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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, 2020
OR
☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
COMMISSION FILE NUMBER: 001-36279
CARA THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of
incorporation or organization)
4 Stamford Plaza
107 Elm Street, 9th Floor
Stamford, Connecticut
(Address of registrant’s principal executive offices)
75-3175693
(I.R.S. Employer
Identification No.)
06902
(Zip Code)
Registrant’s telephone number, including area code: (203) 406-3700
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Common Stock, par value $0.001 per share
Trading Symbol
CARA
Name of each exchange on which registered
The Nasdaq Stock Market LLC
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Act. Yes ⌧ No ☐
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ⌧
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the
preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.
Yes ⌧ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§
232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ⌧ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, 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. ☒
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ⌧
The aggregate market value of the registrant’s Common Stock (the only common equity of the registrant) held by non-affiliates, based on the closing sales price of the
stock on the Nasdaq Global Market for the last business day of the registrant’s most recently completed second fiscal quarter, was $726,180,228. For purposes of this calculation,
shares of common stock held by directors and officers and their affiliated entities at June 30, 2020 were excluded. Exclusion of shares held by any person should not be
construed to indicate that the person possesses the power, direct or indirect, to direct or cause the direction of the management or policies of the registrant, or that the person is
controlled by or under common control with the registrant.
The number of shares outstanding of the registrant’s Common Stock, par value $0.001 per share, as of February 22, 2021 was 49,876,763.
Portions of the registrant’s Proxy Statement for its 2021 Annual Meeting of Stockholders, to be filed with the Securities and Exchange Commission no later than 120
days after December 31, 2020, are incorporated by reference in Part III of this Annual Report on Form 10-K.
Documents Incorporated By Reference
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CARA THERAPEUTICS, INC.
2020 ANNUAL REPORT ON FORM 10-K
TABLE OF CONTENTS
Item 1.
Business.
Item 1A.
Risk Factors.
Item 1B.
Unresolved Staff Comments.
Item 2.
Properties.
Item 3.
Legal Proceedings.
Item 4.
Mine Safety Disclosures.
PART I
PART II
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of
Equity Securities.
Item 6.
Selected Financial Data.
Item 7.
Management’s Discussion and Analysis of Financial Condition and Results of Operations.
Item 7A.
Quantitative and Qualitative Disclosures About Market Risk.
Item 8.
Financial Statements and Supplementary Data.
Item 9.
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure.
Item 9A.
Controls and Procedures.
Item 9B.
Other Information.
Item 10.
Directors, Executive Officers and Corporate Governance.
Item 11.
Executive Compensation.
PART III
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder
Matters.
Item 13.
Certain Relationships and Related Transactions, and Director Independence.
Item 14.
Principal Accounting Fees and Services.
Item 15.
Exhibits and Financial Statement Schedules
PART IV
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PART I
In this Annual Report on Form 10-K, the terms “we,” “us” and “our” refer to Cara Therapeutics, Inc.
Cautionary Note Regarding Forward-Looking Statements
This Annual Report on Form 10-K contains forward-looking statements, within the meaning of the Private Securities
Litigation Reform Act of 1995, that involve substantial risks and uncertainties. The forward-looking statements are
contained principally in the sections of this Annual Report on Form 10-K titled “Risk Factors,” “Management’s Discussion
and Analysis of Financial Condition and Results of Operations” and “Business,” but are also contained elsewhere in this
Annual Report on Form 10-K. In some cases, you can identify forward-looking statements by the words “anticipate,”
“believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “might,” “objective,” “ongoing,” “plan,” “predict,”
“project,” “potential,” “should,” “will,” or “would,” and or the negative of these terms, or other comparable terminology
intended to identify statements about the future. These statements involve known and unknown risks, uncertainties and
other factors that may cause our actual results, levels of activity, performance or achievements to be materially different
from the information expressed or implied by these forward-looking statements. Although we believe that we have a
reasonable basis for each forward-looking statement contained in this Annual Report on Form 10-K, we caution you that
these statements are based on a combination of facts and factors currently known by us and our expectations of the future,
about which we cannot be certain.
The forward-looking statements in this Annual Report on Form 10-K include, among other things, statements about:
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the timing of our regulatory submissions for KORSUVATM (CR845/difelikefalin) injection in chronic kidney
disease associated pruritus, or CKD-aP;
the success and timing of our clinical trials and reporting of our results from these trials, including our clinical
trial programs for KORSUVA (CR845/difelikefalin) injection in CKD-aP, and for Oral KORSUVA
(CR845/difelikefalin) in CKD-aP, chronic liver disease associated pruritus, or CLD-aP, pruritus associated
with atopic dermatitis, or AD, and pruritus associated with notalgia paresthetica, or NP;
our plans to develop and commercialize KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA
(CR845/difelikefalin) and any future product candidates;
the potential results of ongoing and planned preclinical studies and clinical trials and future regulatory and
development milestones for our product candidates;
the size and growth of the potential markets for pruritus management, including CKD-aP in hemodialysis and
non-dialysis markets, CLD-aP, AD, and NP markets as well as post-operative care markets;
the potential regulatory development pathway for KORSUVA (CR845/difelikefalin) injection in CKD-aP and
CR845/difelikefalin injection in acute post-operative setting;
the rate and degree of market acceptance of any approved products;
our ability to obtain and maintain regulatory approval of our product candidates, and the labeling under any
approval we may obtain;
the anticipated commercial launch of our lead product candidate, KORSUVA (CR845/difelikefalin) injection;
the anticipated use of Enteris Biopharma, Inc.’s, or Enteris’s, Peptelligence® technology to develop,
manufacture and commercialize Oral KORSUVA (CR845/difelikefalin);
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the potential of future scheduling of KORSUVA (CR845/difelikefalin) injection by the United States Drug
Enforcement Administration, or DEA, if regulatory approval is received;
the performance of our current and future collaborators and licensees, including Vifor Fresenius Medical Care
Renal Pharma Ltd., or VFMCRP, Vifor (International) Ltd., or Vifor, Maruishi Pharmaceuticals Co. Ltd., or
Maruishi, and Chong Kun Dang Pharmaceutical Corp., or CKDP, as well as sub-licensees, including Kissei
Pharmaceutical Co. Ltd., or Kissei, and our ability to maintain such collaborations;
our ability to establish additional collaborations for our product candidates;
the continued service of our key scientific or management personnel;
our ability to establish commercialization and marketing capabilities;
regulatory developments in the United States and foreign countries;
our ability to obtain and maintain coverage and adequate reimbursement from third-party payers for any
approved products;
our planned use of our cash and cash equivalents and marketable securities and the clinical milestones we
expect to fund with such proceeds;
the accuracy of our estimates regarding expenses, future revenues and capital requirements;
our ability to obtain funding for our operations;
our ability to obtain and maintain intellectual property protection for our product candidates and our ability to
operate our business without infringing on the intellectual property rights of others;
the success of competing drugs that are or may become available;
the performance of third-party manufacturers and clinical research organizations, or CROs; and
the potential effects of the ongoing COVID-19 pandemic on our business, operations and clinical development
and regulatory timelines and plans.
You should refer to Part I Item 1A. “Risk Factors” of this Annual Report on Form 10-K for a discussion of important
factors that may cause our actual results to differ materially from those expressed or implied by our forward-looking
statements. As a result of these factors, we cannot assure you that the forward-looking statements in this Annual Report on
Form 10-K 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. We undertake no obligation to publicly update any forward-looking statements, whether as a
result of new information, future events or otherwise, except as required by law.
You should read this Annual Report on Form 10-K and the documents that we reference in this Annual Report on
Form 10-K and have filed as exhibits to this Annual Report on Form 10-K completely and with the understanding that our
actual future results may be materially different from what we expect. We qualify all of our forward-looking statements by
these cautionary statements.
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Risk Factors Summary
Investing in our common stock involves a high degree of risk because our business is subject to numerous risks and
uncertainties, as fully described below. The principal factors and uncertainties that make investing in our common stock
risky include, among others:
● We have incurred significant losses from our inception, and although we generated net income in 2020, we
anticipate that we may incur losses for the foreseeable future, and may never maintain profitability.
● We may need additional funding and may be unable to raise capital when needed, which would force us to
delay, reduce or eliminate our product development programs or commercialization efforts.
● We are substantially dependent on the success of our lead product candidate, KORSUVA (CR845/difelikefalin)
injection, being developed for the treatment of CKD-aP in hemodialysis patients, and cannot guarantee that this
product candidate will receive regulatory approval or be successfully commercialized.
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The regulatory approval processes of the U.S. Food and Drug Administration, or FDA, and comparable foreign
authorities are lengthy, time consuming and inherently unpredictable. If we are not able to obtain, or if there are
delays in obtaining, required regulatory approvals, we will not be able to commercialize our product candidates
as expected, and our ability to generate revenue will be materially impaired.
The FDA may determine that I.V. CR845/difelikefalin, or any of our other current or future product candidates,
has undesirable side effects that could limit dosage in development, delay or prevent their regulatory approval
or commercialization.
● We face significant competition from other pharmaceutical and biotechnology companies, academic
institutions, government agencies and other research organizations. Our operating results will suffer if we fail to
compete effectively.
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If we or our collaborators are unable to establish effective marketing and sales capabilities, or we are unable to
enter into and maintain agreements with third parties to market and sell our product candidates, if they are
approved, we may be unable to generate product revenues.
● We rely, and expect to continue to rely, on third parties to conduct our preclinical studies and clinical trials, and
those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such
trials.
● We may need to license certain intellectual property from third parties, and such licenses may not be available
or may not be available on commercially reasonable terms.
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Our business, operations and clinical development and regulatory timelines and plans have been, and could
continue to be, adversely affected by the effects of health epidemics, including the ongoing COVID-19
pandemic.
Industry and Market Data
We obtained the industry and market data in this Annual Report on Form 10-K from our own research as well as
from industry and general publications, surveys and studies conducted by third parties. Industry and general publications,
studies and surveys generally state that the information contained therein has been obtained from sources believed to be
reliable. These third parties may, in the future, alter the manner in which they conduct surveys and studies regarding the
markets in which we operate our business. As a result, you should carefully consider the inherent risks and
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uncertainties associated with the industry and market data contained in this Annual Report on Form 10-K, including those
discussed in Part I Item 1A. “Risk Factors.”
Item 1. Business.
Overview
We are a clinical-stage biopharmaceutical company focused on developing and commercializing new chemical
entities designed to alleviate pruritus by selectively targeting peripheral kappa opioid receptors, or KORs. We are
developing a novel and proprietary class of product candidates, led by KORSUVA (CR845/difelikefalin), a first-in-class
KOR agonist that targets KORs located in the peripheral nervous system and on immune cells.
In our KALMTM-1 and KALM-2 Phase 3 trials and two Phase 2 trials, KORSUVA (CR845/difelikefalin) injection
(intravenous formulation) has demonstrated statistically significant reductions in itch intensity and concomitant
improvement in pruritus-related quality of life measures in hemodialysis patients with moderate-to-severe CKD-aP. We
have partnered with VFMCRP, a joint venture between Vifor Pharma Group and Fresenius Medical Care, and Vifor to
commercialize KORSUVA (CR845/difelikefalin) injection in dialysis patients with CKD-aP in the U.S. under profit share
agreements. We have partnered with VFMCRP to commercialize KORSUVA worldwide, excluding Japan (Maruishi/sub-
licensee Kissei), and South Korea (CKDP).
CR845/difelikefalin has also demonstrated statistically significant pain reduction in clinical trials in patients with
moderate-to-severe acute pain in the post-operative setting, without inducing many of the undesirable side effects typically
associated with currently available opioid pain therapeutics. We retain rights to all KORSUVA/CR845 formulations and
indications worldwide, excluding KORSUVA (CR845/difelikefalin) injection in dialysis patients with CKD-aP under our
agreements with VFMCRP and Vifor for U.S. and certain ex-U.S. territories in Japan (Maruishi/sub-licensee Kissei) and
South Korea (CKDP).
The FDA has conditionally accepted KORSUVA as the trade name for CR845/difelikefalin injection. In December
2020, we submitted a New Drug Application, or NDA, to the FDA for KORSUVA (CR845/difelikefalin) injection for the
treatment of moderate-to-severe pruritus in hemodialysis patients, and in February 2021, the NDA was accepted by the
FDA. KORSUVA’s safety and efficacy have not been fully evaluated by any regulatory authority.
We were incorporated and commenced operations in 2004, and our primary activities to date have been organizing
and staffing our company, developing our product candidates, including conducting preclinical studies and clinical trials of
CR845/difelikefalin-based product candidates and raising capital. To date, we have financed our operations primarily
through sales of our equity and debt securities and payments from license agreements. We have no products currently
available for sale, and substantially all of our revenue to date has been revenue from license agreements, although we have
received nominal amounts of revenue under research grants and the sale of clinical compound.
Recent Developments
COVID-19 Update
The extent of the impact of the ongoing COVID-19 pandemic on our business, operations and clinical development
and regulatory timelines and plans remains uncertain, and will depend on certain developments, including the duration and
spread of the outbreak and its impact on our clinical trial enrollment, trial sites, partners, CROs, third-party manufacturers,
and other third parties with whom we do business, as well as its impact on regulatory authorities and our key scientific and
management personnel. The timing of our submission of our NDA to the FDA for KORSUVA (CR845/difelikefalin)
injection was not affected, as we submitted the NDA in December 2020. The COVID-19 pandemic, however, has affected,
and may in the future affect, the initiation of certain trial sites and patient enrollment for our ongoing Phase 2 clinical trials
of Oral KORSUVA (CR845/difelikefalin) for moderate-to-severe pruritus in patients with AD, NP, and for the treatment of
pruritus in patients with hepatic impairment due to primary biliary cholangitis, or PBC. While we currently do not expect
any significant delays in our clinical development or commercial timelines, the ultimate impact of the evolving COVID-19
pandemic remains difficult to predict.
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To the extent possible, we are conducting business as usual, with necessary or advisable modifications to employee
travel and employee work locations. We are continuing to actively monitor the rapidly evolving situation related to
COVID-19 and may take further actions that alter our operations, including those that may be required by federal, state or
local authorities, or that we determine are in the best interests of our employees, partners and other third-parties with whom
we do business. The extent to which the ongoing and evolving COVID-19 pandemic may affect our business, operations
and clinical development and regulatory timelines and plans, including the resulting impact on our expenditures and capital
needs, remains uncertain.
Vifor License and Stock Purchase Agreements
In October 2020, we entered into a license agreement with Vifor pursuant to which we granted Vifor an exclusive
license solely in the United States to use, distribute, offer for sale, promote, sell and otherwise commercialize KORSUVA
(CR845/difelikefalin) injection for all therapeutic uses relating to the inhibition, prevention or treatment of itch associated
with pruritus in hemodialysis and peritoneal dialysis patients in the United States. We retain all rights with respect to the
clinical development of, and activities to gain regulatory approvals of, KORSUVA (CR845/difelikefalin) injection in the
United States. As consideration, we received an upfront payment of $100.0 million and an additional payment of $50.0
million for the purchase of an aggregate of 2,939,552 shares of our common stock. (see Item 7. Management’s Discussion
and Analysis of Financial Condition and Results of Operations - Collaboration and License Agreements – Vifor
(International) Ltd.).
Thomas Reilly Appointed as Chief Financial Officer
Effective October 1, 2020, we appointed Thomas Reilly to serve as our Chief Financial Officer. In this capacity, Mr.
Reilly will serve as our principal financial and accounting officer. There are no arrangements or understandings between
Mr. Reilly and any other persons pursuant to which he was elected as an officer, and there is no family relationship
between Mr. Reilly and any of our directors or other executive officers.
The Market Opportunity – Pruritus
Pruritus, or itch, is defined as an unpleasant sensation that provokes the desire to scratch. Certain systemic diseases
have been known to cause pruritus that ranges in intensity from a mild annoyance to an intractable, disabling condition.
Itch originates in the epidermis and dermal–epidermal junction and is transmitted by itch-selective sensory neuron C
fibers, or pruriceptors. Some of these fibers are sensitive to histamine while others are not, and there is evidence for
histamine-insensitive C fibers that are activated by numerous itch-inducing substances or pruritogens, many of which
initiate signals through interaction with specific G-protein-coupled receptors. In addition, there is increasing evidence for
the differential involvement of these systems in various forms of itch which may involve disease-specific pruritogens. As
an example, chronic pruritus associated with kidney failure is thought to involve complex interactions among peripheral
cells (T cells, mast cells, neutrophils, eosinophils, and keratinocytes) and histamine-insensitive nerve fibers, involving
increased release of cytokines, proteases, and neuropeptides, interacting with multiple receptors that lead to exacerbation of
itch. These different peripheral cell types express kappa opioid receptors, which can regulate the release of these
pruritogenic substances, while the kappa opioid receptors on C fibers are thought to regulate their response to these
pruritogens. Because kappa opioid receptors are expressed in peripheral tissues, there is a potential to modulate itch signals
peripherally without impacting the central kappa opioid receptors. The itch-sensitive sensory nerve fibers transmit signals
to the cell bodies in the dorsal root ganglia (that also have kappa opioid receptors), which send fibers to enter the spinal
cord. Itch signals then ascend via the spinothalamic tract to multiple brain areas for sensory processing and interactions
with cognitive and other systems.
Additionally, the activation of kappa receptors via an agonist is thought to reduce itching by functionally
counteracting increased mu opioid receptor activity which is suggested to be associated with some chronic forms of
pruritus. Activation of the mu opioid receptor in the brain and in the peripheral nerve endings results in itching while non-
selective mu opioid antagonists can inhibit itching. Kappa opioid receptor stimulation inhibits the effects of mu receptor
activation both centrally and peripherally.
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Pruritus may be classified into different categories on the basis of the underlying causative disease: renal or CKD-aP
(previously known as uremic pruritus), cholestatic pruritus, dermatological pruritus, neurological pruritus, hematologic
pruritus, endocrine pruritus, pruritus related to malignancy and idiopathic generalized pruritus. According to a study we
conducted with IMS Health (now IQVIA) utilizing medical claims data from 2013, approximately 21 million patients were
diagnosed with diseases known to trigger chronic pruritus and received a prescription for an anti-pruritic agent such as
corticosteroids, antihistamines, select antidepressants, counterirritants, bile acid sequestrants, rifampin, narcotic antagonists
and partial agonists, topical immunomodulators or gabapentin.
Chronic Kidney Disease-Associated Pruritus (CKD-aP)
According to the National Kidney Foundation, or NKF, it is estimated that 37 million people (15% of the adult
population) have chronic kidney disease, or CKD, in the United States alone, yet many of these patients remain
undiagnosed. According to a study conducted by IQVIA, in 2017, approximately 7.3 million patients were diagnosed with
CKD in the United States and roughly 33% or approximately 2.4 million patients received a prescription for an anti-
pruritic. A separate epidemiological study published in 2019 in the Clinical Journal of American Society of Nephrology
shows that approximately 25% of stage III to V (moderate-to-severe) CKD patients suffer from moderate-to-severe pruritus
or itching.
CKD-aP (also known as uremic pruritus) can occur in patients with CKD as well as End Stage Renal Disease, or
ESRD, and is commonly seen in patients receiving hemodialysis. According to Fresenius Medical Care, a world leading
provider of products and medical care for dialysis patients, there were approximately 3.2 million patients globally
undergoing dialysis in 2017. According to the Dialysis Outcomes and Practice Patterns Study published in December 2017
in the Clinical Journal of the American Society of Nephrologists, it is estimated that nearly 70% of these patients suffer
from some form of CKD-aP with approximately 40% of these patients experiencing moderate to severe pruritus.
Currently, there are no approved products in the United States or Europe to treat CKD-aP. Patients are generally
managed with a multitude of products including corticosteroids, gabapentin, antihistamines, antidepressants and others
with varying degrees of success. There is one product, nalfurafine (Remitch®) marketed by Toray Industries, approved to
treat CKD-aP in Japan only. It is not approved either in the United States or Europe for CKD-aP.
Pruritus Associated with Atopic Dermatitis (AD)
AD is a chronic, pruritic inflammatory dermatosis that affects up to 25% of children and 2% to 5% of adults. Chronic
pruritus is one of the defining features of AD. The itch is so common in AD that AD is often described as the itch that
rashes. The point prevalence of chronic pruritus ranges between 87% to 100% in AD. Both quality of life and psychosocial
well-being are known to negatively correlate with itch severity. The associated psychosocial morbidity of this distressing
symptom includes sleep disruption, depression, agitation, anxiety, altered eating habits, reduced self-esteem and difficulty
concentrating.
The cause of AD is multifactorial, including genetic predisposition, impaired skin barrier, environmental triggers and
immune dysregulation. The sensation of itch in AD is similarly complex. Chronic itch in AD is mediated by a complex
interplay between keratinocytes, cutaneous nerve fibers, pruritogenic molecules and the peripheral and central nervous
system. An imbalance in the epidermal opioid system has also been described as potentially playing a role in the
modulation of pruritus in AD.
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Chronic Liver Disease-Associated Pruritus (CLD-aP)
Millions of Americans suffer from chronic liver disease, or CLD, of various etiologies ranging from hepatitis to
cirrhosis to primary biliary cholangitis, or PBC. Pruritus is a common and irritating symptom in patients who suffer from
CLD, especially those with chronic cholestatic disease. Severe pruritus can have debilitating effects and can lead to a
significant reduction in a patient’s quality of life. According to a study conducted by IQVIA, nearly 7.0 million patients
were diagnosed with CLD in 2013 in the United States and approximately 37% percent or 2.5 million patients received a
prescription for an anti-pruritic.
There are no approved therapies for CLD-aP in the United States. Current antipruritic therapies, primarily
antihistamines and corticosteroids as well as other therapies tried off-label, are largely ineffective in treating the disease
and/or can produce significant side effects.
Notalgia Paresthetica (NP)
NP is a common, although under-recognized chronic, sensory neuropathy affecting the upper back. It is estimated
that chronic pruritus affects up to 13% of the United States population, and about 8% of these patients suffer from
neuropathic itch, including NP. One of the hallmark features of NP is chronic pruritus, which can be significantly
burdensome and undermines the affected subject’s quality of life and overall well-being. The exact etiology of NP still has
not been fully elucidated; however, it is widely accepted that NP is a sensory neuropathy caused by alteration and damage
to thoracic spinal nerves.
The management of NP is challenging and is often resistant to multiple therapies. There is currently no well-defined
treatment for NP and conventional treatments for pruritus, such as antihistamines and topical steroids, are largely
ineffective.
Other Causes of Pruritus
There are many other systemic diseases that can trigger pruritus in patients. They include endocrinologic disease
(e.g. hyperthyroidism), malignancy (e.g. Hodgkin lymphoma), hematologic disease (e.g. polycythemia vera), psoriasis,
hives/urticarial, and lice/scabies. Data from a Cara-sponsored IMS Health (now IQVIA) study, utilizing medical claims
data from 2013, indicate that over 20 million prescriptions for anti-pruritic therapeutics are filled annually in the United
States.
The Market Opportunity – Post-Operative Nausea and Vomiting (PONV) Management
PONV in a hospital or other medical setting in the United States is most often treated with 5-HT3 antagonists (e.g.
ondansetron), NK-1 receptor antagonists (e.g. aprepitant) steroids (dexamethasone), dopamine receptor antagonists
(haloperidol, metoclopramide) as well as Anticholinergics (scopolamine patch) either alone in low risk patients or in
combination in patients with a higher risk of PONV. According to an article published in Best Practice & Research Clinical
Anaesthesiology, PONV is one of the most important factors in determining length of stay after surgery, resulting in
estimated annual costs in the United States in the range of $1 billion. Per IQVIA, in 2017, there were over 700 million
units of PONV drugs sold in the United States.
The market for the prevention and treatment of PONV is highly fragmented. Anesthesiologists utilize a number of
different agents alone or in combination (particularly in patients with a high risk for PONV) with different mechanism of
actions to try to manage PONV. If approved, I.V. CR845/difelikefalin would likely be competing within the overall PONV
market, although we expect that it would primarily be utilized as an add-on therapy in patients with a higher risk of PONV.
Although most of the PONV products are generically available, there is still a significant segment of high-risk patients
where their PONV is not adequately managed, which can increase the hospital length of stay and add significant cost to
managing a post-operative patient.
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Our Strategy
Our strategy is to develop and commercialize a novel and first-in-class portfolio of peripherally-acting kappa opioid
receptor agonists, with KORSUVA (CR845/difelikefalin) injection and Oral KORSUVA (CR845/difelikefalin) as our lead
candidates. We have designed and are developing product candidates which have clearly defined clinical development
programs and target significant commercial market opportunities. The key elements of our strategy are as follows:
Advance KORSUVA (CR845/difelikefalin) injection for the treatment of moderate-to-severe CKD-aP in patients
undergoing hemodialysis. In January 2018, based on positive data from our earlier Phase 2 studies, we initiated the first
pivotal Phase 3 trial (KALM-1) of KORSUVA (CR845/difelikefalin) injection in hemodialysis patients suffering from
moderate to severe CKD-aP. In May 2019, we announced positive top-line results from this trial. The study met the
primary and all secondary efficacy endpoints. In August 2018, we initiated a global Phase 3 study (KALM-2) with
KORSUVA (CR845/difelikefalin) injection in hemodialysis patients with CKD-aP in multiple countries worldwide,
including the United States. In April 2020, we announced positive top line results from the trial. The study met the primary
and key secondary efficacy endpoints. In June 2017, the FDA granted Breakthrough Therapy Designation to KORSUVA
(CR845/difelikefalin) injection for the treatment of CKD-aP in hemodialysis patients, for which there are currently no
approved therapies in the United States. The Breakthrough Therapy Designation was in part supported by positive data
from our previous Phase 2 efficacy studies. In December 2020, we submitted a NDA to the FDA for KORSUVA
(CR845/difelikefalin) injection for the treatment of moderate-to-severe pruritus in hemodialysis patients, and in February
2021, the NDA was accepted by the FDA.
Partner through license and collaboration agreements to commercialize KORSUVA (CR845/difelikefalin)
injection for the treatment of CKD-aP in hemodialysis patients, if approved. If KORSUVA (CR845/difelikefalin)
injection is approved by the FDA for the treatment of CKD-aP in hemodialysis patients, we have entered into license and
collaboration agreements to commercialize KORSUVA (CR845/difelikefalin) injection. We do not intend to build an
internal sales force to market to nephrologists and dialysis centers and we also do not intend to build an internal supportive
commercialization organization. In May 2018, we licensed worldwide rights, excluding the United States, Japan, and South
Korea, to commercialize KORSUVA (CR845/difelikefalin) injection for the treatment CKD-aP in dialysis patients to
VFMCRP. Under the agreement, VFMCRP has the exclusive rights to commercialize KORSUVA (CR845/difelikefalin)
injection for the treatment of CKD-aP in dialysis patients in all countries outside the United States, except for Japan and
South Korea. In October 2020, we entered into a license agreement with Vifor pursuant to which we granted Vifor an
exclusive license solely in the United States to use, distribute, offer for sale, promote, sell and otherwise commercialize
KORSUVA (CR845/difelikefalin) injection for all therapeutic uses relating to the inhibition, prevention or treatment of itch
associated with pruritus in hemodialysis and peritoneal dialysis patients in the United States. In addition, we already have
development and commercialization agreements with Maruishi and CKDP for development of CR845/difelikefalin for the
Japanese and South Korean markets, respectively.
Expand the use of Oral KORSUVA (CR845/difelikefalin) in other pruritic indications by establishing proof-of-
concept in clinical conditions such as non-dialysis stage III-V CKD-aP, CLD-aP, AD, and NP. Based on potent anti-
pruritic effect we observed with KORSUVA (CR845/difelikefalin) injection in CKD-aP in hemodialysis patients as well as
the data we and others have generated in preclinical models of itch, we have initiated clinical programs with Oral
KORSUVA (CR845/difelikefalin) for the treatment of pruritus in patients with stage III to V (moderate-to-severe) CKD, in
patients with CLD-aP, AD, and NP. In July 2018, we initiated a double blind, randomized, placebo-controlled Phase 2
study with Oral KORSUVA (CR845/difelikefalin) in stage III to V (moderate-to-severe) CKD patients with CKD-aP. In
December 2019, we announced top-line data from this trial indicating that patients treated with the 1.0 mg tablet strength
of Oral KORSUVA (CR845/difelikefalin) achieved the primary endpoint of statistically significant reduction in weekly
mean of the daily worst itching NRS scores vs. placebo after the 12-week treatment period (-4.4 KORSUVA vs. -3.3
placebo, p=0.018). In mid-2019, we also initiated Phase 2 trials of Oral KORSUVA (CR845/difelikefalin) for the treatment
of pruritus in patients with hepatic impairment due to PBC and in patients with AD. We aim to report top-line data from
both of these trials in 2021. In January 2021, we initiated a Phase 2 study with Oral KORSUVA (CR845/difelikefalin) for
the treatment of pruritus in patients suffering from NP.
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Establish partnerships for further development and commercialization of I.V. CR845/difelikefalin for the
treatment of moderate-to-severe acute pain and/or PONV in acute care settings in the United States. In June 2018, we
reported positive top-line data from the adaptive Phase 2/3 post-operative pain trial of I.V. CR845/difelikefalin in patients
undergoing abdominal surgeries. At the higher dose of 1.0 mcg/kg dose, I.V. CR845/difelikefalin demonstrated statistically
significant reductions in pain intensity compared to placebo at all pre-specified post-operative assessment periods.
Additionally, I.V. CR845 treatment resulted in statistically significant reductions in the incidence of post-operative nausea
and vomiting over the 24-hour period post-surgery for both the lower and higher doses of 0.5 and 1.0 mcg/kg, respectively.
We are currently assessing the best path forward for I.V. CR845/difelikefalin in the post-operative acute care setting and
have received FDA input regarding PONV as a potential indication. We expect to seek partnerships for further
development of I.V. CR845/difelikefalin in the acute care setting.
