparesis, motion sickness, atopic
dermatitis, and COVID-19 pneumonia;

• VTR-297, a small molecule histone deacetylase (HDAC) inhibitor for the treatment of hematologic malignancies and with potential use as a

treatment for several oncology indications;

•

• VQW-765, a small molecule nicotinic acetylcholine receptor partial agonist, with potential use for the treatment of psychiatric disorders; and

• VHX-896 (formerly P88), the active metabolite of iloperidone.

Basis of Presentation

The accompanying consolidated financial statements includes the accounts of Vanda Pharmaceuticals Inc. and its wholly owned subsidiaries and
have been prepared in accordance with accounting principles generally accepted in the United States of America (GAAP). All intercompany accounts and
transactions have been eliminated in consolidation.

2. Summary of Significant Accounting Policies

Use of Estimates

The preparation of financial statements in conformity with GAAP requires management to make estimates that affect the reported amounts of

assets and liabilities at the date of the financial statements, disclosure of contingent assets and liabilities, and the reported amounts of revenue and expenses
during the reporting period. Management continually re-evaluates its estimates, judgments and assumptions, and management’s evaluation could change.
Actual results could differ from those estimates.

Cash, Cash Equivalents and Restricted Cash

For purposes of the Consolidated Balance Sheets and Consolidated Statements of Cash Flows, cash equivalents represent highly-liquid
investments with a maturity date of three months or less at the date of purchase. Cash and cash equivalents include investments in money market funds
with commercial banks and financial institutions, and commercial paper of high-quality corporate issuers. Restricted cash relates primarily to amounts held
as collateral for letters of credit for leases for office space at the Company’s Washington, D.C. headquarters.

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The following table provides a reconciliation of cash, cash equivalents and restricted cash reported within the Consolidated Balance Sheets to the total end
of period cash, cash equivalents and restricted cash reported within the Consolidated Statement of Cash Flows:

(in thousands)
Cash and cash equivalents
Restricted cash included in:

Prepaid expenses and other current assets
Non-current inventory and other

Total cash, cash equivalents and restricted cash

Marketable Securities

December 31,

2021

2020

52,071 $

—
519
52,590 $

61,031

57
525
61,613

The Company classifies all of its marketable securities as available-for-sale securities. The Company’s investment policy requires the selection of
high-quality issuers. Available-for-sale securities are carried at fair market value, with unrealized gains and losses reported as a component of stockholders’
equity in accumulated other comprehensive income (loss). At each balance sheet date, the Company assesses available-for-sale securities in an unrealized
loss position to determine whether it intends to sell or if it is more likely than not that the Company will be required to sell the security before recovery of
its amortized cost basis. If either of the criteria regarding intent or requirement to sell is met, the security’s amortized cost basis is written down to fair
value. The Company also reviews its available-for-sale securities in an unrealized loss position to determine whether the unrealized loss is the result of a
change in creditworthiness or other factors. If declines in the value of available for-sale securities are determined to be credit-related, a loss is recorded in
earnings in the current period. Interest and dividend income is recorded when earned and included in other income. Premiums and discounts on marketable
securities are amortized and accreted, respectively, to earliest call date and maturity, respectively, and included in other income. The Company uses the
specific identification method in computing realized gains and losses on the sale of investments, which would be included in the Consolidated Statements
of Operations when generated. All available-for-sale marketable securities are available for use in current operations and are classified as current.

Inventory

Inventory, which is recorded at the lower of cost or net realizable value, includes the cost of third-party manufacturing and other direct and
indirect costs and is valued using the first-in, first-out method. The Company evaluates expiry risk by evaluating current and future product demand
relative to product shelf life. The Company builds demand forecasts by considering factors such as, but not limited to, overall market potential, market
share, market acceptance and patient usage. The Company capitalizes inventory costs associated with its products upon regulatory approval when, based on
management’s judgment, future commercialization is considered probable and the future economic benefit is expected to be realized; otherwise, such costs
are expensed as research and development. Inventory levels are evaluated for the amount of inventory that would be sold within one year. At certain times,
the level of inventory can exceed the forecasted level of cost of goods sold for the next 12 months. The Company classifies the estimate of such inventory
as non-current.

Intangible Assets

Costs incurred for products not yet approved by the FDA and for which no alternative future use exists are recorded as research and development
expense. Obligations for milestone payments to other pharmaceutical companies that may result in a capitalized intangible asset are recognized when it is
deemed probable that the milestone event will occur. In the event a product has been approved by the FDA or an alternative future use exists for a product,
patent and license costs are capitalized and amortized on a straight-line basis over the estimated useful economic life of the of the related product patents.
For intangible assets related to HETLIOZ , the estimated useful life is through July 2035, which is the estimated economic useful life of the related product
patents. Intangible assets related Fanapt have been fully amortized on a straight-line basis to November 2016. The useful life estimate for Fanapt was
based on the market participant methodology prescribed by Accounting Standards Codification (ASC) 805, and therefore does not reflect the impact of
additional Fanapt patents solely owned by the Company with varying expiration dates, the latest of which is December 2031.

Property and Equipment

Property and equipment are stated at cost less accumulated depreciation. Depreciation of most property and equipment is provided on a straight-

line basis over the estimated useful lives of the assets. Leasehold improvements are amortized using a

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straight-line basis over the lesser of the estimated useful lives of the assets or the terms of the related leases. The costs of additions and improvements are
capitalized, and repairs and maintenance costs are charged to operations in the period incurred. Upon retirement or disposition of property and equipment,
the cost and accumulated depreciation are removed from the accounts and any resulting gain or loss is reflected in the statement of operations for that
period.

Leases

The Company determines if an arrangement contains a lease at inception. Right-of-use (ROU) assets represent the Company’s right to use an

underlying asset for the lease term and lease liabilities represent the Company’s obligation to make lease payments arising from that lease. For leases with a
term greater than 12 months, ROU assets and liabilities are recognized at the lease commencement date based on the estimated present value of lease
payments over the lease term. The lease term includes the option to extend the lease when it is reasonably certain the Company will exercise that option.
When available, the Company uses the rate implicit in the lease to discount lease payments to present value. In the case the implicit rate is not available, the
Company uses its incremental borrowing rate based on information available at the lease commencement date, including publicly available data for
instruments with similar characteristics, to determine the present value of lease payments. The Company does not combine lease and non-lease elements for
office leases. For existing office leases as of the adoption date of ASC 842, Leases, on January 1, 2019, executory costs are excluded from lease expense,
which is consistent with the Company’s accounting under ASC 840, Leases. For all office leases entered into after January 1, 2019, executory costs are
allocated between lease and non-lease elements based upon their relative stand-alone prices.

Accounts Payable and Accrued Liabilities

The Company’s management is required to estimate accrued liabilities as part of the process of preparing financial statements. The estimation of
accrued liabilities involves identifying services that have been performed on the Company’s behalf, and then estimating the level of service performed and
the associated cost incurred for such services as of each balance sheet date in the financial statements. Accrued liabilities include research and development
expenses, such as accrued costs under contracts with clinical monitors, data management organizations and investigators in conjunction with clinical trials,
fees to contract manufacturers in conjunction with the production of clinical materials, consulting and professional fees, such as lawyers and fees for
marketing and other commercialization activities, accrued compensation and employee benefits, such as accrued bonus, royalties payable under licensing
agreements, and other accrued fees. Pursuant to management’s assessment of the services that have been performed on clinical trials and other contracts,
the Company recognizes these expenses as the services are provided.

Revenue from Net Product Sales

The Company accounts for a contract when it has approval and commitment from both parties, the rights of the parties are identified, payment

terms are identified, the contract has commercial substance and collectability of consideration is probable. The Company recognizes revenue when control
of the product is transferred to the customer in an amount that reflects the consideration the Company expects to be entitled to in exchange for those
product sales, which is typically once the product physically arrives at the customer. Sales taxes, value add taxes, and usage-based taxes are excluded from
revenues.

The Company’s net product sales consist of sales of HETLIOZ and Fanapt . Net sales by product for the years ended December 31, 2021, 2020

and 2019 were as follows:

(in thousands)
HETLIOZ net product sales
Fanapt net product sales
Total net product sales

2021

Year Ended December 31,
2020

2019

173,536 $
95,146
268,682 $

160,686 $
87,482
248,168 $

142,980
84,208
227,188

HETLIOZ is available in the United States (U.S.) for distribution through a limited number of specialty pharmacies, and is not available in retail
pharmacies. Specialty pharmacy customers include OptumRx (a subsidiary of UnitedHealth Group) and Accredo (a subsidiary of Express Scripts). Fanapt
®
is available in the U.S. for distribution through a limited number of wholesalers and is available in retail pharmacies. Wholesaler customers include
Cardinal Health, Inc., AmerisourceBergen Drug Corporation, and McKesson Corporation. The Company invoices and records revenue when its customers,
specialty pharmacies and wholesalers, receive product from the third-party logistics warehouse, which is the point at which control is transferred to the
customer. Revenues and accounts receivable are concentrated with these customers. Outside the U.S., the Company sells HETLIOZ in Germany and has a
distribution agreement for the commercialization of Fanapt in Israel.

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Receivables are carried at transaction price net of allowance for credit losses. Allowance for credit losses is measured using historical loss rates based on
the aging of receivables and incorporating current conditions and forward-looking estimates.

The following table presents each major customer that represented more than 10% of total revenues for the years ended December 31, 2021, 2020

and 2019:

Percent of Net Product Sales
Distributor A
Distributor B
Distributor C
Distributor D
Distributor E

2021

Year Ended December 31,
2020

2019

40 %
18 %
12 %
10 %
11 %

43 %
19 %
12 %
11 %
10 %

38 %
23 %
12 %
12 %
11 %

The following table presents each major customer that represented more than 10% of accounts receivable, net, as of December 31, 2021 and 2020:

Percent of Accounts Receivable, Net
Distributor A
Distributor B
Distributor C
Distributor D
Distributor E

*Represents less than 10% of respective balance.

December 31,

2021

2020

31 %
*
17 %
16 %
14 %

22 %
13 %
22 %
20 %
13 %

The transaction price is determined based upon the consideration to which the Company will be entitled in exchange for transferring product to the

customer. The Company’s product sales are recorded net of applicable product revenue allowances for which reserves are established and include
discounts, rebates, chargebacks, service fees, co-pay assistance and product returns that are applicable for various government and commercial payors.
Where appropriate, the Company’s estimates of variable consideration included in the transaction price consider a range of possible outcomes. Allowances
for rebates, chargebacks and co-pay assistance are based upon the insurance benefits of the end customer, which are estimated using historical activity and,
where available, actual and pending prescriptions for which the Company has validated the insurance benefits. Variable consideration is included in the
transaction price if, in the Company’s judgment, it is probable that a significant future reversal of cumulative revenue under the contract will not occur.
Overall, these reserves reflect the Company’s best estimates of the amount of consideration to which it is entitled based on the terms of the respective
underlying contracts. If actual results in the future vary from the Company’s estimates, it adjusts its estimates in the period identified, which would affect
net product sales in the period such variances become known.

Reserves for variable consideration are classified as product revenue allowances on the Consolidated Balance Sheets, with the exception of
prompt-pay discounts that are classified as reductions of accounts receivable. The reserve for product returns for which the product may not be returned for
a period of greater than one year from the balance sheet date is included as a component of other non-current liabilities in the Consolidated Balance Sheets.
Uncertainties related to variable consideration are generally resolved in the quarter subsequent to period end, with the exception of Medicaid rebates, which
are dependent upon the timing of when states submit reimbursement claims, and product returns that are resolved during the product expiry period
specified in the customer contract. The Company currently records sales allowances for the following:

•

Prompt-pay: Specialty pharmacies and wholesalers are offered discounts for prompt payment. The Company expects that the specialty
pharmacies and wholesalers will earn prompt payment discounts and, therefore, deducts the full amount of these discounts from total product
sales when revenues are recognized.

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purchase the product at a discounted price. The specialty pharmacy or wholesaler, in turn, charges back the difference between the price
initially paid by the specialty pharmacy or wholesaler and the discounted price paid to the specialty pharmacy or wholesaler by the contracted
customer.

• Medicare Part D Coverage Gap: The Medicare Part D prescription drug benefit requires manufacturers to fund approximately 70% of the

Medicare Part D insurance coverage gap for prescription drugs sold to eligible patients for applicable drugs. Vanda accounts for the Medicare
Part D coverage gap using a point of sale model. Estimates for expected Medicare Part D coverage gap are based in part on historical activity
and, where available, actual and pending prescriptions when the Company has validated the insurance benefits.

•

Service Fees: The Company receives sales order management, data and distribution services from certain customers, for which it is assessed
fees. These fees are based on contracted terms and are known amounts. The Company accrues service fees at the time of revenue recognition,
resulting in a reduction of product sales and the recognition of an accrued liability, unless it is a payment for a distinct good or service from
the customer in which case the fair value of those distinct goods or services are recorded as selling, general and administrative expense.

Co-payment Assistance: Patients who have commercial insurance and meet certain eligibility requirements may receive co-payment
assistance. Co-pay assistance utilization is based on information provided by the Company’s third-party administrator.

Product Returns: The Company generally offers direct customers a limited right to return as contractually defined with its customers. The
Company considers several factors in the estimation process, including expiration dates of product shipped to customers, inventory levels
within the distribution channel, product shelf life, historical return activity, including activity for product sold for which the return period has
past, prescription trends and other relevant factors. The Company does not expect returned goods to be resalable. There was no right of return
asset as of December 31, 2021 or 2020. The following table summarizes activity for product returns as of and for the years ended December
31, 2021, 2020 and 2019, all of which relates to sales of Fanapt :
®

(in thousands)
Balances at December 31, 2018
Additions
Credits/payments
Balances at December 31, 2019
Additions
Credits/payments
Balances at December 31, 2020
Additions
Credits/payments
Balances at December 31, 2021

Cost of Goods Sold

Reserve for Product
Returns

5,187
3,138
(2,205)
6,120
3,844
(5,266)
4,698
2,870
(3,017)
4,551

Cost of goods sold includes royalties payable, the cost of inventory sold, costs to write down inventory to net realizable value, manufacturing and

supply chain costs and product shipping and handling costs related to sales of HETLIOZ and Fanapt to the Company’s distribution partners.

Research and Development Expenses

Research and development expenses consist primarily of fees for services provided by third parties in connection with the clinical trials, costs of

contract manufacturing services, milestone payments, costs of materials used in clinical trials and research and development, costs for regulatory
consultants and filings, depreciation of capital resources used to develop products, related facilities costs, and salaries, other employee-related costs and
stock-based compensation for research and development personnel. The Company expenses research and development costs as they are incurred for
products in the development stage, including manufacturing costs and milestone payments made under license agreements prior to FDA approval. Upon
and subsequent to FDA approval, manufacturing and milestone payments related to license agreements are capitalized. Milestone payments are accrued
when it is deemed probable that the milestone event will be achieved. Costs related to the acquisition of intellectual property are expensed as incurred if the
underlying technology is developed in connection with the Company’s research and development efforts and has no alternative future use.

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Selling, General and Administrative Expenses

Selling, general and administrative expenses consist of salaries, other employee-related costs and stock-based compensation, and facilities and

third-party expenses. Selling, general and administrative expenses are associated with the activities of the corporate, finance, accounting, information
technology, business development, commercial support, trade and distribution, sales, marketing, legal, medical affairs and human resource functions.
Additionally, selling, general and administrative expenses included an estimate for the annual Affordable Care Act fee.

Stock-Based Compensation

Compensation costs for all stock-based awards to employees and directors are measured based on the grant date fair value of those awards and

recognized over the period during which the employee or director is required to perform service in exchange for the award. The Company recognizes the
expense over the award’s vesting period. The fair value of stock options granted and restricted stock units (RSUs) awarded are amortized using the straight-
line method. As stock-based compensation expense recognized in the Consolidated Statements of Operations is based on awards ultimately expected to
vest, it has been reduced for estimated forfeitures. Forfeitures are estimated at the time of grant and revised, if necessary, in subsequent periods if actual
forfeitures differ from those estimates.

Advertising Expense

The Company expenses the costs of advertising, including branded promotional expenses, as incurred. Branded advertising expenses, recorded in

selling, general and administrative expenses, were $6.7 million, $12.6 million and $3.2 million for the years ended December 31, 2021, 2020 and 2019,
respectively.

Foreign Currency

The reporting currency of the Company is the U.S. dollar. The functional currency of the Company’s international subsidiaries is the local

currency. Assets and liabilities denominated in foreign currencies, including intercompany balances for which settlement is anticipated in the foreseeable
future, are translated at exchange rates in effect at the balance sheet date. Foreign currency equity balances are translated at historical rates. Revenues and
expenses denominated in foreign currencies are translated at average exchange rates for the respective periods. Foreign currency translation adjustments are
recorded in accumulated other comprehensive income (loss).

Transactions denominated in currencies other than functional currency are recorded based on exchange rates at the time such transactions arise.

Changes in exchange rates with respect to amounts recorded in the Consolidated Balance Sheets related to these items will result in unrealized foreign
currency transaction gains and losses based upon period-end exchange rates. The Company also records realized foreign currency transaction gains and
losses upon settlement of the transactions. Foreign currency transaction gains and losses are included in other income and were not material for the years
ended December 31, 2021, 2020 and 2019, respectively.

Income Taxes

The Company accounts for income taxes using the asset and liability method. Under the asset and liability method, current income tax expense or

benefit is the amount of income taxes expected to be payable or refundable for the current year. A deferred income tax asset or liability is recognized for
future tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their respective
tax bases and tax credits and loss carryforwards. Deferred tax assets are reduced by a valuation allowance when, in the opinion of management, it is more
likely than not that some portion of the deferred tax assets will not be realized. Tax rate changes are reflected in income during the period such changes are
enacted. Changes in ownership may limit the amount of net operating loss (NOL) carryforwards that can be utilized in the future to offset taxable income.
Tax benefits are recognized from an uncertain tax position only if it is more likely than not that the position will be sustained on examination by the taxing
authorities based on the technical merits of the position. The tax benefit recognized in the financial statements for a particular tax position is based on the
largest benefit that is more likely than not to be realized upon settlement. Interest and penalties related to income taxes are recognized as a component of
income tax expense in the Consolidated Statements of Operations, and cumulative accrued interest and penalties are recognized within the related liability
lines in the Consolidated Balance Sheets.

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Certain Risks and Uncertainties

The outbreak of the novel coronavirus known as COVID-19 has resulted in government-imposed quarantines, travel restrictions and other public
health safety measures. As this pandemic endures, the extent to which COVID-19 may impact the Company’s business, financial condition and results of
operations is uncertain and will depend on many factors outside of the Company’s control.

The Company’s products under development require approval from the FDA or other international regulatory agencies prior to commercial sales.

There can be no assurance the products will receive the necessary clearance. If the Company is denied clearance or clearance is delayed, it may have a
material adverse impact on the Company.

The Company’s products are concentrated in rapidly changing, highly competitive markets, which are characterized by rapid technological

advances, changes in customer requirements and evolving regulatory requirements and industry standards. Any failure by the Company to anticipate or to
respond adequately to technological developments in its industry, changes in customer requirements or changes in regulatory requirements or industry
standards or any significant delays in the development or introduction of products or services could have a material adverse effect on the Company’s
business, operating results and future cash flows.

The Company depends on single source suppliers for critical raw materials for manufacturing, as well as other components required for the

administration of its products. The loss of these suppliers could delay the clinical trials or prevent or delay commercialization of the products.

Concentrations of Credit Risk

Financial instruments, which potentially subject the Company to significant concentrations of credit risk, consist primarily of cash, cash
equivalents and marketable securities. The Company places its cash, cash equivalents and marketable securities with highly rated financial institutions. At
December 31, 2021, the Company maintained all of its cash, cash equivalents and marketable securities in two financial institutions. Deposits held with
these institutions may exceed the amount of insurance provided on such deposits. Generally, these deposits may be redeemed upon demand, and the
Company believes there is minimal risk of losses on such balances.

Segment and Geographic Information

The Company operates in one reporting segment and, accordingly, no segment disclosures are presented herein. Foreign sales were not material

for each of the years ended December 31, 2021, 2020 and 2019.

Recent Accounting Pronouncements

In December 2019, the Financial Accounting Standards Board (FASB) issued Accounting Standards Update (ASU) 2019-12, Income Taxes (Topic

740), Simplifying the Accounting for Income Taxes, which clarifies and simplifies certain aspects of the accounting for income taxes. The standard is
effective for years beginning after December 15, 2020, and interim periods within annual periods beginning after December 15, 2020. The adoption of this
standard on January 1, 2021 did not have a material impact on the Company’s consolidated financial statements.

3. Marketable Securities

The following is a summary of the Company’s available-for-sale marketable securities as of December 31, 2021, which all have contractual

maturities of less than two years:

(in thousands)
U.S. Treasury and government agencies
Corporate debt
Total marketable securities

Amortized
Cost

195,076 $
185,933
381,009 $

Gross
Unrealized
Gains

Gross
Unrealized
Losses

Fair
Market
Value

1 $

113
114 $

(358) $
(23)
(381) $

194,719
186,023
380,742

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The following is a summary of the Company’s available-for-sale marketable securities as of December 31, 2020, which all have contractual

maturities of less than two years:

(in thousands)
U.S. Treasury and government agencies
Corporate debt
Total marketable securities

4. Fair Value Measurements

Amortized
Cost

165,966 $
140,538
306,504 $

Gross
Unrealized
Gains

Gross
Unrealized
Losses

Fair
Market
Value

129 $
87
216 $

(3) $
(8)
(11) $

166,092
140,617
306,709

Authoritative guidance establishes a three-tier fair value hierarchy, which prioritizes the inputs used in measuring fair value. These tiers include:

•
•
•

Level 1 — defined as observable inputs such as quoted prices in active markets
Level 2 — defined as inputs other than quoted prices in active markets that are either directly or indirectly observable
Level 3 — defined as unobservable inputs in which little or no market data exists, therefore requiring an entity to develop its own
assumptions

The Company’s assets classified in Level 1 and Level 2 as of December 31, 2021 and 2020 consist of cash equivalents and available-for-sale

marketable securities. The valuation of Level 1 instruments is determined using a market approach and is based upon unadjusted quoted prices for identical
assets in active markets. The valuation of Level 2 instruments is also determined using a market approach based upon quoted prices for similar assets in
active markets, or other inputs that are observable for substantially the full term of the financial instrument. Level 2 securities include certificates of
deposit, commercial paper, corporate notes and asset-backed securities that use as their basis readily observable market parameters.

The Company held certain assets that are required to be measured at fair value on a recurring basis as of December 31, 2021, as follows:

(in thousands)
U.S. Treasury and government agencies
Corporate debt
Total assets measured at fair value

Total Fair Value

194,719 $
186,023
380,742 $

Fair Value Measurement as of December 31, 2021 Using

Quoted Prices in
Active Markets for
Identical Assets
(Level 1)

Significant Other
Observable Inputs
(Level 2)

Significant
Unobservable
Inputs
(Level 3)

194,719 $
—
194,719 $

— $

186,023
186,023 $

The Company held certain assets that are required to be measured at fair value on a recurring basis as of December 31, 2020, as follows:

(in thousands)
U.S. Treasury and government agencies
Corporate debt
Total assets measured at fair value

Total Fair Value

166,092 $
140,617
306,709 $

Fair Value Measurement as of December 31, 2020 Using

Quoted Prices in
Active Markets for
Identical Assets
(Level 1)

Significant Other
Observable Inputs
(Level 2)

Significant
Unobservable
Inputs
(Level 3)

166,092 $
—
166,092 $

— $

140,617
140,617 $

—
—
—

Total assets measured at fair value as of December 31, 2021 and 2020 include no cash equivalents.

The Company also has financial assets and liabilities, not required to be measured at fair value on a recurring basis, which primarily consist of
cash, accounts receivable, restricted cash, accounts payable and accrued liabilities, product revenue allowances, and milestone obligations under license
agreements, the carrying values of which materially approximate their fair values.

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5. Inventory

Inventory consisted of the following as of December 31, 2021 and 2020:

(in thousands)
Current assets
Work-in-process
Finished goods
Total inventory, current

Non-Current assets
Raw materials
Work-in-process
Finished goods
Total inventory, non-current
Total inventory

6. Property and Equipment

December 31, 2021

December 31, 2020

30 $
995
1,025 $

2,143 $
3,934
1,150
7,227
8,252 $

66
1,214
1,280

744
4,045
302
5,091
6,371

The following is a summary of the Company’s property and equipment, at cost, as of December 31, 2021 and 2020:

(in thousands)
Computer and other equipment
Furniture and fixtures
Leasehold improvements
Total property and equipment, gross
Accumulated depreciation and amortization
Total property and equipment, net

Estimated
Useful Life
(Years)
3
5 - 7
5 - 11

December 31, 2021

December 31, 2020

5,481 $
1,546
5,463
12,490
(9,377)
3,113 $

5,212
1,495
5,457
12,164
(8,028)
4,136

Depreciation expense was $1.4 million for each of the years ended December 31, 2021, 2020 and 2019.

7. Leases

The Company’s long-term leases primarily include operating leases and subleases for office space in Washington, D.C. and London, England. The
Company recognized ROU assets and lease liabilities related to fixed payments for these long-term operating leases in its Consolidated Balance Sheet as of
December 31, 2021 and 2020. The Company also has short-term leases, including office space in Berlin, Germany.

In June 2011, the Company entered into an operating lease agreement under which it leases 33,534 square feet of office space for its headquarters
at 2200 Pennsylvania Avenue, N.W. in Washington, D.C. Subject to the prior rights of other tenants, the Company has the right to renew the lease for five
years following its expiration in July 2028. As of December 31, 2021, the renewal period has not been included in the lease term. The Company has the
right to sublease or assign all or a portion of the premises, subject to standard conditions. The lease may be terminated early by the Company or the
landlord under certain circumstances.

In June 2016, the Company entered into a sublease agreement under which it subleases an additional 9,928 square feet of office space for its

headquarters at 2200 Pennsylvania Avenue, N.W. in Washington, D.C. The sublease term began in January 2017 and ends in July 2026 but may be
terminated earlier by either party under certain circumstances. The Company has the right to sublease or assign all or a portion of the premises, subject to
standard conditions.

In May 2016, the Company entered into an operating lease agreement under which it leases 2,880 square feet of office space in London, England.

In November 2020, the Company extended the non-cancellable portion of the lease term from 2021 to 2023 and has the option to renew the lease for an
additional three years following its expiration. As of December 31, 2021, the renewal period has not been included in the lease term.

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The following is a summary of the Company’s ROU assets and operating lease liabilities as of December 31, 2021 and 2020:

(in thousands)
Assets
Operating lease assets

Liabilities
Operating lease current liabilities
Operating lease non-current liabilities

Total lease liabilities

Weighted average remaining lease term
Weighted average discount rate

(1)

Classification on the Balance Sheet

December 31, 2021

December 31, 2020

Operating lease right-of-use assets

Accounts payable and accrued liabilities
Operating lease non-current liabilities

9,272

2,311
10,055
12,366

6.2
8.1 %

10,459

2,117
11,497
13,614

7.1
8.1 %

(1) Upon adoption of the new lease standard, discount rates used for existing leases were established at January 1, 2019.

For each of the years ended December 31, 2021, 2020 and 2019, the Company recognized operating lease cost of $2.3 million and short-term

operating lease cost of $0.4 million. The Company also recognized $1.4 million, $1.5 million and $1.4 million, respectively, of expense related to non-lease
elements, such as building maintenance services and utilities, and executory costs associated with the operating leases. For existing leases as of January 1,
2019, executory costs are excluded from operating lease expense, which is consistent with the Company’s accounting under ASC 840. For all leases
entered into after January 1, 2019, executory costs are allocated between lease and non-lease elements based upon their relative stand-alone prices.

Cash paid for amounts included in the measurement of operating lease liabilities is included in operating cash flows and was $2.3 million, $2.6

million and $2.5 million for the years ended December 31, 2021, 2020 and 2019, respectively.

The table below reconciles the Company’s future cash obligations to operating lease liabilities recorded on the balance sheet as of December 31,

2021:

(in thousands)
2022
2023
2024
2025
2026
Thereafter
Total minimum lease payments
Less: amount of lease payments representing interest
Present value of future minimum lease payments
Less: current obligations under leases

Operating lease non-current liabilities

8. Intangible Assets

Operating Leases

2,608
2,461
2,488
2,557
2,366
3,258
15,738
(3,372)
12,366
(2,311)
10,055

HETLIOZ . In January 2014, the Company announced that the FDA had approved the New Drug Application (NDA) for HETLIOZ . As a result
of this approval, the Company met a milestone under its license agreement with Bristol-Myers Squibb (BMS) that required the Company to make a license
payment of $8.0 million to BMS. The $8.0 million is being amortized on a straight-line basis over the estimated economic useful life of the related product
patents.

In April 2018, the Company met its final milestone under its license agreement with BMS when cumulative worldwide sales of

HETLIOZ reached $250.0 million. As a result of the achievement of this milestone, the Company made a payment to BMS of $25.0 million in 2018. The
$25.0 million, which was capitalized as an intangible asset in the first quarter of 2015, was

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determined to be additional consideration for the acquisition of the HETLIOZ intangible asset and is being amortized on a straight-line basis over the
estimated economic useful life of the related product patents.

The following is a summary of the Company’s intangible assets as of December 31, 2021:

(in thousands)
HETLIOZ
®

Estimated
Useful Life
July 2035

Gross
Carrying
Amount

December 31, 2021

Accumulated
Amortization

Net
Carrying
Amount

33,000 $

12,919 $

20,081

The following is a summary of the Company’s intangible assets as of December 31, 2020:

(in thousands)
HETLIOZ
®

Estimated
Useful Life
July 2035

Gross
Carrying
Amount

December 31, 2020

Accumulated
Amortization

Net
Carrying
Amount

33,000 $

11,441 $

21,559

As of December 31, 2021 and 2020, the Company also had $27.9 million of fully amortized intangible assets related to Fanapt .
®

Intangible assets are amortized over their estimated useful economic life using the straight-line method. Amortization expense for the years ended

December 31, 2021, 2020 and 2019 was as follows:

(in thousands)
HETLIOZ
®

2021

Year Ended December 31,
2020

2019

1,478 $

1,505

The following is a summary of the future intangible asset amortization schedule as of December 31, 2021:
2025

Total

2022

2023

2024

2026

Thereafter

20,081 $

1,478 $

12,691

(in thousands)
HETLIOZ
®

9. Accounts Payable and Accrued Liabilities

The following is a summary of the Company’s accounts payable and accrued liabilities as of December 31, 2021 and 2020:
December 31, 2021

December 31, 2020

(in thousands)
Research and development expenses
Consulting and other professional fees
Compensation and employee benefits
Royalties payable
Operating lease liabilities
Milestone obligations under license agreements
Accounts payable and other accrued liabilities
Total accounts payable and accrued liabilities

10,082 $
8,732
6,515
5,873
2,311
—
925
34,438 $

6,173
5,052
10,951
5,817
2,117
350
1,049
31,509

10. Commitments and Contingencies

Guarantees and Indemnifications

The Company has entered into a number of standard intellectual property indemnification agreements in the ordinary course of its business.