Our Product Candidates
Our product candidate, CR845/difelikefalin, is a new chemical entity, which is designed to selectively stimulate
kappa, rather than mu, and delta opioid receptors. CR845/difelikefalin has been designed with specific chemical
characteristics to restrict its entry into the CNS and further limit its mechanism of action to KORs in the peripheral nervous
system and on immune cells. Activation of kappa receptors in the CNS is known to result in some undesirable effects,
including dysphoria. Since CR845/difelikefalin modulates kappa receptor signals peripherally without any significant
activation of opioid receptors in the CNS, it is generally not expected to produce the CNS-related side effects of mu opioid
agonists (such as addiction and respiratory depression) or centrally-active kappa opioid agonists (such as dysphoria and
hallucinations). CR845/difelikefalin has been administered to more than 3,000 human subjects in Phase 1, Phase 2 and
Phase 3 clinical trials as an I.V. infusion, bolus intravenous injection or oral capsule or tablet, and thus far has been
observed to be generally well tolerated in multiple clinical trials.
Based on the non-clinical and clinical studies we have completed to date, we believe that CR845/difelikefalin, if
approved, would be attractive to both patients and physicians as a treatment for moderate-to-severe pruritus associated with
systematic conditions as CKD and CLD, dermatological conditions such as AD, and neurological conditions such as NP, as
well as moderate-to-severe pain due to the following attributes:
●
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●
●
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novel, peripherally-acting, KOR agonist mechanism of action;
evidence of efficacy in completed clinical trials of pruritus and pain;
potential for reducing mu opioid use and opioid-related adverse events, or AEs, such as nausea and vomiting;
potential for reduction of post-operative nausea and vomiting, or PONV;
avoidance of mu opioid-related CNS side effects, such as respiratory depression and euphoria;
lower potential for addiction or abuse liability;
avoidance of interactions with other drugs because CR845/difelikefalin is not metabolized in the liver and does
not interact with liver enzymes responsible for the metabolism of most commonly used classes of drugs; and
availability in injectable form for the treatment of pruritus in CKD patients undergoing hemodialysis in the
hospital and dialysis center settings as well as for pain and/or PONV treatment in the acute care setting and
oral form for treatment of pruritus or chronic pain conditions in the outpatient setting.
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Our current product candidate pipeline is summarized in the table below:
Program
Pruritus
Product Candidate
Primary Indication
Status
KORSUVA
(CR845/difelikefalin)
Injection
Pruritus CKD -
Hemodialysis
Oral KORSUVA
(CR845/difelikefalin)
Pruritus CKD
(Stage III - V)
• NDA accepted by FDA in
February 2021, Priority Review
request pending
• KALM-2 (Global) Phase 3
pivotal trial completed; top-line
data reported
• KALM-1 pivotal trial
completed; top-line data reported
• Phase 3 safety trials complete
• Breakthrough Therapy
Designation granted by FDA in
June 2017
• Phase 2 trial completed; top-line
data reported
Oral KORSUVA
(CR845/difelikefalin)
Oral KORSUVA
(CR845/difelikefalin)
Pruritus CLD -
Primary Biliary
Cholangitis (PBC)
Pruritus Atopic
Dermatitis
Oral KORSUVA
(CR845/difelikefalin)
Notalgia
Paresthetica
Post-Op
Setting
CR845/difelikefalin
Injection
Acute Post-
Operative
Pain/PONV
• Phase 2 efficacy trial ongoing
• KARE Phase 2 efficacy trial
ongoing; interim assessment
complete - target enrollment
increased to ~400 patients
• KOMFORT Phase 2 efficacy
trial ongoing;
• Adaptive Phase 2/3 trial
completed; top-line data reported
Commercialization Rights
VFMCRP/Vifor (United
States); Maruishi (Japan);
CKDP (South Korea);
VFMCRP (Worldwide,
other than United States,
Japan and South Korea)
Cara (Worldwide, other than
Japan and South Korea);
Maruishi (Japan); CKDP
(South Korea)
Cara (Worldwide, other than
South Korea); CKDP (South
Korea)
Cara (Worldwide, other than
South Korea); CKDP (South
Korea)
Cara (Worldwide, other than
South Korea); CKDP (South
Korea)
Cara (Worldwide, other than
Japan and South Korea);
Maruishi (Japan); CKDP
(South Korea)
KORSUVA (CR845/Difelikefalin) Injection for Treatment of Chronic Kidney Disease-Associated Pruritus (CKD-
aP)
CKD-aP is an intractable systemic itch condition with high prevalence for which there are no approved therapeutics
in the United States or Europe. Based on the results from our efficacy and safety trials highlighted below, we submitted an
NDA to the FDA for KORSUVA (CR845/difelikefalin) injection in December 2020, including a request for Priority
Review under the Breakthrough Therapy Designation granted by the FDA in June 2017, which, if granted, could result in a
six-month review process. In February 2021, the NDA was accepted by the FDA. We expect our partner, VFMCRP, to
submit a Marketing Authorisation Application, or MAA, to the European Medicines Agency, or EMA, in the first quarter
of 2021.
In April 2020, we announced positive top-line results from our KALM-2 pivotal Phase 3 trial of KORSUVA
(CR845/difelikefalin) injection in hemodialysis patients with moderate-to-severe CKD-aP. The trial met the primary and
key secondary endpoints after 12 weeks of treatment. The open label extension phase of this trial is also complete.
The study met the primary efficacy endpoint with 54% of the patients receiving 0.5 mcg/ kg of KORSUVA
(CR845/difelikefalin) injection versus 42% of patients receiving placebo achieving at least a three-point improvement from
baseline with respect to the weekly mean of the daily 24-hour worst itching intensity numeric rating scale, or NRS,
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score at week 12 (p= 0.02). The study also met the key secondary endpoint with 41% of patients receiving KORSUVA
(CR845/difelikefalin) injection achieving a four-point or greater improvement from baseline in the weekly mean of the
daily 24-hour worst itching NRS score at week 12 versus 28% for patients receiving placebo (p= 0.01). In this trial,
KORSUVA (CR845/difelikefalin) injection was generally well-tolerated with a safety profile consistent with that seen in
KALM-1 and the KORSUVA clinical program in patients with CKD-aP. Overall, the incidence of adverse effects, or AEs,
and serious AEs were similar across both KORSUVA (CR845/difelikefalin) injection and placebo groups. The most
common treatment emergent AEs reported in greater than 5% of patients were diarrhea (8.1% KORSUVA vs 5.5%
placebo), falling (6.8% KORSUVA vs 5.1% placebo), vomiting (6.4% KORSUVA vs 5.9% placebo), nausea (6.4%
KORSUVA vs 4.2% placebo) and dizziness (5.5% KORSUVA vs 5.1% placebo).
In May 2019, we announced positive results from the double blinded phase of our KALM-1 pivotal Phase 3 efficacy
trial (KALM-1) of KORSUVA (CR845/difelikefalin) injection for the treatment of CKD-aP in patients undergoing
hemodialysis. The trial met the primary and all secondary endpoints after 12 weeks of treatment. The open label extension
phase of this trial is also complete.
The study met the primary efficacy endpoint with 51% of the patients receiving 0.5 mcg/ kg of KORSUVA
(CR845/difelikefalin) injection versus 28% of patients receiving placebo achieving at least a three-point improvement from
baseline with respect to the weekly mean of the daily 24-hour worst itching intensity NRS score at week 12 (p= 0.000019).
The study also met all secondary endpoints, including assessment of itch-related quality of life changes measured using
self-assessment Skindex-10 (patients receiving KORSUVA experienced 43% improvement versus patients receiving
placebo, p= 0.0004) and 5-D Itch scales (patients receiving KORSUVA experienced 35% improvement versus patients
receiving placebo, p= 0.0009). In addition, 39% of patients receiving KORSUVA (CR845/difelikefalin) injection achieved
a four-point or greater improvement from baseline in the weekly mean of the daily 24-hour worst itching NRS score at
week 12 versus 18% for patients receiving placebo (p= 0.000032), another key secondary endpoint. In this trial,
KORSUVA (CR845/difelikefalin) injection was generally well-tolerated with a safety profile consistent with that seen in
earlier trials. Overall, the incidence of AEs and serious AEs were similar across both KORSUVA (CR845/difelikefalin)
injection and placebo groups. The most common treatment emergent AEs reported in greater than 5% of patients were
diarrhea (9.5% KORSUVA vs 3.7% placebo), dizziness (6.9% KORSUVA vs 1.1% placebo), vomiting (5.3% KORSUVA
vs 3.2% placebo) and nasopharyngitis (3.2% KORSUVA vs 5.3% placebo).
Oral KORSUVA (CR845/Difelikefalin) for Treatment of Chronic Kidney Disease-Associated Pruritus (CKD-aP)
In December 2019, we announced top-line data from our Phase 2 trial of Oral KORSUVA (CR845/difelikefalin) for
the treatment of pruritus in stage III - V (moderate-to-severe) CKD patients. The Phase 2, multicenter, randomized, double-
blind, placebo-controlled 12-week trial is designed to evaluate the safety and efficacy of three tablet strengths (0.25 mg, 0.5
mg and 1 mg, once daily administration) of Oral KORSUVA (CR845/difelikefalin) versus placebo in approximately 240
stage III - V (moderate to severe) CKD patients with moderate-to-severe pruritus. The primary efficacy endpoint was the
change from baseline in the weekly mean of the daily 24-hour worst itching NRS score at week 12 of the treatment period.
Secondary endpoints include change from baseline in itch-related quality of life scores at the end of week 12, as assessed
by the total Skindex-10 and 5-D itch scores, as well as the proportion of patients achieving an improvement from baseline
≥3 points with respect to the weekly mean of the daily 24-hour worst itching NRS score at week 12.
Patients treated with the 1.0 mg tablet strength of Oral KORSUVA (CR845/difelikefalin) achieved the primary
endpoint of statistically significant reduction in weekly mean of the daily worst itching NRS scores vs. placebo after the
12-week treatment period (-4.4 KORSUVA vs. -3.3 placebo, p=0.018). The treatment was statistically significant after two
weeks of treatment and sustained through the 12-week treatment period. Regarding secondary endpoints, the proportion of
patients on 1.0 mg tablet strength achieving a 3 point or greater improvement from baseline in the weekly mean of the daily
worst itching NRS score at week 12 was 72% vs. 58% for placebo but did not achieve statistical significance. Furthermore,
patients on 1.0 mg tablet strength showed positive improvements vs. placebo in itch quality of life endpoints as measured
using self-assessment Skindex-10 and 5-D Itch scales but did not achieve statistical significance. Oral KORSUVA
(CR845/difelikefalin) was generally well-tolerated with a safety profile consistent with that seen in earlier KORSUVA
clinical trials. Overall, the incidence of treatment AEs were similar across KORSUVA
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and placebo groups. The most common AEs reported in >5% of patients in the 1.0 mg KORSUVA group vs. placebo were
dizziness (7.5% KORSUVA vs. 0% placebo), fall (6% KORSUVA vs. 0% placebo), diarrhea (6% KORSUVA vs. 1.5%
placebo) and constipation (6% KORSUVA vs. 3% placebo).
We expect to conduct an End of Phase 2 Meeting with the FDA in the second quarter of 2021 and intend to initiate
the Phase 3 program for Oral KORSUVA (CR845/difelikefalin) for the treatment of pruritus in stage III - V (moderate-to-
severe) CKD in the second half of 2021.
Oral KORSUVA (CR845/Difelikefalin) for Treatment of Chronic Liver Disease-Associated Pruritus (CLD-aP)
Pruritus is a common and serious symptom in patients with CLD, especially those with chronic cholestatic disease.
Pruritus has a prevalence of up to 70% in patients with PBC. Severe pruritus can have debilitating effects and can lead to a
significant reduction in a patient’s quality of life. Although the pathogenesis of CLD-aP remains poorly understood, it is
likely multifactorial including evidence for an imbalance in the endogenous opioid system driven by higher mu receptor
activation (pruritic) versus kappa receptor activation (antipruritic). Consequently, the use of selective kappa-opioid receptor
agonists has been suggested for the treatment of pruritus in patients with CLD.
In June 2019, we announced the initiation of a Phase 2 trial of Oral KORSUVA (CR845/difelikefalin) for the
treatment of pruritus in patients with hepatic impairment due to PBC. The Phase 2 multicenter, randomized, double-blind,
placebo-controlled 16-week trial is designed to evaluate the safety and efficacy of 1 mg tablet of Oral KORSUVA
(CR845/difelikefalin) taken twice daily or BID versus placebo in approximately 60 patients with PBC and moderate-to-
severe pruritus. The primary efficacy endpoint is the change from baseline in the weekly mean of the daily 24-hour worst
itching NRS score at week 16 of the treatment period. Secondary endpoints include change from baseline in itch-related
quality of life scores at the end of week 16 as assessed by the Skindex-10 and 5-D itch scales, as well as the assessment of
proportion of patients achieving an improvement from baseline of ≥3 points with respect to the weekly mean of the daily
24-hour worst itching NRS score at week 16. We continue to screen patients in this ongoing Phase 2 trial of Oral
KORSUVA (CR845/difelikefalin) and aim to have top-line data in the second half of 2021, due in part to delays related to
the ongoing COVID-19 pandemic.
In the fourth quarter of 2017, we submitted an investigational new drug application, or IND, to the FDA for Oral
KORSUVA (CR845/difelikefalin) for the symptomatic relief of CLD-aP and initiated a Phase 1 safety and PK clinical trial
of Oral KORSUVA (CR845/difelikefalin) in patients with CLD in the first quarter of 2018. The open-label study was
designed to evaluate the safety and PK profile of repeated doses of Oral KORSUVA (CR845/difelikefalin) taken twice
daily in up to 60 patients with CLD and up to 12 matched healthy control subjects. Oral KORSUVA (CR845/difelikefalin)
was evaluated over an eight-day treatment period in patients with CLD based on their Child-Pugh classification (i.e.,
Class A, B and C). The study is now complete. The PK parameters were dose-proportional in patients with mild-to-
moderate CLD and Oral KORSUVA (CR845/difelikefalin) was generally well tolerated with no unexpected safety signals
reported.
Oral KORSUVA (CR845/difelikefalin) for Treatment of Moderate-to-Severe Pruritus Associated with Atopic
Dermatitis (AD)
In July 2019, we initiated a Phase 2 randomized, double-blind, placebo-controlled trial that is designed to evaluate
the efficacy and safety of Oral KORSUVA (CR845/difelikefalin) for moderate-to-severe pruritus in approximately 240
adult subjects with AD. Subjects will be randomized to three tablet strengths of Oral KORSUVA (CR845/difelikefalin):
0.25 mg, 0.5 mg and 1 mg twice daily versus placebo for 12 weeks followed by a 4-week active extension phase. The
primary efficacy endpoint is the change from baseline in the weekly mean of the daily 24-hour worst itching NRS score at
week 12 of the treatment period. Secondary endpoints include proportion of patients achieving > 4 point improvement in
itch NRS score at week 12, as well as change from baseline in itch-related quality of life scores at the end of week 12 as
assessed by the total Skindex-10 and 5-D itch scales, and itch related Sleep Quality Assessment. Safety endpoints used to
evaluate the overall safety and tolerability of Oral KORSUVA (CR845/difelikefalin) will also be included.
In January 2020, we expanded this Phase 2 trial to include approximately 320 adult AD patients with moderate-to-
severe pruritus and incorporated an interim conditional power assessment into the design, to be conducted after
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approximately 50% of the targeted patient number complete the designated 12-week treatment period. In June 2020, we
announced that based on the Independent Data Monitoring Committee’s, or IDMC’s, recommendation, the trial would be
increased by approximately 28%, from the previous enrollment target of 320 patients to 410 patients, to maintain the
prespecified statistical power of 80% or greater on the trial’s primary endpoint of change from baseline in the weekly mean
of the daily 24-hour worst itching NRS score and key secondary endpoint of proportion of patients achieving a > 4 point
improvement in itch NRS score at week 12. The IDMC’s recommendation was based on the results of the prespecified
interim conditional power assessment conducted after approximately 50% of the originally targeted patient number
completed the designated 12-week treatment period. In December 2020, we completed full enrollment, having enrolled
approximately 400 patients at multiple clinical sites across the United States. We aim to report the top-line results from this
trial in the first half of 2021, subject to any delays related to the ongoing COVID-19 pandemic.
Oral KORSUVA (CR845/difelikefalin) for Treatment of Moderate-to-Severe Pruritus Associated with Notalgia
Paresthetica (NP)
In January 2021, we initiated a Phase 2 randomized, double-blind, placebo-controlled trial that is designed to
evaluate the efficacy and safety of Oral KORSUVA (CR845/difelikefalin) for moderate-to-severe pruritus in approximately
120 adult subjects with NP. Subjects will be randomized to receive Oral KORSUVA (CR845/difelikefalin) 2.0 mg twice
daily versus placebo for eight weeks followed by a 4-week active extension period and follow up visit approximately 14
days after the last dose of the study. The primary efficacy endpoint is the change from baseline in the weekly mean of the
daily 24-hour worst itching NRS score at week 8 of the treatment period. Secondary endpoints include improvement in
itch-related quality of life assessed by the change from baseline to Week 8 and a change from baseline in itch-related sleep
disturbance subscale measured by the itch medical outcomes study at week 8.
Intravenous CR845/Difelikefalin for Treatment of Acute Postoperative Pain
We have also investigated CR845/difelikefalin for the treatment of pain in an acute care setting. CR845/difelikefalin
is designed to provide pain relief without stimulating mu opioid receptors and therefore potentially without mu opioid-
related side effects, such as nausea, vomiting, respiratory depression and euphoria.
In June 2018, we reported positive top-line date from the adaptive Phase 2/3 study of CR845/difelikefalin in patients
undergoing abdominal surgery. CR845 injection achieved statistical significance for the primary endpoint of pain relief as
measured by Area Under the Curve, or AUC, over 24 hours (AUC 0-24) post-surgery with the 1.0 mcg/kg dose versus
placebo (p=0.032). The 0.5 mcg/kg dose did not achieve statistical significance over the 0-24 hour period (p=0.076). In
addition, improvement in pain AUC was statistically significant for both the 0.5 and 1.0 mcg/kg doses over 0 to 6 hours
(p=0.041, p=0.001) and 0 to 12 hours (p=0.035, p=0.004) periods and also statistically significant for the 1.0 mcg/kg dose
over the 0 to 18-hour period (p=0.013) post-surgery. At 6 and 24 hours after baseline dose post-surgery, there were
statistically significant improvements in PONV impact scores with both doses of CR845 injection compared to placebo:
0.5 mcg/kg (6 hrs.: p=0.0072, 24 hrs.: p<0.006) and 1.0 mcg/kg (6 hrs.: p<0.0001, 24 hrs.: p<0.0001). There were
statistically significant differences between placebo and both doses of CR845 with respect to the total use of anti-emetic
medication over the first 24 hours post-surgery (0.5 mcg/kg: p=0.0003; 1.0 mcg/kg: p< 0.0001). There was a 73%
reduction in the incidence of patient-reported vomiting in the group receiving the 1.0 mcg/kg dose versus placebo
(p=0.029). Although the 0.5 mcg/kg also showed reduction in vomiting, it did not reach statistical significance. Both doses
of CR845 exhibited numerical trends toward reduced use of rescue analgesic medication compared to placebo, but did not
achieve statistical significance. There was no significant effect, compared to placebo, on patient’s global assessment of
medication for either dose of CR845 over the 24-hour period. Common adverse effects reported in the placebo and both
CR845 groups were generally low and similar in incidence, and included nausea, constipation, vomiting, flatulence,
headache and dyspepsia.
We have completed an advisory meeting with the FDA regarding the potential regulatory path forward for PONV
and we are currently evaluating potential next steps.
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Human Abuse Liability Trial of CR845/Difelikefalin Injection
In the fourth quarter of 2014, we successfully completed a Human Abuse Liability, or HAL, trial of
CR845/difelikefalin injection. The results from this HAL trial indicate that I.V. CR845/difelikefalin (5 mcg/kg or 15
mcg/kg) demonstrates statistically significant lower “drug liking” scores as measured by VAS Emax (p <0.0001) when
compared to I.V. pentazocine (0.5 mg/kg), an approved Schedule I.V. opioid receptor agonist. I.V. CR845 also
demonstrated highly statistically significant lower “feeling high,” “overall liking,” and “take drug again” scores (p
<0.0001) as compared to pentazocine. Additionally, CR845/difelikefalin injection showed no “drug liking” dose response
as both doses of CR845/difelikefalin injection exhibited similar responses and were not different from placebo injection.
Those scores represent standard subjective measures recommended by the FDA to assess a drug’s abuse liability. We
believe that the totality of the results from the HAL trial are supportive of the potential for CR845/difelikefalin to be the
first non-scheduled or low (Schedule V) scheduled peripheral kappa opioid for pruritus or additional indications.
Respiratory Safety Phase 1 Trial of CR845/Difelikefalin Injection
In April 2017, we announced summary results from our quantitative Phase 1 trial evaluating respiratory safety of
CR845/difelikefalin injection. Respiratory depression remains the most life-threatening side effect of traditional, centrally
acting, opioid analgesics, the most commonly used drug class for current treatment of postoperative pain in the United
States. The Phase 1 trial was a randomized, double-blind, placebo-controlled, three-way crossover trial of two doses of
CR845/difelikefalin injection (1.0 mcg/kg and 5.0 mcg/kg) versus placebo on three measures of respiratory drive in 15
healthy volunteers. The primary safety endpoints were: a >10 mmHg sustained (>30 seconds duration) increase in end-tidal
CO2, or ETCO2, above baseline or to >50 mmHg, and a sustained reduction in oxygen saturation, or SpO2, to <92%.
There were no statistically significant differences in any respiratory measures observed between groups throughout
the four-hour observation period post-dosing and no individual subject met the threshold for a respiratory safety event.
Additionally, all treatment-emergent adverse events were previously reported with CR845/difelikefalin administration and
were mild, resolving without intervention.
Collaboration and License Agreements
Vifor (International) Ltd.
On October 15, 2020, we entered into a license agreement, or the Vifor Agreement, with Vifor under which we granted
Vifor an exclusive license solely in the United States to use, distribute, offer for sale, promote, sell and otherwise
commercialize KORSUVA (CR845/difelikefalin) injection for all therapeutic uses relating to the inhibition, prevention or
treatment of itch associated with pruritus in hemodialysis and peritoneal dialysis patients in the United States. Under the
Vifor Agreement, we retain all rights with respect to the clinical development of, and activities to gain regulatory approvals
of, KORSUVA (CR845/difelikefalin) injection in the United States.
Under the terms of the Vifor Agreement, we received from Vifor an upfront payment of $100.0 million and an
additional payment of $50.0 million for the purchase of an aggregate of 2,939,552 shares of our common stock at a price of
$17.0094 per share, which represents a premium over a pre-determined average closing price of our common stock. Upon
U.S. regulatory approval of KORSUVA (CR845/difelikefalin) injection, we will also be eligible to receive an additional
$50.0 million common stock investment at a 20% premium to the 30-day trailing average price of our common stock as of
such date. In addition, pursuant to the Vifor Agreement, we are eligible to receive payments of up to $240.0 million upon
the achievement of certain sales-based milestones.
The Vifor Agreement provides full commercialization rights in dialysis clinics to Vifor in the United States under a
profit-sharing arrangement. Pursuant to the profit-sharing arrangement, we will generally be entitled to 60% of the net
profits (as defined in the Vifor Agreement) from sales of KORSUVA (CR845/difelikefalin) injection in the United States
(excluding sales to Fresenius Medical Center dialysis clinics, compensation for which is governed by the VFMCRP
Agreement) and Vifor is entitled to 40% of such net profits, subject to potential temporary adjustment in
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future years based on certain conditions. Under the Vifor Agreement, in consideration of Vifor’s conduct of the marketing,
promotion, selling and distribution of KORSUVA (CR845/difelikefalin) injection in the United States, we will pay a
marketing and distribution fee to Vifor based on the level of annual net sales. This fee will be deducted from product sales
in calculating the net profits that are subject to the profit-sharing arrangement under the Vifor Agreement.
The Vifor Agreement will continue in effect until its expiration upon the cessation of commercial sale of KORSUVA
(CR845/difelikefalin) injection in the United States by Vifor and its affiliates and sublicensees, or until the earlier
termination of the Vifor Agreement.
In addition, upon the earlier of: (1) the acceptance for filing of an NDA covering KORSUVA (CR845/difelikefalin)
injection submitted to the FDA; or (2) October 15, 2023, the Vifor Agreement may be terminated by Vifor in its entirety,
with such termination effective upon 12 months’ notice.
In connection with the Vifor Agreement, the parties entered into a separate stock purchase agreement, or the Vifor
Purchase Agreement, governing the issuance of our common stock to Vifor. Pursuant to the Vifor Purchase Agreement,
Vifor will not, and will not cause any direct or indirect affiliate to, during the period beginning on October 15, 2020 and
ending at the close of business on the earlier of (a) October 15, 2022 and (b) the date that we publicly disclose the receipt
of a complete response letter from the FDA with respect to our NDA for KORSUVA (CR845/difelikefalin) injection, or the
Restricted Period, (i) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or
contract to sell, grant any option, right or warrant to purchase, lend, or otherwise transfer or dispose of, directly or
indirectly, any shares of our common stock or any securities convertible into or exercisable or exchangeable for our
common stock (including without limitation, common stock or such other securities which may be deemed to be
beneficially owned by Vifor in accordance with the rules and regulations of the SEC and securities which may be issued
upon exercise of a stock option or warrant) owned by Vifor as of the date hereof or acquired prior to the end of the
Restricted Period (collectively with the common stock, referred to as the Lock-Up Securities, except any such sale, option
or contract by and between Vifor and one of its affiliates (including Vifor Pharma Group Ltd. or VFMCRP), (ii) enter into
any hedging, swap or other agreement or transaction that transfers, in whole or in part, any of the economic consequences
of ownership of the Lock-Up Securities, whether any such transaction described in clause (i) or (ii) above is to be settled by
delivery of Lock-Up Securities, in cash or otherwise, (iii) make any demand for or exercise any right with respect to the
registration of any Lock-Up Securities, or (iv) publicly disclose the intention to do any of the foregoing.
Under the Vifor Purchase Agreement, the parties also agreed that, in certain circumstances, upon the request of Vifor,
the parties will enter into a registration rights agreement prior to the end of the Restricted Period that would provide Vifor
(or its affiliate transferee) customary registration rights with respect to the shares of common stock issued pursuant to the
stock purchase agreement following the expiration of the Restricted Period.
Vifor Fresenius Medical Care Renal Pharma Ltd.
In May 2018, we entered into a license agreement, or the VFMCRP Agreement, with VFMCRP, a joint venture
between Vifor Pharma Group and Fresenius Medical Care, under which we granted VFMCRP a license to seek regulatory
approval to commercialize, import, export, use, distribute, offer for sale, promote, sell and otherwise commercialize
KORSUVA (CR845/difelikefalin) injection for all therapeutic uses to prevent, inhibit or treat itch associated with pruritus
in hemodialysis and peritoneal-dialysis patients worldwide (excluding the United States, Japan and South Korea). We
retain full development and commercialization rights for KORSUVA injection for the treatment of CKD-aP in dialysis
patients in the U.S. except in the dialysis clinics of Fresenius Medical Care North America, or FMCNA, where we and
VFMCRP will promote KORSUVA injection under a profit-sharing arrangement.
Upon entry into the VFMCRP Agreement, VFMCRP made a non-refundable, non-creditable $50 million upfront
payment to us and Vifor purchased 1,174,827 shares of our common stock for $20 million, at a premium for the price of
$17.024 per share. We are eligible to receive from VFMCRP regulatory and commercial milestone payments in the
aggregate of up to $470 million, consisting of up to $30 million in regulatory milestones and up to $440 million in tiered
commercial milestones, all of which are sales-related. We are also eligible to receive tiered double-digit royalty payments
based on annual net sales, as defined, of KORSUVA (CR845/difelikefalin) injection in the licensed territories.
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In the United States, we and VFMCRP will promote KORSUVA (CR845/difelikefalin) injection in the dialysis clinics of
FMCNA under a profit-sharing arrangement (subject to the terms and conditions of the VFMCRP Agreement) based on net
FMCNA clinic sales recorded by us.
Maruishi Pharmaceutical Co., Ltd.
In April 2013, we entered into a license agreement with Maruishi, or the Maruishi Agreement, under which we
granted Maruishi an exclusive license to develop, manufacture and commercialize drug products containing
CR845/difelikefalin in Japan in the acute pain and uremic pruritus fields. Maruishi has a right of first negotiation for any
other indications for which we develop CR845/difelikefalin and, under certain conditions, Maruishi may substitute another
pruritus indication for the uremic pruritus indication originally included in its license from us. If we abandon development
of CR845/difelikefalin and begin development of another kappa opioid receptor agonist that is covered by the claims of the
patents we licensed to Maruishi, such other agonist will automatically be included in the license to Maruishi. Maruishi is
required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory approval for and
commercialize CR845/difelikefalin in Japan. We are required to use commercially reasonable efforts, at our expense, to
develop, obtain regulatory approval for and commercialize CR845/difelikefalin in the United States.
Under the terms of the Maruishi Agreement, we received a non-refundable and non-creditable upfront license fee of
$15.0 million and are eligible to receive up to an aggregate of $10.5 million in clinical development and regulatory
milestones, of which $2.5 million (before contractual foreign currency exchange adjustments) has been received as of
December 31, 2020. In January 2021, we met the milestone criteria, as set forth in the Maruishi Agreement, for Maruishi’s
first initiation of a Phase III trial for uremic pruritus in Japan. As a result, we received a milestone payment of $2.0 million
($1.9 million after contractual foreign currency exchange adjustments) from Maruishi. We are also eligible to receive a
one-time sales milestone of one billion Yen when a certain sales level is attained. We also receive a mid-double-
digit percentage of all non-royalty payments received by Maruishi from its sublicensees, if any. We are also eligible to
receive tiered royalties based on net sales, if any, with minimum royalty rates in the low double digits and maximum
royalty rates in the low twenties. Maruishi’s obligation to pay us royalties continues, on a product-by-product basis, until
the expiration of the last-to-expire licensed patent covering such product or the later expiration of any market exclusivity
period. The Maruishi Agreement continues until terminated. Either we or Maruishi may terminate the Maruishi Agreement
for the other party’s breach of the agreement or bankruptcy. Maruishi may terminate the agreement at any time at will. We
may terminate the agreement as a whole if Maruishi challenges the licensed patent rights, and we may terminate the
agreement with respect to any indication if Maruishi discontinues its development activities. In addition, in connection with
the Maruishi Agreement, Maruishi made an $8.0 million equity investment in our company.