Pursuant to these agreements, the Company indemnifies, holds harmless, and agrees to reimburse the indemnified party for losses suffered or incurred by
the indemnified party, generally the Company’s business partners or customers, in connection with any U.S. patent or any copyright or other intellectual
property infringement claim by any third party with respect to the Company’s products. The term of these indemnification agreements is generally
perpetual from the date of execution of the agreement. The maximum potential amount of future payments the Company could be required to make under
these indemnification agreements is unlimited. Since inception, the Company has not incurred costs to defend lawsuits or settle claims related to these
indemnification agreements. The Company also indemnifies its officers and directors for certain events or occurrences, subject to certain conditions.

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License Agreements

The Company’s rights to develop and commercialize its products are subject to the terms and conditions of licenses granted to the Company by

other pharmaceutical companies.

HETLIOZ . In February 2004, the Company entered into a license agreement with BMS under which it received an exclusive worldwide license

under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize HETLIOZ . As of December 31,
2021, the Company has paid BMS $37.5 million in upfront fees and milestone obligations, including $33.0 million of regulatory approval and commercial
milestones capitalized as intangible assets (see Note 8). The Company has no remaining milestone obligations to BMS. Additionally, the Company is
obligated to make royalty payments on HETLIOZ net sales to BMS. The royalty period in each territory where the Company commercializes
HETLIOZ is 10 years following the first commercial sale in the territory. In territories outside the U.S., the royalty is 5% on net sales. In the U.S., the
current royalty on net sales is 10%. This royalty will drop to 5% in December 2022 and will end in April 2024. The Company is also obligated under the
license agreement to pay BMS a percentage of any sublicense fees, upfront payments and milestone and other payments (excluding royalties) that it
receives from a third party in connection with any sublicensing arrangement, at a rate which is in the mid-twenties. The Company is obligated to use its
commercially reasonable efforts to develop and commercialize HETLIOZ .
®

Fanapt . Pursuant to the terms of a settlement agreement with Novartis Pharma AG (Novartis), Novartis transferred all U.S. and Canadian rights

in the Fanapt franchise to the Company on December 31, 2014. The Company paid directly to Sanofi S.A. (Sanofi) a fixed royalty of 3% of net sales
through December 2019 related to manufacturing know-how. The Company is also obligated to pay Sanofi a fixed royalty on Fanapt net sales equal to 6%
on Sanofi know-how not related to manufacturing under certain conditions for a period of up to 10 years in markets where the NCE patent has expired or
was not issued. The Company is obligated to pay this 6% royalty on net sales in the U.S. through November 2026.

Tradipitant. In April 2012, the Company entered into a license agreement with Eli Lilly and Company (Lilly) pursuant to which the Company

acquired an exclusive worldwide license under certain patents and patent applications, and other licenses to intellectual property, to develop and
commercialize an NK-1 receptor antagonist, tradipitant, for all human indications. Lilly is eligible to receive future payments based upon achievement of
specified development, regulatory approval and commercialization milestones as well as tiered-royalties on net sales at percentage rates up to the low
double digits. As of December 31, 2021, the Company has paid Lilly $3.0 million in upfront fees and development milestones. As of December 31, 2021,
remaining milestone obligations include a $2.0 million development milestone due upon the filing of the first marketing authorization for tradipitant in
either the U.S. or European Union (E.U.), $10.0 million and $5.0 million for the first approval of a marketing authorization for tradipitant in the U.S. and
E.U., respectively, and up to $80.0 million for sales milestones. The Company is obligated to use its commercially reasonable efforts to develop and
commercialize tradipitant.

Portfolio of CFTR activators and inhibitors. In March 2017, the Company entered into a license agreement with the University of California San
Francisco (UCSF), under which the Company acquired an exclusive worldwide license to develop and commercialize a portfolio of CFTR activators and
inhibitors. Pursuant to the license agreement, the Company will develop and commercialize the CFTR activators and inhibitors and is responsible for all
development costs under the license agreement, including current pre-investigational new drug development work. UCSF is eligible to receive future
payments based upon achievement of specified development and commercialization milestones as well as single-digit royalties on net sales. As of
December 31, 2021, the Company has paid UCSF $1.6 million in upfront fees and development milestones. As of December 31, 2021, remaining milestone
obligations include $11.9 million for development milestones and $33.0 million for future regulatory approval and sales milestones. Included in the $11.9
million of development milestones are $1.1 million of milestone obligations due upon the conclusion of clinical studies for each licensed product but not to
exceed $3.2 million in total for the CFTR portfolio. As a result of completion of the first clinical study initiated by the Company for VSJ-110, the Company
made a $350,000 development milestone payment to UCSF in the fourth quarter of 2021. The likelihood of achieving this milestone was determined to be
probable during 2020 and the obligation of $350,000 tied to such milestone was recorded as research and development expense in the consolidated
Statements of Operations during the year ended December 31, 2020 and as a current liability in the Consolidated Balance Sheet as of December 31, 2020.

VQW-765. In connection with a settlement agreement with Novartis relating to Fanapt , the Company received an exclusive worldwide license

under certain patents and patent applications, and other licenses to intellectual property, to develop and commercialize VQW-765, a Phase II alpha-7
nicotinic acetylcholine receptor partial agonist. Pursuant to the license agreement, the Company is obligated to use its commercially reasonable efforts to
develop and commercialize VQW-765 and is responsible for all development costs. The Company has no milestone obligations; however, Novartis is
eligible to receive tiered-royalties on net sales at percentage rates up to the mid-teens.

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Purchase Commitments

In the course of its business, the Company regularly enters into agreements with third-party vendors under fee service arrangements, which

generally may be terminated on 90 days’ notice without incurring additional charges, other than charges for work completed or materials procured but not
paid for through the effective date of termination and other costs incurred by the Company’s contractors in closing out work in progress as of the effective
date of termination. The Company’s non-cancellable purchase commitments for agreements longer than one year primarily relate to commitments for data
services and are not material. Various other long-term agreements entered into for services with other third-party vendors, such as inventory purchase
commitments, are cancellable in nature or contain variable commitment terms within the agreement.

11. Accumulated Other Comprehensive Income (Loss)

The accumulated balances related to each component of other comprehensive income (loss), net of taxes, were as follows for the years ended

December 31, 2021 and 2020:
(in thousands)
Foreign currency translation
Unrealized gain on marketable securities
Accumulated other comprehensive income (loss)

12. Stock-Based Compensation

December 31, 2021

December 31, 2020

32 $

(207)
(175) $

81
158
239

As of December 31, 2021, there were 5,485,888 shares subject to outstanding options and RSUs under the 2006 Equity Incentive Plan (2006 Plan)

and the Amended and Restated 2016 Equity Incentive Plan (2016 Plan, and together with the 2006 Plan, Plans). The 2006 Plan expired by its terms in
April 2016, and the Company adopted the 2016 Plan. Outstanding options under the 2006 Plan remain in effect and the terms of the 2006 Plan continue to
apply, but no additional awards can be granted under the 2006 Plan. In June 2016, the Company’s stockholders approved the 2016 Plan. The 2016 Plan has
been amended a number of times since to increase the number of shares reserved for issuance, among other administrative changes. Each of the
amendments to the 2016 Plan was approved by the Company’s stockholders. There is a total of 10,790,000 shares of common stock authorized for issuance
under the 2016 Plan, 4,716,342 shares of which remained available for future grant as of December 31, 2021.

Stock Options

The Company has granted option awards under the Plans with service conditions (service option awards) that are subject to terms and conditions
established by the compensation committee of the board of directors. Service option awards have 10-year contractual terms. Service option awards granted
to employees and new directors upon their election vest and become exercisable over four years, with the first 25% of the shares subject to service option
awards vesting on the first anniversary of the grant date and the remaining 75% of the shares subject to the service option awards in 36 equal monthly
installments thereafter. Subsequent annual service option awards granted to directors vest and become exercisable in full on the first anniversary of the
grant date. Certain service option awards granted to employees and executive officers provide for partial acceleration of vesting if the employee or
executive officer is subject to an involuntary termination, and full acceleration of vesting if the employee or executive officer is subject to an involuntary
termination within 24 months after a change in control of the Company. Service option awards granted to directors provide for accelerated vesting if there
is a change in control of the Company or if the director’s service terminates as a result of the director’s death or total and permanent disability.

As of December 31, 2021, $7.9 million of unrecognized compensation costs related to unvested service option awards are expected to be

recognized over a weighted average period of 1.2 years. No option awards are classified as a liability as of December 31, 2021.

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(in thousands, except for share and per share amounts)
Outstanding at December 31, 2020

Granted
Forfeited
Expired
Exercised

Outstanding at December 31, 2021

Exercisable at December 31, 2021

Vested and expected to vest at December 31, 2021

A summary of option activity under the Plans for the year ended December 31, 2021 is as follows:
Weighted Average
Exercise Price at Grant
Date

Number of
Shares

3,606,818 $
708,500
(128,285)
(10,000)
(455,885)
3,721,148

2,616,440

3,604,678

12.24
20.20
15.79
18.30
7.79

14.16

12.69

14.03

Weighted Average
Remaining Term
(Years)

Aggregate
Intrinsic
Value

5.76 $

8,511

5.77

4.56

5.67

4,124

11,327

10,045

11,215

The weighted average grant-date fair value of options granted was $8.91, $5.53 and $10.19 per share for the years ended December 31, 2021,

2020 and 2019, respectively. The total intrinsic value of options exercised was $4.1 million, $2.9 million and $2.5 million for the years ended December
31, 2021, 2020 and 2019, respectively. Proceeds from the exercise of stock options amounted to $3.6 million, $5.6 million and $6.3 million for the years
ended December 31, 2021, 2020 and 2019, respectively.

Restricted Stock Units

An RSU is a stock award that entitles the holder to receive shares of the Company’s common stock as the award vests. The fair value of each RSU
is based on the closing price of the Company’s stock on the date of grant. The Company has granted RSUs under the Plans with service conditions (service
RSUs) that are subject to terms and conditions established by the compensation committee of the board of directors. Service RSUs granted to employees
vest in four equal annual installments provided that the employee remains employed with the Company. Certain service RSUs granted to employees and
executive officers provide for accelerated vesting if the employee or executive officer is subject to an involuntary termination within 24 months after a
change in control. Annual service RSUs granted to directors vest on the first anniversary of the grant date and provide for accelerated vesting if there is a
change in control of the Company.

As of December 31, 2021, $22.0 million of unrecognized compensation costs related to unvested service RSUs are expected to be recognized over

a weighted average period of 1.7 years. No RSUs are classified as a liability as of December 31, 2021.

A summary of RSU activity for the Plans for the year ended December 31, 2021 is as follows:

Unvested at December 31, 2020

Granted
Forfeited
Vested

Unvested at December 31, 2021

Number of
Shares

Weighted
Average
Grant Date Fair Value
15.26
19.57
15.54
15.73

17.27

1,639,563 $
899,305
(194,250)
(579,878)
1,764,740

The weighted average grant-date fair value of RSUs granted was $19.57, $11.28 and $19.46 per share for the years ended December 31, 2021,

2020 and 2019, respectively. The total fair value of the RSUs that vested during the years ended December 31, 2021, 2020 and 2019 was $9.1 million, $9.6
million, and $7.7 million, respectively.

Stock-Based Compensation Expense

Stock-based compensation expense recognized for the years ended December 31, 2021, 2020 and 2019 comprised of the following:

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(in thousands)
Research and development
Selling, general and administrative
Total stock-based compensation expense

2021

Year Ended December 31,
2020

2019

3,955 $
11,419
15,374 $

3,804 $
9,556
13,360 $

3,207
10,251
13,458

The fair value of each option award is estimated on the date of grant using the Black-Scholes-Merton option pricing model that uses the
assumptions noted in the following table. Expected volatility rates are based on the historical volatility of the Company’s publicly traded common stock
and other factors. The expected terms are determined based on a combination of historical exercise data and hypothetical exercise data for unexercised
stock options. The risk-free interest rates are based on the U.S. Treasury yield for a period consistent with the expected term of the option in effect at the
time of the grant. The Company has never paid cash dividends to its stockholders and does not plan to pay dividends in the foreseeable future. Assumptions
used in the Black-Scholes-Merton option pricing model for employee and director stock options granted during the years ended December 31, 2021, 2020
and 2019 were as follows:

Expected dividend yield
Weighted average expected volatility
Weighted average expected term (years)
Weighted average risk-free rate

13. Employee Benefit Plan

2021

Year Ended December 31,
2020

2019

— %
46 %
5.98
0.75 %

— %
51 %
6.07
1.14 %

— %
58 %
5.95
2.26 %

The Company has a defined contribution plan under IRC Section 401(k). This plan covers substantially all employees who meet minimum age and

service requirements and allows participants to defer a portion of their annual compensation on a pre-tax basis. Currently, the Company matches fifty
percent up to the first six percent of employee contributions. All matching contributions have been paid by the Company. The Company match vests over a
4-year period and amounted to $1.0 million, $0.9 million and $0.8 million for the years ended December 31, 2021, 2020 and 2019, respectively.

14. Income Taxes

The following is a summary of the domestic and foreign components of income before income taxes for the years ended December 31, 2021, 2020

and 2019:

(in thousands)
Domestic
Foreign
Total income before income taxes

2021

Year Ended December 31,
2020

2019

42,221 $
143
42,364 $

31,667 $
(12)
31,655 $

28,794
234
29,028

The following is a summary of the provision (benefit) for income taxes for the years ended December 31, 2021, 2020 and 2019:

(in thousands)
Current:

Federal
State
Foreign

Deferred:

Federal
State
Foreign

Provision (benefit) for income taxes

2021

Year Ended December 31,
2020

2019

— $

2,200
267

6,604
119
22
9,212 $

— $

2,061
68

6,076
155
(42)
8,318 $

—
1,161
81

(85,624)
(2,127)
(16)
(86,525)

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The Company assesses the need for a valuation allowance against its deferred tax asset each quarter through the review of all available positive
and negative evidence. Deferred tax assets are reduced by a tax valuation allowance when, in the opinion of management, it is more likely than not that
some portion of the deferred tax assets will not be realized. The analysis depends on historical and projected taxable income. Projected taxable income
includes significant assumptions related to revenue, commercial expenses and research and development activities. During 2019, after considering all
available positive and negative evidence, including but not limited to cumulative income in recent periods, historical, current and future projected results
and significant risks and uncertainties related to forecasts, the Company concluded that it was more likely than not that substantially all of its deferred tax
assets in the U.S. are realizable in future periods. A valuation allowance was retained against certain District of Columbia state deferred tax assets as of
December 31, 2021 and 2020.

The following is reconciliation between the federal statutory tax rate and the Company’s effective tax rate for the years ended December 31, 2021,

2020 and 2019:

Federal tax at statutory rate
State taxes
Change in valuation allowance (1)
Research and development credit (2)
Orphan drug credit (2)
Section 162(m) limitation
Other tax rate changes
Uncertain tax positions (2)
Stock-based compensation
Other items
Effective tax rate

2021

Year Ended December 31,
2020

2019

21.0 %
2.3 %
(0.1)%
(6.5)%
(0.1)%
2.6 %
(0.2)%
4.0 %
(1.8)%
0.5 %
21.7 %

21.0 %
2.6 %
(3.5)%
(5.4)%
(1.3)%
1.7 %
0.2 %
4.7 %
5.1 %
1.2 %
26.3 %

21.0 %
1.8 %
(357.6)%
(10.9)%
17.1 %
2.7 %
(0.5)%
26.3 %
(1.0)%
3.0 %
(298.1)%

(1)

(2)

Reductions in 2020 valuation allowances are attributable to 2020 income before income taxes. Reductions in 2019 valuation allowances include
$7.5 million related to 2019 U.S. income before income taxes, $10.7 related to adjustments for prior period credit carryforwards and uncertain tax
positions and $85.6 million related to a change in beginning-of-the-year balances that resulted from a change in circumstances that caused a
change in judgment about the realizability of U.S. deferred tax assets in future years.

2019 activity includes adjustments to prior year credit carryforwards and prior year tax positions. As a result of the tax valuation allowance
previously recorded against deferred tax assets in the U.S., these adjustments resulted in no change in tax expense.

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The following is a summary of the components of the Company’s net deferred tax assets and the related tax valuation allowance as of December

31, 2021 and 2020.
(in thousands)
Deferred tax assets:
Net operating loss carryforwards
Stock-based compensation
Accrued expenses
Allowance for returns and credit losses
Research and development and orphan drug credit carryforwards
Other

Total deferred tax assets

Deferred tax liabilities:
Intangible assets
Other

Total deferred tax liabilities

Deferred tax assets, net
Less: Valuation allowance
Net deferred tax assets

December 31, 2021

December 31, 2020

35,509 $
4,846
1,409
1,142
39,975
3,081
85,962

(1,919)
(2,140)
(4,059)
81,903
7,025
74,878 $

43,623
4,653
2,429
1,169
37,737
3,279
92,890

(1,911)
(2,412)
(4,323)
88,567
7,051
81,516

The following is a summary of changes in the Company’s tax valuation allowance for the years ended December 31, 2021, 2020 and 2019:

(in thousands)
Year Ended:
December 31, 2021
December 31, 2020
December 31, 2019

Balance at
Beginning
of Year

Additions

Reductions

Balance at
End of
Year

7,051 $
8,155
111,950

— $
—
—

(26) $

(1,104)
(103,795)

7,025
7,051
8,155

The Company has NOL and other tax credit carryforwards in several jurisdictions. As of December 31, 2021, the Company has $27.2 million of

deferred tax assets relating to U.S. federal NOL carryforwards, along with deferred tax assets of $15.5 million and $24.4 million related to U.S. federal
research and development credits and orphan drug credits, respectively. These tax attributes will begin to expire in 2033, 2024 and 2030, respectively. In
addition, the Company has $8.3 million of deferred tax assets relating to other U.S. NOL carryforwards, which primarily relate to the District of Columbia.
NOLs for the District of Columbia will begin to expire in 2032 and state NOLs will begin to expire in 2029.

Tax benefits are recognized from an uncertain tax position only if it is more likely than not that the position will be sustained on examination by

the taxing authorities based on the technical merits of the position. The tax benefit recognized in the financial statements for a particular tax position is
based on the largest benefit that is more likely than not to be realized upon settlement. Interest and penalties related to income taxes are recognized as a
component of income tax expense in the Consolidated Statements of Operations, and cumulative accrued interest and penalties are recognized within the
related liability lines in the Consolidated Balance Sheets.

A reconciliation of the beginning and ending amount of gross unrecognized tax benefits is as follows:

(in thousands)
Unrecognized tax benefits at the beginning of the year

Increases (decreases) related to prior year tax positions
Increases related to current year tax positions

Unrecognized tax benefits at the end of the year

2021

Year Ended December 31,
2020

2019

11,233 $
122
1,580
12,935 $

9,741 $
(121)
1,613
11,233 $

—
8,223
1,518
9,741

The amount of uncertain tax benefits that, if recognized, would impact the effective tax rate is $12.9 million. Unrecognized tax benefits are not

expected to change materially over the next 12 months. Income tax returns filed by the

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Company for all periods are open to examination by tax jurisdictions. As of December 31, 2021, the Company is not under examination by any federal or
state tax jurisdiction.

Certain tax attributes of the Company, including NOLs and credits, would be subject to a limitation should an ownership change as defined under

the Internal Revenue Code of 1986, as amended (IRC), Section 382, occur. The limitations resulting from a change in ownership could affect the
Company’s ability to utilize its NOLs and credit carryforward (tax attributes). Ownership changes occurred in the years ending December 31, 2014 and
December 31, 2008. The Company believes that the ownership changes in 2014 and 2008 will not impact its ability to utilize NOL and credit
carryforwards; however, future ownership changes may cause the Company’s existing tax attributes to have additional limitations.

15. Earnings per Share

Basic earnings per share (EPS) is calculated by dividing the net income by the weighted average number of shares of common stock outstanding.

Diluted EPS is computed by dividing the net income by the weighted average number of shares of common stock outstanding, plus potential outstanding
common stock for the period. Potential outstanding common stock includes stock options and shares underlying RSUs, but only to the extent that their
inclusion is dilutive.

The following table presents the calculation of basic and diluted net income per share of common stock for the years ended December 31, 2021,

2020 and 2019:

(in thousands, except for share and per share amounts)
Numerator:
Net income
Denominator:
Weighted average shares outstanding, basic
Effect of dilutive securities
Weighted average shares outstanding, diluted

Net income per share, basic and diluted:

Basic
Diluted

2021

Year Ended December 31,
2020

2019

33,152 $

23,337 $

115,553

55,548,122
1,373,714
56,921,836

54,427,683
763,119
55,190,802

53,137,562
1,709,498
54,847,060

0.60 $

0.58 $

0.43 $

0.42 $

2.17

2.11

Antidilutive securities excluded from calculations of diluted net income per share

2,176,944

3,407,409

1,932,024

16. Legal Matters

Fanapt . In 2014 and 2015, Roxane Laboratories, Inc. (Roxane) and its affiliates, West-Ward Pharmaceuticals International Limited and West-

Ward Pharmaceuticals Corp (West-Ward), Inventia Healthcare Pvt. Ltd. (Inventia), Lupin Ltd. and Lupin Pharmaceuticals, Inc. (Lupin), Taro
®
Pharmaceuticals USA, Inc. and Taro Pharmaceutical Industries, Ltd. (Taro), and Apotex Inc. and Apotex Corp. (Apotex) (collectively, the Fanapt
Defendants) each submitted an Abbreviated New Drug Applications (ANDA) to the FDA seeking approval to market generic versions of Fanapt prior to
®
the expiration of certain of the Company’s patents covering Fanapt , including U.S. Patent No. 8,586,610 (‘610 Patent) and U.S. Patent No. 9,138,432
(‘432 Patent). In response, the Company filed separate lawsuits in 2014 and 2015 against each of the Fanapt Defendants in the U.S. District Court for the
District of Delaware (Delaware District Court) for patent infringement.

In August 2016, the Delaware District Court ruled in the Company’s favor, permanently enjoining Roxane from manufacturing, using, selling,

offering to sell, distributing or importing any generic iloperidone product described in Roxane’s ANDA until the expiration of the ‘610 Patent in November
2027, or May 2028 if the Company obtains pediatric exclusivity. This ruling was affirmed on appeal by the Federal Circuit Court of Appeals in April 2018.
West-Ward, having replaced Roxane as defendant following the acquisition of Roxane by West-Ward’s parent company, Hikma Pharmaceuticals PLC
(Hikma), petitioned the U.S. Supreme Court for a writ of certiorari, which was denied in January 2020. The Company’s lawsuit against Hikma regarding
the ‘432 Patent remains pending.

The Company entered into separate license agreements with each of Taro, Apotex and Lupin resolving these lawsuits in October 2016, December

2016 and July 2020, respectively. The license agreements grant Taro, Apotex and Lupin non-exclusive licenses to manufacture and commercialize a
version of Fanapt in the U.S. effective as of the expiration of the ‘610 Patent or earlier under certain limited circumstances. The Company entered into a
confidential stipulation with Inventia

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regarding any potential launch of its generic versions of Fanapt , but the Company’s lawsuit against Inventia regarding the ‘610 and ‘432 Patents remains
pending.

HETLIOZ . Between April 2018 and March 2021, the Company filed numerous Hatch-Waxman lawsuits in the Delaware District Court against

Teva Pharmaceuticals USA, Inc. (Teva), MSN Pharmaceuticals Inc. and MSN Laboratories Private Limited (MSN) and Apotex (collectively the
HETLIOZ Defendants) asserting that U.S. Patent Nos. RE46,604, 9,060,995, 9,539,234, 9,549,913, 9,730,910, 9,844,241, 10,071,977, 10,149,829,
10,376,487, 10,449,176, 10,610,510, 10,610,511, 10,829,465, and 10,611,744 will be infringed by the HETLIOZ Defendants’ generic versions of
HETLIOZ , for which they are seeking FDA approval. In January 2022, the Company entered into a license agreement with MSN and Impax Laboratories
LLC (Impax) resolving the lawsuits against MSN. The license agreement, which is subject to review by the U.S. Federal Trade Commission and the U.S.
Department of Justice (the DOJ), grants MSN and Impax a non-exclusive license to manufacture and commercialize MSN’s version of HETLIOZ in the
U.S. effective as of March 13, 2035, unless prior to that date the Company obtains pediatric exclusivity for HETLIOZ , in which case the license will be
effective as of July 27, 2035. MSN and Impax may enter the market earlier under certain limited circumstances. The consolidated lawsuits against the
remaining HETLIOZ Defendants are scheduled for trial in March 2022.

Other Matters. In February 2019, a qui tam action filed against the Company was unsealed by order of the U.S. District Court for the District of
Columbia (DC District Court). The qui tam action, which was filed under seal in March 2017, was brought by a former Company employee on behalf of
the U.S., 28 states and the District of Columbia (collectively, the Plaintiff States) and the policyholders of certain insurance companies under the Federal
False Claims Act and state law equivalents to the Federal False Claims Act and related state laws. The complaint alleged that the Company violated these
laws through the promotion and marketing of its products Fanapt and HETLIOZ and sought, among other things, treble damages, civil penalties for each
alleged false claim, and attorneys’ fees and costs. By virtue of the DC District Court having unsealed the original complaint, the Company learned that in
January 2019, the DOJ, as well as the Plaintiff States, elected not to intervene in the qui tam action at that time. In May 2019, the plaintiff filed an amended
complaint under seal repeating the same allegations and seeking the same relief. According to a filing unsealed in June 2019, the DOJ reaffirmed its
decision not to intervene and incorporated its prior filing, indicating that neither the DOJ nor the Plaintiff States were intervening regarding the original
complaint. Although the DOJ and the Plaintiff States have elected not to intervene, the plaintiff has continued to litigate this action and the DOJ and the
Plaintiff States may later seek to intervene. In August 2019, the Company filed a motion to dismiss, and in May 2020, the DC District Court dismissed the
plaintiff’s complaint in its entirety, without prejudice. In June 2020, the plaintiff filed a second amended complaint with similar allegations and seeking the
same relief. In July 2020, the Company filed another motion to dismiss, which was denied by the DC District Court in March 2021. The Company filed its
answer to the plaintiff’s second amended complaint in April 2021 and intends to continue to vigorously defend itself in the case.

In February 2019, a securities class action, Gordon v. Vanda Pharmaceuticals Inc., was filed in the U.S. District Court for the Eastern District of
New York naming the Company and certain of its officers as defendants. An amended complaint was filed in July 2019. The amended complaint, filed on
behalf of a purported stockholder, asserts claims on behalf of a putative class of all persons who purchased the Company’s publicly traded securities
between November 4, 2015 and February 11, 2019, for alleged violations of Sections 10(b) and 20(a) of the Securities Exchange Act of 1934, as amended,
and Rule 10b-5 promulgated thereunder. The amended complaint alleges that the defendants made false and misleading statements and/or omissions
regarding Fanapt , HETLIOZ and the Company’s interactions with the FDA regarding tradipitant between November 3, 2015 and February 11, 2019. In
March 2020, the Company filed a motion to dismiss the complaint. In March 2021, the motion to dismiss was granted in part and denied in part. In April
2021, the Company filed its answer to the amended complaint. The Company believes that it has meritorious defenses and intends to vigorously defend this
lawsuit. The Company does not anticipate that this litigation will have a material adverse effect on its business, results of operations or financial condition.
However, this lawsuit is subject to inherent uncertainties, the actual cost may be significant, and the Company may not prevail. The Company believes it is
entitled to coverage under its relevant insurance policies, subject to a retention, but coverage could be denied or prove to be insufficient.

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VANDA PHARMACEUTICALS INC.

EXHIBIT INDEX

Description

Form of Amended and Restated Certificate of Incorporation of the registrant (filed as Exhibit 3.8 to Amendment No. 2 to the registrant’s
registration statement on Form S-1 (File No. 333-130759) on March 17, 2006 and incorporated herein by reference).

Fourth Amended and Restated Bylaws of the registrant, as amended and restated on December 17, 2015 (filed as Exhibit 3.1 to the
registrant’s current report on Form 8-K (File No. 001-34186) on December 21, 2015 and incorporated herein by reference).

Specimen certificate representing the common stock of the registrant (filed as Exhibit 4.4 to Amendment No. 2 to the registrant’s
registration statement on Form S-1 (File No. 333-130759) on March 17, 2006, and incorporated herein by reference).

Description of Securities of the registrant

Amended and Restated License, Development and Commercialization Agreement, dated July 24, 2005, by and between Bristol-Myers
Squibb Company and the registrant (relating to HETLIOZ®) (filed as Exhibit 10.3 to Amendment No. 1 to the registrant’s registration
Statement on Form S-1 (File No. 333-130759) on February 16, 2006 and incorporated herein by reference).

Form of Indemnification Agreement entered into by directors and executive officers (filed as Exhibit 10.11 to the registrant’s registration
statement on Form S-1 (File No. 333-130759) on December 29, 2005 and incorporated herein by reference).

2006 Equity Incentive Plan, as amended (filed as Exhibit 10.17 to Amendment No. 2 to the registrant’s Registration Statement on Form S-1
(File No. 333-130759), as filed on March 17, 2006, and incorporated herein by reference).

Amended and Restated Employment Agreement, dated December 16, 2008, by and between Mihael H. Polymeropoulos and the registrant
(filed as Exhibit 10.34 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on August 10, 2009 and incorporated herein
by reference).

Amendment to Amended and Restated Employment Agreement, dated December 16, 2010, by and between Mihael H. Polymeropoulos and

the registrant (filed as Exhibit 10.39 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 10, 2011 and
incorporated herein by reference).

Amended and Restated Tax Indemnity Agreement, dated December 16, 2010, by and between Mihael H. Polymeropoulos and the registrant
(filed as Exhibit 10.41 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 10, 2011 and incorporated herein by
reference).

Lease, effective as of July 25, 2011, by and between Square 54 Office Owner LLC and the registrant (filed as Exhibit 10.42 to the
registrant’s quarterly report on Form 10-Q (File No. 001-34186) on November 7, 2011 and incorporated herein by reference).

Amendment to Amended and Restated License, Development and Commercialization Agreement, dated as of April 15, 2010, by and
between Bristol-Myers Squibb Company and the registrant (filed as Exhibit 10.38 to the registrant’s current report on Form 8-K (File
No. 001-34186) on April 19, 2010 and incorporated herein by reference).

Ninth Amendment to Amended and Restated License, Development and Commercialization Agreement, dated as of May 24, 2012, by and
between Bristol-Myers Squibb Company and the registrant (filed as Exhibit 10.46 to the registrant’s current report on Form 8-K (File No.
001-34186) on May 30, 2012 and incorporated herein by reference).

License, Development and Commercialization Agreement, dated as of April 12, 2012, by and between Eli Lilly and Company and the

registrant (filed as Exhibit 10.48 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on August 3, 2012 and incorporated
herein by reference).

Tenth Amendment to Amended and Restated License, Development and Commercialization Agreement, dated as of April 25, 2013, by and
between Bristol-Myers Squibb Company and the registrant (filed as Exhibit 10.50 to the registrant’s current report on Form 8-K (File No.
001-34186) on April 29, 2013 and incorporated herein by reference).

Manufacturing Agreement, dated January 24, 2014, by and between Patheon Pharmaceuticals Inc. and the registrant (relating to

HETLIOZ ).