Chong Kun Dang Pharmaceutical Corporation
In April 2012, we entered into a license agreement with CKDP, or the CKDP Agreement, under which we granted
CKDP an exclusive license to develop, manufacture and commercialize drug products containing CR845/difelikefalin in
South Korea. CKDP is required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory
approval for and commercialize CR845/difelikefalin in South Korea. We are required to use commercially reasonable
efforts, at our expense, to develop, obtain regulatory approval for and commercialize CR845/difelikefalin in the United
States.
Under the terms of the CKDP Agreement, we received a non-refundable and non-creditable $0.6 million upfront
payment and are eligible to receive up to an aggregate of $3.8 million in development and regulatory milestones (before
South Korean withholding taxes). In May 2020, we met the milestone criteria, as set forth in the CKDP Agreement, for
completion of a Phase 3 trial for uremic pruritus in the United States. As a result, in June 2020, we received a milestone
payment of $0.6 million (net of South Korean withholding tax) from CKDP. As of December 31, 2020, we have received
$2.3 million (before South Korean withholding tax) of development and regulatory milestones. We are also eligible to
receive a mid-double-digit percentage of all non-royalty payments received by CKDP from its sublicensees, if any, and
tiered royalties ranging from the high single digits to the high teens based on net sales, if any. CKDP’s obligation to pay us
royalties continues, on a product-by-product basis, until the expiration of the last-to-expire licensed patent covering such
product or the later expiration of any market exclusivity period. The CKDP Agreement continues until CKDP no longer
has any obligation to pay us royalties on any product. Either we or CKDP may terminate the
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CKDP Agreement for the other party’s breach of the CKDP Agreement or bankruptcy. CKDP may terminate the CKDP
Agreement if any of the licensed patent rights is invalid, unenforceable, is narrowed in scope or is deemed unpatentable,
except as a result of a challenge by CKDP, or a third party commercializes a product containing a compound identical to
CR845/difelikefalin without infringing any of the licensed patent rights in South Korea. We may terminate the CKDP
Agreement if CKDP challenges the licensed patent rights or if a third party in South Korea owns an issued patent that
claims CR845/difelikefalin and CKDP’s sale of products would infringe that patent. In addition, in connection with the
CKDP Agreement, CKDP made a $0.4 million equity investment in our company.
Manufacturing and License Agreements
Enteris Biopharma, Inc.
In August 2019, we entered into a Non-Exclusive License Agreement, or the Enteris License Agreement, with
Enteris. Pursuant to the Enteris License Agreement, Enteris granted to us a non-exclusive, royalty-bearing license,
including the right to grant sublicenses, under certain proprietary technology and patent rights related to or covering
formulations for oral delivery of peptide active pharmaceutical ingredients with functional excipients to enhance
permeability and/or solubility, known as Enteris’s Peptelligence® technology, to develop, manufacture and commercialize
products using such technology worldwide, excluding Japan and South Korea.
As consideration for the licensed rights under the Enteris License Agreement, we paid an upfront fee equal to $8.0
million, consisting of $4.0 million in cash and $4.0 million in shares of our common stock pursuant to the Enteris Purchase
Agreement described below.
We are also obligated, pursuant to the Enteris License Agreement, to pay Enteris (1) milestone payments upon the
achievement of certain development, regulatory and commercial milestones and (2) low-single digit royalty percentages on
net sales of licensed products, subject to reductions in specified circumstances. Until the second anniversary of the entry
into the Enteris License Agreement, we have the right, but not the obligation, to terminate our obligation to pay any
royalties under the Enteris License Agreement in exchange for a lump sum payment in cash, or the Royalty Buyout.
Subject to certain conditions, we may elect to pay 50% of the lump sum due under the Royalty Buyout in shares of our
common stock pursuant to the Enteris Purchase Agreement. During the year ended December 31, 2020, we paid $5.0
million to Enteris for a milestone earned during the year ended December 31, 2020 in relation to the Enteris License
Agreement.
The Enteris License Agreement will expire on a country-by-country, licensed product-by-licensed product basis upon
the later of (1) the expiration (or invalidation) of all valid claims in licensed patent rights that cover such product in such
country, (2) the end of the calendar quarter in which generic competition (as defined in the Enteris License Agreement)
occurs for such product in such country and (3) ten years from the first commercial sale of such product.
Either party may terminate the Enteris License Agreement upon written notice if the other party has failed to remedy
a material breach within 60 days (or 30 days in the case of a material breach of a payment obligation). Enteris may
terminate the Enteris License Agreement upon 30 days’ written notice to us if we or any of our affiliates formally challenge
the validity of any licensed patent rights or assists a third party in doing so. We may terminate the Enteris License
Agreement for any reason or no reason (a) prior to receipt of first regulatory approval for a licensed product in the United
States for any indication upon 30 days’ prior written notice to Enteris or (b) on or after receipt of first regulatory approval
for a licensed product in the United States for any indication upon 60 days’ prior written notice to Enteris.
In connection with the Enteris License Agreement, in August 2019, we entered into the Enteris Purchase Agreement
with Enteris and its affiliate, EBP Holdco LLC, collectively referred to as Purchaser, pursuant to which we issued and sold
to Purchaser 170,793 shares of our common stock in a private placement. Such shares were issued in satisfaction of the
$4.0 million portion of the upfront fee payable in shares of our common stock pursuant to the Enteris License Agreement
and for no additional consideration, based on a purchase price of $23.42 per share, which was equal to the 30-day volume
weighted average price of our common stock on August 20, 2019. In addition, if we exercise our Royalty Buyout option,
we may elect to make 50% of the payment in stock by issuing additional shares of our common
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stock valued at the 30-day volume weighted average price of our common stock as of such exercise. Pursuant to the
Purchase Agreement, we effected the registration and sale of the shares issued and sold to Purchaser thereunder in
accordance with the applicable requirements of the Securities Act of 1933, as amended, or the Securities Act, which
included the filing of a registration statement with the SEC on September 9, 2019. In addition, the Purchase Agreement
includes customary representations, warranties and covenants by us.
Patheon UK Limited
In July 2019, we entered into an MSA with Patheon UK Limited, or Patheon. The MSA governs the general terms
under which Patheon, or one of its affiliates, will provide non-exclusive manufacturing services to us for the drug products
specified by us from time to time. Pursuant to the MSA, we have agreed to order from Patheon at least a certain percentage
of our commercial requirements for a product under a related Product Agreement. Each Product Agreement that we may
enter into from time to time will be governed by the terms of the MSA, unless expressly modified in such Product
Agreement.
The MSA has an initial term ending December 31, 2023, and will automatically renew after the initial term for
successive terms of two years each if there is a Product Agreement in effect, unless either party gives notice of its intention
to terminate the MSA at least 18 months prior to the end of the then current term.
Either party may terminate the MSA or a Product Agreement upon written notice if the other party (1) has failed to
remedy a material breach within a specified time or (2) is declared insolvent or bankrupt, voluntarily files a petition of
bankruptcy or assigns such agreement for the benefit of creditors. We may terminate a Product Agreement (a) upon
90 days’ prior written notice if any governmental agency takes any action that prevents us from selling the relevant product
in the relevant territory, (b) upon six months’ prior written notice if we do not intend to order manufacturing services due to
a product’s discontinuance in the market, or (c) upon 90 days’ prior written notice if we determine that the manufacture or
supply of a product likely infringes third-party rights. Patheon may terminate the MSA or a Product Agreement (i) upon
six months’ prior written notice if we assign such agreement to an assignee that is unacceptable to Patheon for certain
reasons, or (ii) upon 30 days’ prior written notice if, after the first year of commercial sales, we forecast zero volume for
12 months.
The MSA contains, among other provisions, customary representations and warranties by the parties, a grant to
Patheon of certain limited license rights to our intellectual property in connection with Patheon’s performance of the
services under the MSA, certain indemnification rights in favor of both parties, limitations of liability and customary
confidentiality provisions.
Also in July 2019, we entered into two related Product Agreements under the MSA, one with each of Patheon and
Patheon Manufacturing Services LLC, or Patheon Greenville, to govern the terms and conditions of the manufacture of
commercial supplies of CR845/difelikefalin injection, our lead product candidate. Pursuant to the Product Agreements,
Patheon and Patheon Greenville will manufacture commercial supplies of CR845/difelikefalin injection at the Monza, Italy
and Greenville, North Carolina manufacturing sites, respectively, from active pharmaceutical ingredient supplied by us.
Patheon and Patheon Greenville will be responsible for supplying the other required raw materials and packaging
components, and will also provide supportive manufacturing services such as quality control testing for raw materials,
packaging components and finished product.
Sales and Marketing
In executing our strategy, our goal is to commercialize CR845/difelikefalin injection in the dialysis setting by
partnering with out-licensing agreements, and to maintain significant control over the development process and
commercial execution for the Oral formulation of CR845/difelikefalin, if approved.
We have executed out-licensing agreements on KORSUVA (CR845/difelikefalin) injection in the dialysis setting in
the United States and the rest of the world.
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For Oral KORSUVA (CR845/difelikefalin), we plan to develop and commercialize our drug candidate in pruritus
indications, such as CKD-aP, AD, and potentially others, on our own in the United States, while exploring partnerships for
development and commercialization in geographical territories outside the United States.
In 2015, we commissioned a qualitative market research study of nephrologists to evaluate the commercial potential
of KORSUVA (CR845/difelikefalin) for CKD-aP. The study suggests KORSUVA (CR845/difelikefalin) would be well
received by nephrologists, if approved. The key findings from the study were:
●
●
●
●
●
There is a clear unmet need to manage CKD-aP among dialysis patients.
Currently, there are no effective options for severe CKD-aP.
CR845/difelikefalin demonstrates impressive efficacy for CKD-aP.
Physicians were impressed with placebo-like adverse event profile.
KORSUVA (CR845/difelikefalin) injection can easily be incorporated into dialysis sessions.
As a result, we believe that, if successful, KORSUVA (CR845/difelikefalin) is well positioned to address the unmet
needs for hemodialysis patients suffering from CKD-aP.
We had also commissioned market research for I.V. CR845/difelikefalin for the treatment of PONV that suggests it
would be well received by physicians, if approved. This research indicated that anesthesiologists rated efficacy in high-risk
patients and the scarcity of rescue medications as the highest unmet needs. There is an opportunity for greater efficacy in
high-risk patients who typically receive three or more products prophylactically. Anesthesiologists stated the most
favorable attributes of CR845 included its novel mechanism of action, positive efficacy results and favorable side effect
profile. The novel mechanism of action was favorable given its potential additive effect on existing multimodal treatment
regimens as well as its potential as a new option for rescue therapy, a therapy that is used when prophylactic agents have
failed to prevent nausea and vomiting. Anesthesiologists indicated a preference to utilize CR845 in combination with
existing regimens for high-risk patients particularly in invasive surgeries that require narcotics. In our three Phase 2 trials,
I.V. CR845/difelikefalin demonstrated statistically significant reductions in PONV as well as statistically significant
reductions in pain relief. As a result, we believe that, if successful, I.V. CR845/difelikefalin is well positioned to address
unmet needs in the PONV market.
Intellectual Property
We strive to protect the proprietary technologies that we believe are important to our business, including seeking and
maintaining patent protection intended to cover the composition of matter of our product candidates, their methods of use,
related technology and other inventions that are important to our business. As more fully described below, patent
applications have been filed covering compositions of matter for and novel formulations of these compositions, as well as
methods of using CR845/difelikefalin. We own the patent portfolio of seventeen issued U.S. patents covering kappa opioid
receptor agonists, fifteen of which cover CR845/difelikefalin and its uses; six of these include composition of matter claims
directed to CR845/difelikefalin, and nine include claims to its uses. All of these U.S. patents are expected to expire no
earlier than 2027. Additionally, three U.S. patents have been granted with claims to CR845/difelikefalin-like dimer
compounds and their uses. We have filed patent applications in the U.S. and internationally claiming novel oral
formulations of CR845/difelikefalin, which if granted would be expected to expire no earlier than 2039. We also rely on
trade secrets and careful monitoring of our proprietary information to protect aspects of our business that are not amenable
to, or that we do not consider appropriate for, patent protection.
Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for
commercially important technology, inventions and know-how related to our business, defend and enforce our patents,
maintain our licenses to use intellectual property owned by third parties, preserve the confidentiality of our trade secrets
and operate without infringing valid and enforceable patents and other proprietary rights of third parties. We also
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rely on know-how, and continuing technological innovation to develop, strengthen, and maintain our proprietary position in
the field of peripheral analgesia and treatment of pruritus.
A third party may hold intellectual property, including patent rights, which are important or necessary to the
development of our products. It may be necessary for us to use the patented or proprietary technology of third parties to
commercialize our products, in which case we would be required to obtain a license from these third parties on
commercially reasonable terms, or our business could be harmed, possibly materially. If we were not able to obtain a
license or were not able to obtain a license on commercially reasonable terms, our business could be harmed, possibly
materially.
We plan to continue to expand our intellectual property estate by filing patent applications directed to novel
peripheral analgesics, novel formulations and novel uses of our proprietary compounds. We anticipate seeking patent
protection in the United States and internationally for the chemistries and processes for manufacturing these compounds
and novel formulations and uses of these compounds in a variety of therapies.
The patent positions of biopharmaceutical companies like us are generally uncertain and involve complex legal,
scientific and factual questions. In addition, the coverage claimed in a patent application can be significantly reduced
before the patent is issued, and the patent’s scope can be modified after issuance by later judicial decisions. Consequently,
we do not know whether any of our product candidates will be adequately protectable or remain protected by enforceable
patents. We cannot predict whether the patent applications we are currently pursuing will issue as patents in any particular
jurisdiction or whether the claims of any issued patents will provide sufficient proprietary protection from competitors.
Any patents that we hold may be challenged, circumvented or invalidated by third parties.
Because patent applications in the United States and certain other jurisdictions are maintained in secrecy for up to
18 months, and since publication of discoveries in the scientific or patent literature often lags behind actual discoveries, we
cannot be certain of our entitlement to the inventions covered by pending patent applications. Moreover, although unlikely,
we may have to participate in interference proceedings declared by the United States Patent and Trademark Office, or
USPTO, to determine priority of invention, or in post-grant challenge proceedings in the USPTO, or a foreign patent office
such as oppositions, inter-partes review, post grant review, or a derivation proceeding, that challenge our entitlement to an
invention or the patentability of one or more claims in our patent applications or issued patents. Such proceedings could
result in substantial cost, even if the eventual outcome is favorable to us.
The patent portfolios for our most advanced programs are summarized below.
CR845/Difelikefalin
Our synthetic peptide amide kappa opioid agonist patent portfolio is wholly owned by us. The portfolio includes
seventeen issued U.S. patents (U.S. Patent Nos. 7,402,564; 7,713,937; 7,727,963; 7,842,662; 8,217,007; 8,236,766;
8,486,894; 8,536,131; 8,906,859; 8,951,970; 9,321,810; 9,334,305; 9,359,399; 10,017,536; 10,138,270; 10,913,769 and
10,793,596) with claims to compositions of a wide range of synthetic peptide amide kappa opioid agonists, including
CR845/difelikefalin and related molecules, as well as methods of using these compounds. These patents claiming
CR845/difelikefalin compositions are due to expire November 12, 2027, although the patent term of one of the patents
listed in the FDA Orange Book is expected to be extended for up to a further five (5) years, i.e. to November 12, 2032,
based upon the Hatch-Waxman Act. The CR845/difelikefalin patent portfolio also includes pending U.S. patent
applications which claim additional uses and methods of administering CR845/difelikefalin. Related foreign applications
were filed in more than 40 other countries. National patents have been granted in 31 European countries, as well as in
Australia, Brazil, Canada, China, Hong Kong, India, Israel, Japan, Malaysia, Mexico, New Zealand, Russia, Singapore,
South Africa and South Korea. These granted foreign patents with claims to CR845/difelikefalin are due expire no earlier
than November 12, 2027. The Brazilian patent law provides for a patent term extension of up to ten years for
pharmaceutical patents to compensate for the loss of patent term during prosecution.
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Other Cara Patents and Patent Applications
We also own several other U.S. Patents including U.S. Patent Nos. 7,741,350; 7,960,376; 7,960,377; and 8,211,926
with claims to other cannabinoid compounds and U.S. Patent No. 8,217,000 with claims to regulation of prolactin in
mammals including humans.
The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.
In most countries in which we file, the patent term is 20 years from the earliest date of filing a PCT application or a non-
provisional patent application. The term of a patent in the United States can be adjusted and extended due to the failure of
the USPTO following certain statutory and regulation deadlines for progressing prosecution and issuing a patent.
In the United States, the patent term of a patent that covers an FDA-approved drug may also be eligible for patent
term extension, which permits patent term restoration as compensation for a portion of the patent term lost during the FDA
regulatory review process. The Hatch-Waxman Act permits a patent term extension of up to five years beyond the
expiration of the patent. The length of the patent term extension is related to the length of time the drug is under regulatory
review. Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product
approval and only one patent applicable to an approved drug may be extended. Similar provisions are available in Europe
and other non-United States jurisdictions to extend the term of a patent that covers an approved drug. In the future, if and
when our pharmaceutical products receive FDA approval, we expect to apply for patent term extensions on patents
covering those products. Although we intend to seek patent term extensions to any of our issued patents in any jurisdiction
where these are available there is no guarantee that the applicable authorities, including the FDA in the United States, will
agree with our assessment of whether such extensions should be granted, and even if granted, the length of such extensions.
We also rely on trade secret protection for our confidential and proprietary information. Although we take steps to
protect our proprietary information and trade secrets, including through contractual means with our employees and
consultants, third parties may independently develop substantially equivalent proprietary information and techniques or
otherwise gain access to our trade secrets or disclose our technology. Thus, we may not be able to meaningfully protect our
trade secrets. It is our policy to require our employees, consultants, outside scientific collaborators, sponsored researchers
and other advisors to execute confidentiality agreements upon the commencement of employment or consulting
relationships with us. These agreements provide that all confidential information concerning our business or financial
affairs developed or made known to the individual during the course of the individual’s relationship with us is to be kept
confidential and not disclosed to third parties except in specific circumstances. In the case of employees, the agreements
provide that all inventions conceived by the individual, and which are related to our current or planned business or research
and development, or R&D, or made during normal working hours, on our premises or using our equipment or proprietary
information, are our exclusive property.
Competition
The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense
competition and a strong emphasis on proprietary products. While we believe that our technology, knowledge, experience
and scientific resources provide us with competitive advantages, we face potential competition from many different
sources, including large pharmaceutical and biotechnology companies, specialty pharmaceutical and generic drug
companies, and medical technology companies. Any product candidates that we successfully develop and commercialize
will compete with existing therapies and new therapies that may become available in the future.
There are a large number of companies developing or marketing therapies for the indications that we are pursuing.
Many of our competitors, including many of the organizations named below, have substantially greater financial, technical
and human resources than we do and significantly greater experience in the development of product candidates, obtaining
FDA and other regulatory approvals of products and the commercialization of those products. Mergers and acquisitions in
the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller
number of competitors. Small or early stage companies may also prove to be significant competitors, particularly through
collaborative arrangements with large and established companies. We also compete with these
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companies in recruiting and retaining qualified scientific personnel and establishing clinical trial sites and patient
registration for clinical trials.
We believe the key competitive factors that will affect the development and commercial success of our product
candidates, if approved for marketing, are likely to be their safety, efficacy and tolerability profile, reliability, convenience
of dosing, price and reimbursement from government and third-party payers. Our commercial opportunity could be
reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or
less severe side effects, are more convenient or are less expensive than any products that we may develop. Our competitors
also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours,
which could result in our competitors establishing a strong market position before we are able to enter the market. In
addition, our ability to compete may be affected in many cases by insurers or other third-party payers seeking to encourage
the use of generic products. Generic products that broadly address these indications are currently on the market for the
indications that we are pursuing, and additional products are expected to become available on a generic basis over the
coming years. If our product candidates achieve marketing approval, we expect that they will be priced at a significant
premium over competitive generic products.
If our product candidates are approved for the indications for which we are currently undertaking clinical trials, they
will compete with the therapies and currently marketed drugs discussed below:
KORSUVA (CR845/difelikefalin) injection - Uremic Pruritus or CKD-aP. We are developing KORSUVA
(CR845/difelikefalin) injection for the management of CKD-aP in hemodialysis patients. Currently, there are no approved
products for management of CKD-aP in the United States. However, there are many products that are used to help manage
CKD-aP. The most common of these agents are anti-itch creams and emollients as well as oral or injectable antihistamines.
All of these products have limited degrees of efficacy and are available generically. Additionally, patients may try several
other agents such as gabapentin or naltrexone, generally with limited success or therapies such as UVB light therapy with
limited availability.
Because of the substantial unmet need for products that are safe and effective in CKD-aP, there are other companies
that either were in the past or are currently involved in the discovery, development, and/or marketing of such products for
CKD-aP or related conditions. Some of such product candidates or products include SK-1405 from Sanwa Kagaku
Kenkyusho and Remitch® or nalfurafine from Toray Industries.
Oral KORSUVA (CR845/difelikefalin) – Chronic Kidney Disease-Associated Pruritus (CKD-aP) and Chronic
Liver Disease-Associated Pruritus (CLD-aP). We are developing Oral KORSUVA (CR845/difelikefalin) for the
management of moderate-to-severe chronic pruritus conditions like CKD-aP or CLD-aP. There are currently no products
approved in the United States for CKD-aP or CLD-aP. The market for the management of moderate-to-severe chronic
pruritus is highly fragmented and includes numerous generic products, including oral formulations of corticosteroids and
antihistamines. The most common corticosteroids and antihistamines are available generically. Because of the size and
untapped potential of the chronic pruritus market and the substantial unmet need for products that are safe and effective,
there are other companies involved in the discovery, development, and/or marketing of new products for pruritus.
Oral KORSUVA (CR845/difelikefalin) – Atopic Dermatitis-Associated Pruritus (AD). We are developing Oral
KORSUVA (CR845/difelikefalin) for the management of moderate-to-severe chronic pruritus associated with AD. There
are currently two products specifically approved in the United States to treat AD and the itching associated with it:
Dupixent (dupilumab) and Eucrisa (crisaborole). Additionally, the market for the management of mild-to-moderate and
moderate-to-severe AD includes numerous generic products, including topical and oral formulations of corticosteroids and
antihistamines. Because of the size and untapped potential of the AD market, there are other companies involved in the
discovery, development, and/or marketing of new products for pruritus. Multiple companies are studying IL-13 inhibitors
(e.g. tralokinumab, lebrikizumab), IL-31 inhibitors (e.g. nemolizumab), JAK inhibitors (e.g. baricitinib, upadacitinib and
abrocitinib) and OX40 inhibitors for treatment of AD.
I.V. CR845/difelikefalin – Post-Operative Nausea and Vomiting (PONV) Management. The market for the
prevention and treatment of PONV is highly fragmented. Anesthesiologists utilize a number of different agents alone or in
combination (particularly in patients with a high risk for PONV) with different mechanism of actions to try to manage
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PONV. If approved, I.V. CR845/difelikefalin would likely be competing within the overall PONV market, although we
expect that it would primarily be utilized as an add-on therapy in patients with a higher risk of PONV. Although most of the
PONV products are generically available, there is still a significant segment of high-risk patients where their PONV is not
adequately managed, which can increase the hospital length of stay and add significant cost to managing a post-operative
patient.
Manufacturing
We do not have any manufacturing facilities. We currently rely, and expect to continue to rely, on third parties for the
manufacture of our product candidates for preclinical and clinical testing, as well as for commercial manufacture if our
product candidates receive marketing approval. At this time, none of our contract manufacturing agreements limit where,
or with whom we can contract for commercial manufacture or distribution. It is our intention that by the time of any
regulatory approvals for commercialization, we will have negotiated long-term commitments with at least one primary
supplier for each manufacturing and distribution function. At this time, we have entered into a non-exclusive commercial
manufacturing agreement with Patheon for KORSUVA (CR845/difelikefalin) injection.
All of our product candidates are either small peptides or organic small molecules and are manufactured in reliable
and reproducible synthetic processes from readily available starting materials. The chemistry is amenable to scale up and
does not require any special equipment or technology in the manufacturing process. We expect to continue to develop
product candidates that can be produced cost-effectively at contract manufacturing facilities.
Government Regulation and Product Approval
Government authorities in the United States, at the federal, state and local level, and in other countries extensively
regulate, among other things, the research, development, testing, manufacture, packaging, storage, recordkeeping, labeling,
advertising, promotion, distribution, marketing, import and export of pharmaceutical products such as those we are
developing. The processes for obtaining regulatory approvals in the United States and in foreign countries, along with
subsequent compliance with applicable statutes and regulations, require the expenditure of substantial time and financial
resources.
FDA Regulation
In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its
implementing regulations. The process of obtaining regulatory approvals and the subsequent compliance with appropriate
federal, state, local and foreign statutes and regulations requires the expenditure of substantial time and financial resources.
Failure to comply with the applicable United States requirements at any time during the product development process,
approval process or after approval, may subject an applicant to a variety of administrative or judicial sanctions, such as the
FDA’s refusal to approve pending NDAs, withdrawal of an approval, imposition of a clinical hold, issuance of warning or
untitled 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.
The process required by the FDA before a drug may be marketed in the United States generally involves the
following:
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completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the
FDA’s good laboratory practice, or GLP, regulations;
submission to the FDA of an IND which must become effective before human clinical trials may begin;
approval by an independent institutional review board, or IRB, at each clinical site before each trial may be
initiated;
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performance of human clinical trials, including adequate and well-controlled clinical trials, in accordance with
good clinical practices, or cGCP, to establish the safety and efficacy of the proposed drug product for each
indication;
submission to the FDA of an NDA;
satisfactory completion of an FDA advisory committee review, if applicable;
satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is
produced to assess compliance with current good manufacturing practices, or cGMP, and to assure that the
facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity, as well
as satisfactory completion of an FDA inspection of selected clinical sites to determine cGCP compliance;
FDA review and approval of the NDA; and
potential DEA review and scheduling activities prior to launch for some of our product candidates.
Preclinical Studies. Preclinical studies include laboratory evaluation of drug substance chemistry, toxicity and drug
product formulation, as well as animal studies to assess potential safety and efficacy. An IND sponsor must submit the
results of the preclinical tests, together with manufacturing information, analytical data and any available clinical data or
literature, among other things, to the FDA as part of an IND. Manufacture of drug substance, drug product and the labeling
and distribution of clinical supplies must all comply with cGMP standards. Some preclinical testing may continue even
after the IND is submitted. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that
time the FDA raises concerns or questions related to one or more proposed clinical trials and places the trial on a clinical
hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can
begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.
Clinical Trials. Clinical trials involve the administration of the investigational new drug to human subjects under the
supervision of qualified investigators in accordance with cGCP requirements, which include the requirement that all
research subjects provide their informed consent in writing for their participation in any clinical trial. Clinical trials are
conducted under protocols detailing, among other things, the objectives of the trial, the parameters to be used in monitoring
safety and the effectiveness criteria to be evaluated. A protocol for each clinical trial and any subsequent protocol
amendments must be submitted to the FDA as part of the IND. In addition, an IRB at each institution participating in the
clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB
must continue to oversee the clinical trial while it is being conducted. Information about certain clinical trials must be
submitted within specific timeframes to the National Institutes of Health, or NIH, for public dissemination on their
ClinicalTrials.gov website.
Human clinical trials are typically conducted in three sequential phases, which may overlap or be combined. In Phase
1, the drug is initially introduced into healthy human subjects or patients with the target disease or condition and tested for
safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an initial indication of its
effectiveness. In Phase 2, the drug typically is administered to a limited patient population to identify possible adverse
effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine
dosage tolerance and optimal dosage. In Phase 3, the drug is administered to an expanded patient population, generally at
geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate
the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product and to provide
adequate information for the labeling of the product.
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more
frequently if serious adverse events occur. Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully
within any specified period, or at all. Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at
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any time on various grounds, including a finding that the research subjects 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
patients.
Marketing Approval. Assuming successful completion of the required clinical testing, the results of the preclinical
and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and
proposed labeling, among other things, are submitted to the FDA as part of an NDA requesting approval to market the
product for one or more indications. In most cases, the submission of an NDA is subject to a substantial application user
fee. Under the Prescription Drug User Fee Act, or PDUFA, guidelines that are currently in effect, the FDA has agreed to
certain performance goals regarding the timing of its review of an application.
In addition, under the Pediatric Research Equity Act, or PREA, an NDA or supplement to an NDA must contain data
that are adequate to assess the safety and effectiveness of the drug for the claimed indications in all relevant pediatric
subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and
effective. The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or
all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data
requirements.
The FDA also may require submission of a risk evaluation and mitigation strategy, or REMS, to mitigate any
identified or suspected serious risks and ensure safe use of the drug. The REMS plan could include medication guides,
physician communication plans, assessment plans, and elements to assure safe use, such as restricted distribution methods,
patient registries or other risk minimization tools.
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 application must be resubmitted with the
additional information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the
submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA reviews an NDA to determine,
among other things, whether the drug is safe and effective and whether the facility in which it is manufactured, processed,
packaged or held meets standards designed to assure the product’s continued safety, quality and purity.
The FDA may refer an application for a novel drug to an external advisory committee. An advisory committee is a
panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a
recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by
the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.
Before approving an NDA, the FDA typically will inspect the facility or facilities where the product is manufactured,
referred to as a Pre-Approval Inspection. The FDA will not approve an application unless it determines that the
manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent
production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically
inspect one or more clinical trial sites to assure compliance with cGCP.
The testing and approval process for an NDA requires substantial time, effort and financial resources, and each may
take several years to complete. Data obtained from preclinical and clinical testing are not always conclusive and may be
susceptible to varying interpretations, which could delay, limit or prevent regulatory approval. The FDA may not grant
approval of an NDA on a timely basis, or at all.
After evaluating the NDA and all related information, including the advisory committee recommendation, if any, and
inspection reports regarding the manufacturing facilities and clinical trial sites, the FDA may issue an approval letter, or, in
some cases, a complete response letter. A complete response letter generally contains a statement of specific conditions that
must be met in order to secure final approval of the NDA and may require additional clinical or
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preclinical testing in order for FDA to reconsider the application. Even with submission of this additional information, the
FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval. If and when those
conditions have been met to the FDA’s satisfaction, the FDA may issue an approval letter. An approval letter authorizes
commercial marketing of the drug with specific prescribing information for specific indications. For some products, an
additional step of DEA review and scheduling is required.
Even if the FDA approves a product, it may limit the approved indications for use of the product, require that
contraindications, warnings or precautions be included in the product labeling, including a boxed warning, require that
post-approval studies, including Phase 4 clinical trials, be conducted to further assess a drug’s safety after approval, require
testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including
distribution restrictions or other risk management mechanisms under a REMS which can materially affect the potential
market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results
of post-marketing studies or surveillance programs. After approval, some types of changes to the approved product, such as
adding new indications, manufacturing changes, and additional labeling claims, are subject to further testing requirements
and FDA review and approval.
Breakthrough Therapy Designation. The FDA may expedite the review of a product candidate designated as a
breakthrough therapy, which is intended, alone or in combination with one or more other drugs, to treat a serious or life-
threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial
improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects
observed early in clinical development. A sponsor may request the FDA to designate a drug as a breakthrough therapy at
the time of, or any time after, the submission of an IND application for the drug. If the FDA designates a drug as a
breakthrough therapy, it must take actions appropriate to expedite the development and review of the application, which
may include holding meetings with the sponsor and the review team throughout the development of the drug; providing
timely advice to, and interactive communication with, the sponsor regarding the development of the drug to ensure that the
development program to gather the nonclinical and clinical data necessary for approval is as efficient as practicable;
involving senior managers and experienced review staff, as appropriate, in a collaborative, cross-disciplinary review;
assigning a cross-disciplinary project lead for the FDA review team to facilitate an efficient review of the development
program and to serve as a scientific liaison between the review team and the sponsor; and taking steps to ensure that the
design of the clinical trials is as efficient as practicable, when scientifically appropriate, such as by minimizing the number
of patients exposed to a potentially less efficacious treatment. The FDA may rescind a Breakthrough Therapy designation
in the future if further clinical development later shows that the criteria for designation are no longer met. Breakthrough
Therapy designation does not change the standards for approval, but may expedite the development or review process.
Post-Approval Requirements. Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive
and continuing regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic
reporting, product sampling and distribution, advertising and promotion, reporting of adverse experiences with the product,
and compliance with any post-approval requirements imposed as a condition of approval, such as Phase 4 clinical trials and
surveillance to assess safety and effectiveness after commercialization. After approval, most changes to the approved
product, such as adding new indications or other labeling claims are subject to prior FDA review and approval. There also
are continuing, annual program user fee requirements for any marketed products, as well as new application fees for
supplemental applications with clinical data. In addition, drug manufacturers and other entities involved in the manufacture
and distribution of approved drugs are required to register their establishments with the FDA and state agencies and are
subject to periodic announced and unannounced inspections by the FDA and these state agencies for compliance with
cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior FDA approval
before being implemented. FDA regulations also require investigation and correction of any deviations from cGMP and
impose reporting and documentation requirements upon the sponsor and any third-party manufacturers that the sponsor
may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production
and quality control to maintain cGMP compliance.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and
standards is not maintained or if problems occur after the product reaches the market.
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Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity
or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in mandatory
revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical trials to
assess new safety risks; or imposition of distribution or other restrictions under a REMS program. Other potential
consequences include, among other things:
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restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the
market or product recalls;
fines, warning letters or holds on post-approval clinical trials;
refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation
of product license approvals;
product seizure or detention, or refusal to permit the import or export of products; or
injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market.
Although physicians, in the practice of medicine, may prescribe approved drugs for unapproved indications,
pharmaceutical companies are required to promote their drug products only for the approved indications and in accordance
with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations
prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may
be subject to significant liability. However, physicians may, in their independent medical judgment, prescribe legally
available products for off-label uses. The FDA does not regulate the behavior of physicians in their choice of treatments
but the FDA does restrict manufacturer’s communications on the subject of off-label use of their products.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing
Act, or PDMA, which regulates the distribution of drugs and drug samples at the federal level, and sets minimum standards
for the registration and regulation of drug distributors by the states. Both the PDMA and state laws limit the distribution of
prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.
DEA Regulation
I.V. CR845/difelikefalin, Oral CR845/difelikefalin or any of our future product candidates, if approved, may be
regulated as a “controlled substance” as defined in the Controlled Substances Act of 1970, or CSA, which establishes
registration, security, recordkeeping, reporting, storage, distribution and other requirements administered by the DEA. The
DEA is concerned with the control of handlers of controlled substances, and with the equipment and raw materials used in
their manufacture and packaging, in order to prevent loss and diversion into illicit channels of commerce.
The DEA regulates controlled substances as Schedule I, II, III, IV or V substances. Schedule I substances by
definition have no established medicinal use and may not be marketed or sold in the United States. A pharmaceutical
product may be listed as Schedule II, III, IV or V, with Schedule II substances considered to present the highest risk of
abuse and Schedule V substances the lowest relative risk of abuse among such substances. The manufacture, shipment,
storage, sale and use of Schedule II substances are subject to a high degree of regulation.
Annual registration is required for any facility that manufactures, distributes, dispenses, imports or exports any
controlled substance. The registration is specific to the particular location, activity and controlled substance schedule. For
example, separate registrations are needed for import and manufacturing, and each registration will specify which
schedules of controlled substances are authorized.
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The DEA typically inspects a facility to review its security measures prior to issuing a registration. Security
requirements vary by controlled substance schedule, with the most stringent requirements applying to Schedule I and
Schedule II substances. Required security measures include background checks on employees and physical control of
inventory through measures such as cages, surveillance cameras and inventory reconciliations. Records must be maintained
for the handling of all controlled substances, and periodic reports made to the DEA, for example distribution reports for
Schedule I and II controlled substances, Schedule III substances that are narcotics, and other designated substances.
Reports must also be made for thefts or losses of any controlled substance, and to obtain authorization to destroy any
controlled substance. In addition, special authorization and notification requirements apply to imports and exports.
In addition, a DEA quota system controls and limits the availability and production of controlled substances in
Schedule I or II. Distributions of any Schedule I or II controlled substance must also be accompanied by special order
forms, with copies provided to the DEA. The DEA may adjust aggregate production quotas and individual production and
procurement quotas from time to time during the year, although the DEA has substantial discretion in whether or not to
make such adjustments. Our quota of an active ingredient may not be sufficient to meet commercial demand or complete
clinical trials. Any delay or refusal by the DEA in establishing our quota for controlled substances could delay or stop our
clinical trials or product launches.
To meet its responsibilities, the DEA conducts periodic inspections of registered establishments that handle
controlled substances. Individual states also regulate controlled substances, and we and our collaborators will be subject to
state regulation with respect to the distribution of these products.
Fraud and Abuse, Data Privacy and Security and Transparency Laws and Regulations
In addition to FDA restrictions on marketing of pharmaceutical products, federal and state health care regulatory
laws restrict business practices in the biopharmaceutical industry. These laws include, among other things, anti-kickback
and false claims laws and regulations, physician payment transparency laws and regulations, as well as data privacy and
security laws and regulations.
The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully
offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to
induce or in return for purchasing, leasing, ordering, or arranging for or recommending the purchase, lease, or order of any
item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. The term “remuneration” has
been interpreted broadly to include anything of value. The Anti-Kickback Statute has been interpreted to apply to
arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, and formulary managers on
the other. There are a number of statutory exceptions and regulatory safe harbors protecting some common activities from
prosecution. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchases, or
recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor. Failure to meet all of the
requirements of a particular applicable statutory exception or regulatory safe harbor does not make the conduct per se
illegal under the Anti-Kickback Statute. Instead, the legality of the arrangement will be evaluated on a case-by-case basis
based on a cumulative review of all of its facts and circumstances.
Additionally, the intent standard under the federal Anti-Kickback Statute was amended by the Patient Protection and
Affordable Care Act, as amended by the Health Care Education Reconciliation Act (collectively, the “Health Care Reform
Law”), to a stricter standard such that a person or entity no longer needs to have actual knowledge of the statute or specific
intent to violate it in order to have committed a violation. In addition, the Health Care Reform Law provided that the
government may assert that a claim including items or services resulting from a violation of the federal Anti-Kickback
Statute constitutes a false or fraudulent claim for purposes of the federal civil False Claims Act.
Federal false claims laws, including the federal civil False Claims Act prohibit, among other things, any person or
entity from knowingly presenting, or causing to be presented, a false or fraudulent claim for payment to, or approval by, the
federal government or knowingly making, using, or causing to be made or used a false record or statement material to a
false or fraudulent claim to the federal government. A claim includes “any request or demand” for money or property
presented to the U.S. government. The federal civil False Claims Act has been used to assert liability on the
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basis of kickbacks and other improper referrals, improperly reported government pricing metrics such as Best Price or
Average Manufacturer Price, improper use of Medicare provider or supplier numbers when detailing a provider of services,
improper promotion of off-label uses not expressly approved by FDA in a drug’s label, and allegations as to
misrepresentations with respect to the services rendered. Additionally, the civil monetary penalties statute, which, among
other things, imposes fines against any person or entity who is determined to have presented, or caused to be presented,
claims to a federal healthcare program that the person knows, or should know, is for an item or service that was not
provided as claimed or is false or fraudulent. The federal Health Insurance Portability and Accountability Act of 1996, or
HIPAA, created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to
execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations, or promises, any of
the money or property owned by, or under the custody or control of, any healthcare benefit program, including private
third-party payers and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device 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 relating to healthcare matters. Also, many states have similar fraud and abuse statutes
or regulations that apply to items and services reimbursed under Medicaid and other state programs, or, in several states,
apply regardless of the payer.
In addition, we may be subject to data privacy and security regulation by both the federal government and the states
in which we conduct our business. HIPAA, as amended by the Health Information Technology for Economic and Clinical
Health Act, or HITECH, and their respective implementing regulations, including the Final HIPAA Omnibus
Rule published on January 25, 2013, imposes specified requirements on certain types of individuals and entities subject to
the law, known as covered entities, such as certain healthcare providers, health plans, and healthcare clearinghouses, as
well as their business associates that process individually identifiable health information on their behalf, relating to the
privacy, security and transmission of individually identifiable health information as well as their covered subcontractors.
Among other things, HITECH makes security standards and certain privacy standards directly applicable to the business
associates of covered entities that perform services for them that involve the creation, use, maintenance or disclosure of,
individually identifiable health information. 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
attorney’s fees and costs associated with pursuing federal civil actions. In addition, state laws may govern the privacy and
security of health information in certain circumstances, many of which differ from each other in significant ways and may
not have the same effect, thus complicating compliance efforts.
Additionally, federal transparency laws, including the federal Physician Payments Sunshine Act created under
Section 6002 of the Health Care Reform Law and its implementing regulations, require that manufacturers of drugs,
devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health
Insurance Program (with certain exceptions) report annually to the Centers for Medicare & Medicaid Services, or CMS,
information related to payments or other transfers of value made or distributed to physicians (defined to include doctors of
medicine, dentists, optometrists, podiatrists and chiropractors), generally, with some exceptions, and teaching hospitals, or
to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals. Additionally,
applicable manufacturers and applicable group purchasing organizations are required to report annually to CMS certain
ownership and investment interests held by physicians (as defined above) and their immediate family members. Beginning
in 2022, applicable manufacturers also will be required to report such information regarding payments and transfers of
value provided during the previous year to physician assistants, nurse practitioners, clinical nurse specialists,
anesthesiologist assistants, certified nurse anesthetists and certified nurse-midwives.
There are also an increasing number of analogous state laws that require manufacturers to file reports with states on
pricing and marketing information, such as tracking and reporting of gifts, compensations, other remuneration and items of
value provided to healthcare professionals and healthcare entities. Many of these laws contain ambiguities as to what is
required to comply with such laws. For example, several states have enacted legislation requiring pharmaceutical
companies to, among other things, establish and implement commercial compliance programs, file periodic reports with the
state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities and/or register their
sales representatives. Certain state laws also regulate manufacturers’ use of prescriber-identifiable data. These laws may
affect our future sales, marketing and other promotional activities by imposing administrative and compliance
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burdens. In addition, given the lack of clarity with respect to these laws and their implementation, our reporting actions
once we commercialize could be subject to the penalty provisions of the pertinent state and federal authorities.
If our operations are found to be in violation of any of the health regulatory laws described above or any other laws
that apply to us, we may be subject to penalties, including significant criminal, civil and administrative penalties, damages,
fines, imprisonment, exclusion from participation in government healthcare programs, contractual damages, reputational
harm, diminished profits and future earnings, additional reporting requirements and/or oversight if we become subject to a
corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the
curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and
our results of operations. To the extent that any of our products are sold in a foreign country, we may be subject to similar
foreign laws and regulations, which may include, for instance, applicable post-marketing requirements, including safety
surveillance, anti-fraud and abuse laws, and implementation of corporate compliance programs and reporting of payments
or transfers of value to healthcare professionals.
Coverage and Reimbursement Generally
The commercial success of our product candidates and our ability to commercialize any approved product candidates
successfully will depend in part on the extent to which governmental payer programs at the federal and state levels,
including Medicare and Medicaid, private health insurers and other third-party payers provide coverage for and establish
adequate reimbursement levels for our product candidates. In the United States, private health insurers and other third-party
payers often provide reimbursement for products and services based on the level at which the government provides
reimbursement through the Medicare or Medicaid programs for such products and services.
Patients who are prescribed treatments for their conditions and providers performing the prescribed services
generally rely on third-party payers to reimburse all or part of the associated healthcare costs. In addition, many U.S.
hospitals receive a fixed reimbursement amount per procedure for certain surgeries and other treatment therapies they
perform, or a predetermined rate for all hospital inpatient care provided as payment in full. Because this amount may not be
based on the actual expenses the hospital incurs, hospitals may choose to use therapies which are less expensive when
compared to our product candidates. Sales of our product candidates will therefore depend substantially, both domestically
and abroad, on the extent to which the costs of our products will be paid by health maintenance, managed care, pharmacy
benefit and similar healthcare management organizations, or reimbursed by government health administration authorities,
such as Medicare and Medicaid, private health insurers and other third-party payers. Third-party payers are increasingly
imposing additional requirements and restrictions on coverage and limiting reimbursement levels for medical products,
including pharmaceuticals. For example, federal and state governments reimburse covered prescription drugs at varying
rates generally below average wholesale price. These restrictions and limitations influence the purchase of healthcare
services and products. Third-party payers may limit coverage to specific drug products on an approved list, or formulary,
which might not include all of the FDA-approved drug products for a particular indication. Additionally, third-party payers
are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and
services, in addition to their safety and efficacy. Therefore, we may need to conduct expensive pharmacoeconomic studies
in order to demonstrate the medical necessity and cost-effectiveness of our products, in addition to the costs required to
obtain the FDA approvals. Our product candidates may not be considered medically necessary or cost-effective. Moreover,
a payer’s decision to provide coverage for a drug product does not imply that an adequate reimbursement rate will be
approved, and one payer’s determination to provide coverage for a product does not assure that other payers will also
provide coverage. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient
to realize an appropriate return on our investment in drug development. Legislative proposals to reform healthcare or
reduce costs under government insurance programs may result in lower reimbursement for our products and product
candidates or exclusion of our products and product candidates from coverage. The cost containment measures that
healthcare payers and providers are instituting and any healthcare reform could significantly reduce our revenues from the
sale of any approved product candidates.
Healthcare Regulatory Developments
In the United States and some foreign jurisdictions, the legislative landscape with respect to healthcare continues to
evolve. There have been a number of legislative and regulatory changes to the healthcare system that could affect our
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ability to sell our products profitably. Among policy makers and payers in the United States and elsewhere, there is
significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs,
improving quality and expanding access. In the United States, the pharmaceutical industry has been a particular focus of
these efforts and has been significantly affected by major legislative initiatives.
For example, the Health Care Reform Law was passed in March 2010 and includes provisions that have substantially
changed healthcare financing by both governmental and private insurers. Among other provisions that could have an
impact on our business, the Health Care Reform Law revised the methodology by which rebates owed by manufacturers to
the state and federal government for covered outpatient drugs under the Medicaid Drug Rebate Program are calculated,
increased the minimum Medicaid rebates owed by most manufacturers under the Medicaid Drug Rebate Program, extended
the Medicaid Drug Rebate program to utilization of prescriptions of individuals enrolled in Medicaid managed care
organizations, subjected manufacturers to new annual fees and taxes for certain branded prescription drugs, and provided
incentives to programs that increase the federal government’s comparative effectiveness research. Additionally, the Health
Care Reform Law implemented a new Medicare Part D coverage gap discount program in which manufacturers must now
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 outpatient drugs being covered under Medicare Part D. The Health Care
Reform Law’s future impact on our business is unclear.
There have been executive, judicial and Congressional challenges to certain aspects of the Health Care Reform Law.
For example, President Trump has signed several Executive Orders and other directives designed to delay the
implementation of certain provisions of the Health Care Reform Law or otherwise circumvent some of the requirements for
health insurance mandated by the Health Care Reform Law. Concurrently, Congress considered legislation that would
repeal or repeal and replace all or part of the Health Care Reform Law. While Congress has not passed comprehensive
repeal legislation, several bills affecting the implementation of certain taxes under the Health Care Reform Law have been
signed into law. The Tax Cuts and Jobs Act of 2017, or TCJA, includes a provision that repealed, effective January 1, 2019,
the tax-based shared responsibility payment imposed by the Health Care Reform Law on certain individuals who fail to
maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”. In
addition, the 2020 federal spending package permanently eliminates, effective January 1, 2020, the Health Care Reform
Law’s mandated “Cadillac” tax on high cost employer-sponsored health coverage and medical device tax, and effective
January 1, 2021, also eliminated the health insurer tax. On December 14, 2018, a Texas U.S. District Court Judge ruled that
the Health Care Reform Law is unconstitutional in its entirety because the “individual mandate” was repealed by Congress
as part of the TCJA. Additionally, on December 18, 2019, the U.S. Court of Appeals for the Fifth Circuit upheld the
District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to
determine whether the remaining provisions of the Health Care Reform Law are invalid as well. The U.S. Supreme Court is
currently reviewing this case, although it is unclear when a decision will be made. Although the U.S. Supreme Court has
yet ruled on the constitutionality of the Health Care Reform Law, on January 28, 2021, President Biden issued an executive
order to initiate a special enrollment period from February 15, 2021 through May 15, 2021 for purposes of obtaining health
insurance coverage through the Health Care Reform Law marketplace. The executive order also instructs certain
governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including
among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and
policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Health
Care Reform Law. It is also unclear how the Supreme Court ruling, other such litigation and the healthcare reform
measures of the Biden administration will impact the Health Care Reform Law and our business.
In addition, other legislative changes have been proposed and adopted since the Health Care Reform Law was
enacted. In August 2011, President Obama signed into law the Budget Control Act of 2011, as amended, which, among
other things, created the Joint Select Committee on Deficit Reduction to recommend proposals in spending reductions to
Congress. The Joint Select Committee on Deficit Reduction did not achieve its targeted deficit reduction of at least $1.2
trillion for the years 2013 through 2021, triggering the legislation’s automatic reductions to several government programs.
These reductions include aggregate reductions to Medicare payments to providers of up to 2% per fiscal year starting in
2013 and, following passage of the Bipartisan Budget Act of 2015, and subsequent legislative amendments, including the
BBA, will remain in effect until 2030, except for a temporary suspension from May 1, 2020 through March 31, 2021 due to
the COVID-19 pandemic, unless additional Congressional action is taken. In January 2013, President
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Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare
payments to several providers and increased the statute of limitations period for the government to recover overpayments
to providers from three to five years.
In the United States, the European Union, or EU, and other potentially significant markets for our product
candidates, government authorities and third-party payers are increasingly attempting to limit or regulate the price of
medical products and services, particularly for new and innovative products and therapies, which often has resulted in
average selling prices lower than they would otherwise be. Further, the increased emphasis on managed healthcare in the
United States and on country and regional pricing and reimbursement controls in the EU will put additional pressure on
product pricing, reimbursement and utilization, which may adversely affect our future product sales and results of
operations. For example, 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, review the relationship between
pricing and manufacturer patient programs, reduce the cost of drugs under Medicare, and reform government program
reimbursement methodologies for drugs. At the federal level, the Trump administration used several means to propose or
implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives. For
example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related
to prescription drug pricing that seek to implement several of the administration’s proposals. As a result, the FDA released
a final rule on September 24, 2020, effective November 30, 2020, providing guidance for states to build and submit
importation plans for drugs from Canada. Further, on November 20, 2020, HHS finalized a regulation removing safe
harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or
through pharmacy benefit managers, unless the price reduction is required by law. The implementation of the rule has been
delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation. 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, the implementation of which have also been
delayed pending review by the Biden administration until March 22, 2021. On November 20, 2020, CMS issued an interim
final rule implementing President Trump’s Most Favored Nation executive order, which would tie Medicare Part B
payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries,
effective January 1, 2021. On December 28, 2020, the United States District Court in Northern California issued a
nationwide preliminary injunction against implementation of the interim final rule. It is unclear whether the Biden
administration will work to reverse these measures or pursue similar policy initiatives. 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, to encourage importation from other countries
and bulk purchasing. These pressures can arise from rules and practices of managed care groups, judicial decisions and
laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical coverage and reimbursement
policies and pricing in general.
These and other healthcare reform initiatives may result in additional reductions in Medicare payments and other
healthcare funding, which could have a material adverse effect on our financial operations. We expect that additional state
and federal healthcare reform measures will be adopted in the future, particularly in light of the new incoming Presidential
administration, any of which could limit the amounts that federal and state governments will pay for healthcare products
and services, which could further limit the prices we are able to charge, or the amounts of reimbursement available, for our
product candidates once they are approved. Further, it is possible that additional governmental action is taken in response
to the COVID-19 pandemic.
Foreign Regulation
In order to market any product outside of the United States, we would need to comply with numerous and varying
regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials,
marketing authorization, commercial sales and distribution of our products. For example, in the EU, we must obtain
authorization of a clinical trial application, or CTA, in each member state in which we intend to conduct a clinical trial.
Whether or not we obtain FDA approval for a product, we would need to obtain the necessary approvals 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 can involve additional product
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testing and additional administrative review periods. The time required to obtain approval in other countries might differ
from and be longer than that required to obtain FDA approval. Regulatory approval in one country does not ensure
regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact
the regulatory process in others.
Employees and Human Capital
As of February 22, 2021, we had 80 employees, all of whom are located in the United States. None of our employees
are represented by a labor union or covered by a collective bargaining agreement. We consider our relationship with our
employees to be good.
Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing, and
integrating our existing and new employees, advisors, and consultants. The principal purposes of our equity and cash
incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based
compensation awards, in order to increase stockholder value and the success of our company by motivating such
individuals to perform to the best of their abilities and achieve our objectives.
Website Access to Reports
Our website is www.caratherapeutics.com. We are subject to the informational requirements of the Exchange Act and
file or furnish reports, including our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on
Form 8-K, and amendments to reports filed pursuant to Sections 13(a) and 15(d) of the Exchange Act, proxy statements
and other information with the SEC. We make copies of these reports and other information available free of charge
through our website (under the heading “SEC Filings”) as soon as reasonably practicable after we file or furnish them with
the SEC. The SEC maintains a website that contains reports, proxy and information statements and other information
regarding issuers that file electronically with the SEC at www.sec.gov. The information contained on the websites
referenced in this Annual Report on Form 10-K is not incorporated by reference into this filing, and the website addresses
are provided only as inactive textual references.
Item 1A. Risk Factors
In addition to other information contained in this Annual Report on Form 10-K, the following risks should be
considered in evaluating our business and future prospects and an investment in our common stock. The risks and
uncertainties described below are not the only ones we face. If any of the following risks and uncertainties develops into
actual events, our business, financial condition, results of operations and cash flows could be materially adversely
affected. In that case, the price of our common stock could decline and you may lose all or part of your investment.
Risks Related to Our Financial Condition and Capital Requirements
We have incurred significant losses from our inception, and although we generated net income in 2020, we
anticipate that we may incur losses in the foreseeable future, and may never maintain profitability.
We are a clinical-stage biopharmaceutical company. For the last several years, we have focused our efforts primarily
on developing I.V. and Oral CR845/difelikefalin with the goal of achieving regulatory approval. Since inception, we have
incurred significant operating and net losses. We incurred net losses of $106.4 million and $74.0 million for the years
ended December 31, 2019 and 2018, respectively. As of December 31, 2020, we had an accumulated deficit of $392.3
million. Although we generated net income for the year ended December 31, 2020 as a result of a commercial license
transaction, we expect to continue to incur significant expenses and operating and net losses in the foreseeable future, as
we continue to develop and seek marketing approval for I.V. and Oral CR845/difelikefalin. Our financial results may
fluctuate significantly from year to year, depending on the timing of our clinical trials, the receipt of additional milestone
payments, if any, under our agreements with Vifor, VFMCRP, Maruishi and CKDP, the receipt of payments under any
future agreements we may enter into, and our expenditures on other R&D activities as well as any payments owed under
the License Agreement with Enteris and any future similar agreements.
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In addition, we expect to incur significant sales, marketing and manufacturing expenses related to the
commercialization of I.V. and Oral CR845/difelikefalin, if they are approved by the FDA. As a result, we expect to
continue to incur significant losses for the foreseeable future as we:
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continue the development of Oral KORSUVA (CR845/difelikefalin) for CKD-aP and CLD-aP;
expand our Oral KORSUVA (CR845/difelikefalin) program into certain dermatologic conditions, including
AD, and neurological conditions, including NP;
explore further development of CR845/difelikefalin injection in the post-operative setting;
seek regulatory approvals for KORSUVA (CR845/difelikefalin) injection and any other product candidate that
successfully completes clinical trials;
establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to
commercialize any products for which we may obtain regulatory approval;
maintain, expand and protect our global intellectual property portfolio;
hire additional clinical, quality control and scientific personnel; and
add operational, financial and management information systems and personnel, including personnel to support
our drug development and potential future commercialization efforts.
To become and remain profitable from product sales, we must succeed in developing and eventually commercializing
one or more products that generate significant revenue. This will require us to be successful in a range of challenging
activities, including successful registration of KORSUVA (CR845/difelikefalin) injection and Oral KORSUVA
(CR845/difelikefalin), discovering additional product candidates and completing preclinical testing and clinical trials for
those product candidates, potentially entering into collaboration and license agreements, obtaining regulatory approval for
product candidates and manufacturing, marketing and selling any products for which we may obtain regulatory approval.
We may never succeed in these activities and, even if we do, may never achieve profitability.
Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable
to accurately predict the timing or amount of increased expenses or when, or if, we will be able to achieve profitability. If
we are required by the FDA or foreign regulatory authorities, to perform studies in addition to those currently expected, or
if there are any delays in completing our clinical trials or the development of any of our product candidates, our expenses
could increase.
Even if we do achieve profitability from product sales, we may not be able to sustain or increase profitability on a
quarterly or annual basis. Our failure to become and remain profitable would depress the value of our company and could
impair our ability to raise capital, expand our business, maintain our R&D efforts, diversify our product offerings or even
continue our operations. A decline in the value of our company could also cause you to lose all or part of your investment.
Our operating history makes it difficult to evaluate our business and prospects.
We commenced operations in 2004, and our operations to date have been limited to organizing and staffing our
company, business planning, raising capital and advancing our product candidates, including KORSUVA
(CR845/difelikefalin) injection and Oral KORSUVA (CR845/difelikefalin), through clinical development. We have not yet
demonstrated an ability to obtain regulatory approval for, or successfully commercialize, a product candidate. If our
product candidates are approved by the FDA, we will need to expand our capabilities to support commercial activities. We
may not be successful in adding such capabilities. Consequently, any predictions about our future performance may
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not be as accurate as they could be if we had a history of successfully developing and commercializing pharmaceutical
products.
We may need additional funding and may be unable to raise capital when needed, which would force us to delay,
reduce or eliminate our product development programs or commercialization efforts.
Conducting clinical trials, pursuing regulatory approvals, establishing outsourced manufacturing relationships and
successfully manufacturing and commercializing our product candidates is expensive. We may need to raise additional
capital to:
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progress our KORSUVA (CR845/difelikefalin) injection CKD-aP program through NDA approval;
continue the further development of Oral KORSUVA (CR845/difelikefalin) for CKD-aP, CLD-aP, AD, and
NP;
explore further development of CR845/difelikefalin injection in the post-operative setting;
fund our operations and continue our efforts to hire additional personnel for the commercialization of
KORSUVA (CR845/difelikefalin) injection, if approved by the FDA;
qualify and outsource the commercial-scale manufacturing of our products, including KORSUVA
(CR845/difelikefalin) injection under cGMP; and
in-license other product candidates.
We believe that with our available cash and cash equivalents and marketable securities balances as of December 31,
2020, we will have sufficient funds to meet our projected operating requirements into 2023, without giving effect to any
potential milestone payments or potential product revenue we may receive under our collaboration agreements. We have
based this estimate on assumptions that may prove to be wrong and we could spend our available financial resources faster
than we currently expect. Further, because we do not have sufficient financial resources to meet all of our development
objectives, in particular the completion of our development of Oral KORSUVA (CR845/difelikefalin) for the treatment of
CKD-aP, CLD-aP, AD, and NP, we will need to raise additional capital. If we are not able to do so, we could be required to
postpone, scale back or eliminate some, or all, of these objectives. Our future funding requirements will depend on many
factors, including, but not limited to:
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the rate of progress and costs related to Phase 2 and Phase 3 development of Oral KORSUVA
(CR845/difelikefalin) for CKD-aP, CLD-aP, AD, NP, and other indications;
the rate of progress and costs for the submission and review of an NDA for KORSUVA (CR845/difelikefalin)
injection for the treatment of CKD-aP in hemodialysis patients or for any product candidates that we may in-
license or acquire in the future, and the potential that we may need to conduct additional clinical trials to
support applications for regulatory approval;
the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property
rights associated with our product candidates, including any such costs we may be required to expend if our
licensors are unwilling or unable to do so;
the cost and timing of manufacturing sufficient supplies of KORSUVA (CR845/difelikefalin) injection in
preparation for commercialization, if approved;
the effect of competing technological and market developments;
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the terms and timing of any collaborative, licensing, co-promotion or other arrangements that we may
establish; and
the success of the commercialization of KORSUVA (CR845/difelikefalin) injection, if approved, and any
future product candidates.