Exhibit
Number

3.1

3.2

4.1

4.2*

10.1#

10.2†

10.3†

10.4†

10.5†

10.6†

10.7

10.8

10.9

10.10#

10.11

10.12‡*

Table of Contents

Exhibit
Number

Description

10.13

10.14

10.15#

10.16#

10.17#

10.18#

10.19#

10.20

10.21#

10.22

10.23†

10.24†

10.25†

10.26†

10.27†

10.28†

10.29‡*

First Amendment to Lease Agreement, dated March 18, 2014, by and between Square 54 Office Owner LLC and the registrant (filed as

Exhibit 10.54 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 8, 2014 and incorporated herein by reference).

Settlement Agreement and Mutual General Release, dated December 22, 2014, by and among Novartis Pharma AG and the registrant (filed

as Exhibit 10.55 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by
reference).

Asset Transfer Agreement, dated December 22, 2014, by and among Novartis Pharma AG, Novartis AG and the registrant (relating to

Fanapt®) (filed as Exhibit 10.56 to the registrant’s annual report on Form 10-K/A (File No. 001-34186) on June 10, 2015 and incorporated
herein by reference).

Sublicense Agreement, dated November 20, 1997, by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG (filed as Exhibit
10.30 to Titan Pharmaceutical Inc.’s registration statement on Form S-3 (File No. 333-42367) on December 16, 1997 and incorporated
herein by reference).

Amendment No. 1 to Sublicense Agreement by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG, dated November 30,

1998 (filed as Exhibit 10.58 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein
by reference).

Amendment No. 2 to Sublicense Agreement, dated April 10, 2001, by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG

(filed as Exhibit 10.59 to the registrant’s annual report on Form 10-K/A (File No. 001-34186) on June 10, 2015 and incorporated herein by
reference).

Amendment No. 3 to Sublicense Agreement, dated June 4, 2004, by and between Titan Pharmaceuticals, Inc. and Novartis Pharma AG

(filed as Exhibit 10.60 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by
reference).

Stock Purchase Agreement, dated December 22, 2014, by and between Novartis AG and the registrant (filed as Exhibit 10.61 to the

registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by reference).

License Agreement, dated December 22, 2014, by and between Novartis Pharma AG and the registrant (relating to AQW051) (filed as

Exhibit 10.62 to the registrant’s annual report on Form 10-K (File No. 001-34186) on March 13, 2015 and incorporated herein by reference).

Agreement, dated February 2, 2016, by and among Titan Pharmaceuticals, Inc., Aventisub LLC, the successor-in-interest to Aventisub II

Inc. Sanofi-Aventis and the registrant (filed as Exhibit 10.1 to the registrant’s current report on Form 8-K (File No. 001-34186) on
February 4, 2016 and incorporated herein by reference).

Vanda Pharmaceuticals Inc. Amended and Restated 2016 Equity Incentive Plan, as amended effective as of June 10, 2021 (filed as Exhibit
10.1 to the registrant’s registration statement on Form S-8 (File No. 333-256994) on June 10, 2021 and incorporated herein by reference).

Form of Notice of Stock Option Grant and Stock Option Agreement under Amended and Restated 2016 Equity Incentive Plan (filed as
Exhibit 10.2 to the registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by
reference).

Form of Restricted Stock Unit Award Agreement under Amended and Restated 2016 Equity Incentive Plan (filed as Exhibit 10.3 to the

registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by reference).

UK Sub Plan under the Amended and Restated 2016 Equity Incentive Plan (filed as Exhibit 10.4 to the registrant’s registration statement on

Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by reference).

Form of Stock Option Grant and Stock Option Agreement under the UK Sub Plan under the Amended and Restated 2016 Equity Incentive
Plan (filed as Exhibit 10.5 to the registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated
herein by reference).

Form of Restricted Stock Unit Award Agreement under the UK Sub Plan under the Amended and Restated 2016 Equity Incentive Plan (filed
as Exhibit 10.6 to the registrant’s registration statement on Form S-8 (File No. 333-218774) on June 15, 2017 and incorporated herein by
reference).

Manufacturing Agreement, dated May 6, 2016, by and between Patheon Pharmaceuticals Inc. and the registrant (relating to Fanapt ).

Table of Contents

Exhibit
Number

Description

10.30

10.31

10.32#

10.33#

10.34

10.35

10.36†

10.37†

10.38†

10.39†

10.40

10.41

21.1

23.1*

31.1*

31.2*

32.1*

101*

Second Amendment to Lease Agreement, dated June 20, 2016, by and between Square 54 Office Owner LLC and the registrant (filed as

Exhibit 10.43 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on July 28, 2016 and incorporated herein by reference).

Sublease Agreement, dated June 22, 2016, by and between Hunton & Williams LLP and the registrant (filed as Exhibit 10.44 to the

registrant’s quarterly report on Form 10-Q (File No. 001-34186) on July 28, 2016 and incorporated herein by reference).

License Agreement, dated October 24, 2016, by and among Taro Pharmaceuticals USA, Inc., Taro Pharmaceuticals Industries Ltd. and the

registrant (filed as Exhibit 10.45 to the registrant’s annual report on Form 10-K (File No. 001-34186) on February 17, 2017 and incorporated
herein by reference).

License Agreement, dated December 7, 2016, by and between Apotex, Inc. and the registrant (filed as Exhibit 10.46 to the registrant’s

annual report on Form 10-K (File No. 001-34186) on February 17, 2017 and incorporated herein by reference).

Third Amendment to Lease Agreement, dated March 28, 2018, by and between Square 54 Office Owner LLC and the registrant (filed as
Exhibit 10.38 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 2, 2018 and incorporated herein by reference).

Fourth Amendment to Lease Agreement, dated March 29, 2018, by and between Square 54 Office Owner LLC and the registrant (filed as
Exhibit 10.39 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 2, 2018 and incorporated herein by reference).

Amended and Restated Employment Agreement, dated April 30, 2018, by and between Gunther Birznieks and the registrant (filed as
Exhibit 10.40 to the registrant’s quarterly report on Form 10-Q (File No. 001-34186) on May 2, 2018 and incorporated herein by reference).

Employment Agreement, dated August 13, 2018, by and between Timothy Williams and the registrant (filed as Exhibit 10.41 to the
registrant’s quarterly report on Form 10-Q (File No. 001-34186) on November 7, 2018 and incorporated herein by reference).

Employment Agreement, dated August 5, 2019, by and between Joakim Wijkstrom and the registrant (filed as Exhibit 10.41 to the
registrant’s quarterly report on Form 10-Q (File No. 001-34186) on November 7, 2019 and incorporated herein by reference).

Amended and Restated Employment Agreement, dated July 27, 2020, by and between Kevin Moran and the registrant (filed as Exhibit 10.1
to the registrant’s current report on Form 8-K (File No. 001-34186) on July 29, 2020 and incorporated herein by reference).

Fifth Amendment to Lease Agreement, dated April 11, 2019, by and between Square 54 Office Owner LLC and the registrant (filed as
Exhibit 10.40 to the registrant’s annual report on Form 10-K (File No. 001-34186) on February 10, 2021 and incorporated herein by
reference).

Sixth Amendment to Lease Agreement, dated May 7, 2020, by and between Square 54 Office Owner LLC and the registrant (filed as
Exhibit 10.41 to the registrant’s annual report on Form 10-K (File No. 001-34186) on February 10, 2021 and incorporated herein by
reference).

List of Subsidiaries (filed as Exhibit 21.1 to the registrant’s annual report on Form 10-K (File No. 001-34186) on February 10, 2021 and

incorporated herein by reference).

Consent of PricewaterhouseCoopers LLP, Independent Registered Public Accounting Firm.

Certification of the Chief Executive Officer, as required by Section 302 of the Sarbanes-Oxley Act of 2002.

Certification of the Chief Financial Officer as required by Section 302 of the Sarbanes-Oxley Act of 2002.

Certification of the Chief Executive Officer and Chief Financial Officer as required by Section 906 of the Sarbanes-Oxley Act of 2002.

The following financial information from this annual report on Form 10-K for the fiscal year ended December 31, 2021, formatted in Inline
Extensible Business Reporting Language (iXBRL) and furnished electronically herewith: (i) Consolidated Balance Sheets as of December
31, 2021 and 2020; (ii) Consolidated Statements of Operations for the years ended December 31, 2021, 2020 and 2019; (iii) Consolidated
Statements of Comprehensive Income (Loss) for the years ended December 31, 2021, 2020 and 2019; (iv) Consolidated Statements of
Changes in Stockholders’ Equity for the years ended December 31, 2021, 2020 and 2019; (v) Consolidated Statements of Cash Flows for
the years ended December 31, 2021, 2020 and 2019; and (vi) Notes to the Consolidated Financial Statements.

104

Cover Page Interactive Data File (embedded within the Inline XBRL document).

100

Table of Contents

Exhibit
Number

Description

†

‡

Indicates management contract or compensatory plan or arrangement.

Confidential treatment has been granted with respect to certain portions of this exhibit. Omitted portions have been filed separately with the
Securities and Exchange Commission.

Portions of this exhibit have been omitted under rules of the Securities and Exchange Commission permitting the confidential treatment of
select information.

Filed herewith.

101

EXHIBIT 4.2

DESCRIPTION OF THE REGISTRANT’S SECURITIES
REGISTERED PURSUANT TO SECTION 12 OF THE
SECURITIES EXCHANGE ACT OF 1934

The following description is a summary that describes the securities of Vanda Pharmaceuticals Inc. (“Vanda,” the “Company,” “we,” “us” and

“our”) that are registered pursuant to Section 12 of the Securities Exchange Act of 1934, as amended. The description does not purport to be complete and
is subject to, and qualified in its entirety by reference to, the applicable provisions of our Amended and Restated Certificate of Incorporation, as amended
(the “Certificate of Incorporation”), our Fourth Amended and Restated Bylaws (the “Bylaws”) and Delaware law. Our Certificate of Incorporation and
Bylaws are each incorporated by reference as an exhibit to the Annual Report on Form 10-K of which this Exhibit 4.2 is a part.

Authorized Capital Stock

Description of Capital Stock

Our authorized capital stock currently consists of (i) 150,000,000 shares of common stock, par value $0.001 per share (the “Common Stock”), and

(ii) 20,000,000 shares of preferred stock, par value $0.001 per share (the “Preferred Stock”).

Common Stock

Dividend Rights

Our Board of Directors (the “Board”) may, from time to time, declare dividends on the Company’s outstanding shares in the manner and upon

the terms and conditions provided by applicable Delaware law and our Certificate of Incorporation. Subject to the rights of holders of Preferred Stock
outstanding at the time, if any, the holders of Common Stock are entitled to receive dividends on a per share basis, if any, when and as may be declared
by the Board out of any Company assets legally available for the payment of dividends.

Liquidation Rights

In the event of liquidation, dissolution or winding up of the Company, and subject to the rights of holders of Preferred Stock outstanding at

the time, if any, the Company’s assets legally available for distribution to stockholders are distributable ratably among holders of Common Stock after
payment of Company liabilities.

Voting Rights

Holders of our Common Stock are entitled to one vote per share of record on matters voted on by the Company’s stockholders, including the
election of directors, subject to applicable Delaware law and our Bylaws and Certificate of Incorporation; provided, however, that except as required
by applicable Delaware law, holders of Common Stock are not entitled to vote on any amendment to our Certificate of Incorporation solely regarding
the terms of any outstanding Preferred Stock series if the holders of such Preferred Stock series are entitled to vote on such amendment under the
Certificate of Incorporation. Cumulative voting is not permitted.

Other Rights and Preferences

Holders of our Common Stock have no subscription, redemption, conversion or exchange rights. No sinking fund provisions are applicable to
our Common Stock. Holders of Common Stock are subject to, and may be adversely affected by, the rights of holders of any series of Preferred Stock
that the Company may designate and issue in the future.

Preferred Stock

Our Board has the authority, from time to time, to issue shares of Preferred Stock in one or more series without further stockholder approval.
Within the limitations and restrictions stated in our Certificate of Incorporation and those prescribed by Delaware law, our Board is authorized to fix or
alter for any series of Preferred Stock the number of shares constituting such series, designation of such series, dividend rights, dividend rate,
conversion rights, voting rights, rights and terms of redemption (including sinking fund provisions), redemption prices and liquidation preferences, and
including the authority to increase or decrease the number of shares of such series subsequent to the share issuance of that series, but not below the
number of shares of such series then outstanding. These and other subjects or matters may be fixed by resolution of our Board. As of December 31,
2021, no shares of Preferred Stock were outstanding.

Anti-Takeover Provisions

Certain provisions of Delaware law and our Certificate of Incorporation and Bylaws contain provisions that could make the following
transactions more difficult: acquisition of the Company by means of a tender offer; acquisition of the Company by means of a proxy contest or
otherwise; or, removal of our incumbent directors and officers. Such provisions are summarized below and are intended to discourage coercive
takeover practices and inadequate takeover bids.

EXHIBIT 4.2

Delaware Law

We are governed by Section 203 of Delaware General Corporation Law (“Section 203”), which regulates takeovers of Delaware corporations.

Subject to exceptions enumerated in Section 203, Section 203 provides that a corporation shall not engage in any business combination with any
“interested stockholder” for a three-year period following the date that the stockholder becomes an interested stockholder unless:

•

Prior to that date, the corporation’s board of directors approved either the business combination or the transaction that resulted in the
stockholder becoming an interested stockholder;

• Upon consummation of the transaction that resulted in the stockholder becoming an interested stockholder, the interested stockholder owned at
least 85% of the voting stock of the corporation outstanding at the time the transaction commenced, though some shares may be excluded from
the calculation; and

• On or subsequent to that date, the business combination is approved by the corporation’s board of directors and by the affirmative votes of

holders of at least two-thirds of the outstanding voting stock that is not owned by the interested stockholder.

Section 203 generally defines an “interested stockholder” as any entity or person who beneficially owns, directly or indirectly, 15% or more

of the corporation’s outstanding voting stock and any entity or person affiliated with, controlling or controlled by such entity or other person.

Under certain circumstances, Section 203 makes it more difficult for an interested stockholder to effect various business combinations with a
corporation for a three-year period, although the corporation’s stockholders may elect not to be governed by Section 203 by adopting an amendment to
the certificate of incorporation or bylaws, effective 12 months after adoption. A Delaware corporation may opt out of the restrictions imposed under
Section 203 with an express provision in either the corporation’s original certificate of incorporation or the corporation’s certificate of incorporation or
bylaws resulting from a stockholders’ amendment approved by at least a majority of the outstanding voting shares. Our Certificate of Incorporation
and Bylaws do not opt out from the restrictions imposed under Section 203.

Certificate of Incorporation and Bylaw Provisions

Our Certificate of Incorporation and Bylaws contain provisions that may have the effect of deterring hostile takeovers or discouraging,

delaying or preventing changes in control, generally including the following:

•

•
•

Preferred Stock Issuance by Board. Our Board may authorize, without further action by stockholders, the issuance of Preferred Stock. Our
Board could authorize the issuance of Preferred Stock with terms and conditions that could have the effect of discouraging a takeover or other
transaction that holders of our Common Stock might believe to be in their best interests or in which holders of our Common Stock might receive
a premium for their shares over the then-market price of those shares.
No Cumulative Voting. Cumulative voting of shares is not permitted in the election of directors.
Staggered Board. Our Board is divided into three classes of equal size. The members of each class are elected to serve a three-year term, with
the term of office of each of the three classes ending in successive years. As a result, successors to directors having expired terms will be elected
to serve from the successor’s time of election and qualification until the third annual meeting following the successor’s election.

• Director Removal. Our Bylaws require that directors may only be removed from office for cause.
•

Board Vacancies. Vacancies on the Board, including newly created directorships, may be filled only by a majority vote of the directors then in
office. These provisions prevent a stockholder from increasing the size of our Board and gaining control of our Board by filling vacancies with
its own nominees.
Special Meeting of Stockholders. Special meetings of stockholders may be called only by (i) the Chairperson of our Board, (ii) our Chief
Executive Officer or (iii) the Board acting pursuant to a resolution adopted by a majority of the total number of authorized directors, regardless
of whether any vacancies then exist.
No Written Consent of Stockholders. Stockholders may not take required or permitted action by written consent and must take any such action at
a duly called annual or special meeting of stockholders.
Advance Notice Requirements for Stockholder Proposals and Director Candidate Nominations. Our Bylaws establish advance notice
requirements and related procedures for stockholders seeking to bring business before the annual meeting of stockholders or to nominate
candidates for election to the Board. These provisions may preclude our stockholders from bringing matters before, or from making nominations
for directors at, our annual meeting of stockholders.
Amendment of Certificate of Incorporation and Bylaws. Generally, a super majority vote of the stockholders then entitled to vote is required to
amend our Certificate of Incorporation or Bylaws, subject to the notice and other requirements in the relevant provisions thereof.

•

Stock Listing

Our Common Stock is listed on The Nasdaq Stock Market under the trading symbol “VNDA”.

Transfer Agent

The transfer agent and registrar for our Common Stock is American Stock Transfer & Trust Company, LLC (“AST”).

CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS BOTH
NOT MATERIAL AND IS OF THE TYPE THAT VANDA TREATS AS PRIVATE OR CONFIDENTIAL

EXHIBIT 10.12

Manufacturing Agreement

January 24, 2014

Table of Contents

ARTICLE 1

INTERPRETATION

1.1 Definitions.

1.2 Currency.

1.3 Sections and Headings.

1.4 Singular Terms.

1.5 Schedules.

ARTICLE 2

PATHEON’S MANUFACTURING

2.1 Manufacturing.

2.2 Active Material Yield.

ARTICLE 3

CLIENT’S OBLIGATIONS

3.1 Payment.

3.2 Supply of Active Materials.

ARTICLE 4

CONVERSION fees AND COMPONENT COSTS

4.1 Pricing.

4.2 Price Adjustments - Subsequent Years’ Pricing.

4.3 Price Adjustments – Current Year Pricing.

4.4 Adjustments Due to Technical Changes.

4.5 Multi-Country Packaging Requirements.

4.6 Improvement of Manufacturing Efficiency.

ARTICLE 5

ORDERS, SHIPMENT, INVOICING, PAYMENT

5.1 Orders and Forecasts.

5.2 Reliance by Patheon.

5.3 Minimum Orders.

5.4 Shipments.

5.5 On Time Delivery.

5 6

Invoices and Payment

5.6 Invoices and Payment.

ARTICLE 6

PRODUCT CLAIMS AND RECALLS

6.1 Product Claims.

6.2 Product Recalls and Returns.

6.3 Patheon’s Responsibility for Defective and Recalled Products.

6.4 Disposition of Defective or Recalled Products.

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6.5 Customer Questions and Complaints.

6.6 ****.

ARTICLE 7

CO-OPERATION

7.1 Quarterly Review.

7.2 Governmental Agencies.

7.3 Records and Accounting by Patheon.

7.4 Inspection.

7.5 Access.

7.6 Notification of Regulatory Inspections.

7.7 Reports.

7.8 FDA Filings.

ARTICLE 8

TERM AND TERMINATION

8.1 Initial Term.

8.2 Termination for Cause.

8.3 Obligations on Termination.

ARTICLE 9

REPRESENTATIONS, WARRANTIES AND COVENANTS

9.1 Authority.

9.2 Client Warranties.

9.4 Debarred Persons.

9.5 Permits.

9.6 No Warranty.

ARTICLE 10

REMEDIES AND INDEMNITIES

10.1 Consequential Damages.

10.2 Limitation of Liability.

10.3 Patheon.

10.4 Client.

10.5 Reasonable Allocation of Risk.

ARTICLE 11

CONFIDENTIALITY

11.1 Confidentiality.

ARTICLE 12

DISPUTE RESOLUTION

12.1 Commercial Disputes.

12.2 Technical Dispute Resolution.

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12.3 Arbitration.

12.4 Dispute and Termination for Breach.

ARTICLE 13

MISCELLANEOUS

13.1 Inventions.

13.2 Intellectual Property.

13.3 Insurance.

13.4 Independent Contractors.

13.5 No Waiver.

13.6 Assignment.

13.7 Force Majeure.

13.8 Additional Product.

13.9 Notices.

13.10 Severability.

13.11 Entire Agreement.

13.12 Other Terms.

13.13 No Third Party Benefit or Right.

13.14 Execution in Counterparts.

13.15 Governing Law.

SCHEDULE A

SCHEDULE B

SCHEDULE C

SCHEDULE D

SCHEDULE E

SCHEDULE F

SCHEDULE G

SCHEDULE H

SCHEDULE I

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MANUFACTURING AGREEMENT

Date”)

THIS MANUFACTURING AGREEMENT (the “Agreement”) is made as of January 24, 2014 (the “Effective

B E T W E E N:

PATHEON PHARMACEUTICALS INC.,
a corporation existing under the laws of the State of Delaware in the United States of America,

(hereinafter referred to as “Patheon”),

- and -

VANDA PHARMACEUTICALS INC.,
a corporation existing under the laws of the State of Delaware in the United States of America,

(hereinafter referred to as the “Client”).

THIS AGREEMENT WITNESSES THAT in consideration of the rights conferred and the obligations assumed
herein, and for other good and valuable consideration (the receipt and sufficiency of which are acknowledged by each party), and
intending to be legally bound the parties agree as follows:

ARTICLE 1

INTERPRETATION

1.1

Definitions.

The following terms shall, unless the context otherwise requires, have the respective meanings set out below and

grammatical variations of such terms shall have corresponding meanings:

“Active Materials” means the materials listed on Schedule D hereto;

“Active Materials Credit Value” means the value to be attributed to the Active Materials for certain purposes of this
Agreement, as set forth on Schedule D;

“Actual Annual Yield” or “AAY” has the meaning specified in Section 2.2(a);

“Affiliate” means:

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(a)

(b)

(c)

a business entity which owns, directly or indirectly, a controlling interest in a party to this Agreement, by stock
ownership or otherwise, only for so long as such ownership continues to exist; or

a business entity which is controlled by a party to this Agreement, either directly or indirectly, by stock ownership or
otherwise, only for so long as such control continues to exist; or

a business entity, the controlling interest of which is directly or indirectly common to the majority ownership of a party
to this Agreement, only for so long as such controlling interest continues to exist;

For the purposes of this definition, “control” means the ownership of shares carrying at least a majority of the votes in respect
of the election of the directors of a corporation.

“Agreement” has the meaning specified in the preamble;

“Annual Report” means the annual report to the FDA prepared by Client as described in Title 21 of the United States Code
of Federal Regulations, Section 314.81(b)(2);

“Annual Product Review Report” means the annual product review report as described in Title 21 of the United States
Code of Federal Regulations, Section 211.180(e);

“Annual Volume” means the minimum volume of Product estimated to be manufactured in any Year of this Agreement as set
forth in Schedule B hereto, which shall be prorated for the first Year of this Agreement;

“Applicable Laws” means (i) with respect to Patheon, the Laws of the State of Ohio and the United States, being the
jurisdiction where the Manufacturing Site is located; and (ii) with respect to Client, the applicable Laws of all jurisdictions
where the Products are manufactured, distributed and marketed;

“Authority” means any governmental or regulatory authority, department, body or agency or any court, tribunal, bureau,
commission or other similar body, whether federal, state, provincial, county or municipal;

“Bill Back Items” means the expenses for all third party supplier fees for the purchase or use of columns, standards, tooling,
non-standard pallets, PAPR or PPE suits (where applicable), RFID tags and supporting equipment, and other project-specific
items necessary for Patheon to perform the Manufacturing Services, and which are not included as Components;

“Breach Notice” has the meaning specified in Section 8.2(a);

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“Broader Intellectual Property Rights” has the meaning specified in Section 13.1(c);

“Business Day” means a day other than a Saturday, Sunday or a day that is a statutory holiday in the State of Ohio (with
respect to Patheon only) or a day that is a statutory holiday in Washington, D.C. (with respect to Client only);

“cGMPs” means current good manufacturing practices, regulations and guidelines as described in:
(a) Division 2 of Part C of the Food and Drug Regulations (Canada);

(b) Parts 210 and 211 of Title 21 of the United States’ Code of Federal Regulations; and

together with the latest Health Canada, FDA and EMA guidance documents pertaining to manufacturing and quality control
practice, all as updated, amended and revised from time to time;

“Client Property” has the meaning specified in Section 8.3(d);

“CMC” has the meaning specified in Section 7.8(c);

“Components” means, collectively, all packaging components, raw materials and ingredients (including labels, product
inserts and other labelling for the Products), required to be used in order to produce the Products in accordance with the
Specifications, other than the Active Materials;

“Confidentiality Agreement” means the agreement relating to the non-disclosure of confidential information between
Patheon and the Client dated February 28, 2006 as amended September 28, 2009 and February 7, 2013.

“Conforming” with respect to Product, means Product manufactured, packaged and stored by Patheon in accordance with the
Specifications, cGMPs, Applicable Laws, the Quality Agreement and this Agreement.

“Deficiencies” has the meaning specified in Section 7.8(d);

“Deficiency Notice” shall have the meaning ascribed thereto in Section 6.1(a);

“Delivery Date” has the meaning specified in Section 5.1(b);

“Disclosure Obligations” has the meaning set forth in Section 11.1;

“Effective Date” has the meaning specified in the preamble;

“EMA” means the European Medicines Agency;

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“FDA” means the United States government department known as the Food and Drug Administration;

“Firm Order(s)” has the meaning specified in Section 5.1(b);

“Force Majeure Event” has the meaning specified in Section 13.7;

“Health Canada” means the section of the Canadian Government known as Health Canada and includes, among other
departments, the Therapeutic Products Directorate and the Health Products and Food Branch Inspectorate;

“Initial Term” has the meaning specified in Section 8.1;

“Intellectual Property” includes, without limitation, rights in patents, patent applications, formulae, trade-marks, trade-mark
applications, trade-names, Inventions, copyright and industrial designs and all other intellectual and industrial property rights
of any sort throughout the world now known or hereafter recognized;

“Invention” means any idea, concept, innovation, improvement, development, discovery, technology, computer program,
device, trade secret, work of authorship, formula, compound, method, know-how, process, technique or the like, whether or
not written or otherwise fixed in any form or medium, regardless of the media on which it is contained and whether or not
patentable or copyrightable, that is conceived or reduced to practice by one or more person(s) in the course of the
performance of this Agreement;

“Inventory” means all inventories of Components and work-in-process produced or held by Patheon for the manufacture of
the Products but, for greater certainty, does not include the Active Materials;

“JAMS” means Judicial Arbitration and Mediation Services, Inc.;

“Laws” means all laws, statutes, ordinances, regulations, rules, by-laws, judgments, decrees or orders of any Authority;

“Manufacture or Manufacturing “ means any one of more of the manufacturing, quality control, quality assurance and
stability testing, packaging and related services, as contemplated in this Agreement, required to produce Products from Active
Materials and Components;

“Manufacturing Site” means the facility owned and operated by Patheon that is located at 2110 E Galbraith Rd, Cincinnati,
OH 45237;

“Maximum Credit Value” means the maximum value of Active Materials that may be credited by Patheon pursuant to this
Agreement, as set forth on Schedule D;

“Minimum Order Quantity” means the minimum number of units of a Product to be ordered in order to obtain the Price as
set forth in Schedule B hereto.

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“MSDS” has the meaning specified in Section 5.2;

“Order Countries” means, collectively, all countries in the Territory for which Client places Orders hereunder;

“Patheon Requirement” has the meaning specified in 2.1(h);

“Packaged Product(s)” means Product(s) packaged into primary and (where applicable) secondary packaging Components,
including printed packaging Components where specified;

“PPI” has the meaning specified in Section 4.2(a);

“Product(s)” means the products listed on Schedule A hereto;

“Product Claims” has the meaning specified in Section 6.3(c);

“Quality Agreement” means the agreement dated August 22, 2013 between the parties hereto setting out the quality
assurance standards to be applicable to the Manufacturing performed by Patheon, which agreement is attached hereto as
Schedule G;

“Recall” has the meaning specified in Section 6.2(a);

“Regulatory Authority” means the FDA, EMEA and Health Canada and any other foreign regulatory agencies competent to
grant marketing approvals for pharmaceutical products including the Products in the Territory;

“Remediation Period” has the meaning specified in Section 8.2(a);

“SEC” has the meaning set forth in Section 11.1;

“Specifications” means the file, for each Product, which is provided by the Client to Patheon in accordance with the
procedures listed in Schedule A hereto and which contains documents relating to such Product, including, without limitation:

(a)

specifications for Active Materials and Components;

(b) Manufacturing specifications, directions and processes;

(c)

storage requirements;

(d) all environmental, health and safety information relating to the Product including material safety data sheets; and

(e) the finished Product specifications, packaging specifications and shipping requirements for each Product;

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all as updated, amended and revised from time to time by the Client in accordance with the terms of this Agreement;

“Target Yield” has the meaning specified in Section 2.2(a);

“Target Yield Determination Batches” has the meaning specified in Section 2.2(a);

“Technical Dispute” has the meaning specified in Section 12.2;

“Territory” means in the geographic area of the United States of America;

“Third Party Rights” means the Intellectual Property of any third party;

“Wind-Down Period” has the meaning specified in Section 8.3(d);

“Year” means in the first year of this Agreement the period from the Effective Date up to and including December 31 of the
same calendar year, and thereafter shall mean a calendar year.

1.2

Currency.

Unless otherwise indicated, all monetary amounts are expressed in this Agreement in the lawful currency of the United

States of America.

1.3

Sections and Headings.

The division of this Agreement into Articles, sections, subsections and Schedules and the insertion of headings are for
convenience of reference only and shall not affect the interpretation of this Agreement. Unless otherwise indicated, any reference
in this Agreement to a Section or Schedule refers to the specified Section or Schedule to this Agreement. In this Agreement, the
terms “this Agreement”, “hereof”, “herein”, “hereunder” and similar expressions refer to this Agreement and not to any
particular part, Section, Schedule or the provision hereof, and unless the context of this Agreement otherwise requires, “include”,
“includes” and “including” are not limiting.

1.4

Singular Terms.

Except as otherwise expressly provided herein or unless the context otherwise requires, all references to the singular shall

include the plural and vice versa.

1.5

Schedules.

The following Schedules are attached to, incorporated in and form part of this Agreement:

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Schedule A Product List
Schedule B Commercial Pricing
Schedule C Stability Testing
Schedule D Active Materials, Active Materials Credit Value & Maximum Credit Value
Schedule E Batch Numbering & Expiration Dates
Schedule F - Technical Dispute Resolution
Schedule G - Quality Agreement
Schedule H - Quarterly Active Materials Inventory Report
Schedule I - Report of Annual Active Materials Inventory Reconciliation and Calculation of Actual Annual

Yield

2.1 Manufacturing.

ARTICLE 2

PATHEON’S MANUFACTURING

(a)

(b)

Conversion of Active Materials and Components. Patheon shall convert Active Materials and Components into
Products.

Quality Control and Quality Assurance. Patheon shall perform the quality control and quality assurance testing
specified in the Quality Agreement. Batch review and release to the Client shall be the responsibility of Patheon’s
quality assurance group. Patheon shall perform its batch review and release responsibilities in accordance with
Patheon’s standard operating procedures. Upon the Client’s request, Client may review Patheon’s standard
operating procedures at Patheon’s facility. Each time Patheon ships Products to the Client, it shall provide the
Client, in English, a certificate of analysis and certificate of compliance including a statement that the batch has
been manufactured and tested in accordance with Specifications and cGMPs. The Client will have sole
responsibility for the release of Products to the market.

(c)

Components. Patheon shall purchase all Components (with the exception of those that are supplied by the Client,
which for certainty excludes Active Materials), in accordance with the Specifications. Patheon shall test all
Components and Active Materials in accordance with the Specifications.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(d)

(e)

(f)

Stability Testing. Patheon shall conduct stability testing on the Products in accordance with the protocols set out in
Schedule C for the separate fees specified in Schedule C. Patheon shall not make any changes to these testing
protocols without prior written approval from the Client. In the event of a confirmed stability test failure, Patheon
will notify the Client within ****, after which Patheon and the Client shall jointly determine the proceedings and
methods to be undertaken to investigate the causes of such failure, including which party shall bear the cost of
such investigation; ****. Patheon will promptly provide any and all data and results relating to the stability testing
upon request by the Client.

Packaging. Patheon shall package the Products as set out in the Specifications. The Client shall be responsible for
the cost of artwork development. Patheon shall make arrangements for and implement the imprinting of batch
numbers and expiration dates for each Product shipped. Such batch numbers and expiration dates shall be affixed
on the Products and on the shipping carton of each Product as outlined in the Specifications and as required by
cGMPs. The system used by Patheon for batch numbering and expiration dates is detailed in Schedule E hereto.
The Client may, in its sole discretion, make changes to labels, product inserts and other packaging for the
Products, which changes shall be submitted by the Client to all applicable governmental agencies and other third
parties responsible for the approval of the Products. The Client shall be responsible for the cost of labelling
obsolescence when changes occur, as contemplated in Section 4.4. Patheon’s name shall not appear on the label or
anywhere else on the Products unless: (i) required by any applicable Laws; or (ii) Patheon expressly consents to
such use of its name in writing.

Active Materials and Client Supplied Components. Client will **** deliver the Active Materials and any Client-
supplied Components to the Manufacturing Site DDP (Incoterms 2010) at least **** before the scheduled
production date, at no cost to Patheon, in sufficient quantity to enable Patheon to manufacture the desired
quantities of Product and to ship Product on the Delivery Date. If the Active Materials and/or Client-supplied
Components are not received at least **** before the scheduled production date, Patheon will make commercially
reasonable efforts to expedite analytical testing at the Client’s expense to maintain the scheduled production date.
If the Active Materials and/or Client-supplied Components are not received at least **** before the scheduled
production date and expedited release cannot be accomplished to maintain the scheduled production date (after use
of commercially reasonable efforts by Patheon), Patheon may ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****.****. All shipments of Active Materials will be accompanied by certificate(s) of analysis from the Active
Materials manufacturer and the Client, confirming the identity and purity of the Active Materials and its compliance with
the Active Materials specifications.

(g)

(h)

Bill Back Items. The expenses in respect of all third party supplier fees for the purchase of those items specifically
identified in Schedule B that are necessary for Patheon to perform the Manufacturing (or which are not included as
Components or part of the Manufacturing fees in Schedule B), shall be charged to the Client ****. Any invoices
for such items shall include reasonable documentation of the costs of such items. Any and all orders in excess of
**** for any such items require the prior written approval of the Client.

Requirements. Client hereby agrees to order **** of its total Yearly requirement in the Order Countries for new
units of Products **** (the “Patheon Requirement”) from Patheon. However, Client may order the Patheon
Requirement, in whole or in part, from a third party supplier if Patheon ****. In addition, ****. Notwithstanding
the foregoing, Patheon acknowledges and agrees that **** shall not be counted in determining Client’s “total
Yearly requirement in the Order Countries for new units of Products” (i.e., Client may ****). For the sake of
clarity, during those Years in which Client orders Product from a third party supplier in accordance with the terms
in this subsection, then in no event shall Client be deemed to be in breach of this Section 2.1(h) if it does not
purchase **** of its total Yearly requirement for new units of Products in the Order Countries from Patheon.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(i)

(j)

Product Rejection for Finished Product Specification Failure. Patheon shall manufacture Product in accordance
with agreed upon Specifications, including Specifications for Patheon’s internal process. If Patheon manufactures
Product in accordance with the such Specifications, the batch production record, Patheon’s standard operating
procedures for manufacturing (including, without limitation, for cleaning and calibration), all applicable laws, this
Agreement and the Quality Agreement, and **** Client will pay Patheon ****. The API in the non-conforming
Product will ****.

Patheon shall maintain and service all equipment that Client has authorized Patheon to purchase on Client’s
behalf, such equipment to be returned promptly by Patheon to Client in good working order, reasonable wear and
tear excepted, following the termination or expiration of this Agreement. Unless otherwise agreed in a separate
written equipment agreement, Patheon shall not use all or any part of such equipment for any purpose other than
supplying Product to Client under this Agreement.

2.2.

Active Material Yield.

(a) Reporting. Patheon shall provide the Client with a quarterly inventory report of the Active Materials supplied by
Client (if applicable) and held by Patheon in accordance with the inventory report form annexed hereto as Schedule H, which
shall contain the following information for such quarter:

Quantity Received: The total quantity of Active Materials that complies with the Specifications and is received at the
Manufacturing Site during the applicable period.

Quantity Dispensed: The total quantity of Active Materials dispensed at the Manufacturing Site during the applicable
period. The Quantity Dispensed is calculated by adding the Quantity Received to the inventory of Active Materials that
complies with the Specifications and is held at the beginning of the applicable period, less the inventory of Active
Materials that complies with the Specifications and is held at the end of such period. The Quantity Dispensed shall only
include Active Materials received and dispensed in connection with commercial manufacturing of any Products and, for
certainty, shall not include any (i) Active Materials that must be retained by Patheon as samples, (ii) Active Materials
contained in any Product that must be retained as samples, (iii) Active Materials used in connection with testing (if
applicable) and (iv) Active Materials received or dispensed in connection with technical transfer activities or development
activities during the applicable period, including, without limitation, any regulatory, stability, validation or test batches
manufactured during the applicable period.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 10 -

Quantity Converted: The total amount of Active Materials contained in the Products produced with the Quantity
Dispensed (including any additional Products produced in accordance with Section 6.1 or 6.2 or 6.3), delivered by
Patheon, and not rejected, recalled or returned in accordance with Section 6.1 or 6.2 as a result of a failure by Patheon to
provide Manufacturing in accordance with Specifications, cGMPs, Applicable Laws, the Quality Agreement or this
Agreement.

Patheon will target within ****, but within no more than **** after the **** of each ****, Patheon shall prepare an annual
reconciliation of Active Materials in accordance with the reconciliation report form annexed hereto as Schedule I including the
calculation of the “Actual Annual Yield” or “AAY” for the Products (including all strengths) at the Manufacturing Site during
the Year. AAY is the percentage of the Quantity Dispensed that was converted to Products and is calculated as follows:

Quantity Converted during the Year x 100%
Quantity Dispensed during the Year

After ****, the Parties will mutually agree on the target yield in respect of the Products at the Manufacturing Site (a “Target
Yield”); provided, however, that ****. Thereafter, Patheon shall strive to maintain Actual Annual Yield levels for the Products
equal to or above the Target Yield. For the sake of clarity, if applicable, the AAY and the Target Yield are each calculated for
****.

(b) Shortfall Calculation. If the Actual Annual Yield falls **** below the respective Target Yield in a Year, then the

shortfall for such Year (the “Shortfall”) shall be determined based on the following calculation:

The Shortfall shall be disclosed by Patheon on the reconciliation report prepared in the form annexed hereto as Schedule I.

(c) Credit. If there is a Shortfall for the Products in a Year, then Patheon shall credit the Client’s account for the value of

any such Shortfall, as determined using the following formula, not later than **** after the end of each Year.

Shortfall = ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****

Patheon acknowledges that such credit is a liquidated damage reflecting a reasonable measure of actual damages and is not a
penalty. Each credit under this Section 2.2 shall be summarized on the reconciliation report prepared in the form annexed hereto
as Schedule I and shall be made not later than **** after the end of each Year. Upon expiration or termination of this Agreement
any remaining credit amount owing under this Section 2.2 (or other Section under this Agreement) shall be reimbursed to the
Client by payment thereof to the Client.

(d) ****. Notwithstanding the foregoing provisions of this Section 2.2, Patheon’s liability for Active Materials

calculated in accordance with Section 2.2(c) for the Products in a Year ****.

(e) No Material Breach. It shall not constitute a material breach of this Agreement by Patheon, for the purposes of

Section 8.2(a), if ****.

ARTICLE 3

CLIENT’S OBLIGATIONS

3.1

Payment.

Pursuant to the terms of this Agreement, the Client shall pay Patheon for the provision of the Manufacturing according to

the fees specified in Schedules B and C hereto (such fees being subject to adjustment in accordance with the terms hereof).

3.2

Supply of Active Materials.

Client shall, at its sole cost and expense, deliver the Active Materials to Patheon (in accordance with Section 2.1(f)) in
sufficient quantities and at such times as mutually agreed upon by the parties to facilitate the provision of the Manufacturing by
Patheon. Client’s obligation will include obtaining the proper release of the Active Materials from the applicable Customs
Agency and Regulatory Authority. Client or Client’s designated broker will be the “Importer of Record” for Active Materials
imported to the Manufacturing Site. The Active Materials shall be held and stored by Patheon on behalf of the Client on the terms
and subject to the conditions herein contained, the Specifications, cGMPs and any written instructions provided by the Client to
Patheon from time to time. Title to the Active Materials shall at all times belong to and remain the property of the Client. Any
Active Materials received by Patheon shall only be used by Patheon to provide the Manufacturing. Patheon will not chemically or
biologically modify the Active Materials except in accordance with the Specifications. Patheon’s liability with respect to any lost
or damaged Active Materials shall be as set forth in Section 10.2(a).

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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If Client asks Patheon to qualify an additional source for the Active Material or any Component, Patheon will evaluate the
Active Material or Component to be supplied by the additional source to determine if it is suitable for use in the Product. The
parties will agree on the scope of work to be performed by Patheon at Client’s cost. For an Active Material, this work at a
minimum will include:

(a)

(b)

(c)

laboratory testing to confirm the Active Material meets existing specifications;

manufacture of an experimental batch of Product that will be placed on **** accelerated stability; and

manufacture of **** full-scale validation batches that will be placed on concurrent stability (one batch may be the
registration batch if manufactured at full scale).

Section 2.1(i) will apply to all Product manufactured using the newly approved Active Material or Component because of

the limited material characterization that is performed on additional sources of supply.

ARTICLE 4

CONVERSION FEES AND COMPONENT COSTS

4.1

Pricing.

The fees for the Manufacturing through **** are listed in Schedules B and C and are subject to the adjustments set forth

in Section 4.3.

4.2

Price Adjustments - Subsequent Years’ Pricing.

The fees for the Manufacturing during any period following the **** shall be determined in accordance with the

following:

(a)
Manufacturing and Component Costs. On each **** of this Agreement, Patheon and the Client shall be entitled to
an adjustment to the fees (i) for Manufacturing in respect of the Products to reflect inflation, which adjustment shall be
solely based on ****, unless the parties otherwise agree in writing and (ii) for Component costs ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(b)

Annual Quantity.

The Client acknowledges that the fee for Manufacturing in respect of a Product in any Year is quoted based upon the
Annual Volume and Minimum Order Quantity per Product specified in Schedule B and is subject to change following
good faith discussions by the parties if the specified Annual Volume or Minimum Order Quantity increases or decreases.
For greater certainty, if Patheon and the Client agree that the Annual Volume or Minimum Order Quantity in respect of a
Product shall be reduced beyond the range of such values provided in the tables in Schedule B, whether as a result of a
decrease in estimated annual volume or otherwise, and, as a result of such reduction, Patheon’s costs for services relating
to such Product increase on a per unit basis, then Patheon shall be entitled to an increase in the fee for Manufacturing in
respect of such Product. In addition, for greater certainty, if Patheon and the Client agree that the Annual Volume or
Minimum Order Quantity in respect of a Product shall be increased beyond the range of such values provided in the tables
in Schedule B, and, as a result of such increase, Patheon’s costs for services relating to such Product decrease on a per
unit basis, then the Client shall be entitled to a decrease in the fee for Manufacturing in respect of such Product.

In connection with all fee adjustments requests pursuant to this Section 4.2, Patheon shall deliver to the Client by not later than
**** of each **** a revised Schedule B in draft form and such budgetary pricing information or other documentation reasonably
sufficient to demonstrate that an increase or decrease in the fee adjustment is justified (and/or upon the reasonable request of
Client, such budgetary pricing information or other documentation reasonably sufficient to demonstrate to Client that a decrease
in the fee adjustment is not justified), provided that to the extent such documents are subject to obligations of confidentiality
between Patheon and its suppliers, Patheon shall make such documents available, subject to the confidentiality obligations
provided in this Agreement, to a third party designated by Client and approved by Patheon (such approval not to be unreasonably
withheld or delayed) at Patheon’s facility for the purpose of allowing such third party to confirm that the fee adjustments
proposed by Patheon are justified. Upon delivery of such a fee adjustment request pursuant to this Section, each of the Client and
Patheon shall forthwith use reasonable efforts to agree on a revised fee for the Manufacturing in respect of each affected Product,
if any, and Schedule B shall be amended accordingly. If the parties are unable to agree on a revised fee for the Manufacturing in
respect of each affected Product within **** after receipt by Client of Patheon’s fee adjustment request, then ****. The revised
fee shall be effective with respect to any Product ordered after the end of the then current ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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4.3

Price Adjustments – Current Year Pricing.

During any Year of this Agreement, the fees set out in Schedule B shall be subject to adjustment in accordance with the

following:

(a)
Annual Quantity. If at any time and from time to time Patheon or Client determines, acting reasonably and based
on the forecasts and Firm Orders received from the Client, that the current Annual Volume or Minimum Order Quantity
listed in Schedule B for each specific Product strength will either not be met or will be exceeded (i.e., the actual Minimum
Order Quantity and/or the actual Annual Volume, and the costs of such variations, exceed the range of such value(s)
provided in the tables in Schedule B), then Patheon or Client shall be entitled to request an adjustment to the fee for
Manufacturing in respect of that Product to reflect the increased or decreased costs that Patheon will incur as a result of
the increased or reduced volumes beyond the range of such values provided in the tables in Schedule B. To the extent that
the fee for Manufacturing in respect of a Product has been previously adjusted pursuant to this clause (a) to reflect
reduced volumes or increased volumes, the adjustment provided in this clause (a) shall operate based on the fees
attributed to such Product at the time the last of such adjustments were made.

(b)
Extraordinary Increase in Component Costs. If at any time market conditions result in Patheon’s cost of
Components being **** greater than normal forecasted increases, then Patheon shall be entitled to an adjustment to the
fee for Manufacturing in respect of any affected Product solely to compensate it for such increased Component costs that
may be justified by reasonable documentation, provided that to the extent such documents are subject to obligations of
confidentiality between Patheon and its suppliers, Patheon shall make such documents available, subject to the
confidentiality obligations provided in this Agreement, to a third party designated by Client and approved by Patheon
(such approval not to be unreasonably withheld or delayed) at Patheon’s facility for the purpose of allowing such third
party to confirm that the fee adjustments proposed by Patheon are justified. For the purposes of this clause (b), changes
materially greater than normal forecasted increases shall be considered to have occurred only if ****. To the extent that
Component costs have been previously adjusted pursuant to clause (a) of Section 4.2 or this clause (b) to reflect an
increase in the cost of one or more Components, the adjustments provided for in (i) and (ii) above shall operate based on
the costs attributed to such Component (or Components) at the time the last of such adjustments were made.

In connection with a fee adjustment request pursuant to this Section 4.3, Patheon shall deliver to the Client a revised
Schedule B and such budgetary pricing information, adjusted Component costs or other documentation reasonably
sufficient to demonstrate that an increase or decrease in fee adjustment is justified

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(and/or upon the reasonable request of Client, such budgetary pricing information or other documentation reasonably
sufficient to demonstrate to Client that a decrease in the fee adjustment is not justified), provided that to the extent such
documents are subject to obligations of confidentiality between Patheon and its suppliers, Patheon shall make such
documents available, subject to the confidentiality obligations provided in this Agreement, to a third party designated by
Client and approved by Patheon (such approval not to be unreasonably withheld or delayed) at Patheon’s facility for the
purpose of allowing such third party to confirm that the fee adjustments proposed by Patheon are justified. Upon delivery
of such a request, each of the Client and Patheon shall forthwith use all reasonable efforts to agree on a revised fee for the
Manufacturing in respect of each affected Product and Schedule B shall be amended accordingly. If the parties are unable
to agree on a revised fee for the Manufacturing in respect of each affected Product within **** after receipt by Client of
Patheon’s fee adjustment request, then ****.

Patheon will use commercially reasonable efforts to ensure that the increases in cost of Components will not be materially
greater than normal forecasted increases.

4.4

Adjustments Due to Technical Changes.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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any revised Specifications or Quality Agreement that were placed by Patheon with suppliers in order to fill Firm Orders or in
accordance with Section 5.2 shall be cancelled or used in connection with other Patheon services where possible, and where such
orders are not subject to cancellation without penalty or cannot be used in connection with other Patheon services, Client shall
pay to Patheon ****.

4.5 Multi-Country Packaging Requirements.

Prices in Schedule B are for Packaged Product(s) for the specific markets in the Territory requested by Client. Should
Client wish to have Patheon provide Manufacturing in respect of the Product for countries in addition to those countries listed in
Schedule B, then the Client shall inform Patheon of the packaging requirements for each new country and Patheon shall, in good
faith, prepare a quotation for consideration by the Client of the additional Component costs, if any, and the change over fees for
the Product destined for each such new country. The agreed additional packaging requirements and related packaging costs and
change over fees shall be set out in a written amendment to this Agreement mutually agreed upon by the parties.

4.6

Improvement of Manufacturing Efficiency.

Each of Patheon and the Client shall use its reasonable efforts to improve Product manufacturing efficiency, when and
where possible, during the term of this Agreement. Any cost savings resulting in whole or in part from contributions by the Client
shall be ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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ARTICLE 5

ORDERS, SHIPMENT, INVOICING, PAYMENT

5.1

Orders and Forecasts.

(a)

Rolling Forecasts. Concurrent with the execution of this Agreement, the Client shall provide Patheon with a
written **** forecast of the volume of each Product that the Client then anticipates will be required to be produced and delivered
to the Client during ****. Such forecast will be updated by the Client **** on or before the **** of each **** on a ****, and the
Client shall use commercially reasonable efforts to update such forecast forthwith if the Client determines that the volumes
contemplated in the most recent of such forecasts for the next **** have changed by more than ****. The most recent ****
forecast shall prevail.

(b)

Firm Orders. On or before the **** of each ****, the Client shall issue a firm written order (“Firm Order”) for
Manufacturing in respect of the Products to be produced and delivered to the Client on one or more dates not less than**** from
the first day of the calendar month immediately following the date that the Firm Order is submitted (each, a “Delivery Date”).
Such Firm Orders submitted to Patheon shall specify the Client’s Manufacturing purchase order number, quantities by Product
type, monthly delivery schedule, shipment location and any other elements necessary to ensure the timely production and
shipment of the Products. The quantities of Products ordered in such Firm Orders shall be ****. If Client cancels any or part of a
Firm Order, Client shall be responsible for **** of such cancelled part of a Firm Order, provided that if Client informs Patheon at
any time during the **** of this Agreement, at **** prior to the Delivery Date of any Firm Order, that it would like to cancel any
or part of such Firm Order, then ****. ****. Patheon shall indicate its acceptance of Firm Orders for the Product by promptly
acknowledging acceptance of each Firm Order in writing within **** of its receipt; each such acceptance shall include, subject to
Client confirmation, the Delivery Date for the Product ordered. The agreed upon Delivery Date may be amended from time to
time by written agreement of the parties, with the newly agreed upon date becoming the new Delivery Date. For the avoidance of
doubt, Patheon will accept all Firm Orders submitted by the Client for Product so long as ****. ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****. All Firm Orders will be deemed to incorporate all of the terms and conditions in this Agreement.

(c)

**** Forecast. On or before the **** of **** of each ****, the Client shall provide Patheon with a written ****
forecast (broken down by ****) of the volume of each Product the Client then anticipates will be required to be produced and
delivered to the Client during the ****.

5.2

Reliance by Patheon.

The Client understands and acknowledges that Patheon will rely on the Firm Orders and rolling forecasts submitted
pursuant to Sections 5.1(a) and (b) in ordering the Components required to meet such Firm Orders. In addition, the Client
understands that to ensure an orderly supply of such Components and/or to achieve economies of scale in costs, it may be
necessary for Patheon to purchase such Components in sufficient volumes to meet the production requirements for Products
during part of the forecasted periods referred to in Section 5.1(a) or to meet the production requirements of any longer period
agreed to in writing by Patheon and the Client. Accordingly, the Client authorizes Patheon to purchase Components in order to
satisfy the Manufacturing requirements for Products for the **** contemplated in the most recent forecast provided by the Client
pursuant to Section 5.1(a) and agrees that Patheon may make such other purchases of Components to meet Manufacturing
requirements during such longer periods as may be agreed to in writing from time to time by the Client at the request of Patheon
or the Client. If Components of the Product unique to the Client (e.g., packaging labels), ordered by Patheon pursuant to Firm
Orders or this Section 5.2 are not included in finished Products manufactured for the Client within **** after the forecasted
month in respect of which such purchases have been made (or such longer period as the parties may agree) or if such unique
Components have expired during such period, then the Client shall pay to Patheon ****. Patheon shall be responsible for
obtaining material safety data sheets (“MSDS”) of all Components purchased by Patheon pursuant to this Agreement. The MSDS
will be used to establish conformance of the Components to the Specifications and to advise Patheon as to any safety or special
handling requirements related to the Components.

5.3 Minimum Orders.

The Client may only order Manufacturing in respect of batches of Products in multiples of the Minimum Order Quantities

as set out in Schedule B.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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5.4

Shipments.

Shipments of Products shall be made ****, unless otherwise mutually agreed in writing. Risk of loss or of damage to
Products shall remain with **** at which time risk of loss or damage (and title to such Products) shall transfer to ****. ****
shall, in accordance with ****, (i) arrange for shipping to be paid by **** and (ii) at **** risk and expense, obtain any export
license or other official authorization necessary to export the Products. **** shall arrange for insurance and shall select the
freight carrier to be used by **** to ship Products and may monitor **** shipping and freight practices as they pertain to this
Agreement. Products shall be packaged for transport and transported in accordance with the Specifications.

5.5

On Time Delivery.

(a)

Patheon shall ****. Patheon and the Client understand that there may be uncertainties and necessary adjustments
associated with any initial manufacturing period and the parties agree that they will work together closely to expedite deliveries
and manage the scheduling of the initial Product launch.

(b)

If subsequent to the creation of a delivery plan, Patheon is unable to supply the Client with the quantity of Product
ordered pursuant to the Firm Order by **** following the Delivery Date ****, then that inability to supply will constitute a late
delivery of Product (“Late Delivery”), and the Client ****. If the parties mutually agree in writing to change the Delivery Date
for any reason, then that new date becomes the Delivery Date.

****. In no event shall the Late Delivery ****. Patheon acknowledges that ****. No credit for Late Delivery will occur if the
Late Delivery is caused by a Force Majeure Event (as defined below) or by other events outside of Patheon’s reasonable control,
including, but not limited to, delays in: ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 20 -

****. Additionally, on time delivery credits provided for in this Section are only available to Client if ****.

5.6

Invoices and Payment.

Invoices shall be sent by fax or email to such fax number or email address as may be provided by the Client in writing from time
to time. Such invoices for Products may only be sent **** (with respect to which such invoices apply) in accordance with the
Quality Agreement, and such invoices shall reflect any outstanding credit amounts owed under this Agreement by Patheon to
Client. Patheon shall also submit to the Client, with each shipment of Products, a duplicate copy of the invoice covering such
shipment. Patheon shall also provide the Client with an invoice covering any Inventory or Components which are to be purchased
by Patheon pursuant to the terms of this Agreement. Each such invoice shall, to the extent applicable, identify the Client’s
Manufacturing purchase order number, Product numbers, names and quantities, unit price, freight charges and the total amount to
be remitted by the Client (after taking into account any outstanding credit amounts owed under this Agreement by Patheon to
Client). The Client shall pay all such undisputed invoices within **** of the date thereof, provided, however, that payment will
only be for ****. ****. ****. Patheon shall fax or email a copy of the invoice to fax number or email address provided by Client
on the date of invoice

ARTICLE 6

PRODUCT CLAIMS AND RECALLS

6.1

Product Claims.

(a)

Product Claims. The Client has the right to reject any portion of any shipment of Products that deviates from ****
without invalidating any remainder of such shipment. The Client shall inspect the Products manufactured by Patheon upon
receipt thereof and shall give Patheon written notice (a “Deficiency Notice”) of all claims for Products that deviate from ****
within **** after the Client’s receipt thereof (or, in the case of any defects not reasonably susceptible to discovery upon receipt of
the Product, within **** after discovery thereof by the Client, but in no event after the expiration date of the Product). Should the
Client fail to provide Patheon with the Deficiency Notice within the applicable period, then the delivery shall be deemed to have
been accepted by the Client on the **** after delivery or **** after discovery, as applicable. Except as otherwise provided in this
Agreement, Patheon shall have no

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 21 -

liability for any deviations for which it has not received notice within the applicable

period. For the sake of clarity, if the Client does not provide a Deficiency Notice within **** after Client’s receipt of the
applicable Product, but instead provides a Deficiency Notice within **** after discovery of a defect not reasonably susceptible to
discovery upon receipt of the Product, then Client retains its rights and remedies with respect to the defective Product.

(b)

Determination of Deficiency. Upon receipt of a Deficiency Notice, Patheon shall have **** to advise the Client
by notice in writing that it disagrees with the contents of such Deficiency Notice. If the Client and Patheon fail, after good faith
discussions, to agree within **** after Patheon’s notice to the Client as to whether any Products identified in the Deficiency
Notice deviate from ****, then the parties shall mutually select an independent laboratory to evaluate if the Products deviate
from ****. Such evaluation shall be binding on the parties, and if such evaluation certifies that any Products deviate from ****,
the Client may reject those Products in the manner contemplated in this Section 6.1. If such evaluation does not so certify in
respect of any such Products, then the Client shall be deemed to have accepted delivery of such Products on the **** after
delivery (or, in the case of any defects not reasonably susceptible to discovery upon receipt of the Product, on the **** after
discovery thereof by the Client, but in no event after the expiration date of the Product). The decision of the laboratory shall be
binding on the parties, and the party that the decision disfavours shall bear the costs charged by such laboratory in connection
with its decision.

be agreed to by the parties.

6.2.

Product Recalls and Returns.

(a)

Records and Notice. **** shall each maintain such records as may be necessary to permit a Recall (as defined
below) of any Products delivered to the Client or customers of the Client. **** shall promptly notify **** by telephone (to be
confirmed in writing) of any information which is reasonably likely to adversely affect the marketability, safety or effectiveness
of the Products in a material manner and/or which might result in the Recall or seizure of the Products. Upon receiving any such
notice or upon any such discovery, **** shall cease and desist from further shipments of such Products in its possession or
control until a decision has been made whether a Recall or some other corrective action is necessary. The decision to initiate a
Recall or to take some other corrective action, if any, shall be made and implemented by ****. “Recall” shall mean any action (i)
by the Client to recover title to or possession of quantities of the Products sold or shipped to third parties (including, without
limitation, the voluntary withdrawal of Products from the market); or (ii) by any regulatory authorities to detain or destroy any of
the Products. Recall shall also include any action by either party to refrain from selling or shipping quantities of the Products to
third parties which would have been subject to a Recall if sold or shipped.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(b)

Recalls. If: (i) any governmental or regulatory authority issues a directive, order or, following the issuance of a
safety warning or alert with respect to a Product, a written request that any Product be Recalled, (ii) a court of competent
jurisdiction orders such a Recall, or (iii) **** determines that any Product should be Recalled or that a “dear doctor” letter is
required relating to the restrictions on the use of any Product, **** will co-operate as reasonably required by ****, having regard
to all applicable laws and regulations.

(c)

Product Returns. **** shall have the responsibility for handling customer returns of the Products. **** shall

provide **** with such assistance as **** may reasonably require to handle such returns.

6.3

Patheon’s Responsibility for Defective and Recalled Products.

(a)

Defective Product. If the Client rejects Products in accordance with Section 6.1 and the deviation is determined to
have arisen from Patheon’s failure to provide the Manufacturing in accordance with ****, Patheon shall promptly, ****. For
greater certainty, Patheon’s responsibility for ****.

(b)

(c)

Patheon shall have no obligation for any deficiencies in, or other liabilities associated with, any Product

manufactured by it (collectively, “Product Claims”) to the extent such Product Claim ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 23 -

****.

6.4

Disposition of Defective or Recalled Products.

The Client shall not dispose of any damaged, defective, returned or Recalled Products in relation to which it intends to
assert a claim against Patheon without Patheon’s prior written authorization to do so. Alternatively, Patheon may instruct the
Client to return such Products to Patheon. Patheon shall bear the cost of disposition with respect to any damaged, defective,
returned or Recalled Products in relation to which it bears responsibility under Section 6.3 hereof. In all other circumstances, the
Client shall bear the cost of disposition, including all applicable fees for Manufacturing, with respect to any damaged, defective,
returned or Recalled Products.

6.5

Customer Questions and Complaints.

The Client shall have the sole responsibility for responding to questions and complaints from the Client’s customers.
Questions or complaints received by Patheon from the Client’s customers shall be promptly referred to the Client. Patheon shall
cooperate as reasonably required to allow the Client to determine the cause of and resolve any customer questions and
complaints. Such assistance shall include follow-up investigations, including testing. In addition, Patheon shall promptly provide
the Client with all mutually agreed upon information that will enable the Client to respond properly to questions or complaints
relating to the Products as provided in the Quality Agreement. Unless it is determined that the cause of any customer complaint
resulted from a failure by Patheon to provide the Manufacturing in accordance with ****.

6.6

****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 24 -

ARTICLE 7

CO-OPERATION

7.1

Quarterly Review.

Each party shall forthwith upon execution of this Agreement appoint one of its employees to be a relationship manager
responsible for liaison between the parties. The relationship managers shall meet not less than **** to review the current status of
the business relationship and manage any issues that have arisen. Each party may replace its relationship manager at any time and
will fill a vacancy for its relationship manager as soon as reasonably practicable. Each party shall promptly notify the other party
of any substitution of another person as its relationship manager. Each party’s relationship manager shall be available throughout
the term of this Agreement to answer any reasonable questions from the other party’s relationship manager.

7.2

Governmental Agencies.

Client may communicate with any governmental agency, including but not limited to governmental agencies responsible
for granting regulatory approval for the Products, regarding Product specific issues. Subject to Section 7.8, Patheon may
communicate with any governmental agency, including but not limited to governmental agencies responsible for granting
regulatory approval for the Products, regarding Product specific issues, if ****.

7.3

Records and Accounting by Patheon.