Future capital requirements will also depend on the extent to which we acquire or invest in additional complementary
businesses, products and technologies. Until we can generate a sufficient amount of product revenue, if ever, we expect to
finance future cash needs through public or private equity offerings, debt financings, milestone and royalty payments from
corporate collaboration and licensing arrangements, as well as through interest income earned on cash and investment
balances. We cannot be certain that additional funding will be available on acceptable terms, or at all, and our ability to
raise additional capital may be adversely impacted by potential worsening global economic conditions and the recent
disruptions to and volatility in the credit and financial markets in the United States and worldwide resulting from the
ongoing COVID-19 pandemic. If adequate funds are not available, we may be required to delay, reduce the scope of, or
eliminate, one or more of our development programs or our commercialization efforts.
Risks Related to Our Business and the Development of Our Product Candidates
We are substantially dependent on the success of our lead product candidate, KORSUVA (CR845/difelikefalin)
injection being developed for the treatment of CKD-aP in hemodialysis patients, and cannot guarantee that this product
candidate will receive regulatory approval or be successfully commercialized.
We currently have no products approved for commercial distribution. We have invested a significant portion of our
efforts and financial resources in the development of KORSUVA (CR845/difelikefalin) injection for the treatment of CKD-
aP in patients undergoing hemodialysis. Our business depends entirely on the successful development and
commercialization of our product candidates, and in particular, KORSUVA (CR845/difelikefalin) injection, which may
never occur. Our ability to generate product revenues in the near term is dependent on our ability to complete the
development of, obtain regulatory approval for, and then successfully commercialize KORSUVA (CR845/difelikefalin)
injection for the treatment of CKD-aP in patients undergoing hemodialysis. We currently generate no revenues from sales
of any products, and we may never be able to develop or commercialize a marketable product.
Based on the results from our efficacy and safety trials for KORSUVA (CR845/difelikefalin) injection for the
treatment of CKD-aP, we submitted an NDA to the FDA for KORSUVA (CR845/difelikefalin) injection in December
2020, including a request for Priority Review under the Breakthrough Therapy Designation granted by the FDA in June
2017, which, if granted, could result in a six-month review process from the date of FDA’s acceptance for filing of the
NDA. Although our NDA was accepted for filing by the FDA in February 2021, it may not be granted priority review
designation. Even if our NDA is filed for substantive review by the FDA, it may be subject to advisory committee review.
Additionally, review of our NDA may be delayed due to ongoing impact of the COVID-19 pandemic on the FDA,
including the diversion of review personnel and the inability of the FDA to inspect foreign manufacturing or clinical sites.
In the EU, we expect our partner, VFMCRP, to submit a MAA, to the EMA, in the first quarter of 2021; however, we
cannot assure you that the results of our trials will successfully support our regulatory applications for approval.
KORSUVA (CR845/difelikefalin) injection will require regulatory approval, marketing efforts and further
investment before we generate any revenues from product sales. We are not permitted to market or promote any of our
product candidates, including KORSUVA (CR845/difelikefalin) injection, before we receive regulatory approval from the
FDA or comparable foreign regulatory authorities, and we may never receive such regulatory approval for any of our
product candidates. If we do not receive FDA approval for, and successfully commercialize KORSUVA
(CR845/difelikefalin) injection, we will not be able to generate revenue in the United States in the foreseeable future, or at
all. Any significant delays in obtaining approval for and commercializing CR845/difelikefalin injection will have a
substantial adverse impact on our business and financial condition.
We cannot be certain that KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA (CR845/difelikefalin) or any
future product candidates will be successful in clinical trials or receive regulatory approval. Regulatory authorities
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may interpret our data differently than we have. If approved for marketing by applicable regulatory authorities, our ability
to generate revenues from KORSUVA (CR845/difelikefalin) injection will depend on our ability, or Vifor’s ability pursuant
to the Vifor Agreement, as applicable, to:
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create market demand for KORSUVA (CR845/difelikefalin) injection through our own marketing activities in
the United States, and any other arrangements to promote this product candidate we may otherwise establish;
manufacture KORSUVA (CR845/difelikefalin) injection in sufficient quantities and at acceptable quality and
manufacturing cost to meet commercial demand at launch and thereafter;
commercialize KORSUVA (CR845/difelikefalin) injection in the United States;
establish and maintain agreements with wholesalers, distributors and group purchasing organizations on
commercially reasonable terms;
maintain existing partnerships and/or create new partnerships with, or offer licenses to, third parties to promote
and sell KORSUVA (CR845/difelikefalin) injection in foreign markets where we receive marketing approval;
maintain patent and trade secret protection and regulatory exclusivity for KORSUVA (CR845/difelikefalin)
injection;
launch commercial sales of KORSUVA (CR845/difelikefalin) injection, whether alone or in collaboration with
others;
achieve market acceptance of KORSUVA (CR845/difelikefalin) injection by patients, the medical community
and third-party payers;
achieve coverage and adequate reimbursement from third-party payers for KORSUVA (CR845/difelikefalin)
injection;
effectively compete with other competing therapies; and
maintain a continued acceptable safety profile of KORSUVA (CR845/difelikefalin) injection following launch.
As we continue to develop our other current or future product candidates, including Oral KORSUVA
(CR845/difelikefalin), we expect to face similar risks to our ability to develop, obtain regulatory approval for and
successfully commercialize such product candidates as we face with KORSUVA (CR845/difelikefalin) injection.
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Our business, operations and clinical development and regulatory timelines and plans have been, and could
continue to be, adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic.
Our business, operations and clinical development timelines and plans have been, and could continue to be,
adversely affected by health epidemics in regions where we have concentrations of third-party manufacturers, clinical trial
sites or other business operations, and could cause significant disruption in the operations of third-party manufacturers or
CROs upon whom we rely. In December 2019, a novel strain of coronavirus, SARS-CoV-2, causing the Coronavirus
Disease 2019 (COVID-19), was reported and since then, COVID-19 has spread worldwide.
The President of the United States has declared the COVID-19 pandemic a national emergency, and many state, local
and foreign governments have put in place, and continue to enforce in full or in part, quarantines, executive orders, shelter-
in-place orders and similar government orders and restrictions in order to control the spread of the disease. Such orders or
restrictions, and the perception that such orders or restrictions could occur, have resulted in business closures, work
stoppages, slowdowns and delays, work-from-home policies, travel restrictions and cancellation of events, among other
effects that have negatively impacted the global economy and could disrupt our business and operations. We have
implemented a work-from-home policy for all employees, and we may take further actions that alter our operations as may
be required by federal, state or local authorities, or which we determine are in the best interests of our employees.
Moreover, our clinical development and regulatory timelines and plans could be affected by the ongoing COVID-19
pandemic. Site initiation and patient enrollment has been, and could in the future be, affected and some patients may not be
able to comply with clinical trial protocols and the ability to conduct follow up visits with treated patients may be limited if
quarantines impede patient movement or interrupt healthcare services. For example, we experienced a delay in initiation of
certain trial sites for our ongoing Phase 2 clinical trial of Oral KORSUVA (CR845/difelikefalin) for the treatment of
pruritus in patients with hepatic impairment due to PBC, and in patient enrollment for our Phase 2 clinical trial of Oral
KORSUVA (CR845/difelikefalin) for moderate-to-severe pruritus in patients with AD. Similarly, our ability to recruit and
retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to
COVID-19 could be adversely impacted. Furthermore, our third-party manufacturers may be shut-down or have difficulty
meeting their contractual obligations. In addition, COVID-19 may cause our third-party manufacturers of KORSUVA
(CR845/difelikefalin) injection to operate at reduced capacity. While we currently do not expect any significant delays in
our clinical development or commercial timelines, the ultimate impact of the evolving COVID-19 pandemic remains
difficult to predict.
Further, the spread of COVID-19, which has caused a broad impact globally, may materially affect us economically.
While the potential economic impact brought by and the duration of COVID-19 may be difficult to assess or predict, a
widespread pandemic could result in significant disruption of global financial markets, reducing our ability to access
capital, which could in the future negatively affect our liquidity. In addition, a recession or market correction resulting from
the spread of COVID-19 could materially affect our business and the value of our common stock.
The global COVID-19 pandemic continues to rapidly evolve, and we will continue to monitor the COVID-19
situation closely. The ultimate impact of the COVID-19 pandemic or a similar health epidemic is highly uncertain and
subject to change. We do not yet know the full extent of the potential impacts on our business, our clinical trials, healthcare
systems or the global economy as a whole.
CR845/difelikefalin acts as a selective kappa opioid receptor agonist, which is a drug class that has not previously
yielded a successful commercial product for pruritus or pain indications.
The development of product candidates based on peripheral kappa opioid receptor agonists is an emerging field, and
the scientific discoveries that form the basis for our efforts to discover and develop product candidates that work through
this mechanism are relatively recent. The scientific evidence to support the feasibility of developing differentiated product
candidates based on these discoveries is both preliminary and limited. We believe that we are among a relatively small
group of companies that are pursuing the development of product candidates based on peripherally acting kappa opioid
receptor agonists. In addition, we believe that companies that previously explored the development of kappa opioid
receptor agonists abandoned these efforts because those prior generation kappa agonists, which were centrally active,
resulted in psychiatric side effects. Although CR845/difelikefalin is a peripherally acting kappa opioid receptor agonist and
these side effects have not been observed in any of our clinical trials to date, it is
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possible that we could observe similar side effects, or other unacceptable adverse events. As a result, our approach to
developing product candidates based on peripheral kappa opioid receptor agonists may not be successful and may never
lead to marketable products.
We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize
on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we focus on developing product candidates for specific
indications that we identify as most likely to succeed, in terms of both its regulatory approval and commercialization. As
such, we are currently primarily focused on the development of KORSUVA (CR845/difelikefalin) injection for CKD-aP in
hemodialysis patients and Oral KORSUVA (CR845/difelikefalin) for CKD-aP in pre-dialysis patients, CLD-aP, NP, and
certain dermatological conditions, including AD. As a result, we may forego or delay pursuit of opportunities with other
product candidates or for other indications that may prove to have greater commercial potential. Our resource allocation
decisions may cause us to fail to capitalize on viable commercial products or profitable market opportunities. Our spending
on current and future R&D programs and product candidates for specific indications may not yield any commercially
viable products. If we do not accurately evaluate the commercial potential or target market for a particular product
candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty
arrangements in cases in which it would have been more advantageous for us to retain sole development and
commercialization rights to such product candidate.
Our future growth may depend on our ability to identify and develop products and if we do not successfully
identify and develop product candidates or integrate them into our operations, we may have limited growth
opportunities.
A component of our business strategy is to continue to develop a pipeline of product candidates by developing
products that we believe are a strategic fit with our focus on pain and pruritus therapeutics. However, these business
activities may entail numerous operational and financial risks, including:
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difficulty or inability to secure financing to fund development activities for such development;
disruption of our business and diversion of our management’s time and attention;
higher than expected development costs;
exposure to unknown liabilities;
difficulty in managing multiple product development programs; and
inability to successfully develop new products or clinical failure.
We have limited resources to identify and execute the development of products. Moreover, we may devote resources
to potential development that are never completed, or we may fail to realize the anticipated benefits of such efforts. If we
do not successfully develop and commercialize product candidates, we may not be able to obtain product revenues in
future periods.
The regulatory approval processes of the FDA and comparable foreign authorities are lengthy, time consuming
and inherently unpredictable. If we are not able to obtain, or if there are delays in obtaining, required regulatory
approvals, we will not be able to commercialize our product candidates as expected, and our ability to generate revenue
will be materially impaired.
The time required to obtain approval by the FDA and comparable foreign authorities is unpredictable but typically
takes many years following the commencement of clinical trials and depends upon numerous factors, including the
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substantial discretion of the regulatory authorities. In addition, approval policies, regulations, or the type and amount of
clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and
may vary among jurisdictions. We have not obtained regulatory approval for any product candidate and it is possible that
none of our existing product candidates, including KORSUVA (CR845/difelikefalin) injection and Oral KORSUVA
(CR845/difelikefalin), or any product candidates we may seek to develop in the future, will ever obtain regulatory
approval.
Our product candidates and the activities associated with their development and commercialization, including their
design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and
distribution, are subject to comprehensive regulation by the FDA and other regulatory agencies in the United States and by
the EMA, and similar regulatory authorities outside the United States. Failure to obtain marketing approval for a product
candidate will prevent us from commercializing that product candidate. We have no experience in filing and supporting the
applications necessary to gain marketing approvals and expect to rely on third-party CROs and consultants to assist us in
this process. Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting
information to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy
for that indication. Securing marketing approval also requires the submission of information about the product
manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities.
Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure
can occur at any time during the clinical trial process. The results of preclinical studies and early clinical trials of our
product candidates may not be predictive of the results of later-stage clinical trials. Product candidates in later stages of
clinical trials may fail to show the desired safety and efficacy traits despite having progressed through preclinical studies
and initial clinical trials. A number of companies in the biopharmaceutical industry have suffered significant setbacks in
advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials.
Our future clinical trial results may not be successful. We may also experience numerous unforeseen events during, or as a
result of, clinical trials that could delay or prevent our ability to receive marketing approval or commercialize our product
candidates, including:
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regulators or institutional review boards may not authorize us or our investigators to commence a clinical trial
or conduct a clinical trial at a prospective trial site;
we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or
clinical trial protocols with prospective trial sites;
clinical trials of our product candidates may produce negative or inconclusive results, and we may decide, or
regulators may require us, to conduct additional clinical trials or abandon product development programs;
the number of patients required for clinical trials of our product candidates may be larger than we anticipate,
enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these
clinical trials at a higher rate than we anticipate;
our third-party contractors may fail to comply with regulatory requirements or meet their contractual
obligations to us in a timely manner, or at all;
we may have to suspend clinical trials, as in the case of the IND clinical hold placed on our adaptive Phase 3
trial of I.V. CR845/difelikefalin for postoperative pain in February 2016, which was subsequently removed in
April 2016, or terminate clinical trials of our product candidates for various reasons, including a finding that
the participants are being exposed to unacceptable health risks;
regulators or institutional review boards may require that we or our investigators suspend or terminate clinical
research for various reasons, including noncompliance with regulatory requirements or a finding that the
participants are being exposed to unacceptable health risks;
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changes in marketing approval policies during the development period;
changes in or the enactment of additional statutes or regulations;
changes in regulatory review for each submitted product application;
the cost of clinical trials of our product candidates may be greater than we anticipate;
the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our
product candidates may be insufficient or inadequate; and
our product candidates may have undesirable side effects or other unexpected characteristics, causing us or our
investigators, regulators or institutional review boards to suspend or terminate the trials.
In addition, unfavorable changes in our industry or the global economy, including as a result of the ongoing COVID-
19 pandemic, could contribute to some of the events listed above and further impact our ability to progress our clinical
trials, submit for marketing approval or commercialize our product candidates, if approved, as planned. Further, if and to
the extent, global health concerns prevent the FDA or other regulatory authorities from conducting their regular
inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA or other regulatory
authorities to timely review and process our regulatory submissions, which could affect our ability to obtain marketing
approval for any of our product candidates, including KORSUVA (CR845/difelikefalin), for which we submitted our NDA
to the FDA in December 2020, and our MAA to the EMA expected to be submitted in the first quarter of 2021.
Moreover, if we are required to conduct additional clinical trials or other testing of our product candidates beyond
those that we currently contemplate, if we are unable to successfully complete clinical trials of our product candidates or
other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety
concerns, we may:
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be delayed in obtaining marketing approval for our product candidates;
not obtain marketing approval at all;
obtain approval for indications or patient populations that are not as broad as intended or desired;
obtain approval with labeling that includes significant use or distribution restrictions or safety warnings;
be subject to additional post-marketing testing requirements; or
have the product removed from the market after obtaining marketing approval.
Furthermore, regulatory authorities have substantial discretion in the approval process and may refuse to accept any
application or may decide that our data is insufficient for approval and require additional preclinical, clinical or other
studies, including with respect to third-party technology used in any of our product candidates such as the excipient we
intend to use for Oral KORSUVA (CR845/difelikefalin). In addition, varying interpretations of the data obtained from
preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any marketing
approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the
approved product not commercially viable.
Finally, even if we were to obtain approval, regulatory authorities may approve any of our product candidates for
fewer or more limited indications than we request, may grant approval contingent on the performance of costly post-
marketing clinical trials, or may approve a product candidate with a label that does not include the labeling claims
necessary or desirable for the successful commercialization of that product candidate. Any of these scenarios could
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compromise the commercial prospects for our product candidates to assure safe use of the product candidates, either as a
condition of product candidate approval or on the basis of new safety information.
If we experience delays in obtaining approval, if we fail to obtain approval of a product candidate or if the label for a
product candidate does not include the labeling claims necessary or desirable for the successful commercialization of that
product candidate, the commercial prospects for such product candidate may be harmed and our ability to generate
revenues will be materially impaired.
We have been granted breakthrough therapy designation for KORSUVA (CR845/difelikefalin) injection for the
treatment of moderate-to-severe pruritus associated with CKD in hemodialysis patients, however, it may not lead to a
faster development or regulatory review or approval process, and it does not increase the likelihood that KORSUVA
(CR845/difelikefalin) injection will receive marketing approval.
In June 2017, the FDA granted breakthrough therapy designation for KORSUVA (CR845/difelikefalin) injection for
the treatment of moderate-to-severe uremic pruritus in CKD patients undergoing hemodialysis. A breakthrough therapy is
defined as a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-
threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial
improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects
observed early in clinical development. For drugs that have been designated as breakthrough therapies, interaction and
communication between the FDA and the sponsor of the trial can help to identify the most efficient path for clinical
development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as
breakthrough therapies by the FDA may also be eligible for accelerated approval if the relevant criteria are met.
The receipt of a breakthrough therapy designation for KORSUVA (CR845/difelikefalin) injection for the treatment of
moderate-to-severe uremic pruritus in CKD patients undergoing hemodialysis may not result in a faster development
process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not
assure ultimate approval by the FDA. In addition, the FDA may later decide that it no longer meets the conditions for
qualification or decide that the time period for FDA review or approval will not be shortened.
The FDA may determine that I.V. CR845/difelikefalin, or any of our other current or future product candidates,
has undesirable side effects that could limit dosage in development, delay or prevent their regulatory approval or
commercialization.
Undesirable side effects caused by our product candidates could cause us or regulatory authorities to limit dosage in
development or interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of
regulatory approval by the FDA or other comparable foreign authorities. For example, in February 2016, the FDA placed
our adaptive trial of I.V. CR845/difelikefalin for postoperative pain on IND clinical hold pending a safety review. The
clinical hold was based on a stopping rule related to elevated serum sodium levels of greater than 150 mmol/L. After the
safety review was completed, the FDA removed this clinical hold in April 2016 and the clinical trial was resumed in
June 2016. If other concerns are raised regarding the safety of a new drug as a result of undesirable side effects identified
during clinical testing, the FDA may order us to cease further development, decline to approve the drug or issue a letter
requesting additional data or information prior to making a final decision regarding whether or not to approve the drug. The
number of such requests for additional data or information issued by the FDA in recent years has increased and resulted in
substantial delays in the approval of several new drugs. Undesirable side effects caused by I.V. CR845/difelikefalin or any
of our other current or future product candidates could also result in denial of regulatory approval by the FDA or other
regulatory authorities for any or all targeted indications or the inclusion of unfavorable information in our product labeling,
and in turn prevent us from commercializing and generating revenues from the sale of I.V. CR845/difelikefalin or any other
product candidate. Approval of KORSUVA may include aspects of product labeling that limit its commercial use,
including a Boxed Warning, Risk Evaluation and Mitigation Strategies, or REMS, or other limitations of use.
To date, the side effects observed in the completed I.V. CR845/difelikefalin clinical trials include dizziness, transient
facial tingling, a state of near-sleep, or somnolence, and hypernatremia, an electrolyte disturbance that is
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defined by an elevated sodium level in the blood, which we believe is secondary, at least in part, to another side effect,
aquaresis, that is defined as electrolyte-free urination. As described above, the observation of mild to moderate
hypernatremia in our adaptive trial for postoperative pain triggered a stopping rule in the trial protocol and led the FDA to
institute an IND clinical hold related to the trial, pending a safety review. Prolonged aquaresis can result in a negative fluid
balance if the excreted water is not replaced by oral or intravenous fluids, and although we recommend steps to control
fluid balance, we cannot be certain that such instructions will be followed by healthcare providers and/or patients, and
failure to follow such instructions may be accompanied by adverse events associated with negative fluid balance, including
disability and death. We believe that one such adverse event, which has been observed, postural tachycardia, an elevation
of heart rate upon standing up, is a physiological reflex that can be triggered as a result of decreased intravascular volume
caused by a negative fluid balance. We have observed transient prolactin elevations, which are brief increases in the
concentration of the hormone prolactin in the bloodstream, in response to I.V. CR845/difelikefalin, which we have
measured as a nonselective opioid biomarker since both kappa and mu opioids elicit this effect. We cannot be certain that
such elevations in prolactin will be transient, safe, and well tolerated in all patients. In addition, previously developed
kappa opioid agonists, the pharmacological class of drugs that CR845/difelikefalin belongs to, have been associated with
poorly tolerated psychiatric side effects, such as a feeling of emotional and mental discomfort, or dysphoria, and
hallucinations, at high doses, particularly for prior generations of kappa opioid agonists with substantially unrestricted or
only partially restricted entry to the CNS. Although we have not observed psychiatric side effects in any
CR845/difelikefalin clinical trials to date, we cannot be certain that these side effects or others will not be observed in the
future, or that the FDA will not require additional trials or impose more severe labeling restrictions due to these side effects
or other concerns. The drug-related side effects could affect patient recruitment or the ability of enrolled patients to
complete the trial or result in potential product liability claims. Any of these occurrences may harm our business, financial
condition and prospects significantly.
Additionally, if one or more of our product candidates receives marketing approval, and we or others later identify
undesirable side effects caused by such products, a number of potentially significant negative consequences could result,
including:
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regulatory authorities may withdraw approvals of such product;
regulatory authorities may require additional warnings on the label;
we may be required to create a medication guide outlining the risks of such side effects for distribution to
patients, if not already required pursuant to a REMS;
we could be sued and held liable for harm caused to patients; and
our reputation may suffer.
Any of these events could prevent us from achieving or maintaining market acceptance of the particular product
candidate, if approved, and could significantly harm our business, results of operations and prospects.
If we experience delays or difficulties in the enrollment of patients in clinical trials, our receipt of necessary
regulatory approvals could be delayed or prevented.
We may not be able to initiate or continue conducting clinical trials for our product candidates if we are unable to
locate and enroll a sufficient number of eligible patients to participate in these trials as required by the FDA or similar
regulatory authorities outside the United States. Some of our competitors have ongoing clinical trials for product
candidates that treat the same indications as our product candidates, and patients who would otherwise be eligible for our
clinical trials may instead enroll in clinical trials of our competitors’ product candidates. Patient enrollment is affected by
other factors including:
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the severity of the disease under investigation;
the eligibility criteria for, and design of, the trial in question;
the perceived risks and benefits of the product candidate under study;
competition in recruiting and enrolling patients in clinical trials;
the efforts to facilitate timely enrollment in clinical trials;
the patient referral practices of physicians;
the ability to monitor patients adequately during and after treatment;
the proximity and availability of clinical trial sites for prospective patients; and
delays or difficulties due to the ongoing COVID-19 pandemic.
For example, we experienced a delay in patient enrollment for our Phase 2 clinical trial of Oral KORSUVA
(CR845/difelikefalin) for moderate-to-severe pruritus in patients with AD due to closure of certain clinical sites, and could
in the future experience delays in either of our ongoing Phase 2 clinical trials as patient enrollment in both of these trials is
not yet complete.
Our inability to enroll a sufficient number of patients for our clinical trials would result in significant delays and
could require us to abandon one or more clinical trials altogether. We may encounter difficulties and/or delays in
completing our planned enrollments. Enrollment delays in our clinical trials may result in increased development costs for
our product candidates, or the inability to complete development of our product candidates, which would cause the value of
our company to decline, limit our ability to obtain additional financing, and materially impair our ability to generate
revenues.
CR845/difelikefalin is a kappa opioid receptor agonist and, if approved, will exist in the marketplace with mu
opioid products that are subject to restrictive marketing and distribution regulations, which if applied to our product
candidates would restrict their use and harm our ability to generate profits.
Many currently approved mu opioid receptor agonists require REMS as part of their approval by the FDA. REMS
programs may require medication guides for patients, special communication plans to healthcare professionals or elements
to assure safe use, such as restricted distribution methods, patient registries and/or other risk minimization tools. While
CR845/difelikefalin has been well tolerated in clinical trials to date and has not shown any evidence of the euphoria that
has led to misuse, abuse and addiction of mu opioids, including the results of our Human Abuse Liability, or HAL, trial,
which we successfully completed in the fourth quarter of 2014, the FDA may still determine that CR845/difelikefalin-
based products require a REMS program, including for its use in non-pain indications such as KORSUVA
(CR845/difelikefalin) injection for CKD-aP in hemodialysis patients or Oral KORSUVA (CR845/difelikefalin) for CKD-
aP in pre-dialysis patients and CLD-aP. We cannot predict whether REMS will be required as part of the FDA’s approval of
our product candidates and, if required, what those requirements might be. Any limitations on approval or marketing could
restrict the commercial promotion, distribution, prescription or dispensing of our product candidates, if approved. If a
REMS program is required, depending on the extent of the REMS requirements, the program might significantly increase
our costs to commercialize these product candidates. Furthermore, risks of our product candidates that are not adequately
addressed through proposed REMS for such product candidates may also prevent or delay their approval for
commercialization.
In addition, currently approved mu opioids with which CR845/difelikefalin -based products may compete are
controlled substances, which are subject to state, federal and foreign laws and regulations regarding their manufacture, use,
sale, importation, exportation and distribution. Controlled substances are regulated under the federal Controlled
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Substances Act of 1970 and regulations of the DEA. The DEA regulates controlled substances as Schedule I, II, III, IV or
V substances. Schedule I substances by definition have no established medicinal use and may not be marketed or sold in
the United States. A pharmaceutical product may be listed as Schedule II, III, IV or V, with Schedule II substances
considered to present the highest risk of abuse and Schedule V substances the lowest relative risk of abuse among such
substances.
The results from our HAL trial suggest that CR845/difelikefalin may have the potential to be a Schedule V or non-
scheduled peripheral opioid. However, while CR845/difelikefalin-based products have not demonstrated any evidence of
the euphoria that has led to misuse, abuse, and addiction of mu opioids, and while CR845/difelikefalin-based products are
not being treated as a controlled substance in clinical trials, it is possible that the DEA could determine that
CR845/difelikefalin-based products should be regulated as controlled substances. Even if the DEA does not regulate
CR845/difelikefalin-based products, including KORSUVA (CR845/difelikefalin) injection for the treatment of CKD-aP in
hemodialysis patients and Oral KORSUVA (CR845/difelikefalin) for other pruritic conditions such as CKD-aP in pre-
dialysis patients and CLD-aP, as controlled substances, public perception surrounding opioids as a class may lead to public
opposition to approvability of CR845/difelikefalin and limit its commercial potential. The ‘opioid crisis’ currently
discussed among federal, state and local policymakers fails to distinguish between mu opioids and other opioids.
Various states also independently regulate controlled substances. Though state-controlled substances laws often
mirror federal law, because the states are separate jurisdictions, they may separately schedule drugs as well. While some
states automatically schedule a drug when the DEA does so, in other states there must be rulemaking or a legislative action.
State scheduling may delay commercial sale of any controlled substance drug product for which we obtain federal
regulatory approval and adverse scheduling could impair the commercial attractiveness of such product. We or our
collaborators may also be requested to obtain separate state registrations in order to be able to obtain, handle and distribute
controlled substances for clinical trials or commercial sale, and failure to meet applicable regulatory requirements could
lead to enforcement and sanctions from the states in addition to those from the DEA or otherwise arising under federal law.
If any of our product candidates are classified as controlled substances, we and our suppliers, manufacturers,
contractors, customers and distributors would be required to obtain and maintain applicable registrations from state, federal
and foreign law enforcement and regulatory agencies and comply with state, federal and foreign laws and regulations
regarding the manufacture, use, sale, importation, exportation and distribution of controlled substances. Also, if any of our
product candidates were classified as controlled substances, there is a risk that DEA regulations could limit the supply of
the compounds used in clinical trials and, in the future, the ability to produce and distribute our products in the volume
needed to meet commercial demand.
Regulations associated with controlled substances govern manufacturing, labeling, packaging, testing, dispensing,
production and procurement quotas, record keeping, reporting, handling, shipment and disposal. These regulations increase
the personnel needs and the expense associated with development and commercialization of product candidates including
controlled substances. The DEA, and some states, conduct periodic inspections of registered establishments that handle
controlled substances. Failure to obtain and maintain required registrations or comply with any applicable regulations could
delay or preclude us from developing and commercializing our product candidates containing controlled substances and
subject us to enforcement action. The DEA may seek civil penalties, refuse to renew necessary registrations or initiate
proceedings to revoke those registrations. In some circumstances, violations could lead to criminal proceedings. Because of
the restrictive nature of these regulations, if it were determined that our product candidates are subject to these restrictions,
the commercialization of our product candidates could be limited.
We will need to obtain FDA approval of any proposed product names, and any failure or delay associated with
such approval may adversely affect our business.
We have received conditional approval from the FDA for the use of KORSUVA as the proprietary name for our
product candidate I.V. CR845/difelikefalin for the treatment of itch or pruritus. However, this approval is conditional upon
a further and final review by the FDA at the time of NDA approval. Additionally, any name we intend to use for our other
current or future product candidates will require approval from the FDA regardless of whether we have secured a formal
trademark registration from the USPTO. The FDA typically conducts a review of proposed product names,
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including an evaluation of the potential for confusion with other product names. The FDA may also object to a product
name if it believes the name inappropriately implies medical claims or contributes to an overstatement of efficacy. If the
FDA objects to any of our proposed product names, we may be required to adopt alternative names for our product
candidates. If we adopt alternative names, we would lose any goodwill or brand recognition developed for the KORSUVA
mark as well as the benefit of our existing trademark applications for such product candidate and may be required to
expend significant additional resources in an effort to identify a suitable product name that would qualify under applicable
trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA. We may be unable to build a
successful brand identity for a new trademark in a timely manner or at all, which would limit our ability to commercialize
our product candidates.