Patheon shall keep records of the Manufacture, testing and shipping of the Products, and retain samples of such Products
as are necessary to comply with manufacturing regulatory requirements applicable to Patheon, as well as to assist with resolving
Product complaints and other similar investigations. Copies of such records and samples shall be retained for a period of ****
following the date of Product expiry, or longer if required by law, at which time the Client will be contacted in writing concerning
the delivery and destruction of such documents and/or Products, ****. The Client is responsible for retaining samples of the
Products necessary to comply with the legal/regulatory requirements applicable to the Client.

7.4

Inspection.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 25 -

this Agreement, including without limitation relating to the invoices issued hereunder, during normal business hours and with
reasonable advance notice, provided a Patheon representative is present during any such inspection.

7.5

Access.

Patheon shall provide the Client with reasonable access at mutually agreeable times (as discussed in good faith) to the
areas of the Manufacturing Site in which the Products are manufactured, stored, handled or shipped in order to permit the Client’s
verification of the performance of the Manufacturing in accordance with the Specifications, cGMPs, Applicable Laws, the
Quality Agreement and this Agreement. For greater certainty, the right of access provided in this Section 7.5 shall not include a
right to access or inspect Patheon’s financial records.

7.6

Notification of Regulatory Inspections.

In accordance with applicable laws and regulations governing regulatory inspections, and without waiving any rights and
protections afforded Patheon under such laws and regulations, Patheon shall permit authorized representatives of relevant
regulatory authorities, including the FDA, to inspect any plant and production facilities (including the Manufacturing Site)
relating to or used in connection with the Manufacturing and/or the Product. Patheon shall notify the Client within **** of any
inspections by any governmental agency that may bear directly on the Products. ****.

7.7

Reports.

Patheon will supply on an annual basis the Annual Product Review Report. Patheon will also supply on an annual basis or
as requested by Client at any other time all Product data in its control, including release test results, complaint test results, and all
investigations (in manufacturing, testing and storage), that the Client reasonably requires in order to complete any filing under
any applicable regulatory regime, including any Annual Report that the Client is required to file with the FDA. Any additional
reports requested by Client beyond the scope of cGMPs and customary FDA requirements will be subject to an additional fee to
be agreed upon in writing. All rights, title and interest in any and all data related to Product that is generated or derived by
Patheon in the course of performing the Manufacturing shall be the exclusive property of **** (and the confidential information
of ****). **** hereby makes, and agrees to make, any and all assignments necessary to effect, exclusively and throughout the
world, the ownership by **** of such data. **** shall, and shall cause its employees and contractors to, fully cooperate with and
sign any documents reasonably requested by **** to

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 26 -

evidence, perfect or take any other action with respect to such assignments or to obtain protection, maintain or take any other
action regarding such assigned data.

7.8 FDA Filings.

(a)

Regulatory Authority. The Client shall have the sole responsibility for filing all documents with all Regulatory
Authorities and taking any other actions that may be required for the receipt and/or maintenance of Regulatory Authority
approval for the commercial manufacture of the Products. Patheon shall assist the Client, as is reasonable, to obtain Regulatory
Authority approval for the commercial Manufacture of all Products as quickly as reasonably possible.

(b)

Verification of Data. At least **** prior to filing any documents with any Regulatory Authority that incorporate

data generated by Patheon, the Client shall ****.

(c)

Verification of CMC. At least **** prior to filing with any Regulatory Authority any documentation which is or is
equivalent to the FDA’s Chemistry and Manufacturing Controls (“CMC”) related to any Marketing Authorization, such as a New
Drug Application or Abbreviated New Drug Application, the Client shall ****.

(d)

Deficiencies. If in Patheon’s sole discretion, acting reasonably, Patheon determines that any of the information
provided by the Client in accordance with paragraphs (b) and (c) above is inaccurate or deficient in any manner whatsoever, and
Patheon reasonably believes that Patheon’s standing with regulatory authorities may be jeopardized thereby (the “Deficiencies”),
Patheon shall notify the Client in writing of such Deficiencies promptly but in no event less than **** prior to Client’s applicable
scheduled filing with the Regulatory Authority. The parties shall work together in good faith to have such Deficiencies resolved
prior to any pre-approval inspection.

(e)

Client Responsibility. For clarity, the parties agree that ****. Subject to the foregoing, Patheon will not assume
any responsibility for the accuracy of any application for receipt of an approval by a Regulatory Authority. The Client is solely
responsibility for the preparation and filing of the application for approval by the Regulatory Authority and any relevant costs
will be borne by the Client.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 27 -

(f)

Inspection by Regulatory Authorities. If Client does not ****.

ARTICLE 8

TERM AND TERMINATION

8.1

Initial Term.
This Agreement shall become effective as of the Effective Date and shall continue for five years following the Effective
Date (the “Initial Term”), unless terminated earlier by one of the parties in accordance herewith. This Agreement shall
automatically continue after the Initial Term for successive terms of one year each unless either party gives written notice to the
other party of its intention to terminate this Agreement at least 12 months prior to the end of the then current term.

8.2

Termination for Cause.

(a)

Either party at its sole option may terminate this Agreement upon written notice in circumstances where the other
party has failed to remedy a material breach of any of its representations, warranties or other obligations under this Agreement
within **** following receipt of a written notice (the “Remediation Period”) of said breach that expressly states that it is a
notice under this Section 8.2(a) (a “Breach Notice”).

(b)

Either party at its sole option may immediately terminate this Agreement upon written notice, but without prior
advance notice, to the other party in the event that: (i) the other party is declared insolvent or bankrupt by a court of competent
jurisdiction; (ii) a voluntary petition of bankruptcy is filed in any court of competent jurisdiction by such other party; or (iii) this
Agreement is assigned by such other party for the benefit of creditors.

(c)

The Client may terminate this Agreement as to any Product upon **** prior written notice if any governmental
agency takes any action, or raises any objection, that prevents the Client from importing, exporting, purchasing or selling such
Product. In addition, the Client may terminate this Agreement **** written notice to Patheon in the event that any governmental
agency in the Territory makes a decision not to grant marketing authorization to the Client with respect to Product.

(d)

Patheon may terminate this Agreement upon **** prior written notice if the Client assigns pursuant to Section
13.6 any of its rights under this Agreement to an assignee that, in the opinion of Patheon acting reasonably, is: (i) not a credit
worthy substitute for the Client; or (ii) a competitor of Patheon, where a “competitor of Patheon” means a corporation which (a)
specializes in the business of manufacturing

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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pharmaceutical products for third parties and (b) does not directly or indirectly own or market pharmaceutical products in its own
name.

(e)

A party may terminate this Agreement when permitted pursuant to Section 13.7.

(f)

The Client may terminate this Agreement due to Client’s discontinuation of the development of Product

manufactured at the Manufacturing Site, upon written notice delivered at least **** prior to such discontinuation.

(g)

The Client may, upon the completion of **** of this Agreement, terminate this Agreement at any time, for any or
no reason, upon not less than **** notice to Patheon, provided that ****. The Client may, upon the completion of **** of this
Agreement, terminate this Agreement at any time, for any or no reason, upon not less than **** notice to Patheon, provided that
****. ****.

8.3

Obligations on Termination.

If this Agreement expires or is terminated in whole or in part for any reason, then following the expiration or termination
of this Agreement, or the end of the Wind-Down Period, if applicable (in addition to any other remedies either party may have in
the event of default by the other party):

(a)

(b)

the Client shall take delivery of and pay for (in accordance with Section 5.6) all undelivered Products that are
manufactured and/or packaged pursuant to a Firm Order, at the price in effect at the time the Firm Order was
placed.

the Client shall purchase, at Patheon’s cost ****, (i) the remaining Components applicable to the Products which
were purchased by Patheon in contemplation of filling Firm Orders or in accordance with Section 5.2 prior to
notice of termination being given to the extent that such Components cannot be returned or used to produce
product for another client; and (ii) all remaining work-in-process produced by Patheon in contemplation of filling
Firm Orders prior to notice of termination being given.

(c)

the Client acknowledges that no competitor of Patheon (as defined in Section 8.2(d)) shall be permitted access to
the Manufacturing Site.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(d)

Client will make commercially reasonable efforts, at its own expense but with Patheon’s reasonable cooperation,
to remove from Patheon site(s), within ****, all of Client’s Components, Inventory and supplies, undelivered
Product, chattels, equipment or other moveable property owned by Client, related to the Agreement and located at
a Patheon site or that is otherwise under Patheon’s care and control (“Client Property”). If Client fails to remove
the Client Property within **** following the termination or expiration of the Agreement (or following the end of
the Wind-Down Period, if applicable), Client will pay Patheon **** per pallet, per month, one pallet minimum
(**** per pallet, per month, one pallet minimum, for any of the Client Property that contains controlled substances
or requires refrigeration) thereafter for storing the Client Property and will assume any third party storage charges
invoiced to Patheon regarding the Client Property. Patheon will invoice Client for the storage charges as set forth
in Section 5.6 of this Agreement.

If this Agreement expires or is terminated in whole or in part for any reason, then (in addition to any other remedies the Client
may have in the event of default by Patheon), Patheon shall return to the Client promptly all unused Active Materials and provide
to the Client all Inventory purchased by the Client (with shipping and related expenses, if any, to be borne by the Client),
following such expiration or termination or the end of the Wind-Down Period, if applicable.
In addition, for a period of **** after the termination or expiration of this Agreement (the “Wind-Down Period”), Client may
continue to order Manufacturing, and Patheon shall continue to provide Manufacturing in accordance with such orders from
Client (if any), in each case subject to the terms and conditions of this Agreement. In the event of termination by Patheon
pursuant to Section 8.2(a) due to Client’s failure to pay undisputed amounts, Patheon may require that Client pay such amounts
before filling any Firm Orders and may require that Client pre-pay for any Manufacturing Services provided during the Wind-
Down Period. Furthermore, upon reasonable request by Client, Patheon will use commercially reasonable and good faith efforts
to discuss with Client and come to an agreement with Client with respect to the terms for the performance of other transition
services that are reasonably requested by Client.
Any termination or expiration of this Agreement shall not affect any outstanding obligations or payments due hereunder prior to
such termination or expiration, nor shall it prejudice any other remedies that the parties may have under this Agreement. For
greater certainty, termination of this Agreement for any reason shall not affect the obligations and responsibilities of the parties
pursuant to Articles 6, 8, 9, 10, 11, 12 and 13 and Sections 1.1, 7.3, 7.4, 7.5, 7.6 and 7.7, all of which survive any termination.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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ARTICLE 9

REPRESENTATIONS, WARRANTIES AND COVENANTS

9.1

Authority.

Each party covenants, represents and warrants that (i) it has the full right and authority to enter into this Agreement, and
that it is not aware of any impediment that would inhibit its ability to perform its obligations hereunder and (ii) it is a corporation
duly organized, validly existing and in good standing under the laws of its incorporating jurisdiction and has all requisite power
and authority to enter into this Agreement.

9.2

Client Warranties.

The Client covenants, represents and warrants that, to the Client’s knowledge as of the Effective Date:

(a)

(b)

(c)

the provision of the Manufacturing by Patheon solely in respect of any Product pursuant to this Agreement as
directed in the new drug application for the Product that was approved by the U.S. Food and Drug Administration
or use or other disposition of any Product by Patheon as may be required to perform its obligations under this
Agreement does not and will not infringe any Third Party Rights;

there are no actions or other legal proceedings in the Territory, the subject of which is the infringement of Third
Party Rights related to any of the Specifications, or the Product or any of the Active Materials and the
Components provided by the Client to Patheon, or the sale, use or other disposition of any Product Manufactured
in accordance with the Specifications; and

the Products, if labelled and Manufactured in accordance with the Specifications and in compliance with
applicable cGMPs, Applicable Laws, the Quality Agreement and this Agreement (i) may be lawfully sold and
distributed in every jurisdiction in which the Client has Regulatory Authority approval to market such Products,
(ii) ****, and (iii) will be safe for human consumption as directed on the approved labelling for such Products.

In addition, Client covenants, represents and warrants that:

(i)

the Specifications for each of the Products are its or its Affiliate’s property or licensed to the Client and that the
Client may lawfully disclose the Specifications to Patheon;

(ii) to the Client’s knowledge as of the Effective Date, any Intellectual Property provided by the Client to Patheon in

connection with the provision of the Manufacturing according to the Specifications (i) is the

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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Client’s or its Affiliate’s unencumbered property or is licensed to the Client, (ii) may be lawfully used as directed
by the Client, and (iii) ****; and

(iii) the Specifications for all Products, as provided by the Client to Patheon, conform to all applicable cGMPs and

Applicable Laws.

9.3

Patheon Warranties.

Patheon covenants, represents and warrants that to Patheon’s knowledge as of the Effective Date:

(a)

(b)

(c)

any Intellectual Property owned by Patheon and utilized by Patheon in connection with the provision of the
Manufacturing which has not been provided by Client or used at the direction of Client, (i) is Patheon’s or its
Affiliate’s unencumbered property, (ii) may be lawfully used by Patheon and (iii) does not infringe and will not
infringe any Third Party Rights;

it and its Manufacturing Site are in compliance with all laws and regulations applicable to their operations,
including, without limitation, cGMPs and Applicable Laws;

all Patheon personnel are fully qualified (by education, training and experience) to properly perform their tasks
under this Agreement.

In addition, Patheon covenants, represents and warrants that:

(i) it shall perform the Manufacturing in accordance with the Specifications, cGMPs, Applicable Laws, the Quality

Agreement and this Agreement;

(ii) it will convey good title to the Product, free of all liens of any kind whatsoever; and

(iii) the Products, when delivered to Client, will be Manufactured according to the Specifications. For the sake of
clarity, if Patheon performs any additional steps not specified in the Specifications in Manufacturing Products
(e.g., by adding one or more additional components to the Products that are not specified in the Specifications),
then Patheon will be deemed to have failed to Manufacture such Products in accordance with the Specifications.

The warranties provided in (i), (ii) and (iii) above shall survive inspection, test, acceptance and use of the Product.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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9.4

Debarred Persons.

Patheon covenants that it will not in the performance of its obligations under this Agreement use the services of any
person debarred or suspended under 21 U.S.C. §335(a) or (b) or by Health Canada or any comparable European regulatory
authority. Patheon represents that it does not currently have, and covenants that it will not hire, as an officer, an employee or an
independent contractor in connection with the Manufacturing any person who has been convicted of a felony under the laws of
the United States for conduct relating to the regulation of any drug product under the Federal Food, Drug, and Cosmetic Act
(United States) or any comparable Canadian or European law. If Patheon becomes aware of any breaches of the Section, it will
promptly notify the Client.

9.5

Permits.

Patheon shall maintain at all relevant times all governmental permits, licenses, approvals, and authorities to the extent
required to enable it lawfully to properly perform the Manufacturing. The Client shall be solely responsible for obtaining or
maintaining, on a timely basis, any permits or other regulatory approvals in respect of the Products or the Specifications,
including, without limitation, all marketing and post-marketing approvals.

9.6

No Warranty.

EXCEPT AS OTHERWISE PROVIDED HEREIN, NEITHER PATHEON NOR CLIENT MAKES ANY
WARRANTY OF ANY KIND, EITHER EXPRESSED OR IMPLIED, BY FACT OR LAW, OTHER THAN THOSE
EXPRESSLY SET FORTH IN THIS AGREEMENT. PATHEON MAKES NO IMPLIED WARRANTY OF FITNESS
FOR A PARTICULAR PURPOSE OR WARRANTY OF MERCHANTABILITY WITH RESPECT TO THE
PRODUCTS. THE CLIENT MAKES NO WARRANTY OF FITNESS FOR A PARTICULAR PURPOSE OR
WARRANTY OF MERCHANTABILITY WITH RESPECT TO THE ACTIVE MATERIALS OR COMPONENTS
PROVIDED BY THE CLIENT TO PATHEON.

ARTICLE 10

REMEDIES AND INDEMNITIES

10.1 Consequential Damages.

To the maximum extent permitted by applicable law, except with respect to ****, under no circumstances whatsoever
shall **** be liable to the other hereunder in contract, tort, negligence, breach of statutory duty or otherwise for any indirect,
punitive, incidental, reliance, special, exemplary or consequential damages, including without limitation direct or indirect loss of
profits, of production, of anticipated savings, of business or goodwill, regardless of any notice of the possibility of such damages.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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10.2 Limitation of Liability.

(a)

Active Materials. Except as expressly set forth in Section 2.2 hereof and this Section 10.2, under no circumstances

whatsoever shall Patheon be responsible for any loss or damage to the Active Materials. ****.

(b)

Maximum Liability. To the maximum extent permitted by applicable law, except with respect to ****, ****
maximum liability per Year under this Agreement for any reason whatsoever, including, without limitation, any liability resulting
from a breach of its representations, warranties or other obligations under this Agreement, shall not exceed **** of the total fees
paid under this Agreement by Client to Patheon in such Year, up to a maximum value **** in the aggregate.

10.3

Patheon.

Patheon agrees to defend, indemnify and hold the Client, its Affiliates and their respective officers, employees and agents
harmless against any and all losses, damages, costs, claims, demands, judgments and liability to, from and in favour of third
parties (other than Affiliates) resulting from, or relating to ****.

If a claim occurs, the Client shall: (a) promptly notify Patheon of any such claim; (b) use commercially reasonable efforts
to mitigate the effects of such claim; (c) reasonably cooperate with Patheon in the defence of such claim; and (d) permit Patheon
to control the defence and settlement of such claim, each at Patheon’s cost and expense, provided that any settlement of such
claim that does not contain an unconditional release of an indemnitee will require the prior written consent of such indemnitee,
which such consent will not be unreasonably withheld.

10.4 Client.

The Client agrees to defend, indemnify and hold Patheon, its Affiliates and their respective officers, employees and agents
harmless against any and all losses, damages, costs, claims, demands, judgments and liability to, from and in favour of third
parties (other than Affiliates) resulting from, or relating to any claim ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****.

If a claim occurs, Patheon shall: (a) promptly notify the Client of any such claims; (b) use commercially reasonable
efforts to mitigate the effects of such claim; (c) reasonably cooperate with the Client in the defence of such claim; (d) permit the
Client to control the defence and settlement of such claim, each at the Client’s cost and expense, provided that any settlement of
such claim that does not contain an unconditional release of an indemnitee will require the prior written consent of such
indemnitee, which such consent will not be unreasonably withheld.

10.5 Reasonable Allocation of Risk.

The provisions of this Agreement (including, without limitation, this Article 10) are reasonable and create a reasonable

allocation of risk having regard to the relative profits the parties respectively expect to derive from the Products.

ARTICLE 11

CONFIDENTIALITY

11.1 Confidentiality.

The provisions of the Confidentiality Agreement shall apply to all confidential information of the parties under this
Agreement, which agreement remains in effect in accordance with its terms; provided, however, that the terms of the
Confidentiality Agreement shall continue to govern the parties’ obligations of confidentiality with respect to any confidential or
proprietary information of the parties, for the term of this Agreement and for a period of five years following termination or
expiration of this Agreement, except that the parties’ obligations of confidentiality with respect to any confidential or proprietary
information of the parties that is a trade secret under applicable law shall survive and continue in effect thereafter, in each case as
though such agreement remained in full force and effect. For the sake of clarity, the Product manufacturing process, including
without limitation the Product formulation process, and the analytical methods specific to the Product are all deemed to be the
trade secrets of Client for the purposes of this Section 11.1. Promptly following any expiration or termination of this Agreement,
each party shall return to the other party all originals and copies of the other party’s confidential information and destroy all
information, records

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 35 -

and materials developed there from, unless otherwise expressly provided herein (e.g., under Section 7.3 (Records and Accounting
by Patheon)).

Notwithstanding the foregoing, the parties acknowledge that Client will be permitted, and may be required pursuant to the
rules and regulations promulgated under the Securities Exchange Act of 1934, as amended, to file a Current Report on Form 8-K
disclosing the entry into this Agreement by Client and a brief description of the terms and conditions hereof that are material to
Client. To the extent that either party reasonably determines that it is required to make a filing or any other public disclosure
(other than as set forth in the preceding sentence) with respect to this Agreement or the terms or existence hereof to comply with
the requirements, rules, laws or regulations of any applicable stock exchange, Nasdaq or any governmental or regulatory
authority or body, including without limitation the U.S. Securities and Exchange Commission (the “SEC”) (collectively, the
“Disclosure Obligations”), such party shall promptly inform the other party thereof and shall use reasonable efforts to maintain
the confidentiality of the other party’s confidential information in any such filing or disclosure. To the extent that either party
reasonably determines that it is required to file a copy of this Agreement to comply with the Disclosure Obligations, such party
shall promptly inform the other party thereof. Prior to making any such filing of a copy of this Agreement, the parties shall
mutually agree on the provisions of this Agreement for which the parties shall seek confidential treatment, it being understood
that if one party determines to seek confidential treatment for a provision for which the other party does not, then the parties will
use reasonable efforts in connection with such filing to seek the confidential treatment of any such provision. The parties shall
cooperate, each at its own expense, in such filing, including without limitation such confidential treatment request, and shall
execute all documents reasonably required in connection therewith. In furtherance of the foregoing, the parties will agree as
promptly as practicable after the Effective Date on the confidential treatment request to be filed with the SEC and the redacted
form of this Agreement related thereto. In furtherance thereof, any redaction reasonably requested by either party shall be
included in such filing. The parties will reasonably cooperate in responding promptly to any comments received from the SEC
with respect to such filing in an effort to achieve confidential treatment of such redacted form; provided, however, that a party
shall be relieved of such obligation to seek confidential treatment for a provision requested by the other party if such treatment is
not achieved after the second round of responses to comments from the SEC. This paragraph shall apply with respect to the filing
of a copy of this Agreement or any public disclosure relating to this Agreement to comply with the Disclosure Obligations,
notwithstanding the provisions of the Confidentiality Agreement.

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ARTICLE 12

DISPUTE RESOLUTION

12.1 Commercial Disputes.

If any dispute arises out of or in connection with this Agreement (other than a dispute determined in accordance with
Section 6.1(b) or a Technical Dispute), the parties shall first try to solve it amicably. In this regard, any party may send a notice of
dispute to the other, and each party shall appoint, within **** from receipt of such notice of dispute, a single representative
having full power and authority to solve the dispute. The representatives so designated shall meet as necessary in order to solve
such dispute. If these representatives fail to solve the matter within **** from their appointment, or if a party fails to appoint a
representative within the **** period set forth above, such dispute shall immediately be referred to the Chief Operating Officer
(or such other officer as he/she may designate) of each party who will meet and discuss as necessary in order to try to solve the
dispute amicably. Should the parties fail to reach a resolution under this Section 12.1, either party may refer the dispute to
arbitration in accordance with Section 12.3. Notwithstanding the foregoing, neither party shall be prohibited from seeking
injunctive or other equitable relief in any court of competent jurisdiction (including without limitation, in any case where issues
involving the protection or unauthorized use or disclosure of a party’s confidential information, trade secrets or intellectual
property are involved).

12.2 Technical Dispute Resolution.

If a dispute (other than disputes in relation to the matters set out in Sections 6.1(b) and 12.1) arises between the parties
that is exclusively related to technical aspects of the manufacturing, packaging, labelling, quality control testing, handling,
storage or other activities under this Agreement (a “Technical Dispute”), the parties shall make all reasonable efforts to resolve
the dispute by amicable negotiations. In this regard, senior representatives of each party shall, as soon as practicable and in any
event no later than **** after a written request from either party to the other, meet in good faith to resolve any Technical Dispute.
If, despite such meeting, the parties are unable to resolve a Technical Dispute within a reasonable time, and in any event within
**** after such written request, the Technical Dispute shall, at the request of either party, be referred for determination to an
expert in accordance with the provisions of Schedule F. In the event that the parties cannot agree whether a dispute is a Technical
Dispute, Section 12.1 shall prevail. For greater certainty, the parties agree that the release of the Products for sale or distribution
pursuant to the applicable marketing approval for such Products shall not by itself indicate compliance by Patheon with its
obligations in respect of the Manufacturing and further that nothing in this Agreement (including Schedule F) shall remove or
limit the authority of the relevant qualified person (as specified by the Quality Agreement) to determine whether the Products are
to be released for sale or distribution. Notwithstanding the foregoing, neither party shall be prohibited from seeking injunctive or
other equitable relief in any court of competent jurisdiction (including without limitation, in any case where issues involving the
protection or

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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unauthorized use or disclosure of a party’s confidential information, trade secrets or intellectual property are involved).

12.3 Arbitration.

If any dispute cannot be resolved in accordance with Section 12.1, such dispute shall be finally settled by arbitration in
**** using the English language in accordance with the Arbitration Rules and Procedures of Judicial Arbitration and Mediation
Services, Inc. (“JAMS”) then in effect, by one or more commercial arbitrator(s) with substantial experience in resolving complex
commercial contract disputes, who may or may not be selected from the appropriate list of JAMS arbitrators. If the parties cannot
agree upon the number and identity of the arbitrators within **** following the date on which a party referred the applicable
dispute to arbitration, then a single arbitrator shall be selected on an expedited basis in accordance with the Arbitration Rules and
Procedures of JAMS. Any arbitrator so selected shall have substantial experience in the pharmaceutical industry. The arbitrator(s)
shall have the authority to grant specific performance and to allocate between the parties the costs of arbitration allocate between
the parties the costs of arbitration (including service fees, arbitrator fees and all other fees related to the arbitration) in such
equitable manner as the arbitrator(s) may determine. The prevailing party in the arbitration shall be entitled to receive
reimbursement of its reasonable expenses (including reasonable lawyers’ fees, expert witness fees and all other expenses)
incurred in connection therewith. Judgment upon the award so rendered may be entered in a court having jurisdiction or
application may be made to such court for judicial acceptance of any award and an order of enforcement, as the case may be.
Notwithstanding the foregoing, each party shall have the right to institute an action in a court of proper jurisdiction for
preliminary injunctive relief pending a final decision by the arbitrator(s), provided that a permanent injunction and damages shall
only be awarded by the arbitrator(s).

12.4 Dispute and Termination for Breach.

Notwithstanding any statement to the contrary in this Agreement, a non-breaching party shall not be entitled to terminate
this Agreement pursuant to Section 8.2(a) on account of a disputed breach until the dispute is resolved by mutual agreement or
arbitration pursuant to Section 12.3 confirming the existence of the breach.

ARTICLE 13

MISCELLANEOUS

13.1

Inventions.
(a) For the term of this Agreement, Client hereby grants to Patheon a non-exclusive, paid-up, royalty-free, non-
sublicensable, non-transferable license of Client’s Intellectual Property, including without limitation that assigned to the Client
pursuant to Section 13.1(b) below, which Patheon must use in order to perform the Manufacturing, solely to perform the
Manufacturing. Without limitation, Patheon agrees that it shall not

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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use any such Client Intellectual Property or Client confidential information to enable itself or any third party to develop, make,
have made, offer, sell or exploit the Products.

(b) All Inventions (including any and all Intellectual Property Rights therein) conceived, generated, derived or reduced
to practice by Patheon in the course of performing the Manufacturing, to the extent it is related to the development, Manufacture,
packaging, use or sale of the Client’s Product that is the subject of the Manufacturing or contains the Client’s confidential
information, shall be the exclusive property of Client. Patheon shall give the Client written notice, as promptly as practicable, of
all such Inventions, and all such Inventions shall be deemed to be the confidential information of Client. Patheon hereby makes,
and agrees to make, any and all assignments necessary to effect, exclusively and throughout the world, the ownership by the
Client of Inventions under Section 13.1(b). Patheon shall, and shall cause its employees and contractors to, fully cooperate with
and sign any documents reasonably requested by the Client to evidence, perfect or take any other action with respect to such
assignments or to obtain protection, maintain or take any other action regarding such assigned Inventions.

(c) All Intellectual Property generated or derived by Patheon in the course of performing the Manufacturing to the
extent it (i) is not related to the development, Manufacture, packaging, use or sale of the Client’s Product that is the subject of the
Manufacturing and (ii) does not contain the Client’s confidential information, shall be the exclusive property of Patheon (the
“Broader Intellectual Property Rights”). Patheon hereby grants and agrees to grant to the Client a nonexclusive, transferable,
perpetual, irrevocable, paid up, royalty-free, worldwide right and license (including the right to sublicense) to practice and use all
Broader Intellectual Property Rights solely in connection with ****

(d) Each party shall be solely responsible for the costs of filing, prosecution and maintenance of patents and patent

applications on its own Inventions.

13.2

Intellectual Property.

Subject to Section 13.1, all Intellectual Property of the Client, including without limitation any Intellectual Property that
the Client owns prior to the Effective Date, shall be owned by the Client and all Intellectual Property of Patheon, including
without limitation any Intellectual Property that Patheon owns prior to the Effective Date, shall be owned by Patheon. Neither
party has, nor shall it acquire, any interest in any of the other party’s Intellectual Property unless otherwise expressly agreed to in
writing. Neither party shall use any Intellectual Property of the other party, except as specifically authorized by the other party or
as required for the performance of its obligations under this Agreement. Except as expressly set forth in Section 13.1, no licenses
are granted by either party, whether by implication, estoppel or otherwise, and all other rights are reserved.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 39 -

13.3

Insurance.

Each party shall maintain commercial general liability insurance, including blanket contractual liability insurance
covering the obligations of that party under this Agreement through the term of this Agreement and for a period of ****
thereafter, which insurance shall afford limits of not less than (i) **** for each occurrence for personal injury, bodily injury or
property damage liability; and (ii) **** in the aggregate per annum with respect to product and completed operations liability. If
requested each party will provide the other with a certificate of insurance evidencing the above and showing the name of the
issuing company, the policy number, the effective date, the expiration date and the limits of liability. The insurance certificate
shall further provide for a minimum of **** written notice to the insured of a cancellation of, or material change in, the
insurance. If a party is unable to maintain the insurance policies required under this Agreement through no fault on the part of
such party, then such party shall forthwith notify the other party in writing and the parties shall in good faith negotiate appropriate
amendments to the insurance provision of this Agreement in order to provide adequate assurances, provided that in no event shall
such party terminate its insurance policies until such amendments to the insurance provision of this Agreement that are mutually
agreed upon by the parties in writing are enacted.

13.4

Independent Contractors.

The parties are independent contractors and this Agreement shall not be construed to create between Patheon and the
Client any other relationship such as, by way of example only, that of employer-employee, principal agent, joint-venturer, co-
partners or any similar relationship, the existence of which is expressly denied by the parties hereto.

13.5 No Waiver.

Either party’s failure to require the other party to comply with any provision of this Agreement shall not be
deemed a waiver of such provision or any other provision of this Agreement. No waiver of any provision of this Agreement shall
bind either party unless in writing and signed by the party against which enforcement is sought.

13.6 Assignment.

(a)

Patheon may not assign, transfer, delegate or subcontract this Agreement or any of its rights or obligations hereunder
except with the written consent of the Client, such consent not to be unreasonably withheld; provided, however, that
Patheon may arrange for subcontractors solely to perform specific testing services arising under this Agreement without
the consent of the Client. Patheon shall be responsible and liable for any breaches of this Agreement by its
subcontractors.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 40 -

(b) Subject to Section 8.2(d), the Client may assign this Agreement or any of its rights or obligations hereunder without
approval from Patheon; provided, however, that the Client shall give prior written notice of any assignment to Patheon,
and any assignee shall covenant in writing with Patheon to be bound by the terms of this Agreement. ****.

(c) Notwithstanding the foregoing provisions of this Section 13.6, either party may assign this Agreement, without the
consent of the other party, to any of its Affiliates or to a successor to or purchaser of all or substantially all of its
business to which the subject matter of this Agreement relates, provided that such party provides prior written notice of
such assignment to the other party and the assignee executes an agreement with the non-assigning party hereto whereby
it agrees to be bound hereunder.

13.7

Force Majeure.

Neither party shall be liable for the failure to perform its obligations under this Agreement if such failure is occasioned by
a cause or contingency beyond such party’s reasonable control, including, but not limited to, strikes or other labour disturbances,
lockouts, riots, quarantines, communicable disease outbreaks, wars, acts of terrorism, fires, floods, storms, interruption of or
delay in transportation, defective equipment, lack of or inability to obtain fuel, power or components or compliance with any
order or regulation of any government entity acting within colour of right (a “Force Majeure Event”). A party claiming a right
to excused performance under this Section 13.7 shall promptly notify the other party in writing of the extent of its inability to
perform, which notice shall specify the occurrence beyond its reasonable control that prevents such performance, and shall use
commercially reasonable efforts to overcome the Force Majeure Event. Notwithstanding the foregoing, if either party is
prevented or delayed in performing its obligations under this Agreement on more than (i) **** or (ii) **** in the aggregate
during any ****, then the party not so affected may terminate this Agreement upon written notice to the affected party. Neither
party shall be entitled to rely on a Force Majeure Event to relieve it from an obligation to pay money (including any interest for
delayed payment) which would otherwise be due and payable under this Agreement.

13.8 Additional Product.

Additional products may be added to this Agreement and such additional products shall be governed by the general

conditions hereof with any special terms (including, without limitation, price) governed by an addendum hereto.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 41 -

13.9 Notices.

Any notice, approval, instruction or other written communication required or permitted hereunder shall be sufficient if
made or given to the other party by personal delivery, by telecopier or facsimile communication or by sending the same by first
class mail, postage prepaid, return receipt requested to the mailing address, or telecopier or facsimile number set forth below:

If to the Client:

Vanda Pharmaceuticals Inc.
2200 Pennsylvania Ave NW, Suite 300E
Washington, DC 20037
U.S.A.

Attention: Chief Financial Officer

Telecopier No.: ****

If to Patheon:

Patheon Pharmaceuticals Inc.
2110 East Galbraith Road
Cincinnati, OH 45237-1625
Attention: Director of Legal Services
Telecopier No.: ****

Email address: ****

With a copy to:

Patheon Inc.
4721 Emperor Boulevard
Research Triangle Park,
NC 27703
Attention: General Counsel
Telecopier No.: ****
Email address: ****

or to such other addresses or telecopier or facsimile numbers provided to the other party in accordance with the terms of this
Section 13.9. Notices or written communications made or given by personal delivery or by telecopier or facsimile shall be
deemed to have been sufficiently made or given when sent (receipt acknowledged), or if mailed, five days after being deposited
in the United States or Canadian mail, postage prepaid, return receipt requested or upon receipt, whichever is sooner.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 42 -

13.10 Severability.

If any provision of this Agreement is determined by a court of competent jurisdiction to be invalid, illegal or
unenforceable in any respect, such determination shall not impair or affect the validity, legality or enforceability of the remaining
provisions hereof, and each provision is hereby declared to be separate, severable and distinct.

13.11 Entire Agreement.

This Agreement, together with the Schedules, the Quality Agreement and the Confidentiality Agreement, constitutes the
full, complete, final and integrated agreement between the parties hereto relating to the subject matter hereof and supersedes all
previous written or oral negotiations, commitments, agreements, transactions or understandings with respect to the subject matter
hereof. Any modification, amendment or supplement to this Agreement must be in writing and signed by authorized
representatives of both parties. In case of conflict, the prevailing order of documents shall be this Agreement, the Quality
Agreement and the Confidentiality Agreement.

13.12 Other Terms.

No terms, provisions or conditions of any purchase order or other business form or written authorization used by the
Client or Patheon will have any effect on the rights, duties or obligations of the parties under or otherwise modify this
Agreement, regardless of any failure of the Client or Patheon to object to such terms, provisions, or conditions. For greater
certainty, the Client’s purchase order is only effective as its unqualified commitment to obtain and pay for the Manufacturing
upon the terms (and only the terms) set forth herein.

13.13 No Third Party Benefit or Right.

For greater certainty, nothing in this Agreement shall confer or be construed as conferring on any third party any benefit

or the right to enforce any express or implied term of this Agreement.

13.14 Execution in Counterparts.

This Agreement may be executed in two counterparts, by original or facsimile signature, each of which shall be deemed

an original, but all of which together shall constitute one and the same instrument.

13.15 Governing Law.

This Agreement shall be construed and enforced in accordance with the laws of the State of ****, without regard to its
conflicts of law provisions. The UN Convention on Contracts for the International Sale of Goods shall not apply to this
Agreement. Unless expressly provided otherwise, each right and remedy in this Agreement is in addition to any other right or
remedy, at law or in equity, and the exercise of one right or remedy will not be deemed a waiver of any other right or remedy.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 43 -

the date first written above.

IN WITNESS WHEREOF, the duly authorized representatives of the parties have executed this Agreement as of

PATHEON PHARMACEUTICALS INC.

By __/s/ Dean Wilson______________

Name: Dean Wilson

Title: VP corporate controller 1/24/2014

VANDA PHARMACEUTICALS INC.

By __/s/ M. H. Polymeropoulos, M.D._

Name: M. H. Polymeropoulos, M.D.

Title: CEO

GDSVF&H\1872159.1

- 44 -

SCHEDULE A

PRODUCT LIST

Products

Hetlioz™ 20 mg Capsules in ****

Specifications

Prior to the commencement of commercial manufacturing of Product under this Agreement, the Client shall provide Patheon with
copies of the FDA approved NDA Specifications. If the Specifications provided are subsequently amended, then the Client shall
provide Patheon with revised copies of such revised Specifications. Upon acceptance of the revised Specifications pursuant to
Section 4.4, Patheon shall provide the Client with a signed and dated receipt evidencing such acceptance of the revised
Specifications by Patheon.

- 45 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE B

COMMERCIAL PRICING

****
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****
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****
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****

****

****
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****
****

****

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****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

****

****
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****

****

****
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****

****

- 47 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

****

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****

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- 48 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

****
****

****

****
****
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****
****
****
****
****
****

****

- 49 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE C

STABILITY TESTING

****

****
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****

****
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- 50 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE D

****

- 51 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE E

BATCH NUMBERING & EXPIRATION DATES

****

- 52 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE F

TECHNICAL DISPUTE RESOLUTION

****

- 53 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

****

- 54 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE G

QUALITY AGREEMENT

- 55 -

SCHEDULE H

QUARTERLY ACTIVE MATERIALS INVENTORY REPORT

****

- 56 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

REPORT OF ANNUAL ACTIVE MATERIALS INVENTORY RECONCILIATION AND CALCULATION OF
ACTUAL ANNUAL YIELD

SCHEDULE I

****

- 57 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

****

- 58 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

CERTAIN IDENTIFIED INFORMATION HAS BEEN EXCLUDED FROM THIS EXHIBIT BECAUSE IT IS BOTH
NOT MATERIAL AND IS OF THE TYPE THAT VANDA TREATS AS PRIVATE OR CONFIDENTIAL

EXHIBIT 10.29

Manufacturing Agreement

May 6, 2016

Table of Contents

ARTICLE 1

INTERPRETATION
1.1 Definitions.
1.2 Currency
1.3 Sections and Headings.
1.4 Singular Terms.
1.5 Schedules

ARTICLE 2
PATHEON'S MANUFACTURING SERVICES

2.1 Manufacturing Services.

ARTICLE 3
CLIENT'S OBLIGATIONS

3.1 Payment.

ARTICLE 4
CONVERSION FEES AND COMPONENT COSTS

4.1 First Year Pricing.
4.2 Price Adjustments - Subsequent Years’ Pricing.
4.3 Price Adjustments – Current Year Pricing.
4.4 Adjustments Due to Technical Changes.
4.5 Multi-Country Packaging Requirements.

ARTICLE 5
ORDERS, SHIPMENT, INVOICING, PAYMENT

5.1 Orders and Forecasts.
5.2 Reliance by Patheon.
5.3 Minimum Orders.
5.4 Shipments.
5.5 Invoices and Payment.

ARTICLE 6
PRODUCT CLAIMS AND RECALLS

6.1 Product Claims.
6.2 Product Recalls and Returns.
6.3 Patheon’s Responsibility for Defective and Recalled Products.
6.4 Disposition of Defective or Recalled Products.
6.5 Customer Questions and Complaints.
6.6 ****.

2
2
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7
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8
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8
13
13
13
13
13
13
13
15
17
17
18
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20
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25
27
27
27

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****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

ARTICLE 7
CO-OPERATION

7.1 Quarterly Review.
7.2 Governmental Agencies.
7.3 Records and Accounting by Patheon.
7.4 Inspection.
7.5 Access.
7.6 Notification of Regulatory Inspections.
7.7 Reports.
7.8 FDA Filings

ARTICLE 8
TERM AND TERMINATION

8.1 Initial Term.
8.2 Termination for Cause.
8.3 Obligations on Termination.

ARTICLE 9
REPRESENTATIONS, WARRANTIES AND COVENANTS

9.1 Authority.
9.2 Client Warranties.
9.3 Patheon Warranties.
9.4 Debarred Persons.
9.5 Permits.
9.6 No Warranty.

ARTICLE 10
REMEDIES AND INDEMNITIES
10.1 Consequential Damages.
10.2 Limitation of Liability.
10.3 Patheon.
10.4 Client.
10.5 Reasonable Allocation of Risk.

ARTICLE 11
CONFIDENTIALITY

11.1 Confidentiality.

ARTICLE 12
DISPUTE RESOLUTION

12.1 Commercial Disputes.
12.2 Technical Dispute Resolution.

ARTICLE 13

- ii -

27
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28
28
28
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29
29
30
30
30
30
32
33
33
33
33
34
35
35
36
36
36
36
36
37
37
38
38
38
38
39
39
39
40
41

MISCELLANEOUS
13.1 Inventions.
13.2 Intellectual Property.
13.3 Insurance.
13.4 Independent Contractors.
13.5 No Waiver.
13.6 Assignment.
13.7 Force Majeure.
13.8 Additional Product.
13.9 Notices.
13.10 Severability.
13.11 Entire Agreement.
13.12 Other Terms.
13.13 No Third Party Benefit or Right.
13.14 Execution in Counterparts.
13.15 Governing Law.

- iii -

41
41
42
42
43
43
43
44
44
44
45
45
46
46
46
46

MANUFACTURING AGREEMENT

THIS MANUFACTURING AGREEMENT (the "Agreement") made as of the 6 day of May, 2016

(“Effective Date”)

B E T W E E N:

PATHEON INC.,
a corporation existing under the laws of Canada,

(hereinafter referred to as "Patheon"),

- and -

VANDA PHARMACEUTICALS INC.,
a corporation existing under the laws of the State of Delaware in the United States of America,

(hereinafter referred to as the "Client").

America (“USA”) and Canada; and

WHEREAS, Client previously held the rights to the Product in the whole world other than the United States of

WHEREAS, Novartis previously held the rights to the Product for the USA and Canada; and

the Product for the USA and Canada were transferred to Client (the “Settlement Agreement”); and

WHEREAS, Novartis and Client entered into a settlement agreement on December 22, 2014 wherein the rights to

MSA”) to Client in connection with the Settlement Agreement; and

WHEREAS, Novartis assigned its manufacturing agreement with Patheon in respect of the Product (the “Novartis

WHEREAS, Client and Patheon intend that this Agreement shall supersede and replace, as of the Effective Date,

the Novartis MSA with respect to the Product;

- 1 -

(b)

(c)

ARTICLE 1

INTERPRETATION

1.1

Definitions.

The following terms shall, unless the context otherwise requires, have the respective meanings set out below and

grammatical variations of such terms shall have corresponding meanings:
"Active Materials" means the materials listed on Schedule D hereto;
"Active Materials Credit Value" means the value to be attributed to the Active Materials for certain purposes of this
Agreement, as set forth on Schedule D;
"Affiliate" means:
(a)

a business entity which owns, directly or indirectly, a controlling interest in a party to this Agreement, by stock
ownership or otherwise, only for so long as such ownership continues to exist; or
a business entity which is controlled by a party to this Agreement, either directly or indirectly, by stock ownership or
otherwise, only for so long as such control continues to exist; or

For the purposes of this definition, "control" means the ownership of shares carrying at least a majority of the votes in respect
of the election of the directors of a corporation.

“Agreement” has the meaning specified in the preamble;
“Annual Product Review Report” means the annual product review report as described in Title 21 of the United States
Code of Federal Regulations, Section 211.180(e);

"Annual Report" means the annual report to the FDA prepared by Client as described in Title 21 of the United States Code
of Federal Regulations, Section 314.81(b)(2);
"Annual Volume" means, if applicable, the minimum volume of Product estimated to be manufactured in any Year of this
Agreement as set forth in Schedule B hereto, which shall be prorated for the first Year of this Agreement;

- 2 -

"Applicable Laws" means (i) with respect to Patheon, the Laws of the Province of Ontario, being the jurisdiction where the
Manufacturing Site is located; and (ii) with respect to Client, the applicable Laws of all jurisdictions where the Products are
manufactured, distributed and marketed;

"Authority" means any governmental or regulatory authority, department, body or agency or any court, tribunal, bureau,
commission or other similar body in the Territory, whether federal, state, provincial, county or municipal;

“Bill Back Items” means third party fees and other items listed in Schedule B, excluding Components.

“Billing Currency” has the meaning specified in Section 1.2;

“Breach Notice” has the meaning specified in Section 8.2(a);

“Broader Intellectual Property Rights” has the meaning specified in Section 13.1(c);

"Business Day" means a day other than a Saturday, Sunday or a day that is a statutory holiday in the Province of Ontario,
Canada (with respect to Patheon only) or a day that is a statutory holiday in Washington, DC, USA (with respect to Client
only);

"cGMPs" means the rules concerning current and future good manufacturing practices specified by the EU/PIC guidelines
(and the corresponding national laws and regulations), the US Code of Federal Regulations, or any other regulatory
guidelines made thereunder, as applicable;

“Change of Control” shall mean the merger with, transfer to or acquisition of beneficial ownership of more than fifty percent
(50%) of the outstanding voting shares of Patheon by a competitor of Client; “competitor” shall mean a pharmaceutical
manufacturer which manufactures, markets, or has in its pipeline for development or commercialization, proprietary
pharmaceutical and/or proprietary consumer health products within the therapeutic area of the Product.

“Client Property” has the meaning specified in Section 8.3(d);

“CMC” has the meaning specified in Section 7.8(c);

“Components” means Raw Materials, Primary and Secondary Packaging Components and Printed Packaging Components,
but for certainty, excludes Active Materials.

"Confidentiality Agreement" means the agreement relating to the non-disclosure of confidential information between
Patheon and the Client dated February 28, 2006, as amended;

- 3 -

“Deficiencies” has the meaning specified in Section 7.8(d);

"Deficiency Notice" shall have the meaning ascribed thereto in Section 6.1(a);

“Delivery Date” has the meaning specified in Section 5.1(b);

“Disclosure Obligations” has the meaning set forth in Section 11.1;

“Effective Date” has the meaning specified in the preamble;

"EMEA" means the European Medicines Agency;

"FDA" means the United States government department known as the Food and Drug Administration;

"Firm Orders" has the meaning specified in Section 5.1(b);

“Force Majeure Event” has the meaning specified in Section 13.7;

"Health Canada" means the section of the Canadian Government known as Health Canada and includes, among other
departments, the Therapeutic Products Directorate and the Health Products and Food Branch Inspectorate;

“Initial Set Exchange Rate” means 1.374 (3 digits) as of the Effective Date of the Agreement being the initial exchange rate
to convert one unit of the Billing Currency into Patheon’s Manufacturing Site local currency;

"Initial Term" has the meaning specified in Section 8.1;

"Intellectual Property" includes, without limitation, rights in patents, patent applications, formulae, trade-marks, trade-mark
applications, trade-names, Inventions, copyright and industrial designs and all other intellectual and industrial property rights
of any sort throughout the world now known or hereafter recognized;

"Invention" means any idea, concept, innovation, improvement, development, discovery, technology, computer program,
device, trade secret, work of authorship, formula, compound, method, know-how, process, technique or the like, whether or
not written or otherwise fixed in any form or medium, regardless of the media on which it is contained and whether or not
patentable or copyrightable, that is conceived or reduced to practice by one or more person(s) in the course of the
performance of this Agreement;

“JAMS” means Judicial Arbitration and Mediation Services, Inc.;

- 4 -

“Late Delivery” has the meaning specified in Section 5.5;

"Laws" means all laws, statutes, ordinances, regulations, rules, by-laws, judgments, decrees or orders of any Authority;

"Manufacture or Manufacturing " means any one of more of the manufacturing, quality control, quality assurance and
stability testing, packaging and related services, as contemplated in this Agreement, required to produce Products from Active
Materials, Raw Materials, Primary and Secondary Packaging Components and Printed Packaging Components;

“Manufacturing License” has the meaning specified in Section 5.5(c);

"Manufacturing Site" means the facility owned and operated by Patheon that is located at 2100 Syntex Court, Mississauga,
Ontario, Canada;

****

“Minimum Order Quantity” or “Run Quantity” means the minimum number of units of a Product to be Manufactured (if
applicable) in order to obtain the Price as set forth in Schedule B hereto.

“Order Countries” means, collectively, all countries in the Territory for which Vanda places Orders hereunder;

“PPI” has the meaning specified in Section 4.2(a);

"Primary and Secondary Packaging Components" means, collectively, all packaging components required to be used in
order to produce the Products in accordance with the Specifications, other than the Printed Packaging Components;

"Printed Packaging Components” means labels, inserts or other printed materials affixed to or accompanying Product(s) as
required by the Specifications;

Product(s)" means the products listed on Schedule A hereto;

“Product Claims” has the meaning specified in Section 6.3(c);

"Quality Agreement" means the agreement between the parties hereto setting out the quality assurance standards to be
applicable to the Manufacturing performed by Patheon, which agreement shall be finalized and entered into by the parties
within thirty (30) days after the Effective Date and may be amended from time to time by mutual written agreement of the
parties;

“Raw Materials” means all excipients or other starting materials used to manufacture a batch of bulk, unpackaged
Product(s), excluding the Active Materials;

- 5 -
****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

“Recall” has the meaning specified in Section 6.2(a);

"Regulatory Authority" means the FDA, EMEA and Health Canada and any other foreign regulatory agencies competent to
grant marketing approvals for pharmaceutical products including the Products in the Territory;

“Remediation Period” has the meaning specified in Section 8.2(a);

“Reset Date” means, with reference to any particular (and applicable) Year, the date on which Patheon is to provide Client
with updated pricing for the Product for the next Year; which date will be not less than one month prior to the beginning of
that Year;

“SEC” has the meaning set forth in Section 11.1;

“Set Exchange Rate” means the exchange rate to convert one unit of the Billing Currency into Patheon’s Manufacturing Site
local currency for each applicable Year, calculated as the average daily interbank exchange rate for conversion of one unit of
the billing currency into Patheon’s Manufacturing Site local currency during the one year period immediately preceding the
Reset Date by one month as published by OANDA.com “The Currency Site” under the heading “FxHistory: historical
currency exchange rates” at www.OANDA.com/convert/fxhistory;

"Specifications" means the file, for each Product, which is provided by the Client to Patheon in accordance with the
procedures listed in Schedule A hereto and which contains documents relating to such Product, including, without limitation:

(a)

specifications for Active Materials, Raw Materials, Primary and Secondary Packaging Components and Printed
Packaging Components;

(b) Manufacturing specifications, directions and processes;

(c)

storage requirements;

(d) all environmental, health and safety information relating to the Product including material safety data sheets; and

(e) the finished Product specifications, packaging specifications and shipping requirements for each Product;

all as updated, amended and revised from time to time by the Client in accordance with the terms of this Agreement;

“Surplus New Product” has the meaning specified in Section 5.3;

"Technical Dispute" has the meaning specified in Section 12.2;

- 6 -

"Technical Information" means all documents and materials generated by the Client and Patheon, as the case may be, as
well as all written amendments thereto, including without limitation, manufacturing and quality control instructions or
requirements under any quality control agreements between the parties (including the Quality Agreement), and specifications
necessary to manufacture, label, package, store, handle, stability test, quality control test and release of the Product, all in
accordance with this Agreement.

“Territory” means in the geographic area of the United States of America, Canada, European Union, Israel, Singapore,
South Korea, Mexico and Australia and any other geographic areas as may be added to this definition from time-to-time by
Client (in its sole discretion) by written notice to Patheon;

"Third Party Rights" means the Intellectual Property of any third party;

“Wind-Down Period” has the meaning specified in Section 8.3(d);

"Year" means in the first year of this Agreement the period from the Effective Date up to and including December 31 of the
same calendar year, and thereafter shall mean a calendar year.

1.2

Currency.

Unless otherwise indicated, all monetary amounts are expressed in this Agreement in the lawful currency of the United

States of America.

1.3

Sections and Headings.

The division of this Agreement into Articles, sections, subsections and Schedules and the insertion of headings are for
convenience of reference only and shall not affect the interpretation of this Agreement. Unless otherwise indicated, any reference
in this Agreement to a Section or Schedule refers to the specified Section or Schedule to this Agreement. In this Agreement, the
terms "this Agreement", "hereof", "herein", "hereunder" and similar expressions refer to this Agreement and not to any
particular part, Section, Schedule or the provision hereof, and unless the context of this Agreement otherwise requires, "include",
"includes" and "including" are not limiting.

1.4

Singular Terms.

Except as otherwise expressly provided herein or unless the context otherwise requires, all references to the singular shall

include the plural and vice versa.

1.5

Schedules.

The following Schedules are attached to, incorporated in and form part of this Agreement:

- 7 -

Schedule A - Product List
Schedule B - Commercial Pricing
Schedule C - Stability Testing
Schedule D - Active Materials, Active Materials Credit Value & ****
Schedule E - Batch Numbering & Expiration Dates
Schedule F - Technical Dispute Resolution
Schedule G - Intentionally Omitted
Schedule H - Quarterly Active Materials Inventory Report
Schedule I - Report of Annual Active Materials Inventory Reconciliation and Calculation of Actual Annual

Yield

**** - ****
Schedule K - Intentionally Omitted
Schedule L - Example of Price Adjustments under Section 4.2

ARTICLE 2

PATHEON'S MANUFACTURING

2.1 Manufacturing.

In accordance with Client’s Firm Orders, Patheon shall perform Manufacturing for the Territory at the Manufacturing Site
for the fees specified in Schedules B and C in order to produce Products for the Client. Patheon may change the Manufacturing
Site for the Products ****. If Manufacturing has not commenced within **** months after the date of execution of this
Agreement, Patheon reserves the right, in good faith, to amend the fees set out in Schedules B and C provided that the delay in
the commencement of the Manufacturing does not arise or result from the acts or omissions of Patheon. In providing the
Manufacturing, Patheon and the Client agree that:

(a)

(b)

Conversion of Active Materials and Components. Patheon shall convert Active Materials and Components into
Products.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 8 -

(c)

(d)

(e)

Components. Patheon shall purchase and test all Components (with the exception of those that are supplied by the
Client), in accordance with the Specifications. The parties shall agree upon a list of key components and shall
work together to identify a list of critical vendors of such key components. Patheon shall, with the reasonable
assistance of the Client where applicable, use commercially reasonable efforts to ****. The cost of Components is
included in the Price quoted in Schedule B.

Stability Testing. If applicable, Patheon shall conduct stability testing on the Products in accordance with the
protocols set out in Schedule C for the separate fees specified in Schedule C. Patheon shall not make any changes
to these testing protocols without prior written approval from the Client. In the event of a confirmed stability test
failure, Patheon will notify the Client within ****, after which Patheon and the Client shall jointly determine the
proceedings and methods to be undertaken to investigate the causes of such failure, including which party shall
bear the cost of such investigation****. Patheon will promptly provide any and all data and results relating to the
stability testing upon request by the Client.

Packaging. Patheon shall package the Products as set out in the Specifications. The Client shall be responsible for
the cost of artwork development for the Printed Packaging Components. Patheon will be responsible for obtaining
the Components. Patheon shall make arrangements for and implement the imprinting of batch numbers and
expiration dates for each Product shipped. Such batch numbers and expiration dates shall be affixed on the
Products and on the shipping carton of each Product as outlined in the Specifications and as required by cGMPs.
The system used by Patheon for batch numbering and expiration dates is detailed in Schedule E hereto. The Client
may, in its sole discretion, make changes to labels, product inserts and other packaging for the Products, which
changes shall be submitted by the Client to all applicable governmental agencies and other third parties
responsible for the approval of the Products. The Client shall be responsible for the cost of labelling obsolescence
when changes occur, as contemplated in Section 4.4. Patheon's name shall not appear on the label or anywhere
else on the Products unless: (i) required by any applicable Laws; or (ii) Patheon expressly consents to such use of
its name in writing.

(f)

Active Materials. The Client will deliver all Active Materials as mutually agreed upon by the parties to Patheon
DDP (Incoterms 2010).

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 9 -

(g)

(h)

Bill Back Items. The expenses in respect of all third party supplier fees for the purchase of those items specifically
identified in Schedule B as Bill Back Items that are necessary for Patheon to perform the Manufacturing shall be
charged to the Client ****. Any invoices for such items shall include reasonable documentation of the costs of
such items. Any and all orders in excess of **** for any such items require the prior written approval of the
Client. For certainty, the cost of Components is included in the Price quoted in Schedule B, and therefore,
Components are not included in Bill Back Items.

Requirements. Client hereby agrees to order at least **** of its total Yearly requirement in the Territory for new
units of Products **** (the “Patheon Requirement”) from Patheon. However, Client may order any part or all of
the Patheon Requirement from a third party supplier in the event that Patheon ****. In addition, ****.
Notwithstanding the foregoing, Patheon acknowledges and agrees **** shall not be counted in determining
Client’s “total Yearly requirement in the Territory for new units of Products” (i.e., Client may order Product from
other suppliers at any time during the term of this Agreement as reasonably necessary to validate such suppliers,
and Client may use, market, sell, distribute or transfer such Product, without breach of this Section 2.1(h)). For the
sake of clarity, during those Years in which Client orders Product from a third party supplier in accordance with
the terms in this subsection, then in no event shall Client be deemed to be in breach of this Section 2.1(h) if it does
not purchase at least **** of its total Yearly requirement for new units of Products from Patheon.

2.2

Active Material Yield.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 10 -

Quantity Received: The total quantity of Active Materials that complies with the Specifications and is received at the
Manufacturing Site during the applicable period.
Quantity Dispensed: The total quantity of Active Materials dispensed at the Manufacturing Site during the applicable
period. The Quantity Dispensed is calculated by adding the Quantity Received to the inventory of Active Materials that
complies with the Specifications and is held at the beginning of the applicable period, less the inventory of Active
Materials that complies with the Specifications and is held at the end of such period. The Quantity Dispensed shall only
include Active Materials received and dispensed in connection with commercial manufacturing of any Products and, for
certainty, shall not include any (i) Active Materials that must be retained by Patheon as samples, (ii) Active Materials
contained in any Product that must be retained as samples, (iii) Active Materials used in connection with testing (if
applicable) and (iv) Active Materials received or dispensed in connection with technical transfer activities or development
activities during the applicable period, including, without limitation, any regulatory, stability, validation or test batches
manufactured during the applicable period.

Patheon will target within ****, but within no more than **** after the **** of each ****, Patheon shall prepare an annual
reconciliation of Active Materials in accordance with the reconciliation report form annexed hereto as Schedule I including the
calculation of the "Actual Annual Yield" or "AAY" for the Products (including all strengths) at the Manufacturing Site during
the Year. AAY is the percentage of the Quantity Dispensed that was converted to Products and is calculated as follows:

Quantity Converted during the Year x 100%
Quantity Dispensed during the Year

Patheon shall use its commercially reasonable efforts to obtain maximum yield of the Products from Active Materials provided
by the Client in connection with its Manufacturing services provided hereunder. The target yield in respect of the Products at the
Manufacturing Site is **** ("Target Yield"). The parties will meet annually to

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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review the acceptable Target Yield and adjust it as appropriate in order to achieve the parties’ objective to move towards an
improved target yield. Patheon shall strive to maintain Actual Annual Yield levels for the Products equal to or above the current
Target Yield. For the sake of clarity, the AAY and the Target Yield are each calculated for all of the Products as a whole, and not
on a strength-by-strength or packaging-by-packaging basis.

(b) Shortfall Calculation. If the Actual Annual Yield falls more than **** below the respective Target Yield in a Year,

then the shortfall for such Year (the "Shortfall") shall be determined based on the following calculation:

The Shortfall shall be disclosed by Patheon on the reconciliation report prepared in the form annexed hereto as Schedule I.

(c) Credit. If there is a Shortfall for the Products in a Year, then Patheon shall credit the Client’s account for the value of

any such Shortfall, as determined using the following formula, not later than **** after the end of each Year.

Shortfall = ****

****

(d) ****. Notwithstanding the foregoing provisions of this Section 2.2, Patheon's liability for Active Materials

calculated in accordance with Section 2.2(c) for the Products in a Year ****.

(e) No Material Breach. It shall not constitute a material breach of this Agreement by Patheon, for the purposes of

Section 8.2(a), if the ****.

(f) Use of Active Materials. Patheon shall always use the first-expiry, first-out (FEFO) method of material usage.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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ARTICLE 3

CLIENT'S OBLIGATIONS

3.1

Payment.

Pursuant to the terms of this Agreement, the Client shall pay Patheon for the provision of the Manufacturing according to

the fees specified in Schedules B and C hereto (such fees being subject to adjustment in accordance with the terms hereof).
3.2 Supply of Active Materials.

Client shall, at its sole cost and expense, deliver the Active Materials to Patheon (in accordance with Section 2.1(f)) in
sufficient quantities and at such times as mutually agreed upon by the parties to facilitate the provision of the Manufacturing by
Patheon. The Active Materials shall be held and stored by Patheon on behalf of the Client on the terms and subject to the
conditions herein contained, the Specifications, cGMPs and any written instructions provided by the Client to Patheon from time
to time. Title to the Active Materials shall at all times belong to and remain the property of the Client. Any Active Materials
received by Patheon shall only be used by Patheon to provide the Manufacturing. Patheon will not chemically or biologically
modify the Active Materials except in accordance with the Specifications. Patheon's liability with respect to any lost or damaged
Active Materials shall be as set forth in Section 10.2(a). Patheon will store Active Materials in a secure manner and in accordance
with the Specifications.

ARTICLE 4

CONVERSION FEES AND COMPONENT COSTS

4.1

First Period Pricing.

The fees for the Manufacturing through **** are listed in Schedules B and C and are subject to the adjustments set forth

in Section 4.3.

4.2

Price Adjustments - Subsequent Years’ Pricing.