Failure to obtain marketing approval in international jurisdictions would prevent our product candidates from
being marketed abroad.
In order to market and sell our products in the EU and many other jurisdictions, we or our collaborators or partners
must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval
procedure varies among countries and can involve additional testing. The time required to obtain approval may differ
substantially from that required to obtain FDA approval. The regulatory approval process outside the United States
generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the
United States, it is required that the product be approved for reimbursement before the product can be approved for sale in
that country. We or these third parties may not obtain approvals from regulatory authorities outside the United States on a
timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or
jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory
authorities in other countries or jurisdictions or by the FDA. However, the failure to obtain approval in one jurisdiction
may compromise our or our collaborators’ or partners’ ability to obtain approval elsewhere. We or our collaborators or
partners may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our
products in any market.
Regulatory approval is limited by the FDA to those specific indications and conditions for which clinical safety
and efficacy have been demonstrated, and we may be subject to fines, penalties or injunctions if we are determined to be
promoting the use of our products for unapproved or “off-label” uses, resulting in damage to our reputation and
business.
When the FDA or comparable foreign regulatory authorities issue regulatory approval for a product candidate, the
regulatory approval is limited to those specific indications for which a product is approved. If we are not able to obtain
FDA approval for any desired future indications for our products and product candidates, our ability to effectively market
and sell our products may be reduced and our business may be adversely affected.
While physicians may choose to prescribe drugs for uses that are not described in the product’s labeling and for uses
that differ from those tested in clinical studies and approved by the regulatory authorities, we are prohibited from
marketing and promoting the products for indications that are not specifically approved by the FDA. These “off-label” uses
are common across medical specialties and may constitute an appropriate treatment for some patients in varied
circumstances. Regulatory authorities in the United States generally do not restrict or regulate the behavior of physicians in
their choice of treatment within the practice of medicine. Regulatory authorities do, however, restrict communications by
pharmaceutical companies on off-label use. If the FDA determines that our promotional activities constitute promotion of
an off-label use, it could request that we modify our promotional materials or subject us to regulatory or enforcement
actions by other agencies, including issuance of warning letters or untitled letters, suspension or withdraw an approved
product from the market, mandatory or voluntary recalls, civil fines, disgorgement of money, operating restrictions,
additional reporting requirements and/or oversight if we become subject to a corporate integrity agreement or similar
agreement, injunctions or criminal prosecution, any of which could significantly harm our business.
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Even if one of our CR845/difelikefalin-based product candidates receives regulatory approval, we will be subject
to ongoing obligations and continued regulatory review, which may result in significant additional expense.
Additionally, our product candidates, if approved, could be subject to labeling and other restrictions and market
withdrawal and we may be subject to penalties if we fail to comply with regulatory requirements or experience
unanticipated problems with our products.
Any product candidate for which we obtain marketing approval, along with the manufacturing processes, post-
approval clinical data, labeling, packaging, distribution, adverse event reporting, storage, recordkeeping, export, import,
advertising and promotional activities for such product, will be subject to extensive and ongoing requirements of and
review by the FDA and other regulatory authorities. These requirements include submissions of safety and other post-
marketing information and reports, registration and listing requirements, continued compliance with cGMP requirements
relating to manufacturing, quality control, quality assurance and corresponding maintenance of records and documents,
requirements regarding the distribution of samples to physicians and recordkeeping and cGCPs for any clinical trials that
we conduct post-approval. Even if marketing approval of a product candidate is granted, the approval may be subject to
limitations on the indicated uses for which the product may be marketed or to the conditions of approval, including any
requirement to implement a REMS. If any of our product candidates receives marketing approval, the accompanying label
may limit the approved use of our drug, which could limit sales of the product.
The FDA may also impose requirements for costly post-marketing studies or clinical trials and surveillance to
monitor the safety or efficacy of the product. The FDA closely regulates the post-approval marketing and promotion of
drugs to ensure drugs are marketed only for the approved indications and in accordance with the provisions of the approved
labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use and if we do
not market our products for their approved indications, we may be subject to enforcement action for off-label marketing.
Violations of the Federal Food, Drug, and Cosmetic Act relating to the promotion of prescription drugs may lead to
investigations alleging violations of federal and state health care fraud and abuse laws, as well as state consumer protection
laws.
In addition, later discovery of previously unknown adverse events or other problems with our products,
manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results,
including:
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restrictions on manufacturing such products;
restrictions on the labeling or marketing of a product;
restrictions on product distribution or use;
requirements to conduct post-marketing studies or clinical trials;
warning letters;
withdrawal of the products from the market;
refusal to approve pending applications or supplements to approved applications that we submit;
recall of products;
fines, restitution or disgorgement of profits or revenues;
suspension or withdrawal of marketing approvals;
refusal to permit the import or export of our products;
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product seizure; or
injunctions or the imposition of civil or criminal penalties.
The FDA’s policies may change and additional government regulations may be enacted that could prevent, limit or
delay regulatory approval of our product candidates. If we are slow or unable to adapt to changes in existing requirements
or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any
marketing approval that we may have obtained.
Risks Related to the Commercialization of Our Product Candidates
We face significant competition from other pharmaceutical and biotechnology companies, academic institutions,
government agencies and other research organizations. Our operating results will suffer if we fail to compete effectively.
The development and commercialization of new drug products is highly competitive. We face competition with
respect to our current product candidates and will face competition with respect to any product candidates that we may
seek to develop or commercialize in the future, from major pharmaceutical companies, specialty pharmaceutical companies
and biotechnology companies worldwide. There are a number of large pharmaceutical and biotechnology companies that
currently market and sell products or are pursuing the development of products for the treatment of pain and pruritus.
Potential competitors also include academic institutions, government agencies and other public and private research
organizations that conduct research, seek patent protection and establish collaborative arrangements for research,
development, manufacturing and commercialization.
There are a large number of companies developing or marketing therapies for the treatment and management of
pruritus, including many major pharmaceutical and biotechnology companies. Among the companies that currently market
or are developing therapies that, if approved, our product candidates may potentially compete with include: Pfizer, AbbVie,
Eli Lilly, Amgen, Regeneron, Leo Pharma, Chugai and others. Additionally, the market for the prevention and treatment of
PONV is highly fragmented. There are a number of different agents alone or in combination (particularly in patients with a
high risk for PONV) with different mechanism of actions to try to manage PONV. If approved, I.V. CR845/difelikefalin
would likely be competing within the overall PONV market, although we expect that it would primarily be utilized as an
add-on therapy in patients with a higher risk of PONV. Although most of the PONV products are generically available,
there is still a significant segment of high-risk patients where their PONV is not adequately managed, which can increase
the hospital length of stay and add significant cost to managing a post-operative patient.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products
that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than any
products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more
rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position
before we are able to enter the market. In addition, our ability to compete may be affected in many cases by insurers or
other third-party payers seeking to encourage the use of generic products. Generic products are currently on the market for
some of the indications that we are pursuing, and additional products are expected to become available on a generic basis
over the coming years. If our product candidates achieve marketing approval, we expect that they will be priced at a
significant premium over competitive generic products.
Many of the companies against which we are competing or against which we may compete in the future have
significantly greater financial resources and expertise in R&D, manufacturing, preclinical testing, conducting clinical trials,
obtaining regulatory approvals and marketing approved products than we do. Mergers and acquisitions in the
pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller
number of our competitors. Early stage companies may also prove to be significant competitors, particularly through
collaborative arrangements with large and established companies. These third parties compete with us in recruiting and
retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical
trials, as well as in acquiring technologies complementary to, or necessary for, our programs.
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If we or our collaborators are unable to establish effective marketing and sales capabilities, or if we are unable to
enter into or maintain agreements with third parties to market and sell our product candidates, if they are approved, we
may be unable to generate product revenues.
We currently do not have a commercial infrastructure for the marketing, sale and distribution of pharmaceutical
products. If approved, in order to commercialize our products, we must build our marketing, sales and distribution
capabilities or make and maintain arrangements with third parties to perform these services. We have no prior experience in
the marketing, sale and distribution of pharmaceutical products, and there are significant risks involved in the building and
managing of a commercial infrastructure to the extent we choose to do so in the future. The establishment and development
of our own sales force and related plans to market any products we may develop will be expensive and time consuming and
could delay any product launch, and we may not be able to successfully develop this capability. We have entered into
agreements with Vifor and VFMCRP to commercialize KORSUVA (CR845/difelikefalin) injection, if approved by the
FDA. We are dependent on Vifor and VFMCRP to successfully commercialize KORSUVA (CR845/difelikefalin) injection
with their own, or their collaborators’, sales force.
We, or our partners or collaborators, will have to compete with other pharmaceutical and biotechnology companies to
recruit, hire, train, manage and retain marketing and sales personnel. In the event that we or our partners or our
collaborators are unable to develop a marketing and sales infrastructure, we may not be able to commercialize KORSUVA
(CR845/difelikefalin) injection or any of our other current or future product candidates, which would limit our ability to
generate product revenues. Factors that may inhibit our or our partners’ or collaborators’ efforts to commercialize
KORSUVA (CR845/difelikefalin) injection or our other current or future product candidates include:
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inability to recruit, train, manage and retain adequate numbers of effective sales and marketing personnel;
inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to
prescribe KORSUVA (CR845/difelikefalin) injection or our other current or future product candidates;
inability to effectively oversee a geographically dispersed sales and marketing team;
the lack of complementary products to be offered by sales personnel, which may put us at a competitive
disadvantage relative to companies with more extensive product lines; and
unforeseen costs and expenses associated with creating an independent sales and marketing organization.
Our or our partners’ or our collaborators’ sales force and marketing teams may not be successful in commercializing
KORSUVA (CR845/difelikefalin) injection or any of our other current or future product candidates.
In the event that we are unable to collaborate with a third-party marketing and sales organization to commercialize
any approved product candidates outside the United States, our ability to generate product revenues may be limited. To the
extent that we rely on third parties to commercialize any products for which we obtain regulatory approval, we may receive
less revenues than if we commercialized these products ourselves. In addition, we would have less control over the sales
efforts of any other third parties involved in our commercialization efforts.
To the extent that any of our product candidates, if approved, does not achieve broad market acceptance, the
revenues that we generate from its sales will be limited.
We have never commercialized a product candidate for any indication. Even if KORSUVA (CR845/difelikefalin)
injection, Oral KORSUVA (CR845/difelikefalin) or any of our other current or future product candidates is approved by
the appropriate regulatory authorities for marketing and sale, it may not gain acceptance among physicians, hospitals,
dialysis providers, patients and third-party payers. If any product candidates for which we obtain regulatory approval do
not gain an adequate level of market acceptance, we may not generate significant product revenues or become profitable.
Market acceptance of KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA (CR845/difelikefalin) and any future
product candidate by physicians, hospitals, dialysis providers, patients and third-party payers will depend on a
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number of factors, some of which are beyond our control. The degree of market acceptance of any of our product
candidates will depend on a number of factors, including:
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the prevalence and severity of adverse events associated with such product candidate;
limitations or warnings contained in the product’s FDA-approved labeling, including potential limitations or
warnings for such product candidate, that may be more restrictive than other pain management or pruritus
products;
changes in the standard of care for the targeted indications for such product candidate, which could reduce the
marketing impact of any claims that we could make following FDA approval, if obtained;
the relative convenience and ease of administration of such product candidate;
cost of treatment versus economic and clinical benefit in relation to alternative treatments or therapies;
the availability of coverage and adequate reimbursement by third-party payers, such as insurance companies
and other healthcare payers, and by government healthcare programs, including Medicare and Medicaid;
the extent and strength of our marketing and distribution of such product candidate;
the safety, efficacy and other potential advantages over, and availability of, alternative treatments already used
to treat acute pain, chronic pain and/or pruritus;
distribution and use restrictions imposed by the FDA with respect to such product candidate or to which we
agree as part of a mandatory risk evaluation and mitigation strategy or voluntary risk management plan;
the timing of market introduction of such product candidate, as well as competitive products;
our ability to offer such product candidate for sale at competitive prices;
the willingness of the target patient population to try new therapies and of physicians to prescribe these
therapies; and
the clinical indications for such product candidate if approved.
Our ability to effectively promote and sell KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA
(CR845/difelikefalin) and any future product candidates, if approved, will also depend on pricing and cost effectiveness,
including our ability to produce a product at a competitive price and achieve acceptance of the product onto dialysis
organization or hospital formularies, and our ability to obtain sufficient third-party coverage or reimbursement. Generally,
before we can attempt to sell CR845/difelikefalin injection in a hospital or dialysis provider, CR845/difelikefalin injection
must be approved for addition to that institution’s list of drugs approved for use in that institution, or formulary list. In
evaluating drugs for inclusion on the formulary list, hospitals and dialysis providers evaluate a variety of factors, including
cost. The frequency with which hospitals and dialysis providers add and remove drugs from their formulary lists varies
from organization to organization, and institutions often require additional information prior to adding new drugs to their
formulary, which may result in substantial delays in our receiving formulary approval for CR845/difelikefalin
injection. Since most hospitals are members of group purchasing organizations, which leverage the purchasing power of a
group of entities to obtain discounts based on the collective buying power of the group, our ability to attract customers in
the hospital marketplace will also depend on our ability to effectively promote our product candidates to group purchasing
organizations. We will also need to demonstrate acceptable evidence of safety and efficacy, as well as relative convenience
and ease of administration. Market acceptance could be limited depending on the prevalence and severity of any expected
or unexpected adverse side effects associated with our product candidates.
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Our efforts to educate the medical community and third-party payers on the benefits of our product candidates may
require significant resources and may never be successful. Even if the medical community accepts that one of our product
candidates is safe and effective for its approved indications, physicians and patients may not immediately be receptive to
such product candidate and may be slow to adopt it as an accepted treatment of pain or pruritus. It is unlikely that any
labeling approved by the FDA will contain claims that one of our product candidates is safer or more effective than
competitive products or will permit us to promote such product candidate as being superior to competing products. Further,
the availability of inexpensive generic forms of products for acute and chronic pain as well as pruritus may also limit
acceptance of our product candidates among physicians, patients and third-party payers. If KORSUVA
(CR845/difelikefalin) injection, Oral KORSUVA (CR845/difelikefalin) or any future product candidate, is approved but
does not achieve an adequate level of acceptance among physicians, patients and third-party payers, we may not generate
meaningful revenues from KORSUVA (CR845/difelikefalin) injection, Oral CR845/difelikefalin or such other product
candidate, and we may not become profitable.
We face potential product liability exposure, and if successful claims are brought against us, we may incur
substantial liability for KORSUVA (CR845/difelikefalin) injection or other product candidates that we may develop and
may have to limit their commercialization.
The use of KORSUVA (CR845/difelikefalin) injection or Oral KORSUVA (CR845/difelikefalin) and any future
product candidate in clinical trials and the sale of any products for which we obtain regulatory approval expose us to the
risk of product liability claims. We face inherent risk of product liability related to the testing of our product candidates in
human clinical trials and will face an even greater risk if we commercially sell any products that we may develop. For
example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during
clinical testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in
manufacturing, defects in design, a failure to warn of dangers inherent in the product, negligence, strict liability or a breach
of warranties. Product liability claims might be brought against us by consumers, healthcare providers or others using,
administering or selling our products. If we cannot successfully defend ourselves against these claims, we will incur
substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
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loss of revenue from decreased demand for our products and/or product candidates;
impairment of our business reputation or financial stability;
costs of related litigation;
substantial monetary awards to patients or other claimants;
diversion of management attention;
withdrawal of clinical trial participants and potential termination of clinical trial sites or entire clinical
programs;
the inability to commercialize our product candidates;
significant negative media attention;
initiation of investigations by regulators; and
product recalls, withdrawals or labeling, marketing or promotional restrictions.
We have obtained limited product liability insurance coverage for our products and our clinical trials with a $10.0
million annual aggregate coverage limit in the United States and various other coverage limits outside of the United States.
However, our insurance coverage may not reimburse us or may not be sufficient to reimburse us for any expenses or losses
we may suffer. Moreover, insurance coverage is becoming increasingly expensive, and, in the future, we may
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not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to
liability. We intend to expand our insurance coverage to include the sale of commercial products if we obtain FDA
approval for our product candidates in development, but we may be unable to obtain commercially reasonable product
liability insurance for any products approved for marketing, or at all. On occasion, large judgments have been awarded in
class action lawsuits based on drugs that had unanticipated side effects. A successful product liability claim or series of
claims brought against us could cause our stock price to fall and, if judgments exceed our insurance coverage, could
decrease our cash and adversely affect our business.
Risks Related to Our Dependence on Third Parties
We rely, and expect to continue to rely, on third parties to conduct our preclinical studies and clinical trials, and
those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials.
We rely on third-party CROs to conduct our preclinical and clinical trials for all of our product candidates, and do not
plan to independently conduct clinical trials of any other potential product candidates. We expect to continue to rely on
third parties, such as CROs, clinical data management organizations, medical institutions and clinical investigators, to
conduct our preclinical studies and clinical trials. These agreements might terminate for a variety of reasons, including a
failure to perform by the third parties. If we need to enter into alternative arrangements, that would delay our product
development activities and adversely affect our business.
Our reliance on these third parties for development activities will reduce our control over these activities.
Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the applicable
protocol, legal, regulatory and scientific standards and our reliance on the CROs does not relieve us of our regulatory
responsibilities. For example, we will remain responsible for ensuring that each of our clinical trials is conducted in
accordance with the general investigational plan and protocols for the trial and for ensuring that our preclinical trials are
conducted in accordance with GLP, as appropriate. Moreover, the FDA and comparable foreign regulatory authorities
require us to comply with standards, commonly referred to as good clinical practices, or GCPs, for conducting, recording
and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the
rights, integrity and confidentiality of trial participants are protected. Regulatory authorities enforce these requirements
through periodic inspections of trial sponsors, clinical investigators and trial sites. If we or any of our CROs fail to comply
with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or
comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our
marketing applications. We cannot assure you that upon inspection by a given regulatory authority, such regulatory
authority will determine that any of our clinical trials complies with GCP regulations. In addition, our clinical trials must
be conducted with product produced under cGMP regulations. Our failure to comply with these regulations may require us
to repeat clinical trials, which would delay the regulatory approval process. We also are required to register certain clinical
trials and post the results of certain completed clinical trials on a government-sponsored database, ClinicalTrials.gov,
within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
Our CROs may also have relationships with other entities, some of which may be our competitors. In addition, our
CROs are not our employees, and except for remedies available to us under our agreements with such CROs, we cannot
control whether or not they devote sufficient time and resources to our on-going clinical, non-clinical and preclinical
programs. In addition, the operations of our CROs may be constrained or disrupted by the ongoing COVID-19 pandemic.
If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our
preclinical studies or clinical trials in accordance with regulatory requirements or our stated protocols, if they need to be
replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our
clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated
and we may not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and will
not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates. As a result, our
results of operations and the commercial prospects for our product candidates would be harmed, our costs could increase
and our ability to generate revenues could be delayed.
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If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with
alternative CROs or to do so on commercially reasonable terms. Switching or adding additional CROs involves additional
cost and requires management time and focus. In addition, there is a natural transition period when a new CRO commences
work. As a result, delays could occur, which could compromise our ability to meet our desired development timelines.
Though we carefully manage our relationships with our CROs, there can be no assurance that we will not encounter similar
challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business,
financial condition and prospects.
If the manufacturers upon whom we rely fail to produce our product candidates in the volumes that we require on
a timely basis, or to comply with stringent regulations applicable to pharmaceutical drug manufacturers, we may face
delays in the development and commercialization of, or be unable to meet demand for, our products and may lose
potential revenues.
We do not manufacture any of our product candidates, and we do not currently plan to develop any capacity to do so.
We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates for
preclinical and clinical testing, as well as for commercial manufacture if our product candidates receive marketing
approval. It is our intention that by the time of any regulatory approvals for commercialization, we will have negotiated
long-term commitments with at least one primary supplier for each manufacturing and distribution function, and in July
2019, we entered into a non-exclusive commercial manufacturing agreement with Patheon for KORSUVA
(CR845/difelikefalin) injection. Any problems or delays we experience in preparing for commercial-scale manufacturing of
a product candidate may result in a delay in FDA approval of the product candidate or may impair our ability to
manufacture commercial quantities, which would adversely affect our business. For example, our manufacturers will need
to produce specific batches of our product candidates to demonstrate acceptable stability under various conditions and for
commercially viable lengths of time. We and our contract manufacturers will need to demonstrate to the FDA and other
regulatory authorities this acceptable stability data for our product candidates, as well as validate methods and
manufacturing processes, in order to receive regulatory approval to commercialize KORSUVA (CR845/difelikefalin)
injection or any other product candidates. Furthermore, if our commercial manufacturers fail to deliver the required
commercial quantities of bulk drug substance or finished product on a timely basis and at commercially reasonable prices,
we would likely be unable to meet demand for our products and we would lose potential revenues.
The manufacture of pharmaceutical products requires significant expertise and capital investment, including the
development of advanced manufacturing techniques and process controls. Manufacturers of pharmaceutical products often
encounter difficulties in production, particularly in scaling up initial production. These problems include difficulties with
production costs and yields, quality control, including stability of the product candidate and quality assurance testing,
shortages of qualified personnel, as well as compliance with strictly enforced federal, state and foreign regulations. Our
manufacturers may not perform as agreed. If our manufacturers were to encounter any of these difficulties, our ability to
provide product candidates to patients in our clinical trials would be jeopardized.
Further, we may rely on proprietary technology developed by our contract manufacturers for purposes of
manufacturing certain of our product candidates and our failure to negotiate or maintain the long-term use of any such
proprietary technology or the inability for our contract manufacturers to produce our product candidates or components of
our product candidates in the volumes that we require on a timely basis, may lead to delays or interruptions in the
regulatory approval or commercialization process, as well as increased costs. For example, in August 2019, we entered into
the Enteris License Agreement and intend to use Enteris’s Peptelligence® technology to develop, manufacture and
commercialize Oral KORSUVA (CR845/difelikefalin). If we experience any interruptions in the manufacture, delivery or
scale-up of the Enteris formulation technology, we may experience delays in the development and commercialization of
Oral KORSUVA (CR845/difelikefalin). Further, if we are unable to maintain our relationship with Enteris, we may be
forced to reformulate Oral KORSUVA (CR845/difelikefalin) which could result in significantly delaying commercializing
Oral KORSUVA (CR845/difelikefalin) and require us to incur additional costs in connection with such reformulation and
potentially needed to seek additional approvals from the FDA. The operations of our third-party manufacturers have been
and may in the future be constrained or disrupted and their operating capacity may be reduced by the ongoing COVID-19
pandemic, which could negatively impact our clinical development and commercialization timelines.
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In addition, all manufacturers of our product candidates must comply with cGMP requirements enforced by the FDA
through its facilities inspection program. These requirements include quality control, quality assurance and the
maintenance of records and documentation. Manufacturers of our product candidates may be unable to comply with these
cGMP requirements and with other FDA, state and foreign regulatory requirements. If our contract manufacturers cannot
successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or
other regulatory authorities, they will not be able to secure and/or maintain regulatory approval for their manufacturing
facilities. We have little control over our manufacturers’ compliance with these regulations and standards. If the FDA or a
comparable foreign regulatory authority does not approve these facilities for the manufacture of our product candidates or
if it withdraws any such approval in the future, we may need to find alternative manufacturing facilities, which would
significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved. A
failure to comply with these requirements may result in fines and civil penalties, suspension of production, suspension,
delay or denial of product approval, product seizure or recall, or withdrawal of product approval. If the safety of any
quantities supplied is compromised due to our manufacturers’ failure to adhere to applicable laws or for other reasons, we
may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
We may rely on third parties to perform many essential services for any products that we commercialize, including
services related to warehousing and inventory control, distribution, customer service, accounts receivable management,
cash collection and adverse event reporting. If these third parties fail to perform as expected or to comply with legal and
regulatory requirements, our ability to commercialize I.V. CR845/difelikefalin or any other product candidate, will be
significantly impacted and we may be subject to regulatory sanctions.
We may retain third-party service providers to perform a variety of functions related to the sale and distribution of
KORSUVA (CR845/difelikefalin) injection and our other current or future product candidates, key aspects of which will be
out of our direct control. These service providers may provide key services related to warehousing and inventory control,
distribution, customer service, accounts receivable management and cash collection, and, as a result, most of our inventory
may be stored at a single warehouse maintained by one such service provider. If we retain this provider, we would
substantially rely on it as well as other third-party providers that perform services for us, including entrusting our
inventories of products to their care and handling. If these third-party service providers fail to comply with applicable laws
and regulations, fail to meet expected deadlines, or otherwise do not carry out their contractual duties to us, or encounter
physical or natural damage at their facilities, our ability to deliver product to meet commercial demand would be
significantly impaired. In addition, we may engage third parties to perform various other services for us relating to adverse
event reporting, safety database management, fulfillment of requests for medical information regarding our product
candidates and related services. If the quality or accuracy of the data maintained by these service providers is insufficient,
or these third parties otherwise fail to comply with regulatory requirements related to adverse event reporting, we could be
subject to regulatory sanctions.
We are dependent on our collaboration agreements for certain revenues, and if our commercial partners do not
perform their obligations under such agreements, we could lose revenues.
In October 2020, we entered into a license agreement with Vifor under which we granted Vifor an exclusive license
solely in the United States to use, distribute, offer for sale, promote, sell and otherwise commercialize our product
candidate KORSUVA (CR845/difelikefalin) injection for all therapeutic uses relating to the inhibition, prevention or
treatment of itch associated with pruritus in hemodialysis and peritoneal dialysis patients in the United States. In
May 2018, we entered into an agreement with VFMCRP under which we granted VFMCRP a license to seek regulatory
approval to commercialize, import, export, use, distribute, offer for sale, promote, sell and otherwise commercialize
KORSUVA (CR845/difelikefalin) injection for all therapeutic uses to prevent, inhibit or treat itch associated with pruritus
in hemodialysis and peritoneal-dialysis patients worldwide (excluding the United States, Japan and South Korea). In
April 2013, we entered into an agreement with Maruishi under which we granted Maruishi an exclusive license to develop,
manufacture and commercialize products containing CR845/difelikefalin in Japan. Also, in April 2012, we entered into an
agreement with CKDP under which we granted CKDP an exclusive license to develop, manufacture and commercialize
products containing CR845/difelikefalin in South Korea. Under the VFMCRP Agreement, we are responsible, at our own
cost, to undertake clinical and non-clinical development. We are also responsible to provide all content and subject matter
expertise required for registration with the EMA in the EU that will
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be needed by VFMCRP for such registration, including participation in regulatory meetings, as needed. If third-party costs
incurred by us with respect to our clinical development for the EMA registration exceed $20,000, such excess costs will be
shared equally by us and VFMCRP. VFMCRP will contribute, at its own cost, its clinical development expertise as
reasonably useful for such development activities, such as preparing the clinical results that we present to it in a format
acceptable to the EMA to obtain marketing approval in the EU. Maruishi and CKDP are required to use commercially
reasonable efforts, at their expense, to develop, obtain regulatory approval for and commercialize CR845/difelikefalin in
Japan and South Korea, respectively. Our receipt of milestone payments and royalties under these agreements is dependent
on the continued efforts by VFMCRP, Maruishi and CKDP, respectively, and their failure to adequately develop or
commercialize the licensed products, or any default or inability to meet their payment obligations under their respective
agreements, could harm our revenues and business.
Any collaboration arrangements that we are a party to or may enter into in the future may not be successful,
which could adversely affect our ability to develop and commercialize our product candidates.
Our business model is to commercialize our product candidates in the United States and generally to seek
collaboration arrangements with pharmaceutical or biotechnology companies for the development or commercialization of
our product candidates in the rest of the world. We currently have license agreements with Vifor and VFMCRP (I.V.
CR845/difelikefalin for CKD-aP in dialysis patients) as well as Maruishi and CKDP (CR845/difelikefalin – both I.V. and
Oral). In addition to our existing agreements, we may enter into additional collaboration arrangements in the future on a
selective basis. Our existing collaborations and future collaboration arrangements may not be successful. The success of
our existing and future collaboration arrangements will depend heavily on the efforts and activities of our collaborators.
Collaborators generally have significant discretion in determining the efforts and resources that they will apply to
these collaboration arrangements. Disagreements between parties to a collaboration arrangement regarding clinical
development and commercialization matters can lead to delays in the development process or commercializing the
applicable product candidate and, in some cases, termination of the collaboration arrangement. These disagreements can be
difficult to resolve if neither of the parties has final decision-making authority.
Collaborations with pharmaceutical companies and other third parties often are terminated or allowed to expire by
the other party. For example, the Vifor, VFMCRP, Maruishi and CKDP Agreements may be terminated by our collaborator
for our breach or insolvency, each of Vifor and VFMCRP may terminate its respective agreement (in its entirety or with
respect to any countries within the Territory upon written notice to us) upon the earlier of (1) acceptance for filing of an
NDA covering Licensed Product filed with the FDA (after completion of the Phase 3 program) or (2) the third anniversary
of the Effective Date. Maruishi may terminate its agreement with us at will, and CKDP may terminate its agreement with
us in certain circumstances relating to patent invalidity or unenforceability or generic entry by a third party, as further
described in the section titled “Management’s Discussion and Analysis of Financial Condition and Results of Operations –
Collaboration and License Agreements” above. Any such termination or expiration would adversely affect us financially
and could harm our business reputation. Our current collaborations and any future collaborations we might enter into may
pose a number of risks, including the following:
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collaborators may not perform their obligations as expected;
collaborators may not pursue development and commercialization of any product candidates that achieve
regulatory approval or may elect not to continue or renew development or commercialization programs based
on clinical trial results, changes in the collaborators’ strategic focus or available funding, or external factors,
such as an acquisition, that divert resources or create competing priorities;
collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical
trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a
product candidate for clinical testing;
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collaborators may not comply with all applicable regulatory requirements or may fail to report safety data in
accordance with all applicable regulatory requirements;
collaborators could independently develop, or develop with third parties, products that compete directly or
indirectly with our products or product candidates if the collaborators believe that competitive products are
more likely to be successfully developed or can be commercialized under terms that are more economically
attractive than ours;
product candidates discovered in collaboration with us may be viewed by our collaborators as competitive
with their own product candidates or products, which may cause collaborators to cease to devote resources to
the commercialization of our product candidates;
a collaborator with marketing and distribution rights to one or more of our product candidates that achieve
regulatory approval may not commit sufficient resources to the marketing and distribution of such product or
products;
disagreements with collaborators, including disagreements over proprietary rights, contract interpretation or
the preferred course of development, might cause delays or termination of the research, development or
commercialization of product candidates, might lead to additional responsibilities for us with respect to
product candidates, or might result in litigation or arbitration, any of which would be time-consuming and
expensive;
collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary
information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or
proprietary information or expose us to potential litigation;
collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation
and potential liability; and
collaborations, including our collaboration with Maruishi, may be terminated for the convenience of the
collaborator and, if terminated, we could be required to raise additional capital to pursue further development
or commercialization of the applicable product candidates.
If our current collaborations or any other collaborations we might enter into in the future do not result in the
successful development and commercialization of products or if one of our collaborators terminates its agreement with us,
we may not receive any future research funding or milestone or royalty payments under the collaboration. If we do not
receive the funding we expect under these agreements, our development of our product candidates could be delayed and we
may need additional resources to develop our product candidates and our product platform. All of the risks relating to our
product development, regulatory approval and commercialization described in this Annual Report on Form 10-K also apply
to the activities of our collaborators in their respective jurisdictions.
Additionally, if any current or future collaborator of ours is involved in a business combination, the collaborator
might deemphasize or terminate development or commercialization of any product candidate licensed to it by us. If one of
our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our
reputation in the business and financial communities could be adversely affected.
For KORSUVA (CR845/difelikefalin) injection and any other current or future product candidates, we may in the
future determine to collaborate with additional pharmaceutical and biotechnology companies for their development and
potential commercialization. We face significant competition in seeking appropriate collaborators. Our ability to reach a
definitive agreement for collaboration will depend, among other things, upon our assessment of the collaborator’s resources
and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a
number of factors. If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms,
or at all, we may have to curtail the development of a product candidate, reduce or delay its
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development program or one or more of our other development programs, delay its potential commercialization or reduce
the scope of any sales or marketing activities, or increase our expenditures and undertake development or
commercialization activities at our own expense. If we elect to fund and undertake development or commercialization
activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us
on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to
undertake the necessary development and commercialization activities, we may not be able to further develop our product
candidates or bring them to market or continue to develop our product platform and our business may be materially and
adversely affected.
We are dependent on third parties to decide to utilize KORSUVA (CR845/difelikefalin) injection and to make it
readily available at the point of care throughout their dialysis centers or hospitals.
In addition to extensive internal efforts, the successful commercialization of KORSUVA (CR845/difelikefalin)
injection will require many third parties, over whom we have no control, to decide to utilize KORSUVA
(CR845/difelikefalin) injection and to make it readily available at the point of care throughout their hospitals. These third
parties include physicians, dialysis providers, pharmacists and hospital pharmacy and therapeutics committees, which are
commonly referred to as P&T committees. Generally, even if CR845/difelikefalin injection is approved by the FDA, before
we can attempt to sell CR845/difelikefalin injection in a hospital or dialysis center, CR845/difelikefalin injection must be
approved for addition to that hospital or dialysis center’s list of approved drugs, or formulary list, by the institution’s P&T
committee. An institutional P&T committee typically governs all matters pertaining to the use of medications within the
institution, including review of medication formulary data and recommendations for the appropriate use of drugs within the
institution to the medical staff. The frequency of P&T committee meetings at various institutions varies considerably, and
P&T committees often require additional information to aid in their decision-making process, so we may experience
substantial delays in obtaining formulary approvals. Additionally, institutions may be concerned that the cost of acquiring
CR845/difelikefalin injection for use in their institutions will adversely impact their overall pharmacy budgets, which could
cause institution staff to resist efforts to add CR845/difelikefalin injection to the formulary, or to implement restrictions on
the usage of the drug in order to control costs, either initially or later, when the increasing use of CR845/difelikefalin
injection within their institution begins to significantly impact their budgets. We cannot guarantee that we will be
successful in getting the approvals we need from enough P&T committees and overcoming any financial objections raised
by institution staff quickly enough to maintain and grow institutional sales of CR845/difelikefalin injection.
Risks Related to Legal and Compliance Matters
If we fail to comply with federal and state healthcare laws, including fraud and abuse, and transparency laws, we
could face substantial penalties and our business, results of operations, financial condition and prospects could be
adversely affected.
As a pharmaceutical company, even though we do not and will not control referrals of healthcare services or bill
directly to Medicare, Medicaid or other third-party payers, certain federal and state healthcare laws and regulations
pertaining to fraud and abuse, transparency and patients’ rights may be applicable to our business. The healthcare laws and
regulations that may affect our ability to operate include, but are not limited to:
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the federal Anti-Kickback Statute, which regulates, among other things, our marketing practices, educational
programs, pricing policies, and relationships with healthcare providers or other entities, by prohibiting, among
other things, any person or entity from knowingly and willfully soliciting, receiving, offering or paying any
remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce, or in return for, the
purchase, recommendation, lease, order or furnishing of an item or service reimbursable, in whole or in part,
under a federal healthcare program, such as the Medicare and Medicaid programs;
federal civil and criminal false claims laws, including without limitation the federal civil False Claims Act, and
civil monetary penalties law, which prohibit, among other things, individuals or entities from knowingly
presenting, or causing to be presented, false or fraudulent claims for payment or approval from a federal health
care program (including Medicare and Medicaid);
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HIPAA, which created additional federal criminal statutes that prohibit, among other things, knowingly and
willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or to obtain,
by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned
by, or under the custody or control of, any health care benefit program, regardless of the payer (e.g., public or
private) and knowingly and willfully falsifying, concealing, or covering up by any trick, scheme or device a
material fact or making any materially false statements in connection with the delivery of, or payment for,
health care benefits, items or services relating to healthcare matters;
federal transparency laws, including the federal Physician Payments Sunshine Act, that requires certain
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 to CMS, or Centers for
Medicare & Medicaid Services, information related to payments and other transfers of value provided to
physicians (defined to include doctors of medicine, dentists, optometrists, podiatrists and chiropractors) and
teaching hospitals, and applicable manufacturers and group purchasing organizations to report annually to
CMS ownership and investment interests held by physicians and their immediate family members; Beginning
in 2022, applicable manufacturers also will be required to report such information regarding payments and
transfers of value provided during the previous year to physician assistants, nurse practitioners, clinical nurse
specialists, anesthesiologist assistants, certified nurse anesthetists and certified nurse-midwives; and
state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may
apply to items or services reimbursed by any third-party payer, including commercial insurers; state laws that
require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance
guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict
payments that may be made to healthcare providers and other potential referral sources; state laws that require
drug manufacturers to report information related to the pricing of certain drugs, as well as payments and other
transfers of value to physicians and other healthcare providers or marketing expenditures; and state and local
laws that require the registration of pharmaceutical sales representatives, many of which differ from each other
in significant ways and may not have the same effect, thus complicating compliance efforts.
Because of the breadth of these laws and the narrowness of the statutory exceptions and regulatory safe harbors
available under these laws, it is possible that some of our business activities could be subject to challenge under one or
more of such laws. Pharmaceutical and other healthcare companies continue to be prosecuted under the federal false claims
laws for numerous activities, including those related to research, sales, marketing and promotional programs. In addition,
recent health care reform legislation has strengthened these laws. For example, the Health Care Reform Law among other
things, amends the intent requirement of the federal Anti-Kickback Statute and certain other criminal healthcare fraud
statutes. As a result, a person or entity no longer needs to have actual knowledge of these statutes or specific intent to
violate them in order to commit a violation. Moreover, the Health Care Reform Law provides that the government may
assert that a claim including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a
false or fraudulent claim for purposes of the federal civil False Claims Act. To the extent that any product we make is sold
in a foreign country, we may be subject to similar foreign laws and regulations. If we or our operations are found to be in
violation of any of the laws described above or any other governmental regulations that apply to us, we may be subject to
significant penalties, including administrative, civil and criminal penalties, damages, fines, disgorgement, exclusion from
participation in U.S. federal or state health care programs, contractual damages, reputational harm, imprisonment,
diminished profits and future earnings, additional reporting requirements and/or oversight if we become subject to a
corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the
curtailment or restructuring of our operations, any of which could materially adversely affect our ability to operate our
business and our financial results. Although an effective compliance program can mitigate the risk of investigation and
prosecution for violations of these laws, the risks cannot be entirely eliminated. Any action against us for violation of these
laws, even if we successfully defend against it, could cause us to incur significant legal expenses and divert our
management’s attention from the operation of our business. Moreover, achieving and sustaining compliance with
applicable federal and state transparency and fraud and abuse laws may prove costly. If any of the physicians or other
healthcare providers or entities with whom we expect to do business, including
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our collaborators, is found not to be in compliance with applicable laws, it may be subject to significant criminal, civil or
administrative sanctions, including but not limited to, exclusions from participation in government healthcare programs,
which could also materially affect our business.
Changes in and failures to comply with applicable U.S. and foreign privacy and data protection laws, regulations
and standards may subject us to liabilities and adversely affect our business, operations and financial performance.
We are subject to or affected by numerous federal, state and foreign laws and regulations, as well as regulatory
guidance, governing the collection, use, disclosure, retention, and security of personal data, such as information that we
collect about participants and healthcare providers in connection with clinical trials in the U.S. and abroad. The global data
protection landscape is rapidly evolving, and implementation standards and enforcement practices are likely to remain
uncertain for the foreseeable future. This evolution may create uncertainty in our business, affect our or our service
providers’ ability to operate in certain jurisdictions or to collect, store, transfer use and share personal data, result in
liability or impose additional costs on us. The cost of compliance with these laws, regulations and standards is high and is
likely to increase in the future. Any failure or perceived failure by us to comply with federal, state, or foreign laws or self-
regulatory standards could result in negative publicity, diversion of management time and effort and proceedings against us
by governmental entities or others. In many jurisdictions, enforcement actions and consequences for noncompliance are
rising.
In the U.S., HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of
2009, or HITECH, imposes certain requirements relating to the privacy, security and transmission of individually
identifiable health information without appropriate authorization by entities subject to the rule, including health plans,
healthcare clearinghouses, certain healthcare providers, and their business associates and covered subcontractors that
perform services for them that involve the creation, use, maintenance or disclosure of, individually identifiable health
information. In the event we are subject to HIPAA and we or our covered subcontractors fail to properly maintain the
privacy and security of certain individually identifiable health information, or we or our covered subcontractors are
responsible for an inadvertent disclosure or security breach of such individually identifiable health information, we could
be subject to enforcement measures, including civil and criminal penalties and fines for violations of state and federal
privacy or security standards, such as HIPAA and HITECH, and their respective implementing regulations. Additionally,
certain states have adopted comparable privacy and security laws and regulations, some of which may be more stringent
than HIPAA. On June 28, 2018, California enacted the California Consumer Privacy Act, or CCPA, which takes effect on
January 1, 2020. The CCPA gives California residents expanded rights to access and delete their personal information, opt
out of certain personal information sharing, and receive detailed information about how their personal information is used.
The CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that is expected to
increase data breach litigation. The CCPA may increase our compliance costs and potential liability. Some observers have
noted that the CCPA could mark the beginning of a trend toward more stringent privacy legislation in the U.S., which could
increase our potential liability and adversely affect our business.
Our operations abroad may also be subject to increased scrutiny or attention from data protection authorities. Many
countries in these regions have established or are in the process of establishing privacy and data security legal frameworks
with which we or our partners, collaborators, customers, or service providers must comply. For example, the EU has
adopted the General Data Protection Regulation, or GDPR, which went into effect in May 2018 and introduced strict
requirements for processing personal data. The GDPR is likely to increase compliance burden on us, including by
mandating potentially burdensome documentation requirements and granting certain rights to individuals to control how
we collect, use, disclose, retain and leverage information about them or how we obtain consent from them. The processing
of sensitive personal data, such as physical health condition, may impose heightened compliance burdens under the GDPR
and is a topic of active interest among foreign regulators and supervisory bodies involved in the review and approval of
clinical trials. In addition, the GDPR provides for breach reporting requirements, more robust regulatory enforcement and
fines of up to 20 million euros or up to 4% of the annual global revenue. As we continue to expand into other foreign
countries and jurisdictions, we may be subject to additional laws and regulations that may affect how we conduct business.
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U.S. and foreign data protection laws, regulations and standards are subject to interpretation by various courts and
other governmental authorities, thus creating potentially complex compliance issues for us and our future customers and
strategic partners. Any liability from failure to comply with the requirements of these laws, to the extent such requirements
are deemed to apply to our operations, could adversely affect our financial condition. The costs of complying with privacy
and security related legal and regulatory requirements are burdensome and could have a material adverse effect on our
results of operations.
If the government or other third-party payers fail to provide coverage and adequate reimbursement and payment
rates for KORSUVA (CR845/difelikefalin) injection or any of our other current or future product candidates, if any, or
if providers choose to use therapies that are less expensive, our revenue and prospects for profitability will be limited.
In both domestic and foreign markets, sales of our future products will depend in part upon the availability of
coverage and reimbursement from third-party payers. Such third-party payers include government health programs such as
Medicare and Medicaid, managed care providers, private health insurers and other organizations. Coverage decisions may
depend upon clinical and economic standards that disfavor new drug products when more established or lower cost
therapeutic alternatives are already available or subsequently become available. Assuming coverage is approved, the
resulting reimbursement payment rates might not be adequate. KORSUVA (CR845/difelikefalin) injection for the treatment
of pruritus in hemodialysis patients may be designated as a component of the government’s bundled reimbursement for end
stage renal disease treatment.
On October 31, 2019, CMS issued a final rule that revises payment policies and rates under the End-Stage Renal
Disease Prospective Payment System, or ESRD PPS, for renal dialysis services furnished to beneficiaries on or after
January 1, 2020. The final rule also updates the Transitional Drug Add-On Payment Adjustment, or TDAPA. In the final
rule, CMS revised ESRD PPS eligibility to focus on innovative drugs and excluded certain drugs from being eligible for
the TDAPA. CMS will pay the revised TDAPA adjustment, which is called the Transitional Add-on Payment Adjustment
for New and Innovative Equipment and Supplies , or TPNIES, for equipment and supplies that: (1) have been designated
by CMS as a renal dialysis service, (2) are new, meaning granted marketing authorization by FDA on or after January 1,
2020, (3) are commercially available by January 1 of the particular calendar year, meaning the year in which the payment
adjustment would take effect, (4) have a Healthcare Common Procedure Coding System, or HCPCS, application
submitted in accordance with the official Level II HCPCS coding procedures by September 1 of the particular calendar
year, (5) are innovative, meaning they meet the substantial clinical improvement criteria specified in the Inpatient
Prospective Payment System regulations and related guidance, and (6) are not capital-related assets. On November 2, 2020,
CMS issued a final rule outlining its payment policies and rates under the ESRD PPS for the 2021 calendar year. In
addition to the annual technical updates to the ESRD PPS, the final rule, among other things, expands eligibility under the
TPNIES. In particular, the final rule provided for biannual coding cycles for new HCPCS Level II code applications,
revised the definition of “new” to be three (3) years beginning on the date of FDA marketing authorization, and expanded
eligibility under the TPNIES to include certain home dialysis capital-related assets. We expect KORSUVA
(CR845/difelikefalin) injection, if approved for CKD-aP in hemodialysis patients, will qualify for TDAPA payments for
two years post approval. However, there is no assurance that KORSUVA (CR845/difelikefalin) injection will qualify for
TDAPA payments or, even if it does, that it will be able to maintain its price established in the TDAPA period in the post-
TDAPA timeframe.
Additionally, many U.S. hospitals receive a fixed reimbursement amount per procedure for certain surgeries and
other treatment therapies they perform, or a pre-determined rate for all hospital inpatient care provided as payment in full.
Because, in these instances, the amount of reimbursement that such providers receive may not be based on the actual
expenses the provider incurs, providers may choose to use therapies which are less expensive when compared to our
product candidates. Accordingly, KORSUVA (CR845/difelikefalin) injection or any of our other current or future product
candidates, if approved, will face competition from other therapies and drugs for these limited provider financial resources.
We may need to conduct post-marketing studies in order to demonstrate the cost-effectiveness of any future products to the
satisfaction of hospitals, other target customers and their third-party payers. Such studies might require us to commit a
significant amount of management time and financial and other resources. Our future products might not ultimately be
considered cost-effective. Third-party coverage and adequate reimbursement might not be available to enable us to
maintain price levels sufficient to realize an appropriate return on investment in product development.
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Third-party payers, whether foreign or domestic, or governmental or commercial, are developing increasingly
sophisticated methods of controlling healthcare costs. In addition, in the United States, no uniform policy of coverage and
reimbursement for drug products exists among third-party payers. Therefore, coverage and reimbursement for drug
products can differ significantly from payer to payer. Further, we believe that future coverage and reimbursement will
likely be subject to increased restrictions both in the United States and in international markets. Third-party coverage and
reimbursement for our products or product candidates for which we receive regulatory approval may not be available or
adequate in either the United States or international markets, which could have a negative effect on our business, results of
operations, financial condition and prospects.
We are subject to recent legislation, regulatory proposals and healthcare payer initiatives that may increase our
costs of compliance and adversely affect our ability to market our products, obtain collaborators and raise capital.
In March 2010, President Obama signed the Health Care Reform Law, which includes provisions that have changed,
and likely will continue to change, health care financing and the delivery of health care in the United States. Among the
provisions of the Health Care Reform Law of importance to the pharmaceutical industry are the following:
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an annual, nondeductible fee on any entity that manufactures or imports certain branded prescription drugs and
biologic agents, apportioned among these entities according to their market share in certain government
healthcare programs;
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate
Program to 23.1% and 13% of the average manufacturer price for most branded and generic drugs,
respectively;
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;
a new Medicare Part D coverage gap discount program, in which manufacturers must now 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;
extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are
enrolled in Medicaid managed care organizations;
expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer
Medicaid coverage to additional individuals with income at or below 133% of the Federal Poverty Level,
thereby potentially increasing both the volume of sales and manufacturers’ Medicaid rebate liability;
expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing
program;
new transparency requirements under the federal Physician Payments Sunshine Act;
a new requirement to annually report certain drug samples that manufacturers and distributors provide to
licensed practitioners, or to pharmacies of hospitals or other healthcare entities;
a licensure framework for follow-on biologic products;
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative
clinical effectiveness research, along with funding for such research;
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establishment of a Center for Medicare & Medicaid Innovation at the CMS to test innovative payment and
service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug
spending; and
expansion of healthcare fraud and abuse laws, including the federal civil False Claims Act and the federal
Anti-Kickback Statute, new government investigative powers and enhanced penalties for non-compliance.
There have been executive, judicial and Congressional challenges to certain aspects of the Health Care Reform Law.
For example, President Trump has signed several Executive Orders and other directives designed to delay the
implementation of certain provisions of the Health Care Reform Law or otherwise circumvent some of the requirements for
health insurance mandated by the Health Care Reform Law. Concurrently, Congress considered legislation that would
repeal or repeal and replace all or part of the Health Care Reform Law. While Congress has not passed comprehensive
repeal legislation, several bills affecting the implementation of certain taxes under the Health Care Reform Law have been
signed into law. The Tax Cuts and Jobs Act, or TCJA, includes a provision that repealed, effective January 1, 2019, the tax-
based shared responsibility payment imposed by the Health Care Reform Law on certain individuals who fail to maintain
qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”. In addition,
the 2020 federal spending package permanently eliminated, effective January 1, 2020, the Health Care Reform Law’s
mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1,
2021, also eliminated the health insurer tax. On December 14, 2018, a Texas U.S. District Court Judge ruled that the Health
Care Reform Law is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of
the TCJA. Additionally, on December 18, 2019, the U.S. Court of Appeals for the 5th Circuit upheld the District Court
ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine
whether the remaining provisions of the Health Care Reform Law are invalid as well. The U.S. Supreme Court is currently
reviewing this case, although it is unclear when a decision will be made. Although the U.S. Supreme Court has yet ruled on
the constitutionality of the Health Care Reform Law, on January 28, 2021, President Biden issued an executive order to
initiate a special enrollment period from February 15, 2021 through May 15, 2021 for purposes of obtaining health
insurance coverage through the Health Care Reform Law marketplace. The executive order also instructs certain
governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including
among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and
policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Health
Care Reform Law. It is also unclear how the Supreme Court ruling, other such litigation and the healthcare reform
measures of the Biden administration will impact the Health Care Reform Law and our business.
In addition, other legislative changes have been proposed and adopted since the Health Care Reform Law was
enacted. These changes include, among other things, aggregate reductions to Medicare payments to providers of up to
2% per fiscal year, which went effective on April 1, 2013 and, following passage of the Bipartisan Budget Act of 2015, and
subsequent legislative amendments, including the BBA, will remain in effect until 2030, except for a temporary suspension
from May 1, 2020 through March 31, 2021 due to the COVID-19 pandemic, unless additional Congressional action is
taken. In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other
things, further reduced Medicare payments to several providers and increased the statute of limitations period for the
government to recover overpayments to providers from three to five years. These new laws may result in additional
reductions in Medicare and other healthcare funding, which could have a material adverse effect on customers for our
drugs, if approved, and, accordingly, our financial operations.
We expect that the Health Care Reform Law, as well as other federal and state healthcare reform measures that may
be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price
that we receive for any approved drug. Any reduction in reimbursement from Medicare or other government healthcare
programs may result in a similar reduction in payments from private payers. In addition, 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, review the relationship between pricing and manufacturer patient programs, reduce the
cost of drugs under Medicare, and reform government program reimbursement methodologies for drugs. At the federal
level, the Trump administration used several means to propose or implement drug pricing reform, including through federal
budget proposals, executive orders and policy initiatives. For example, on July 24, 2020 and
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September 13, 2020, the Trump administration announced several executive orders related to prescription drug pricing that
seek to implement several of the administration’s proposals. As a result, the FDA released a final rule on September 24,
2020, effective November 30, 2020, providing guidance for states to build and submit importation plans for drugs from
Canada. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions
from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers,
unless the price reduction is required by law. The implementation of the rule has been delayed by the Biden administration
from January 1, 2022 to January 1, 2023 in response to ongoing litigation. 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, the implementation of which have also been delayed pending review by the Biden
administration until March 22, 2021. On November 20, 2020, CMS issued an interim final rule implementing President
Trump’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-
administered drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021. On
December 28, 2020, the United States District Court in Northern California issued a nationwide preliminary injunction
against implementation of the interim final rule. It is unclear whether the Biden administration will work to reverse these
measures or pursue similar policy initiatives. 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, to encourage importation from other countries and bulk purchasing. The implementation of
cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain
profitability or commercialize our drugs.
Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and
promotional activities for drugs. We cannot be sure whether additional legislative changes will be enacted, or whether the
FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing
approvals of our product candidates, if any, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s
approval process may significantly delay or prevent marketing approval, as well as subject us to more stringent product
labeling and post-marketing testing and other requirements. Moreover, the Drug Supply Chain Security Act imposes
obligations on manufacturers of pharmaceutical products, among others, related to product tracking and tracing.
Legislation and regulations that, among other things, reduce drug prices or require the implementation of costly
compliance measures could result in decreased net revenues from our pharmaceutical products and decrease potential
returns from our development efforts, and we cannot predict what legislation will be enacted in the future. Further, it is
possible that additional governmental action is taken in response to the COVID-19 pandemic.
Governments outside the United States tend to impose strict price controls, which may adversely affect our
revenues, if any.
In international markets, reimbursement and health care payment systems vary significantly by country, and many
countries have instituted price ceilings on specific products and therapies. In some countries, particularly the countries of
the EU, the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing
negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product.
To obtain coverage and reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial
that compares the cost-effectiveness of our product candidate to other available therapies. There can be no assurance that
our products will be considered cost-effective by third-party payers, that an adequate level of reimbursement will be
available or that the third-party payers’ reimbursement policies will not adversely affect our ability to sell our products
profitably. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at
unsatisfactory levels, our business could be harmed, possibly materially.
Our employees, independent contractors, consultants, and commercial partners may engage in misconduct or
other improper activities, including noncompliance with regulatory standards and requirements, which could have a
material adverse effect on our business.
We are exposed to the risk of fraud or other misconduct by our employees, independent contractors, consultants and
commercial partners. Misconduct by such individuals could include intentional failures to comply with FDA
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regulations, provide accurate information to the FDA, report financial information or data accurately or disclose
unauthorized activities to us. Third party misconduct could also involve the improper use or misrepresentation of
information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our
reputation. It is not always possible to identify and deter such misconduct, and the precautions we take to detect and
prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from
governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or
regulations. If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our
rights, those actions could have a significant impact on our business and financial results, including the imposition of civil,
criminal and administrative penalties, damages, disgorgement, monetary fines, possible exclusion from participation in
Medicare, Medicaid and other federal healthcare programs, individual imprisonment, contractual damages, reputational
harm, diminished profits and future earnings, additional reporting requirements and/or oversight if we become subject to a
corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and
curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and
our results of operations.
Our business involves the use of hazardous materials and we must comply with environmental laws and
regulations, which can be expensive and restrict how we do business.
Our manufacturing activities involve the controlled storage, use and disposal of hazardous materials, including the
components of our products, product candidates and other hazardous compounds. We are subject to federal, state and local
laws and regulations governing the use, manufacture, storage, handling, release and disposal of, and exposure to, these
hazardous materials. Violation of these laws and regulations could lead to substantial fines and penalties. Although we
believe that our safety procedures for handling and disposing of these materials comply with the standards prescribed by
these laws and regulations, we cannot eliminate the risk of accidental contamination or injury from these materials. In the
event of an accident, state or federal authorities may curtail our use of these materials and interrupt our business operations.
In addition, we could become subject to potentially material liabilities relating to the investigation and cleanup of any
contamination, whether currently unknown or caused by future releases.
Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to
injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage
against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be
asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety
laws and regulations. These current or future laws and regulations may impair our research, development or production
efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other
sanctions.
Risks Related to Intellectual Property
It is difficult and costly to protect our proprietary rights and as a result we may not be able to ensure their
protection and all patents will eventually expire.
Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret
protection for CR845/difelikefalin and for any other product candidates that we may develop, license or acquire and the
methods we use to manufacture them, as well as successfully defending these patents and trade secrets against third-party
challenges. We will only be able to protect our technologies from unauthorized use by third parties to the extent that valid
and enforceable patents or trade secrets cover them.
The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute to
issuance all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we
will fail to identify patentable aspects of our R&D output before it is too late to obtain patent protection. Moreover, should
we enter into additional collaborations we may be required to consult with or cede control to collaborators regarding the
prosecution, maintenance and enforcement of our patents. Therefore, these patents and applications may
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not be successfully prosecuted to issuance and enforced in a manner consistent with the best interests of our business. The
patent positions of pharmaceutical and biotechnology companies can be highly uncertain and involve complex legal and
factual questions for which important legal principles remain unresolved. No consistent policy regarding the breadth of
claims allowed in pharmaceutical or biotechnology patents has emerged to date in the United States. The patent situation
outside the United States is even more uncertain. Changes in either the patent laws or in interpretations of patent laws in
the United States and other countries may diminish the value of our intellectual property. Accordingly, we cannot predict
the breadth of claims that may be allowed or enforced in our patents or in third-party patents. The degree of future
protection for our proprietary rights is uncertain, because legal means afford only limited protection and may not
adequately protect our rights or permit us to gain or keep our competitive advantage. Moreover, the patent application
process is also subject to numerous risks and uncertainties, and there can be no assurance that we or any of our future
development partners will be successful in protecting CR845/difelikefalin and any other product candidates that we may
develop, license or acquire by obtaining and defending patents. For example:
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we may not have been the first to make the inventions covered by each of our pending patent applications and
issued patents;
we may not have been the first to file patent applications for these inventions;
others may independently develop similar or alternative technologies or duplicate any of our product
candidates or technologies;
it is possible that none of the pending patent applications will result in issued patents;
the issued patents covering our product candidates may not provide a basis for commercially viable active
products, may not provide us with any competitive advantages, or may be challenged by third parties;
we may not develop additional proprietary technologies that are patentable;
patents of others may have an adverse effect on our business;
competitors may file trademark infringement claims or challenges to the validity of our trademark(s);
noncompliance with governmental patent agencies requirements can result in abandonment or lapse of a patent
or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction,
potentially allowing competitors to enter the market earlier than would otherwise have been the case;
our competitors, many of whom have substantially greater resources than we do and many of whom have
made significant investments in competing technologies, may seek or may have already obtained patents that
will limit, interfere with, or eliminate our ability to make, use, and sell our potential product candidates; or
there may be significant pressure on the U.S. government and international governmental bodies to limit the
scope of available patent protection both inside and outside the United States for disease treatments that prove
successful, as a matter of public policy regarding worldwide health concerns.
Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent
applications and the enforcement or defense of our issued patents. On September 16, 2011, the Leahy-Smith America
Invents Act, or the Leahy-Smith Act, was signed into law. The Leahy-Smith Act includes a number of significant changes
to United States patent law. These include provisions that affect the way patent applications are prosecuted and may also
affect patent litigation. The United States Patent Office has developed new regulations and procedures to govern
administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith
Act, including and in particular, the first to file provisions, became effective on March 16, 2013. The Leahy-Smith Act and
its implementation could increase the uncertainties and costs surrounding the
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prosecution of our currently pending and future patent applications and the enforcement or defense of our issued patents,
all of which could have a material adverse effect on our business and financial condition.