The fees for the Manufacturing during any period following the date set forth in Section 4.1 of this Agreement shall be

determined in accordance with the following:

(a)
Manufacturing and Component Costs. On each **** of this Agreement after **** (i.e., on **** and each ****
thereafter during the term of this Agreement), Patheon and the Client shall be entitled to an adjustment to the fees (i) for
Manufacturing in respect of the Products to reflect inflation, which adjustment shall be solely based on ****

****, unless the parties otherwise agree in writing and (ii) for Component costs ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(b)

Annual Quantity.

The Client acknowledges that the fee for Manufacturing in respect of a Product in any Year is quoted based upon the
Annual Volume and Minimum Order Quantity per Product specified in Schedule B (if applicable) and is subject to change
following good faith discussions by the parties if the specified Annual Volume or Minimum Order Quantity (if and as
applicable) increases or decreases. For greater certainty, if Patheon and the Client agree that the Annual Volume or
Minimum Order Quantity (if and as applicable) in respect of a Product shall be reduced beyond the range of such values
provided in the tables in Schedule B, and, as a result of such reduction, Patheon's costs for services relating to such
Product increase on a per unit basis, then Patheon shall be entitled to an increase in the fee for Manufacturing in respect of
such Product. In addition, for greater certainty, if Patheon and the Client agree that the Annual Volume or Minimum Order
Quantity (if and as applicable) in respect of a Product shall be increased beyond the range of such values provided in the
tables in Schedule B, and, as a result of such increase, Patheon's costs for services relating to such Product decrease on a
per unit basis, then the Client shall be entitled to a decrease in the fee for Manufacturing in respect of such Product.

(c)
Adjustments Due to Currency Fluctuations. On each **** following the date set forth in Section 4.1 of this
Agreement (i.e., on **** and each **** thereafter during the term of this Agreement), ****. The adjustment will be
calculated after all other fee adjustments under this Section 4.2 have been made. The adjustment will proportionately
reflect the increase or decrease, if any, in the Set Exchange Rate compared to the Set Exchange Rate established for the
prior Year or the Initial Set Exchange Rate, as the case may be. An example of the calculation of the price adjustment is
set forth in Schedule K.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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documents available, subject to the confidentiality obligations provided in this Agreement, to a third party designated by Client
and approved by Patheon (such approval not to be unreasonably withheld or delayed) at Patheon’s facility for the purpose of
allowing such third party to confirm that the fee adjustments proposed by Patheon are justified. Upon delivery of such a fee
adjustment request pursuant to this Section, each of the Client and Patheon shall forthwith use reasonable efforts to agree on a
revised fee for the Manufacturing in respect of each affected Product, if any, and Schedule B shall be amended accordingly. If the
parties are unable to agree on a revised fee for the Manufacturing in respect of each affected Product within **** after receipt by
Client of Patheon’s fee adjustment request, then ****. The revised fee shall be effective with respect to any Product ordered after
the end of the then current **** or the date set forth in Section 4.1 of this Agreement, as applicable. For the sake of clarity, the
revised fee shall not affect any Product ordered before the end of the then current **** or the date set forth in Section 4.1 of this
Agreement, as applicable, even if such Product has not yet been delivered by the date of the fee change. An example of price
adjustments under this Section 4.2 is shown in Schedule L.

4.3

Price Adjustments – Current Year Pricing.

During any Year of this Agreement, the fees set out in Schedule B shall be subject to adjustment in accordance with the

following:

(a)
Minimum Order Quantity. Subject to and without limiting Section 5.3, if at any time and from time to time
Patheon or Client determines, acting reasonably and based on the forecasts and Firm Orders received from the Client, that
the current Minimum Order Quantity (if applicable) listed in Schedule B for each specific Product strength will either not
be met or will be exceeded (i.e., the actual Minimum Order Quantity and the costs of such variations, exceed the range of
such value(s) provided in the tables in Schedule B), then Patheon or Client shall be entitled to request an adjustment to the
fee for Manufacturing in respect of that Product to reflect the increased or decreased costs that Patheon will incur as a
result of the increased or reduced volumes beyond the range of such values provided in the tables in Schedule B. To the
extent that the fee for Manufacturing in respect of a Product has been previously adjusted pursuant to this clause (a) to
reflect reduced volumes or increased volumes, the adjustment provided in this clause (a) shall operate based on the fees
attributed to such Product at the time the last of such adjustments were made.

Extraordinary Increase or Decrease in Component Costs. If at any time market conditions result in Patheon's Components
costs being *** than normal forecasted increases or decreases, then Patheon or Client shall be entitled

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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to an adjustment to the fee for Manufacturing in respect of any affected Product solely to compensate it for such increased
or decreased Components costs that may be justified by reasonable documentation, provided that to the extent such
documents are subject to obligations of confidentiality between Patheon and its suppliers, Patheon shall make such
documents available, subject to the confidentiality obligations provided in this Agreement, to a third party designated by
Client and approved by Patheon (such approval not to be unreasonably withheld or delayed) at Patheon’s facility for the
purpose of allowing such third party to confirm that the fee adjustments proposed by Patheon are justified. For the
purposes of this clause (b), changes materially greater than normal forecasted increases or decreases shall be considered to
have occurred only if: (i) ****; or (ii) ****. To the extent that Component costs have been previously adjusted pursuant to
clause (a) of Section 4.2 or this clause (b) to reflect an increase or decrease in the cost of one or more Components, the
adjustments provided for in (i) and (ii) above shall operate based on the costs attributed to such Components at the time
the last of such adjustments were made.

In connection with a fee adjustment request pursuant to this Section 4.3, Patheon shall deliver to the Client a revised
Schedule B and such budgetary pricing information or other documentation reasonably sufficient to demonstrate that an
increase or decrease in fee adjustment is justified (and/or upon the reasonable request of Client, such budgetary pricing
information or other documentation reasonably sufficient to demonstrate to Client that a decrease in the fee adjustment is
not justified), provided that to the extent such documents are subject to obligations of confidentiality between Patheon and
its suppliers, Patheon shall make such documents available, subject to the confidentiality obligations provided in this
Agreement, to a third party designated by Client and approved by Patheon (such approval not to be unreasonably withheld
or delayed) at Patheon’s facility for the purpose of allowing such third party to confirm that the fee adjustments proposed
by Patheon are justified. Upon delivery of such a request, each of the Client and Patheon shall forthwith use all reasonable
efforts to agree on a revised fee for the Manufacturing in respect of each affected Product and Schedule B shall be
amended accordingly. If the parties are unable to agree on a revised fee for the Manufacturing in respect of each affected
Product within **** after receipt by Client of Patheon’s fee adjustment request, then ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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Patheon will use commercially reasonable efforts to ensure that the increases in cost of Components and Bill Back Items
will not be materially greater than normal forecasted increases.

4.4

Adjustments Due to Technical Changes.

Amendments to the Specifications or the Quality Agreement requested by the Client will only be implemented following
a good faith technical and cost review by Patheon and are subject to the Client and Patheon reaching agreement in writing as to
revisions, if any, to the fees specified in Schedules B or C necessitated by any such amendment. Amendments to the
Specifications, the Quality Agreement or the Manufacturing Site or any material deviations from the assumptions specified in
Schedule B requested by Patheon will only be implemented following the written approval of Client, such approval not to be
unreasonably withheld. If the Client accepts the proposed fee change (if any), the proposed change in the Specifications or the
Quality Agreement requested by Client shall be implemented, and the fee change shall become effective only with respect to
those orders of Products that are manufactured in accordance with the revised Specifications or Quality Agreement. In addition,
the Client agrees ****. If the parties are unable to agree on what costs incurred by Patheon are reasonable, then the parties shall
resolve such issue in accordance with Section 12.1 Open purchase orders for Components and Bill Back Items no longer required
under any revised Specifications or Quality Agreement that were placed by Patheon with suppliers in order to fill Firm Orders or
in accordance with Section 5.2 shall be cancelled or used in connection with other Patheon services where possible, and where
such orders are not subject to cancellation without penalty or cannot be used in connection with other Patheon services, Client
shall pay to Patheon ****.

4.5 Multi-Country Packaging Requirements.

Prices in Schedule B are for bulk or packaged (with Primary and Secondary Packaging Components and/or Printed
Packaging Components, as applicable) Product(s). Should Client wish to have Patheon provide Manufacturing in respect of the
Product in

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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additional packaging formats, Patheon shall, in good faith, prepare a quotation for consideration by the Client of the additional
Primary and Secondary Packaging Component costs and Printed Packaging Components costs, if any, and the change over fees
for the Product. The agreed additional packaging requirements and related packaging costs and change over fees shall be set out
in a written amendment to this Agreement mutually agreed upon by the parties.

4.6

Improvement of Manufacturing Efficiency.

EACH OF PATHEON AND THE CLIENT SHALL USE ITS REASONABLE EFFORTS TO IMPROVE PRODUCT
MANUFACTURING EFFICIENCY, WHEN AND WHERE POSSIBLE, DURING THE TERM OF THIS
AGREEMENT. ANY COST SAVINGS RESULTING IN WHOLE OR IN PART FROM CONTRIBUTIONS BY THE
CLIENT SHALL BE ****.

ARTICLE 5

ORDERS, SHIPMENT, INVOICING, PAYMENT

5.1

Orders and Forecasts.

(a)

Rolling Forecasts. Concurrent with the execution of this Agreement, the Client shall provide Patheon with a
written **** forecast of the volume of each Product that the Client then anticipates will be required to be produced and delivered
to the Client during ***. Such forecast will be updated by the Client **** on or before the **** of **** on a ****, and the
Client shall use commercially reasonable efforts to update such forecast forthwith if the Client determines that the volumes
contemplated in the most recent of such forecasts for the next **** has changed by more than ****. The most recent ****
forecast shall prevail.

(b)

Firm Orders. On or before the **** of each ****, the Client shall issue a firm written order ("Firm Order") for
Manufacturing in respect of the Products to be produced and released to the Client on one (1) or more dates not less than ****
from the first day of the calendar month immediately following the date that the Firm Order is submitted (each, a “Delivery
Date”). For clarity, Products will be placed at Client’s disposal for collection by Client’s carrier on the date of release by Patheon
Quality Control. Such date of Patheon Quality Control release shall be deemed to be the Delivery Date. Such Firm Orders
submitted to Patheon shall specify the Client's Manufacturing purchase order number, quantities by Product type, monthly
delivery schedule, shipment location and any other elements necessary to ensure the timely production and shipment of the
Products. The quantities of Products ordered in such Firm Orders shall be ****. In the event that Client cancels

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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any or part of a Firm Order, Client shall be responsible for **** of such cancelled part of a Firm Order, provided that if Client
informs Patheon at any time during the **** of this Agreement, at **** prior to the commencement of dispensing, that it would
like to cancel any or part of such Firm Order, then ****. Patheon shall indicate its acceptance of Firm Orders for the Product by
promptly acknowledging acceptance of each Firm Order in writing within **** of its receipt; each such acceptance shall include,
subject to Client confirmation, the Delivery Date for the Product ordered. The agreed upon Delivery Date may be amended from
time to time by written agreement of the parties, with the newly agreed upon date becoming the new Delivery Date. For the
avoidance of doubt, Patheon will accept all Firm Orders submitted by the Client for Product so long as ****. All Firm Orders
will be deemed to incorporate all of the terms and conditions in this Agreement.

(c)

**** Forecast. On or before the **** of **** of ****, the Client shall provide Patheon with a written ****
forecast (broken down by ****) of the volume of each Product the Client then anticipates will be required to be produced and
delivered to the Client during the ****.

5.2

Reliance by Patheon.

(a) The Client understands and acknowledges that Patheon will rely on the Firm Orders and rolling forecasts submitted
pursuant to Sections 5.1(a) and (b) in ordering the Components required to meet such Firm Orders. In addition, the Client
understands that to ensure an orderly supply of such Components and/or to achieve economies of scale in costs, it may be
necessary for Patheon to purchase such Components in sufficient volumes to meet the production requirements for Products
during part of the forecasted periods referred to in Section 5.1(a) or to meet the production requirements of any longer period
agreed to in writing by Patheon and the Client. Accordingly, the Client authorizes Patheon to purchase Components in order to
satisfy the Manufacturing requirements for Products for the **** contemplated in the most recent forecast provided by the Client
pursuant to Section 5.1(a)

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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or in order to satisfy the vendor’s minimum order quantity for such Components, whichever is greater, and agrees that Patheon
may make such other purchases of Components to meet Manufacturing requirements during such longer periods as may be
agreed to in writing from time to time by the Client at the request of Patheon or the Client. If Components ordered by Patheon
pursuant to Firm Orders or this Section 5.2 are not included in finished Products manufactured for the Client within **** after
the forecasted month in respect of which such purchases have been made (or such longer period as the parties may agree) or if
such Components have expired during such period, then the Client shall pay to Patheon ****. If the parties are unable to agree on
what costs incurred by Patheon are reasonable, then the parties shall resolve such issue in accordance with Section 12.1 Patheon
shall use commercially reasonable efforts to use such Components in connection with third party clients. Patheon shall be
responsible for obtaining material safety data sheets (“MSDS”) and certificates of analysis or compliance of all Raw Materials
purchased by Patheon pursuant to this Agreement. The MSDS and certificates of analysis or compliance will be used to establish
conformance of the Raw Materials to the Specifications and to advise Patheon as to any safety or special handling requirements
related to the Raw Materials.

(b) Patheon shall provide Client, initially upon execution of this Agreement and thereafter on an annual basis, with a
listing of all components which are unique to the Client, which Patheon anticipates purchasing pursuant to the terms of this
Agreement (in accordance with rolling forecasts and Firm Orders as per Section 5.2(a)) (the “Exclusive Component Purchasing
Summary”). The Exclusive Component Purchasing Summary shall indicate which components have a limited shelf-life and that
are subject to minimum order quantities as specified by the supplier.

5.3 Minimum Orders.

Patheon will only Manufacture Products in multiples of the Minimum Order Quantities as set out in Schedule B. Notwithstanding
the foregoing, the parties acknowledge and agree that ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****. With respect to Product supplied, after the **** following release by Patheon of the respective batch from which the
Product has been supplied (such release date to be notified by Patheon to the Client promptly following the release), the Client
shall pay Patheon **** per pallet per month thereafter for the time that Patheon is required to store any Surplus New Product on
behalf of the Client. If Surplus New Product requires refrigeration, then the applicable storage fee will be **** per pallet per
month for the time that Patheon is required to store such Surplus New Product on behalf of the Client. Storage fees are subject to
a ****. Patheon shall provide the Client with an annual invoice setting forth the cumulative storage fees associated with any
Surplus New Product.

Subject to the paragraph immediately below, the Client shall use commercially reasonable efforts to place Firm Orders with
Patheon in a timely manner to ensure that Surplus New Product can be packaged or shipped in compliance with the required
levels of remaining shelf life as indicated in this Agreement. In the event that the Client does not place Firm Orders in a timely
manner with the direct result that Surplus New Product cannot be supplied in accordance with the shelf life, and in the event that
the Client will not accept the Product with less than the required remaining shelf life, then the Client ****.

Without prejudice to any other rights and obligations that Patheon may have under the Agreement, Patheon will use
commercially reasonable efforts to manage its inventory so that such Surplus New Product can be supplied in accordance with
the terms of the Agreement for future Firm Orders placed by the Client and to manage its inventory of Surplus New Product to
comply with the requirements regarding shelf life mentioned above. In the event that the Client places a purchase order with
Patheon and the difference between the amount of new Product ordered and the amount of Surplus New Product that Patheon has
on stock is more or less than ****, then Patheon shall immediately inform the Client and provide the Client with an opportunity
to modify such purchase order.

5.4

Shipments.

Shipments of Products shall be made ****, unless otherwise mutually agreed in writing. Risk of loss or of damage to
Products shall remain with **** at which time risk of loss or damage (and title to such Products) shall transfer to ****. ****
shall, in accordance with ****, (i) arrange for shipping to be paid by the Client and (ii) at **** risk and expense, obtain any
export license or other official authorization necessary to export the Products. **** shall arrange for insurance and shall select
the freight carrier to be used by **** to ship Products and may

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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monitor **** shipping and freight practices as they pertain to this Agreement. Products shall be packaged for transport and
transported in accordance with the Specifications, and temperature monitors (as mutually agreed upon by the parties) will be
included with each shipment of Products. The residual shelf life of the Product must be at least **** following release of the
Product by Patheon.

5.5

On Time Delivery

(a)

(b)

If subsequent to the creation of a delivery plan, Patheon is unable to supply the Client with the quantity of Product
ordered pursuant to the Firm Order within **** following the Delivery Date and ****, then that inability to supply will constitute a
late delivery of Product (“Late Delivery”), and the Client ****. If the parties mutually agree in writing to change the Delivery
Date for any reason then that new date becomes the Delivery Date.

**** In no event shall the Late Delivery ****. Patheon acknowledges that ****.

No credit for Late Delivery will occur in the event the Late Delivery is caused by a Force Majeure Event (as defined below) or by
other events outside of Patheon’s reasonable control, including, but not limited to, delays in: ****. Additionally, on time delivery
credits provided for in this Section are only available to Client if ****.

(c)

Upon the written request of Client, Patheon shall agree to assist, at Client’s cost, in ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****. Patheon shall ensure that it has enforceable written agreements with its approved subcontractors ****. Upon Client’s
request, Patheon shall immediately co-operate with Client to ****.

Notwithstanding the foregoing, ****.

Client shall not be liable to pay the direct costs incurred by Patheon and/or any approved subcontractor in assisting and/or

supporting the respective ****. All such reasonable costs shall be borne by Patheon and/or its approved subcontractors.

5.6

Invoices and Payment.

Invoices shall be sent by fax or email to such fax number or email address as may be provided by the Client in writing
from time to time. Such invoices for Products may only be sent **** (with respect to which such invoices apply) in accordance
with the Quality Agreement, and such invoices shall reflect any outstanding credit amounts owed under this Agreement by
Patheon to Client. Patheon shall also submit to the Client, with each shipment of Products, a duplicate copy of the invoice
covering such shipment. Patheon shall also provide the Client with an invoice covering any Component which has been
purchased by Patheon pursuant to the terms of this Agreement and which has not been used in accordance with the terms of this
Agreement. Patheon will include sufficient details in all such invoices to enable identification of such Component. Each such
invoice shall, to the extent applicable, identify the Client’s Manufacturing purchase order number, Product numbers, names and
quantities, unit price, freight charges and the total amount to be remitted by the Client (after taking into account any outstanding
credit amounts owed under this Agreement by Patheon to Client). The Client shall pay all undisputed amounts in such invoices
within **** of the date thereof provided, however, that payment will only be for ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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5.7

Inventory Reports.

Patheon hereby agrees to provide to the Client a monthly inventory statement at the end of each calendar month of this
Agreement setting out as a minimum the amount of Active Materials and Product (in bulk and finished form) that Patheon is
holding in stock at the Manufacturing Site.

ARTICLE 6

PRODUCT CLAIMS AND RECALLS

6.1

Product Claims.

(a)

Product Claims. The Client has the right to reject any portion of any shipment of Products that deviates from the
**** any remainder of such shipment. The Client shall inspect the Products manufactured by Patheon upon receipt thereof and
shall give Patheon written notice (a "Deficiency Notice") of all claims for Products that deviate from the **** within **** after
the Client’s receipt thereof (or, in the case of any defects not reasonably susceptible to discovery upon receipt of the Product,
within **** after discovery thereof by the Client, but in no event after the expiration date of the Product). Should the Client fail
to provide Patheon with the Deficiency Notice within the applicable period, then the delivery shall be deemed to have been
accepted by the Client on the **** after delivery or **** after discovery, as applicable. Except as otherwise provided in this
Agreement, Patheon shall have no liability for any deviations for which it has not received notice within the applicable period.
For the sake of clarity, if the Client does not provide a Deficiency Notice within **** after Client’s receipt of the applicable
Product, but instead provides a Deficiency Notice within **** after discovery of a defect not reasonably susceptible to discovery
upon receipt of the Product, then Client retains its rights and remedies with respect to the defective Product.

(b)

Determination of Deficiency. Upon receipt of a Deficiency Notice, Patheon shall have **** to advise the Client
by notice in writing that it disagrees with the contents of such Deficiency Notice. If the Client and Patheon fail, after good faith
discussions, to agree within **** after Patheon's notice to the Client as to whether any Products identified in the Deficiency
Notice deviate from the Specifications or cGMPs, then the parties shall mutually select an independent laboratory to evaluate if
the Products deviate from ****. Such evaluation shall be binding on the parties, and if such evaluation certifies that any Products
deviate from ****, the Client may reject those Products in the manner contemplated in this Section 6.1. If such evaluation does
not so certify in respect of any such Products, then the Client shall be deemed to have accepted delivery of such Products on the
**** after delivery (or, in the case of any defects not reasonably susceptible to discovery upon receipt of the Product, on the ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 24 -

after discovery thereof by the Client, but in no event after the expiration date of the Product). The decision of the laboratory shall
be binding on the parties, and the party that the decision disfavours shall bear the costs charged by such laboratory in connection
with its decision.

be agreed to by the parties.

6.2

Product Recalls and Returns.
(a)

Records and Notice. **** shall each maintain such records as may be necessary to permit a Recall (as defined
below) of any Products delivered to the Client or customers of the Client. **** shall promptly notify **** by telephone (to be
confirmed in writing) of any information which is reasonably likely to adversely affect the marketability, safety or effectiveness
of the Products in a material manner and/or which might result in the Recall or seizure of the Products. Upon receiving any such
notice or upon any such discovery, **** shall cease and desist from further shipments of such Products in its possession or
control until a decision has been made whether a Recall or some other corrective action is necessary. The decision to initiate a
Recall or to take some other corrective action, if any, shall be made and implemented by ****. "Recall" shall mean any action (i)
by the Client to recover title to or possession of quantities of the Products sold or shipped to third parties (including, without
limitation, the voluntary withdrawal of Products from the market); or (ii) by any regulatory authorities to detain or destroy any of
the Products. Recall shall also include any action by either party to refrain from selling or shipping quantities of the Products to
third parties which would have been subject to a Recall if sold or shipped.

(b)

Recalls. In the event (i) any governmental or regulatory authority issues a directive, order or, following the
issuance of a safety warning or alert with respect to a Product, a written request that any Product be Recalled, (ii) a court of
competent jurisdiction orders such a Recall, or (iii) **** determines that any Product should be Recalled or that a "dear doctor"
letter is required relating to the restrictions on the use of any Product, Patheon will co-operate as reasonably required by the
Client, having regard to all applicable laws and regulations.

(c)

Product Returns. **** shall have the responsibility for handling customer returns of the Products. **** shall

provide **** with such assistance as **** may reasonably require to handle such returns.

6.3

Patheon’s Responsibility for Defective and Recalled Products.
(a)

Defective Product. In the event the Client rejects Products in accordance with Section 6.1 and the deviation is
determined to have arisen from Patheon’s failure to provide the Manufacturing in accordance with ****, Patheon shall promptly,
****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****. For greater certainty, Patheon’s responsibility for ****.

(b)

Recalled Product. To the extent that a Recall results from, or arises out of, a failure by Patheon to provide the
Manufacturing in accordance with ****, Patheon shall be responsible for ****. For greater certainty, Patheon’s responsibility for
****. In the event that Patheon is unable to replace the Recalled Products, then the Client may request Patheon to ****. In all
other circumstances, Recalls shall be made at the Client's cost and expense. Notwithstanding anything to the contrary in this
Agreement, PATHEON shall only be required to ****. The quantity of Active Materials contained in Product described above
shall be included in the Quantity Dispensed but not in the Quantity Converted for purposes of determining the Shortfall.

(c)

Patheon shall have no obligation for any deficiencies in, or other liabilities associated with, any Product

manufactured by it (collectively, “Product Claims”) to the extent such Product Claim ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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****.

6.4

Disposition of Defective or Recalled Products.

The Client shall not dispose of any damaged, defective, returned or Recalled Products in relation to which it intends to assert a
claim against Patheon without Patheon’s prior written authorization to do so. Alternatively, Patheon may instruct the Client to
return such Products to Patheon. Patheon shall bear the cost of disposition with respect to any damaged, defective, returned or
Recalled Products in relation to which it bears responsibility under Section 6.3 hereof. In all other circumstances, the Client shall
bear the cost of disposition, including all applicable fees for Manufacturing, with respect to any damaged, defective, returned or
Recalled Products.

6.5

Customer Questions and Complaints.

The Client shall have the sole responsibility for responding to questions and complaints from the Client's customers.
Questions or complaints received by Patheon from the Client's customers shall be promptly referred to the Client. Patheon shall
cooperate as reasonably required to allow the Client to determine the cause of and resolve any customer questions and
complaints. Such assistance shall include follow-up investigations, including testing. In addition, Patheon shall promptly provide
the Client with all mutually agreed upon information that will enable the Client to respond properly to questions or complaints
relating to the Products as provided in the Quality Agreement. Unless it is determined that the cause of any customer complaint
resulted from a failure by Patheon to provide the Manufacturing in accordance with ****.

6.6

****.

ARTICLE 7

CO-OPERATION

7.1

Quarterly Review.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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business relationship and manage any issues that have arisen. Each party may replace its relationship manager at any time and
will fill a vacancy for its relationship manager as soon as reasonably practicable. Each party shall promptly notify the other party
of any substitution of another person as its relationship manager. Each party’s relationship manager shall be available throughout
the term of this Agreement to answer any reasonable questions from the other party’s relationship manager.

7.2

Governmental Agencies.

7.3

Records and Accounting by Patheon.

7.4

Inspection.

During the term of this Agreement and for **** thereafter, or alternatively the period of time less than **** in which
Patheon is required to keep reports and records pursuant to Section 7.3, the Client may inspect Patheon reports and records
relating to this Agreement, including without limitation relating to the invoices issued hereunder, during normal business hours
and with reasonable advance notice, provided a Patheon representative is present during any such inspection.

7.5

Access.

Patheon shall provide the Client with reasonable access at mutually agreeable times (as discussed in good faith) to the

areas of the Manufacturing Site in which the

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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Products are manufactured, stored, handled or shipped in order to permit the Client's verification of the performance of the
Manufacturing in accordance with the Specifications, cGMPs, Applicable Laws, the Quality Agreement and other Technical
Information and this Agreement. For greater certainty, the right of access provided in this Section 7.5 shall not include a right to
access or inspect Patheon’s financial records.

7.6

Notification of Regulatory Inspections.

7.7

Reports.

Patheon will supply on an annual basis or as requested by Client at any other time all Product data in its control, including
release test results, complaint test results, and all investigations (in manufacturing, testing and storage), that the Client reasonably
requires in order to complete any filing under any applicable regulatory regime, including any Annual Report that the Client is
required to file with the FDA. All rights, title and interest in any and all data related to Product that is generated or derived by
Patheon in the course of performing the Manufacturing shall be the exclusive property of Client (and the confidential information
of ****). **** hereby makes, and agrees to make, any and all assignments necessary to effect, exclusively and throughout the
world, the ownership by **** of such data. **** shall, and shall cause its employees and contractors to, fully cooperate with and
sign any documents reasonably requested by **** to evidence, perfect or take any other action with respect to such assignments
or to obtain protection, maintain or take any other action regarding such assigned data.

7.8 FDA Filings

(a)

Regulatory Authority. The Client shall have the sole responsibility for filing all documents with all Regulatory
Authorities and taking any other actions that may be required for the receipt and/or maintenance of Regulatory Authority
approval for the commercial Manufacture of the Products. Patheon shall assist the Client, as is reasonable, to obtain Regulatory
Authority approval for the commercial Manufacture of all Products as quickly as reasonably possible.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(b)

Verification of Data. At least **** prior to filing any documents with any Regulatory Authority that incorporate

data generated by Patheon, the Client shall ****.

(c)

(d)

Deficiencies. If in Patheon’s sole discretion, acting reasonably, Patheon determines that any of the information
provided by the Client in accordance with paragraphs (b) and (c) above is inaccurate or deficient in any manner whatsoever, and
Patheon reasonably believes that Patheon’s standing with regulatory authorities may be jeopardized thereby (the "Deficiencies"),
Patheon shall notify the Client in writing of such Deficiencies promptly but in no event less than **** prior to Client’s applicable
scheduled filing with the Regulatory Authority. The parties shall work together in good faith to have such Deficiencies resolved
prior to any pre-approval inspection.

ARTICLE 8

TERM AND TERMINATION

8.1

Initial Term.

This Agreement shall become effective as of the Effective Date and shall continue for five (5) years following the
Effective Date (the "Initial Term"), unless terminated earlier by one of the parties in accordance herewith. This Agreement shall
automatically continue after the Initial Term for successive terms of one (1) year each unless either party gives written notice to
the other party of its intention to terminate this Agreement at least twelve (12) months prior to the end of the then current term.

8.2

Termination.

(a)

Either party at its sole option may terminate this Agreement as a whole or on a country-by-country basis upon
written notice in circumstances where the other party has failed to remedy a material breach of any of its representations,
warranties or other

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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obligations under this Agreement within **** following receipt of a written notice (the "Remediation Period") of said breach
that expressly states that it is a notice under this Section 8.2(a) (a "Breach Notice").

(b)

(c)

The Client may terminate this Agreement as to any Product or on a country-by-country basis upon **** prior
written notice in the event that any governmental agency takes any action, or raises any objection, that prevents the Client from
importing, exporting, purchasing or selling such Product.

(d)

(e)

A party may terminate this Agreement when permitted pursuant to Section 13.7.

(f)

The Client may terminate this Agreement as a whole or on a country-by-country basis due to Client’s
discontinuation of the development of Product manufactured at the Manufacturing Site, upon written notice delivered at least
**** prior to such discontinuation.

(g)

The Client may, upon the completion of **** of this Agreement, terminate this Agreement as a whole or with
respect to a particular countr(ies) at any time, for any or no reason, upon **** notice to Patheon, provided ****. The Client may,
upon the completion of **** of this Agreement, terminate this Agreement as a whole or with respect to a particular country(ies)
at any time, for any or no reason, upon ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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8.3

Obligations on Termination.

If this Agreement expires or is terminated in whole for any reason, then following the expiration or termination of this
Agreement, or the end of the Wind-Down Period, if applicable (in addition to any other remedies either party may have in the
event of default by the other party):

(a)

(b)

(c)

(d)

the Client shall purchase, at Patheon's cost ****, the remaining Components which were purchased by Patheon in
contemplation of filling Firm Orders or in accordance with Section 5.2 prior to notice of termination being given
to the extent that such Components cannot be returned or used to produce product for another client; and (ii) all
remaining work-in-process produced by Patheon in contemplation of filling Firm Orders prior to notice of
termination being given. If the parties are unable to agree on what costs incurred by Patheon are reasonable, then
the parties shall resolve such issue in accordance with Section 12.1

the Client acknowledges that no competitor of Patheon (as defined in Section 8.2(d)) shall be permitted access to
the Manufacturing Site.

Client will make commercially reasonable efforts, at its own expense but with Patheon’s reasonable cooperation,
to remove from Patheon site(s), within ****, all of Client’s Components, Active Materials and supplies,
undelivered Product and works-in-progress, chattels, equipment or other moveable property owned by Client,
related to the Agreement and located at a Patheon site or that is otherwise under Patheon’s care and control
(“Client Property”). If Client fails to remove the Client Property within **** following the termination or
expiration of the Agreement (or following the end of the Wind-Down Period, if applicable), Client will pay
Patheon **** per pallet, per month, one pallet minimum (**** per pallet, per month, one pallet minimum, for any
of the Client Property that contains controlled substances or requires refrigeration) thereafter for storing the Client
Property and will assume any third party storage charges invoiced to Patheon regarding the Client Property.
Patheon will invoice Client for the storage charges as set forth in Section 5.6 of this Agreement.

If this Agreement expires or is terminated in whole for any reason, then (in addition to any other remedies the Client may have in
the event of default by Patheon), Patheon shall

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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return to the Client all Client Property (with shipping and related expenses, if any, to be borne by the Client), following such
expiration or termination or the end of the Wind-Down Period, if applicable.

In addition, for a period of **** after the termination or expiration of this Agreement (the “Wind-Down Period”), Client may
continue to order Manufacturing, and Patheon shall continue to provide Manufacturing in accordance with such orders from
Client (if any), in each case subject to the terms and conditions of this Agreement. In the event of termination by Patheon
pursuant to Section 8.2(a) due to Client’s failure to pay undisputed amounts, Patheon may require that Client pay such amounts
before filling any Firm Orders and may require that Client pre-pay for any Manufacturing provided during the Wind-Down
Period. Furthermore, upon reasonable request by Client, Patheon will use commercially reasonable and good faith efforts to
discuss with Client and come to an agreement with Client with respect to the terms for the performance of other transition
services that are reasonably requested by Client.

Without limiting the foregoing, upon termination of this Agreement by Client pursuant to sections 8.1, 8.2 (a) or (b) or 13.7,
Client shall have the right, where applicable, to ****. In such circumstances, Patheon and its affiliates will co-operate, and use its
commercially reasonable efforts to cause its approved subcontractors to co-operate, in good faith with Client to ****. Any
termination or expiration of this Agreement shall not affect any outstanding obligations or payments due hereunder prior to such
termination or expiration, nor shall it prejudice any other remedies that the parties may have under this Agreement. For greater
certainty, termination of this Agreement for any reason shall not affect the obligations and responsibilities of the parties pursuant
to Articles 6, 8, 9, 10, 11, 12 and 13 and Sections 1.1, 7.3, 7.4, 7.5, 7.6 and 7.7, all of which survive any termination.

ARTICLE 9

REPRESENTATIONS, WARRANTIES AND COVENANTS

9.1

Authority.

9.2

Client Warranties.

The Client covenants, represents and warrants that, to the Client’s knowledge as of the Effective Date:

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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(a)

(b)

(c)

there are no actions or other legal proceedings in the Territory, the subject of which is the infringement of Third
Party Rights related to any of the Specifications, or the bulk Product or any of the Active Materials provided by
the Client to Patheon, or the sale, use or other disposition of any Product Manufactured in accordance with the
Specifications; and

the Products, if labelled and Manufactured in accordance with the Specifications and in compliance with
applicable cGMPs, Applicable Laws, the Quality Agreement and other Technical Information and this Agreement
(i) may be lawfully sold and distributed in every jurisdiction in which the Client has Regulatory Authority
approval to market such Products, (ii) ****, and (iii) will be safe for human consumption as directed on the
approved labelling for such Products.

In addition, Client covenants, represents and warrants that:

(i)

(ii)

the Specifications for each of the Products are its or its Affiliate's property or licensed to the Client and that the
Client may lawfully disclose the Specifications to Patheon;

to the Client’s knowledge as of the Effective Date, any Intellectual Property provided by the Client to Patheon in
connection with the provision of the Manufacturing according to the Specifications (i) is the Client’s or its
Affiliate's unencumbered property or is licensed to the Client, (ii) may be lawfully used as directed by the Client,
and (iii) to the Client’s knowledge as of the Effective Date, such use does not infringe and will not infringe any
Third Party Rights; and

(iii) the Specifications for all Products, as provided by the Client to Patheon, conform to all applicable cGMPs and

Applicable Laws.

9.3

Patheon Warranties.

Patheon covenants, represents and warrants that to Patheon’s knowledge as of the Effective Date:

(a)

any Intellectual Property owned by Patheon and utilized by Patheon in connection with the provision of the
Manufacturing which has not been

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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provided by Client or used at the direction of Client, (i) is Patheon’s or its Affiliate's unencumbered property, (ii) may be

lawfully used by Patheon and (iii) does not infringe and will not infringe any Third Party Rights;

(b)

(c)

it and its Manufacturing Site are in compliance with all laws and regulations applicable to their operations,
including, without limitation, cGMPs and Applicable Laws;

all Patheon personnel are fully qualified (by education, training and experience) to properly perform their tasks
under this Agreement.

In addition, Patheon covenants, represents and warrants that:

(i)

(ii)

(iii)

it shall perform the Manufacturing in accordance with the Specifications, cGMPs, Applicable Laws, the Quality
Agreement and other Technical Information and this Agreement;
it will convey good title to the Product, free of all liens of any kind whatsoever; and

the Products, when delivered to Client, will be Manufactured according to the Specifications. For the sake of
clarity, if Patheon performs any additional steps not specified in the Specifications in Manufacturing Products
(e.g., by adding one or more additional components to the Products that are not specified in the Specifications),
then Patheon will be deemed to have failed to Manufacture such Products in accordance with the Specifications.

The warranties provided in (i), (ii) and (iii) above shall survive inspection, test, acceptance and use of the Product.

Debarred Persons.

9.4
Patheon covenants that it will not in the performance of its obligations under this Agreement use the services of any person
debarred or suspended under 21 U.S.C. §335(a) or (b) or by Health Canada or any comparable European regulatory authority.
Patheon represents that it does not currently have, and covenants that it will not hire, as an officer, an employee or an independent
contractor in connection with the Manufacturing any person who has been convicted of a felony under the laws of the United
States for conduct relating to the regulation of any drug product under the Federal Food, Drug, and Cosmetic Act (United States)
or any comparable Canadian or European law. If Patheon becomes aware of any breaches of this Section, it will promptly notify
the Client.

9.5

Permits.
Patheon shall maintain at all relevant times all governmental permits, licenses, approvals, and authorities to the extent

required to enable it lawfully to properly perform

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the Manufacturing. The Client shall be solely responsible for obtaining or maintaining, on a timely basis, any permits or other
regulatory approvals in respect of the Products or the Specifications, including, without limitation, all marketing and post-
marketing approvals.

9.6

No Warranty.

ARTICLE 10

REMEDIES AND INDEMNITIES

10.1 Consequential Damages.

To the maximum extent permitted by applicable law, except with respect to ****, under no circumstances
whatsoever shall **** be liable to the other hereunder in contract, tort, negligence, breach of statutory duty or otherwise for any
indirect, punitive, incidental, reliance, special, exemplary or consequential damages, including without limitation direct or
indirect loss of profits, of production, of anticipated savings, of business or goodwill, regardless of any notice of the possibility of
such damages.

10.2 Limitation of Liability.

(a)

Active Materials. Except as expressly set forth in Section 2.2 hereof and this Section 10.2, under no circumstances

whatsoever shall Patheon be responsible for any loss or damage to the Active Materials. ****.

(b)

Maximum Liability. To the maximum extent permitted by applicable law, except with respect to breaches of
confidentiality, Patheon’s obligations under Article 6 and amounts owed to **** maximum liability per Year under this
Agreement for any reason whatsoever, including, without limitation, any liability arising under Article 6 hereof or resulting from
a breach of its representations, warranties or other obligations under this Agreement, shall not exceed the greater of (i) ****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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**** and (ii) **** of the total fees paid under this Agreement by Client to Patheon in such Year, up to a maximum value of t****
in the aggregate.

10.3

Patheon.

Patheon agrees to defend, indemnify and hold the Client, its Affiliates and their respective officers, employees and
agents harmless against any and all losses, damages, costs, claims, demands, judgments and liability to, from and in favour of
third parties (other than Affiliates) resulting from, or relating to ****.

In the event of a claim, the Client shall: (a) promptly notify Patheon of any such claim; (b) use commercially reasonable efforts to
mitigate the effects of such claim; (c) reasonably cooperate with Patheon in the defence of such claim; and (d) permit Patheon to
control the defence and settlement of such claim, each at Patheon's cost and expense, provided that any settlement of such claim
that does not contain an unconditional release of an indemnitee will require the prior written consent of such indemnitee, which
such consent will not be unreasonably withheld.

10.4 Client.

The Client agrees to defend, indemnify and hold Patheon, its Affiliates and their respective officers, employees
and agents harmless against any and all losses, damages, costs, claims, demands, judgments and liability to, from and in favour of
third parties (other than Affiliates) resulting from, or relating to any claim ****.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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In the event of a claim, Patheon shall: (a) promptly notify the Client of any such claims; (b) use commercially reasonable efforts
to mitigate the effects of such claim; (c) reasonably cooperate with the Client in the defence of such claim; (d) permit the Client
to control the defence and settlement of such claim, each at the Client's cost and expense, provided that any settlement of such
claim that does not contain an unconditional release of an indemnitee will require the prior written consent of such indemnitee,
which such consent will not be unreasonably withheld.
10.5 Reasonable Allocation of Risk.

reasonable allocation of risk having regard to the relative profits the parties respectively expect to derive from the Products.

The provisions of this Agreement (including, without limitation, this Article 10) are reasonable and create a

ARTICLE 11
CONFIDENTIALITY

11.1 Confidentiality.

The provisions of the Confidentiality Agreement shall apply to all confidential information of the parties under
this Agreement, which agreement remains in effect in accordance with its terms; provided, however, that the terms of the
Confidentiality Agreement shall continue to govern the parties’ obligations of confidentiality with respect to any confidential or
proprietary information of the parties, for the term of this Agreement and for a period of **** following termination or expiration
of this Agreement, except that the parties’ obligations of confidentiality with respect to any confidential or proprietary
information of the parties that is a trade secret under applicable law shall survive and continue in effect thereafter, in each case as
though such agreement remained in full force and effect. For the sake of clarity, the Product manufacturing process, including
without limitation the Product formulation process, and the analytical methods specific to the Product are all deemed to be the
trade secrets of Client for the purposes of this Section 11.1. Promptly following any expiration or termination of this Agreement,
each party shall return to the other party all originals and copies of the other party’s confidential information and destroy all
information, records and materials developed therefrom, unless otherwise expressly provided herein (e.g., under Section 7.3
(Records and Accounting by Patheon)).

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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including without limitation the U.S. Securities and Exchange Commission (the “SEC”) (collectively, the “Disclosure
Obligations”), such party shall promptly inform the other party thereof and shall use reasonable efforts to maintain the
confidentiality of the other party’s confidential information in any such filing or disclosure. To the extent that either party
reasonably determines that it is required to file a copy of this Agreement to comply with the Disclosure Obligations, such party
shall promptly inform the other party thereof. Prior to making any such filing of a copy of this Agreement, the parties shall
mutually agree on the provisions of this Agreement for which the parties shall seek confidential treatment, it being understood
that if one party determines to seek confidential treatment for a provision for which the other party does not, then the parties will
use reasonable efforts in connection with such filing to seek the confidential treatment of any such provision. The parties shall
cooperate, each at its own expense, in such filing, including without limitation such confidential treatment request, and shall
execute all documents reasonably required in connection therewith. In furtherance of the foregoing, the parties will agree as
promptly as practicable after the Effective Date on the confidential treatment request to be filed with the SEC and the redacted
form of this Agreement related thereto. In furtherance thereof, any redaction reasonably requested by either party shall be
included in such filing. The parties will reasonably cooperate in responding promptly to any comments received from the SEC
with respect to such filing in an effort to achieve confidential treatment of such redacted form; provided, however, that a party
shall be relieved of such obligation to seek confidential treatment for a provision requested by the other party if such treatment is
not achieved after the **** round of responses to comments from the SEC. Notwithstanding anything to the contrary in this
Agreement, Client may make reference to the existence of this Agreement and describe in general terms the relationship between
the parties in connection with any required securities filings without seeking Patheon’s prior consent. This paragraph shall apply
with respect to the filing of a copy of this Agreement or any public disclosure relating to this Agreement to comply with the
Disclosure Obligations, notwithstanding the provisions of the Confidentiality Agreement.

ARTICLE 12

DISPUTE RESOLUTION

12.1 Commercial Disputes.

In the event of any dispute arising out of or in connection with this Agreement (other than a dispute determined in
accordance with Section 6.1(b) or a Technical Dispute), the parties shall first try to solve it amicably. In this regard, any party
may send a notice of dispute to the other, and each party shall appoint, within **** from receipt of such notice of dispute, a
single representative having full power and authority to solve the dispute. The representatives so designated shall meet as
necessary in order to solve such dispute. If these representatives fail to solve the matter within **** from their appointment, or if
a party fails to appoint a representative within the **** period set forth above, such dispute shall immediately be referred to the
Chief Operating Officer (or such other officer as he/she

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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may designate) of each party who will meet and discuss as necessary in order to try to solve the dispute amicably. Should the
parties fail to reach a resolution under this Section 12.1, either party may refer the dispute to arbitration in accordance with
Section 12.3. Notwithstanding the foregoing, neither party shall be prohibited from seeking injunctive or other equitable relief in
any court of competent jurisdiction (including without limitation, in any case where issues involving the protection or
unauthorized use or disclosure of a party’s confidential information, trade secrets or intellectual property are involved).

12.2 Technical Dispute Resolution.

In the event of a dispute (other than disputes in relation to the matters set out in Sections 6.1(b) and 12.1) between
the parties that is exclusively related to technical aspects of the manufacturing, packaging, labelling, quality control testing,
handling, storage or other activities under this Agreement (a "Technical Dispute"), the parties shall make all reasonable efforts to
resolve the dispute by amicable negotiations. In this regard, senior representatives of each party shall, as soon as practicable and
in any event no later than **** after a written request from either party to the other, meet in good faith to resolve any Technical
Dispute. If, despite such meeting, the parties are unable to resolve a Technical Dispute within a reasonable time, and in any event
within **** after such written request, the Technical Dispute shall, at the request of either party, be referred for determination to
an expert in accordance with the provisions of Schedule F. In the event that the parties cannot agree whether a dispute is a
Technical Dispute, Section 12.1 shall prevail. For greater certainty, the parties agree that the release of the Products for sale or
distribution pursuant to the applicable marketing approval for such Products shall not by itself indicate compliance by Patheon
with its obligations in respect of the Manufacturing and further that nothing in this Agreement (including Schedule F) shall
remove or limit the authority of the relevant qualified person (as specified by the Quality Agreement) to determine whether the
Products are to be released for sale or distribution. Notwithstanding the foregoing, neither party shall be prohibited from seeking
injunctive or other equitable relief in any court of competent jurisdiction (including without limitation, in any case where issues
involving the protection or unauthorized use or disclosure of a party’s confidential information, trade secrets or intellectual
property are involved).

12.3 Arbitration.

In the event that any dispute cannot be resolved in accordance with Section 12.1, such dispute shall be finally
settled by arbitration in **** using the English language in accordance with the Arbitration Rules and Procedures of Judicial
Arbitration and Mediation Services, Inc. (“JAMS”) then in effect, by one or more commercial arbitrator(s) with substantial
experience in resolving complex commercial contract disputes, who may or may not be selected from the appropriate list of
JAMS arbitrators. If the parties cannot agree upon the number and identity of the arbitrators within **** following the date on
which a party referred the applicable dispute to arbitration, then a single arbitrator shall be selected on an expedited

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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basis in accordance with the Arbitration Rules and Procedures of JAMS. Any arbitrator so selected shall have substantial
experience in the pharmaceutical industry. The arbitrator(s) shall have the authority to grant specific performance and to allocate
between the parties the costs of arbitration (including service fees, arbitrator fees and all other fees related to the arbitration) in
such equitable manner as the arbitrator(s) may determine. The prevailing party in the arbitration shall be entitled to receive
reimbursement of its reasonable expenses (including reasonable lawyers’ fees, expert witness fees and all other expenses)
incurred in connection therewith. Judgment upon the award so rendered may be entered in a court having jurisdiction or
application may be made to such court for judicial acceptance of any award and an order of enforcement, as the case may be.
Notwithstanding the foregoing, each party shall have the right to institute an action in a court of proper jurisdiction for
preliminary injunctive relief pending a final decision by the arbitrator(s), provided that a permanent injunction and damages shall
only be awarded by the arbitrator(s).
12.4 Dispute and Termination for Breach.

Notwithstanding any statement to the contrary in this Agreement, a non-breaching party shall not be entitled to terminate this
Agreement pursuant to Section 8.2(a) on account of a disputed breach until the dispute is resolved by mutual agreement or
arbitration pursuant to Section 12.3 confirming the existence of the breach.

ARTICLE 13

MISCELLANEOUS

13.1

Inventions.

(a) For the term of this Agreement, Client hereby grants to Patheon a non-exclusive, paid-up, royalty-free, non-
sublicensable, non-transferable license of Client’s Intellectual Property, including without limitation that assigned to the Client
pursuant to Section 13.1(b) below, which Patheon must use in order to perform the Manufacturing, solely to perform the
Manufacturing. ****.

(b) All Inventions (including any and all Intellectual Property Rights therein) conceived, generated, derived or reduced

to practice by Patheon in the course of performing the Manufacturing, to the extent it is related to the development,

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

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Manufacture, packaging, use or sale of the Client’s Product that is the subject of the Manufacturing or contains the Client’s
confidential information, shall be the exclusive property of Client. Patheon shall give the Client written notice, as promptly as
practicable, of all such Inventions, and all such Inventions shall be deemed to be the confidential information of Client. Patheon
hereby makes, and agrees to make, any and all assignments necessary to effect, exclusively and throughout the world, the
ownership by the Client of Inventions under Section 13.1(b). Patheon shall, and shall cause its employees and contractors to,
fully cooperate with and sign any documents reasonably requested by the Client to evidence, perfect or take any other action with
respect to such assignments or to obtain protection, maintain or take any other action regarding such assigned Inventions.

(c) All Intellectual Property generated or derived by Patheon in the course of performing the Manufacturing to the
extent it (i) is not related to the development, Manufacture, packaging, use or sale of the Client’s Product that is the subject of the
Manufacturing and (ii) does not contain the Client’s confidential information, shall be the exclusive property of Patheon (the
"Broader Intellectual Property Rights"). Patheon hereby grants and agrees to grant to the Client a nonexclusive, transferable,
perpetual, irrevocable, paid up, royalty-free, worldwide right and license (including the right to sublicense) to practice and use all
Broader Intellectual Property Rights solely in connection with the ****.

(d) Each party shall be solely responsible for the costs of filing, prosecution and maintenance of patents and patent

applications on its own Inventions.
13.2

Intellectual Property.

Subject to Section 13.1, all Intellectual Property of the Client, including without limitation any Intellectual Property
that the Client owns prior to the Effective Date, shall be owned by the Client and all Intellectual Property of Patheon, including
without limitation any Intellectual Property that Patheon owns prior to the Effective Date, shall be owned by Patheon. Neither
party has, nor shall it acquire, any interest in any of the other party’s Intellectual Property unless otherwise expressly agreed to in
writing. Neither party shall use any Intellectual Property of the other party, except as specifically authorized by the other party or
as required for the performance of its obligations under this Agreement. Except as expressly set forth in Section 13.1, no licenses
are granted by either party, whether by implication, estoppel or otherwise, and all other rights are reserved.
13.3

Insurance.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 42 -

the aggregate per annum with respect to product and completed operations liability. Each party may satisfy the foregoing
minimum limits by any combination of primary liability and umbrella excess liability coverage. If requested each party will
provide the other with a certificate of insurance evidencing the above and showing the name of the issuing company, the policy
number, the effective date, the expiration date and the limits of liability. The insurance certificate shall further provide for a
minimum of **** written notice to the insured of a cancellation of the insurance. If a party is unable to maintain the insurance
policies required under this Agreement through no fault on the part of such party, then such party shall forthwith notify the other
party in writing and the parties shall in good faith negotiate appropriate amendments to the insurance provision of this Agreement
in order to provide adequate assurances, provided that in no event shall such party terminate its insurance policies until such
amendments to the insurance provision of this Agreement that are mutually agreed upon by the parties in writing are enacted.

13.4

Independent Contractors.

The parties are independent contractors and this Agreement shall not be construed to create between Patheon and
the Client any other relationship such as, by way of example only, that of employer-employee, principal agent, joint-venturer, co-
partners or any similar relationship, the existence of which is expressly denied by the parties hereto.

13.5 No Waiver.

Either party's failure to require the other party to comply with any provision of this Agreement shall not be
deemed a waiver of such provision or any other provision of this Agreement. No waiver of any provision of this Agreement shall
bind either party unless in writing and signed by the party against which enforcement is sought.

13.6 Assignment.

(a)

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 43 -

****.

13.7

Force Majeure.

Neither party shall be liable for the failure to perform its obligations under this Agreement if such failure is
occasioned by a cause or contingency beyond such party's reasonable control, including, but not limited to, strikes or other labour
disturbances, lockouts, riots, quarantines, communicable disease outbreaks, wars, acts of terrorism, fires, floods, storms,
interruption of or delay in transportation, defective equipment, lack of or inability to obtain fuel, power or components or
compliance with any order or regulation of any government entity acting within colour of right (a "Force Majeure Event"). A
party claiming a right to excused performance under this Section 13.7 shall promptly notify the other party in writing of the
extent of its inability to perform, which notice shall specify the occurrence beyond its reasonable control that prevents such
performance, and shall use commercially reasonable efforts to overcome the Force Majeure Event. Notwithstanding the
foregoing, if either party is prevented or delayed in performing its obligations under this Agreement on more than (i) **** or (ii)
**** in the aggregate during any **** period, then the party not so affected may terminate this Agreement upon written notice to
the affected party. Neither party shall be entitled to rely on a Force Majeure Event to relieve it from an obligation to pay money
(including any interest for delayed payment) which would otherwise be due and payable under this Agreement.

13.8 Additional Product.

Versions of Products with different packaging configurations than those specified in Schedule B may be added to
this Agreement and such additional products shall be governed by the general conditions hereof with any special terms
(including, without limitation, price) governed by an addendum hereto.

13.9 Notices.

Any notice, approval, instruction or other written communication required or permitted hereunder shall be
sufficient if made or given to the other party by personal delivery, by telecopier or facsimile communication or by sending the
same by first class mail, postage prepaid, return receipt requested to the mailing address, or telecopier or facsimile number set
forth below:

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 44 -

If to the Client:

Vanda Pharmaceuticals Inc.
2200 Pennsylvania Ave NW, Suite 300E
Washington, DC 20037
U.S.A.

Attention: Legal Department

Fax No.: ****

If to Patheon:

Patheon Inc.
2100 Syntex Court
Mississauga, Ontario L5N 7K9
Canada
Attention: Legal Department

Fax No.: ****

or to such other addresses or telecopier or facsimile numbers provided to the other party in accordance with the terms of this
Section 13.9. Notices or written communications made or given by personal delivery or by telecopier or facsimile shall be
deemed to have been sufficiently made or given when sent (receipt acknowledged), or if mailed, five (5) days after being
deposited in the United States or Canadian mail, postage prepaid, return receipt requested or upon receipt, whichever is sooner.

13.10 Severability.

13.11 Entire Agreement.

This Agreement, together with the Schedules, the Quality Agreement and the Confidentiality Agreement,
constitutes the full, complete, final and integrated agreement between the parties hereto relating to the subject matter hereof and
supersedes all previous written or oral negotiations, commitments, agreements, transactions or understandings with respect to the
subject matter hereof, except the Packaging Services Agreement between the parties, dated August 20, 2012 (the “Packaging
Services Agreement”). Any modification, amendment or supplement to this Agreement must be in writing and signed by
authorized representatives of both parties. In case of conflict, the

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 45 -

prevailing order of documents shall be this Agreement, the Quality Agreement and the Confidentiality Agreement.
Notwithstanding anything to the contrary in the Packaging Services Agreement, the parties hereby agree that the Packaging
Services Agreement will automatically terminate on the Effective Date, and the parties will discuss diligently, reasonably and in
good faith the parties’ obligations under the Packaging Services Agreement following such termination.

13.12 Other Terms.

No terms, provisions or conditions of any purchase order or other business form or written authorization used by
the Client or Patheon will have any effect on the rights, duties or obligations of the parties under or otherwise modify this
Agreement, regardless of any failure of the Client or Patheon to object to such terms, provisions, or conditions. For greater
certainty, the Client’s purchase order is only effective as its unqualified commitment to obtain and pay for the Manufacturing
upon the terms (and only the terms) set forth herein.

13.13 No Third Party Benefit or Right.

For greater certainty, nothing in this Agreement shall confer or be construed as conferring on any third party any

benefit or the right to enforce any express or implied term of this Agreement.

13.14 Execution in Counterparts.

deemed an original, but all of which together shall constitute one and the same instrument.

This Agreement may be executed in two counterparts, by original or facsimile signature, each of which shall be

13.15 Governing Law.

This Agreement shall be construed and enforced in accordance with the laws of the State of ****, without regard
to its conflicts of law provisions. The UN Convention on Contracts for the International Sale of Goods shall not apply to this
Agreement. Unless expressly provided otherwise, each right and remedy in this Agreement is in addition to any other right or
remedy, at law or in equity, and the exercise of one right or remedy will not be deemed a waiver of any other right or remedy.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 46 -

the date first written above.

IN WITNESS WHEREOF, the duly authorized representatives of the parties have executed this Agreement as of

PATHEON INC.

By: /s/ Nick Postic

Name: Nick Postic

Title: Executive Director and General Manager

VANDA PHARMACEUTICALS INC.

By: /s/ Mihael Polymeropoulos

Name: Mihael Polymeropoulos

Title: Chief Executive Officer

- 47 -

SCHEDULE A

PRODUCT LIST

Products

Fanapt

(Iloperidone Tablets) – ****

Specifications

Prior to the commencement of commercial manufacturing of Product under this Agreement, the Client shall provide Patheon with
copies of the FDA approved NDA Specifications. If the Specifications provided are subsequently amended, then the Client shall
provide Patheon with copies of such revised Specifications. Upon acceptance of the revised Specifications pursuant to Section
4.4, Patheon shall provide the Client with a signed and dated receipt evidencing such acceptance of the revised Specifications by
Patheon.

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 1 -

2016 Price
****

SCHEDULE B

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 2 -

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 3 -

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 4 -

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 5 -

****.

SCHEDULE C
STABILITY TESTING

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 6 -

ACTIVE MATERIALS, ACTIVE MATERIALS CREDIT VALUE ****

SCHEDULE D

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 7 -

MAXIMUM CREDIT VALUE

****

- 8 -

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

SCHEDULE E

BATCH NUMBERING & EXPIRATION DATES

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 9 -

SCHEDULE F

TECHNICAL DISPUTE RESOLUTION

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 10 -

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 11 -

SCHEDULE G

INTENTIONALLY OMITTED

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 12 -

SCHEDULE H

QUARTERLY ACTIVE MATERIALS INVENTORY REPORT

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 13 -

REPORT OF ANNUAL ACTIVE MATERIALS INVENTORY RECONCILIATION AND CALCULATION OF
ACTUAL ANNUAL YIELD

SCHEDULE I

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 14 -

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 15 -

SCHEDULE J

****

- 16 -

SCHEDULE K
INTENTIONALLY OMITTED

- 17 -

SCHEDULE L
EXAMPLE OF PRICE ADJUSTMENTS PER SECTION 4.2

****

****CERTAIN INFORMATION HAS BEEN OMITTED UNDER RULES PERMITTING THE CONFIDENTIAL TREATMENT OF SUCH
INFORMATION.

- 18 -

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We hereby consent to the incorporation by reference in the Registration Statements on Form S-8 (No. 333-133368, No. 333-138070, No. 333-141571,
No. 333-148924, No. 333-156995, No. 333-164567, No. 333-171962, No. 333-179265, No. 333-186509, No. 333-193614, No. 333-201754, No. 333-
209144, No. 333-212255, No. 333-218774, No. 333-225599, No. 333-239103, and No. 333-256994) of Vanda Pharmaceuticals Inc. of our report dated
February 24, 2022 relating to the financial statements and the effectiveness of internal control over financial reporting, which appears in this Form 10-K.

Exhibit 23.1

/s/ PricewaterhouseCoopers LLP

Baltimore, Maryland
February 24, 2022

EXHIBIT 31.1

CERTIFICATION OF CHIEF EXECUTIVE OFFICER
PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002

I, Mihael H. Polymeropoulos, certify that:

I have reviewed this annual report on Form 10-K of Vanda Pharmaceuticals Inc.;

Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the
statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this
report;

Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the
financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;

The registrant’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-
15(f)) for the registrant and have:

Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by
others within those entities, particularly during the period in which this report is being prepared;

Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for
external purposes in accordance with generally accepted accounting principles;

Evaluated the effectiveness of the registrant’s disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and

Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred during the registrant’s most
recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably
likely to materially affect, the registrant’s internal control over financial reporting; and

The registrant’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to
the registrant’s auditors and the audit committee of the registrant’s board of directors (or persons performing the equivalent functions):

All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the registrant’s ability to record, process, summarize and report financial information; and

Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal
control over financial reporting.

February 24, 2022

/s/ Mihael H. Polymeropoulos, M.D.
Mihael H. Polymeropoulos, M.D.
President, Chief Executive Officer and Chairman of the Board of
Directors
(Principal Executive Officer)

EXHIBIT 31.2

CERTIFICATION OF CHIEF FINANCIAL OFFICER
PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002

I, Kevin Moran, certify that:

I have reviewed this annual report on Form 10-K of Vanda Pharmaceuticals Inc.;

Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant’s internal
control over financial reporting.

February 24, 2022

/s/ Kevin Moran
Kevin Moran
Senior Vice President, Chief Financial Officer and Treasurer
(Principal Financial Officer and Principal Accounting Officer)

CERTIFICATION OF CHIEF EXECUTIVE OFFICER AND CHIEF FINANCIAL OFFICER

Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002
(Subsections (a) and (b) of Section 1350, Chapter 63 of Title 18, United States Code)

EXHIBIT 32.1

Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002 (subsections (a) and (b) of section 1350, chapter 63 of title 18, United States Code), each of the
undersigned officers of Vanda Pharmaceuticals Inc., (the “Company”), does hereby certify, to the best of such officer’s knowledge, that:

The Annual Report on Form 10-K for the year ended December 31, 2021 (the Form 10-K) of the Company fully complies with the requirements of
Section 13(a) or 15(d) of the Securities Exchange Act of 1934, and the information contained in the Form 10-K fairly presents, in all material respects, the
consolidated financial condition and results of operations of the Company.

February 24, 2022

/s/ Mihael H. Polymeropoulos, M.D.
Mihael H. Polymeropoulos, M.D.
President, Chief Executive Officer and
Chairman of the Board of Directors
(Principal Executive Officer)

/s/ Kevin Moran
Kevin Moran
Senior Vice President, Chief Financial Officer and Treasurer
(Principal Financial Officer and Principal Accounting Officer)

A signed original of this written statement required by Section 906 has been provided to the Company and will be retained by the Company and furnished
to the Securities and Exchange Commission (SEC) or its staff upon request. This certification “accompanies” the Form 10-K to which it relates, is not
deemed filed with the SEC and is not to be incorporated by reference into any filing of the Company under the Securities Act of 1933, as amended, or the
Securities Exchange Act of 1934, as amended (whether made before or after the date of the Form 10-K), irrespective of any general incorporation
language contained in such filing.