Patent applications in the United States are generally maintained in confidence for at least 18 months after their
earliest effective filing date and in certain circumstances not until granted when no foreign counterpart patent applications
are filed. Furthermore, published patent applications may issue at a later date with new and/or amended claims
substantially different from those published earlier. Consequently, we cannot be certain we were the first to invent or the
first to file patent applications on CR845/difelikefalin or any other product candidates that we may develop, license or
acquire.
Until recent changes to the U.S. Patent Laws, patents and patent applications relating to substantially similar claimed
inventions were potentially subject to interference proceedings to determine the first applicant to invent the claimed subject
matter. For an interference to be declared against our patents and patent applications, any such interference would be under
the 1952 law which was eliminated by the America Invents Act, or AIA, enacted in 2011 and fully effective in 2013. Such
an interference would therefore have to relate to a patent or application with an effective filing date before March 16, 2013.
No interference with such a patent or application has been declared to date. Therefore, it seems extremely unlikely that we
may have to participate in interference proceedings declared by the USPTO to determine priority of invention in the United
States against one or more parties claiming the same or similar invention. However, in the unlikely event that such
interference was to be declared, the costs of these proceedings could be substantial and it is possible that our efforts would
be unsuccessful, resulting in a material adverse effect on our U.S. patent position. The results of these types of proceedings
could reduce the scope of, or invalidate, our patent rights, allow third parties to commercialize our technology or products
and compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products
without infringing third-party patent rights. In addition, if the breadth or strength of protection provided by our patents and
patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or
commercialize current or future product candidates. Such results could have a material adverse effect on our results of
operations.
In addition, the patentability of claims in pending patent applications covering a CR845/difelikefalin-based product
can be challenged by third parties during prosecution in the USPTO under the new AIA law of 2013, for example by third
party observations and derivation proceedings, and the validity of claims in issued patents can be challenged by third
parties in various post-grant proceedings such as Post-Grant Review, Inter-partes Reexamination, and Inter-partes Review
proceedings.
Furthermore, we may not have identified all United States and foreign patents or published applications that affect
our business either by blocking our ability to commercialize our drugs or by covering similar technologies that affect our
drug market. In addition, some countries, including many in Europe, do not grant patent claims directed to methods of
treating humans, and in these countries patent protection may not be available at all to protect our product candidates. Even
if patents issue, we cannot guarantee that the claims of those patents will be valid and enforceable or provide us with any
significant protection against competitive products, or otherwise be commercially valuable to us.
We also rely on trade secrets to protect our technology, particularly where we do not believe patent protection is
appropriate or obtainable. However, trade secrets are difficult to protect. While we use reasonable efforts to protect our
trade secrets, our licensors, employees, consultants, contractors, outside scientific collaborators and other advisors may
unintentionally or willfully disclose our information to competitors. Enforcing a claim that a third party illegally obtained
and is using our trade secrets is expensive and time consuming, and the outcome is unpredictable. In addition, courts
outside the United States are sometimes less willing to protect trade secrets. Moreover, our competitors may independently
develop equivalent knowledge, methods and know-how.
If we fail to obtain or maintain patent protection or trade secret protection for CR845/difelikefalin or any other
product candidate that we may develop, license or acquire, third parties could use our proprietary information, which could
impair our ability to compete in the market and adversely affect our ability to generate revenues and achieve profitability.
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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.
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 United States and abroad. Such challenges may
result in loss of 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. Given the amount of time
required for the development, testing and regulatory review of new product candidates, patents protecting such product
candidates might expire before or shortly after such product candidates are commercialized. As a result, our owned and
licensed patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar
or identical to ours.
If we or any current or future collaboration partner are sued for infringing intellectual property rights of third
parties, it will be costly and time consuming, and an unfavorable outcome in any litigation would harm our business.
Our ability to develop, manufacture, market and sell KORSUVA (CR845/difelikefalin) injection or any of our other
current of future product candidates depends upon our ability to avoid infringing the proprietary rights of third parties, and
our commercial success depends upon our ability, and the ability of our collaborators, to develop, manufacture, market and
sell our product candidates and use our proprietary technologies without infringing the proprietary rights of third parties.
There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. Numerous U.S.
and foreign issued patents and pending patent applications, which are owned by third parties, exist in the general field of
pain management and cover the use of numerous compounds and formulations in our targeted markets. Third parties may
assert infringement claims against us based on existing patents or patents that may be granted in the future. Because of the
uncertainty inherent in any patent or other litigation involving proprietary rights, we and our licensors may not be
successful in defending intellectual property claims by third parties, which could have a material adverse effect on our
results of operations. Regardless of the outcome of any litigation, defending the litigation may be expensive, time-
consuming and distracting to management. In addition, because patent applications can take many years to issue, there may
be currently pending applications, unknown to us, which may later result in issued patents that KORSUVA
(CR845/difelikefalin) injection or our other current or future product candidates may infringe. There could also be existing
patents of which we are not aware that KORSUVA (CR845/difelikefalin) injection or our other current or future product
candidates may inadvertently infringe.
There is a substantial amount of litigation involving patent and other intellectual property rights in the biotechnology
and biopharmaceutical industries generally. If a third-party claims that we infringe on their products or technology, we
could face a number of issues, including:
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infringement and other intellectual property claims which, with or without merit, can be expensive and time
consuming to litigate and can divert management’s attention from our core business;
substantial damages for past infringement which we may have to pay if a court decides that our product
infringes on a competitor’s patent;
a court prohibiting us from selling or licensing our product unless the patent holder licenses the patent to us,
which it would not be required to do;
if a license is available from a patent holder, we may have to pay substantial royalties or grant cross licenses to
our patents; and
redesigning our processes so they do not infringe, which may not be possible or could require substantial funds
and time.
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If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from
such third party to continue developing and marketing our products and technology. However, we may not be able to obtain
any required license on commercially reasonable terms or at all. Even if we were able to obtain a license, it could be non-
exclusive, thereby giving our competitors access to the same technologies licensed to us. We could be forced, including by
court order, to cease commercializing the infringing technology or product. In addition, we could be found liable for
monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent. A
finding of infringement could prevent us from commercializing our product candidates or force us to cease some of our
business operations, which could materially harm our business. Claims that we have misappropriated the confidential
information or trade secrets of third parties could have a similar negative impact on our business.
We may be involved in lawsuits to protect or enforce our patents or the patents of our licensors, which could be
expensive, time consuming and may ultimately be unsuccessful.
Competitors may infringe our issued patents or other intellectual property. To counter infringement or unauthorized
use, we may be required to file infringement claims, which can be expensive and time consuming. Any claims we assert
against perceived infringers could provoke these parties to assert counterclaims against us alleging that we infringe their
patents. In addition, in a patent infringement proceeding, a court may decide that a patent of ours is invalid or
unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to stop the other party from using the
technology at issue on the grounds that our patents do not cover the technology in question. An adverse result in any
litigation proceeding could put one or more of our patents at risk of being invalidated or interpreted narrowly. Furthermore,
because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk
that some of our confidential information could be compromised by disclosure during this type of litigation.
Most of our competitors are larger than we are and have substantially greater resources. They are, therefore, likely to
be able to sustain the costs of complex patent litigation longer than we could. In addition, the uncertainties associated with
litigation could have a material adverse effect on our ability to raise the funds necessary to continue our clinical trials,
continue our internal research programs, in-license needed technology, or enter into development partnerships that would
help us bring our product candidates to market.
We may need to license certain intellectual property from third parties, and such licenses may not be available or
may not be available on commercially reasonable terms.
A third party may hold intellectual property, including patent rights that are important or necessary to the
development or commercialization of our products. It may be necessary for us to use the patented or proprietary technology
of third parties to commercialize our products, in which case we would be required to obtain a license from these third
parties. Such a license may not be available on commercially reasonable terms or at all, which could materially harm our
business.
We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their
former employers.
As is common in the biotechnology and pharmaceutical industry, we employ individuals who were previously
employed at other biotechnology or pharmaceutical companies, including our competitors or potential competitors.
Although no claims against us are currently pending, we may be subject to claims that these employees or we have
inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers.
Litigation may be necessary to defend against these claims. Even if we are successful in defending against these claims,
litigation could result in substantial costs and be a distraction to management.
We may not be able to protect our intellectual property rights throughout the world.
Filing, prosecuting and defending patents on product candidates in all countries throughout the world would be
prohibitively expensive, and our intellectual property rights in some countries outside the United States can be less
extensive than those in the United States. In addition, the laws of some foreign countries do not protect intellectual
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property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to
prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing
products made using our inventions in and into the United States or other jurisdictions. Competitors may use our
technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may
export otherwise infringing products to territories where we have patent protection, but enforcement rights are not as strong
as those in the United States. These products may compete with our product candidates and our patents or other intellectual
property rights may not be effective or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in
foreign jurisdictions. The legal systems of certain countries do not favor the enforcement of patents and other intellectual
property protection, which could make it difficult for us to stop the infringement of our patents generally. Proceedings to
enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from
other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent
applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any
lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful.
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a
significant commercial advantage from the intellectual property that we develop or license.
The validity and enforceability of the patents and applications that cover our CR845/difelikefalin product
candidates can be challenged by competitors.
If KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA (CR845/difelikefalin) or any future product
candidate is approved by the FDA, one or more third parties may challenge the patents covering these product candidates,
which could result in the invalidation of, or render unenforceable, some or all of the relevant patent claims. For example, if
a third party files an Abbreviated New Drug Application, or ANDA, for a generic drug product containing
CR845/difelikefalin, and relies in whole or in part on studies conducted by or for us, the third party will be required to
certify to the FDA that either: (1) there is no patent information listed in the FDA’s Orange Book with respect to our NDA
for KORSUVA (CR845/difelikefalin) injection; (2) the patents listed in the Orange Book have expired; (3) the listed
patents have not expired, but will expire on a particular date and approval is sought after patent expiration; or (4) the listed
patents are invalid or will not be infringed by the manufacture, use or sale of the third-party’s generic drug product. A
certification that the new product will not infringe the Orange Book-listed patents for CR845/difelikefalin, or that such
patents are invalid, is called a paragraph IV certification. If the third party submits a paragraph IV certification to the FDA,
a notice of the paragraph IV certification must also be sent to us once the third-party’s ANDA is accepted for filing by the
FDA. We may then initiate a lawsuit to defend the patents identified in the notice. The filing of a patent infringement
lawsuit within 45 days of receipt of the notice automatically prevents the FDA from approving the third-party’s ANDA
until the earliest of 30 months or the date on which the patent expires, the lawsuit is settled, or the court reaches a decision
in the infringement lawsuit in favor of the third party. If we do not file a patent infringement lawsuit within the required 45-
day period, the third-party’s ANDA will not be subject to the 30-month stay. Litigation or other proceedings to enforce or
defend intellectual property rights are often very complex in nature, may be very expensive and time-consuming, may
divert our management’s attention from our core business, and may result in unfavorable results that could adversely
impact our ability to prevent third parties from competing with our products.
Risks Related to Employee Matters and Managing Growth
Our internal information technology systems, or those of our CROs, contract manufacturers or other contractors
or consultants, may fail or suffer security breaches, loss or leakage of data and other disruptions, which could result in
a material disruption of our development programs, compromise sensitive information related to our business or prevent
us from accessing critical information, potentially exposing us to liability, which could adversely affect our business.
We are increasingly dependent upon information technology systems, infrastructure and data to operate our business.
In the ordinary course of business, we collect, store and transmit confidential information (including but not limited to
intellectual property, proprietary business information and personal information). It is critical that we do so in
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a secure manner to maintain the confidentiality and integrity of such confidential information. We also have outsourced
elements of our operations to third parties, and as a result we manage a number of third-party contractors who have access
to our confidential information.
Despite the implementation of security measures, given their size and complexity and the increasing amounts of
confidential information that they maintain, our internal information technology systems and those of our third-party
CROs, contract manufacturers and other contractors and consultants are potentially vulnerable to breakdown or other
damage or interruption from service interruptions, system malfunction, natural disasters, terrorism, war and
telecommunication and electrical failures, as well as security breaches from inadvertent or intentional actions by our
employees, contractors, consultants, business partners and/or other third parties, or from cyber-attacks by malicious third
parties (including the deployment of harmful malware, ransomware, denial-of-service attacks, social engineering and other
means to affect service reliability and threaten the confidentiality, integrity and availability of information), which may
compromise our system infrastructure or lead to data leakage. To the extent that any disruption or security breach were to
result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary
information, we could incur liability and reputational damage and the further development and commercialization of our
product candidates could be delayed.
While we have not experienced any such system failure, accident or security breach to date, we cannot assure you
that our data protection efforts and our investment in information technology will prevent significant breakdowns, data
leakages, breaches in our systems or other cyber incidents that could adversely affect our business. For example, if such an
event were to occur and cause interruptions in our operations, it could result in a material disruption of our programs and
the development and commercialization of CR845/difelikefalin injection, if approved, could be delayed. In addition, the
loss of clinical trial data could result in delays in our marketing approval efforts and significantly increase our costs to
recover or reproduce the data. Furthermore, significant disruptions of our internal information technology systems or
security breaches could result in the loss, misappropriation and/or unauthorized access, use, or disclosure of, or the
prevention of access to, confidential information (including trade secrets or other intellectual property, proprietary business
information and personal information), which could result in financial, legal, business and reputational harm to us. For
example, any such event that leads to unauthorized access, use, or disclosure of personal information, including personal
information regarding our clinical trial subjects or employees, could harm our reputation directly, compel us to comply
with federal and/or state breach notification laws and foreign law equivalents, subject us to mandatory corrective action,
and otherwise subject us to liability under laws and regulations that protect the privacy and security of personal
information, which could result in significant legal and financial exposure and reputational damages that could adversely
affect our business.
We will need to significantly increase the size of our organization, and we may experience difficulties in managing
growth.
As of February 22, 2021, we had 80 employees. Our management and personnel systems and facilities currently in
place may not be adequate to support future growth. In addition, we may not be able to recruit and retain qualified
personnel in the future, particularly for sales and marketing positions, due to competition for personnel among
pharmaceutical businesses, and the failure to do so could have a significant negative impact on our future product revenues
and business results. Our need to effectively manage our operations, growth and various projects requires that we:
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continue the hiring and training of an effective organization in anticipation of the potential approval of
KORSUVA (CR845/difelikefalin) injection, and establish appropriate systems, policies and infrastructure to
support that organization;
ensure that our consultants and other service providers successfully carry out their contractual obligations,
provide high quality results, and meet expected deadlines;
continue to carry out our own contractual obligations to our licensors and other third parties; and
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continue to improve our operational, financial and management controls, reporting systems and procedures.
We may be unable to successfully implement these tasks on a larger scale and, accordingly, may not achieve our
development and commercialization goals.
We may not be able to manage our business effectively if we are unable to attract and retain key personnel.
We may not be able to attract or retain qualified management and commercial, scientific and clinical personnel due to
the intense competition for qualified personnel among biotechnology, pharmaceutical and other businesses. If we are not
able to attract and retain necessary personnel to accomplish our business objectives, we may experience constraints that
will significantly impede the achievement of our development objectives, our ability to raise additional capital and our
ability to implement our business strategy.
Our industry has experienced a high rate of turnover of management personnel in recent years. We are highly
dependent on the skills and leadership of our management team, including Derek Chalmers, our President and Chief
Executive Officer. Our senior management may terminate their employment with us at any time. If we lose one or more
members of our senior management team, our ability to successfully implement our business strategy could be seriously
harmed. Replacing these employees may be difficult and may take an extended period of time because of the limited
number of individuals in our industry with the breadth of skills and experience required to develop, gain regulatory
approval of and commercialize products successfully. Competition to hire from this limited pool is intense, and we may be
unable to hire, train, retain or motivate additional key personnel. We do not maintain “key person” insurance for any of our
executives or other employees.
If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements
on a timely basis could be impaired.
We are subject to the reporting requirements of the Securities Exchange Act of 1934, as amended, the Sarbanes-
Oxley Act of 2002 and the rules and regulations of The Nasdaq Global Market. Pursuant to Section 404 of the Sarbanes-
Oxley Act of 2002, or Section 404, we are now required to perform system and process evaluation and testing of our
internal control over financial reporting to allow our management to report on the effectiveness of our internal control over
financial reporting and we are also required to have our independent registered public accounting firm issue an opinion on
the effectiveness of our internal control over financial reporting on an annual basis.
During the evaluation and testing process, if we identify one or more material weaknesses in our internal control over
financial reporting, we will be unable to assert that our internal control over financial reporting is effective. Further, we
may in the future discover weaknesses in our system of internal financial and accounting controls and procedures that
could result in a material misstatement of our financial statements. Moreover, our internal controls over financial reporting
will not prevent or detect all errors and all fraud. A control system, no matter how well designed and operated, can provide
only reasonable, not absolute, assurance that the control system’s objectives will be met. Because of the inherent
limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error
or fraud will not occur or that all control issues and instances of fraud will be detected. Moreover, we are aware that the
remote working arrangements implemented in connection with the COVID-19 pandemic potentially present new areas of
risk, and we are carefully monitoring any impact to our internal controls and procedures.
If we are unable to assert that our internal control over financial reporting is effective, or if our independent
registered public accounting firm is unable to express an opinion on the effectiveness of our internal control over financial
reporting, investors could lose confidence in the reliability of our financial statements, the market price of our stock could
decline and we could be subject to sanctions or investigations by The Nasdaq Global Market, the SEC or other regulatory
authorities.
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Risks Related to Ownership of Our Common Stock
The market price of our common stock has been, and is likely to continue to be, highly volatile, and you may not
be able to resell your shares at or above the price you paid for them.
Since our initial public offering in January 2014, our stock price has been volatile and it is likely that the trading
price of our common stock will continue to be volatile. As a result of this volatility, investors may not be able to sell their
common stock at or above the price paid for the shares. The market price for our common stock may be influenced by
many factors, including:
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delays in the commencement, enrollment and ultimate completion of our clinical trials, including our planned
trials for KORSUVA (CR845/difelikefalin) injection and Oral KORSUVA;
any delay or refusal on the part of the FDA in approving an NDA for KORSUVA (CR845/difelikefalin)
injection or our other current or future product candidates;
the commercial success of KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA (CR845/difelikefalin)
or any future product candidates, if approved by the FDA;
results of clinical trials of Oral KORSUVA (CR845/difelikefalin) or any future product candidate or those of
our competitors;
actual or anticipated variations in quarterly or annual operating results;
failure to meet or exceed financial projections we provide to the public;
failure to meet or exceed the estimates and projections of the investment community, including securities
analysts;
introduction of competitive products or technologies;
changes or developments in laws or regulations applicable to our product candidates;
the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment
community;
general trends in our industry or economic and market conditions and overall fluctuations in U.S. equity
markets, including as a result of the ongoing COVID-19 pandemic;
developments concerning our sources of manufacturing supply, warehousing and inventory control;
disputes or other developments relating to patents or other proprietary rights;
additions or departures of key scientific or management personnel;
announcements of investigations or regulatory scrutiny of our operations or lawsuits filed against us;
capital commitments;
investors’ general perception of our company and our business;
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announcements and expectations of additional financing efforts, including the issuance of debt, equity or
convertible securities;
sales of our common stock, including sales by our directors and officers or significant stockholders;
changes in the market valuations of companies similar to us;
announcements by us or our competitors of significant acquisitions, strategic partnerships, or divestitures;
changes in the structure of healthcare payment systems; and
the other factors described in this “Risk Factors” section.
In addition, the stock market in general, and the market for small pharmaceutical and biotechnology companies in
particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to
the operating performance of these companies. Broad market and industry factors, such as those related to the ongoing
COVID-19 pandemic, may negatively affect the market price of our common stock, regardless of our actual operating
performance.
Further, in the past, stockholders have initiated class action lawsuits against pharmaceutical and biotechnology
companies following periods of volatility in the market prices of these companies’ stock. Such litigation, if instituted
against us, could cause us to incur substantial costs and divert management’s attention and resources from our business.
If equity research analysts cease to publish research or reports about us or if they publish unfavorable research or
reports about us, our business or our market, our stock price and trading volume could decline.
The trading market for our common stock is likely to be influenced by the research and reports that equity research
analysts publish about us and our business. As a relatively newly public company, to date we have only limited equity
research analyst coverage. Additionally, we do not have any control over the analysts or the content and opinions included
in their reports. The price of our stock could decline if one or more equity research analysts downgrade our stock or issue
other unfavorable commentary or research. If one or more equity research analysts ceases coverage of our company or fails
to publish reports on us regularly, demand for our stock could decrease, which in turn could cause our stock price or trading
volume to decline.
Our quarterly operating results may fluctuate significantly.
We expect our operating results to be subject to quarterly fluctuations. Our operating results will be affected by
numerous factors, including:
●
●
●
the successful progress of our clinical trials for KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA
(CR845/difelikefalin) and other potential future product candidates;
whether the FDA requires us to complete additional, unanticipated studies, tests or other activities prior to
approving KORSUVA (CR845/difelikefalin) injection or our other current or future product candidates, which
would likely further delay any such approval;
if KORSUVA (CR845/difelikefalin) injection or any of our other current or future product candidates is
approved, our or our partners’ or our collaborators’ ability to establish the necessary commercial infrastructure
to launch this product candidate without substantial delays, including hiring sales and marketing personnel and
contracting with third parties for warehousing, distribution, cash collection and related commercial activities;
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●
●
●
●
●
●
our ability to identify, enter into and maintain third party manufacturing arrangements capable of
manufacturing KORSUVA (CR845/difelikefalin) injection or our other current or future product candidates in
commercial quantities;
our execution of other collaborative, licensing or similar arrangements and the timing of payments we may
make or receive under these arrangements;
variations in the level of expenses related to our future development programs;
any product liability or intellectual property infringement lawsuit in which we may become involved;
regulatory developments affecting KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA
(CR845/difelikefalin), any of our future product candidates, or the product candidates of our competitors; and
if KORSUVA (CR845/difelikefalin) injection, Oral KORSUVA (CR845/difelikefalin) or any of our future
product candidates receives regulatory approval, the level of underlying demand for such product candidate
and wholesaler buying patterns.
If our quarterly or annual operating results fall below the expectations of investors or securities analysts, the price of
our common stock could decline substantially. Furthermore, any quarterly or annual fluctuations in our operating results
may, in turn, cause the price of our stock to fluctuate substantially. We believe that quarterly comparisons of our financial
results are not necessarily meaningful and should not be relied upon as an indication of our future performance.
Raising additional funds by issuing securities may cause dilution to existing stockholders and raising funds
through lending and licensing arrangements may restrict our operations or require us to relinquish proprietary rights.
Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs
through a combination of equity offerings, debt financings, grants and license and development agreements in connection
with any collaborations. We do not have any committed external source of funds. To the extent that we raise additional
capital by issuing equity securities, our existing stockholders’ ownership will be diluted, and the terms of these securities
may include liquidation or other preferences that adversely affect your rights as a common stockholder. Debt financing and
preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to
take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.
If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing
arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams,
research programs or product candidates or grant licenses on terms that may not be favorable to us. Any debt financing that
we enter into may involve covenants that restrict our operations. These restrictive covenants may include limitations on
additional borrowing and specific restrictions on the use of our assets as well as prohibitions on our ability to create liens,
pay dividends, redeem our stock or make investments. If we are unable to raise additional funds through equity or debt
financings when needed, we may be required to delay, limit, reduce or terminate our product development or future
commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to
develop and market ourselves.
The use of our net operating loss carryforwards and research tax credits may be limited.
A portion of our net operating loss, or NOL, carryforwards and R&D tax credits may expire and not be used. As of
December 31, 2020, we had federal and state NOL carryforwards of approximately $368.2 million and $273.0 million,
respectively, and we also had federal and state R&D tax credit carryforwards of approximately $18.4 million and $1.8
million, respectively. Our NOL carryforwards will begin expiring in 2026 for federal purposes (to the extent such federal
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NOLs are generated in taxable years beginning on or before December 31, 2017) and 2027 for state purposes if we have
not used them prior to that time, and our federal R&D tax credits will begin expiring in 2025 unless previously used. Under
the TCJA, as modified by the Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act, NOLs generated in
taxable years beginning after December 31, 2017 can be carried forward indefinitely subject, in the case of tax years
beginning after 2020, to a limitation of 80% of taxable income, but, except for NOLs arising in taxable years beginning
after 2017 and before 2021, for which a 5-year carryback period applies, may not be carried back. It is uncertain if and to
what extent various states will conform to the TCJA, as modified by the CARES Act. To the extent that we have not
exchanged our Connecticut R&D tax credits for a tax refund, those tax credits carry forward indefinitely. Additionally, our
ability to use any NOL and R&D tax credit carryforwards to offset taxable income or tax, respectively, in the future will be
limited under Internal Revenue Code Sections 382 and 383, respectively, if we have a cumulative change in ownership of
our stock of more than 50% within a three-year period. The completion of our initial public offering in 2014 and our
follow-on public offerings in 2015, 2017, 2018 and 2019, together with private placements and other transactions that have
occurred, may have triggered such ownership changes. In addition, since we will need to raise substantial additional
funding to finance our operations, we may undergo ownership changes in the future. We are currently in the process of
conducting a 382 analysis and expect this analysis to be completed in the first half of 2021. If the analysis shows a change
of ownership has occurred, we will be limited regarding the amount of NOL carryforwards and R&D tax credits that could
be utilized annually in the future to offset taxable income or tax, respectively. Any such annual limitation may significantly
reduce the utilization of the NOL carryforwards and R&D tax credits before they expire. In addition, certain states have in
the past suspended use of NOL carryforwards for certain taxable years (including without limitation legislation enacted by
California in June 2020 that suspends the use of California NOLs and limits the use of California R&D tax credits for
certain years), and other states are considering similar measures. As a result, we may incur higher state income tax expense
in the future. Depending on our future tax position, limitations on our ability to use NOL carryforwards in states in which
we are subject to income tax could have an adverse impact on our results of operations and financial condition.
New or future changes to tax laws could materially adversely affect our company.
On December 22, 2017, President Trump signed into law the TCJA, which significantly amends the Internal Revenue
Code of 1986, which was modified by the CARES Act. The TCJA, as modified by the CARES Act, among other things,
reduces the corporate tax rate from a top marginal rate of 35% to a flat rate of 21%, limits the tax deduction for interest
expense to 30% of taxable income, eliminates certain NOL carrybacks, imposes a one-time tax on offshore earnings at
reduced rates regardless of whether they are repatriated, allows immediate deductions for certain new investments instead
of deductions for depreciation expense over time, and modifies or repeals many business deductions and credits. We
continue to examine the impact these changes may have on our business. Notwithstanding the reduction in the corporate
income tax rate, the overall impact of the TCJA and CARES Act is uncertain and our business and financial condition
could be adversely affected. The impact of the TCJA and CARES Act on holders of our common stock is also uncertain
and could be adverse.
Because we do not intend to pay dividends on our common stock, your returns will be limited to any increase in
the value of our stock.
We have never declared or paid any cash dividends on our capital stock. We currently intend to retain all available
funds and any future earnings to support our operations and finance the growth and development of our business and do not
anticipate declaring or paying any cash dividends on our common stock for the foreseeable future. Any return to
stockholders will therefore be limited to the appreciation of their stock, if any. Investors seeking cash dividends should not
purchase our common stock.
Provisions in our corporate charter documents and under Delaware law may prevent or frustrate attempts by our
stockholders to change our management and hinder efforts to acquire a controlling interest in us, and the market price
of our common stock may be lower as a result.
There are provisions in our certificate of incorporation and bylaws, as amended, that may make it difficult for a third
party to acquire, or attempt to acquire, control of our company, even if a change in control was considered favorable by you
and other stockholders. For example, our Board of Directors has the authority to issue up to 5,000,000
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shares of preferred stock and to fix the price, rights, preferences, privileges, and restrictions of the preferred stock without
any further vote or action by our stockholders. The issuance of shares of preferred stock may delay or prevent a change in
control transaction. As a result, the market price of our common stock and the voting and other rights of our stockholders
may be adversely affected. An issuance of shares of preferred stock may result in the loss of voting control to other
stockholders.
Our charter documents also contain other provisions that could have an anti-takeover effect, including:
●
●
●
●
●
our Board of Directors are divided into three classes, with only one class of directors elected each year;
our stockholders are entitled to remove directors only for cause upon a 66 2/3% vote;
our stockholders are not permitted to take actions by written consent;
our stockholders are not permitted to call a special meeting of stockholders; and
our stockholders must give us advance notice of their intent to nominate directors or submit proposals for
consideration at stockholder meetings.
In addition, we are subject to the anti-takeover provisions of Section 203 of the Delaware General Corporation Law,
which regulates corporate acquisitions by prohibiting Delaware corporations from engaging in specified business
combinations with particular stockholders of those companies. These provisions could discourage potential acquisition
proposals and could delay or prevent a change in control transaction. They could also have the effect of discouraging others
from making tender offers for our common stock, including transactions that may be in your best interests. These
provisions may also prevent changes in our management or limit the price that investors are willing to pay for our stock.
Item 1B. Unresolved Staff Comments.
None.
Item 2. Properties.
Our principal offices occupy approximately 36,000 square feet of office space in Stamford, Connecticut under leases
that expire in December 2023. We believe that the office space in Stamford is suitable and adequate to meet our current
needs and to allow for expansion as we increase our headcount. See Note 17 of Notes to Financial Statements,
Commitments and Contingencies, in this Annual Report on Form 10-K.
Item 3. Legal Proceedings.
From time to time, we may become subject to arbitration, litigation or claims arising in the ordinary course of
business. We are not currently a party to any arbitration or legal proceeding that, if determined adversely to us, would have
a material adverse effect on our business, operating results or financial condition. The results of any future claims or
proceedings cannot be predicted with certainty, and regardless of the outcome, litigation can have an adverse impact on us
because of defense and litigation costs, diversion of management resources, and other factors.
Item 4. Mine Safety Disclosures.
Not applicable.
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PART II
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity
Securities.
Market Information for Common Stock
Our common stock is traded on The Nasdaq Global Market under the ticker symbol “CARA”.
Stockholders
As of February 22, 2021, there were 29 holders of record of our common stock. This number does not reflect the
beneficial holders of our common stock who hold shares in street name through brokerage accounts or other nominees.
Dividend Policy
We have never declared or paid any cash dividends on our capital stock. We currently intend to retain all available
funds and any future earnings to support our operations and finance the growth and development of our business. We do
not intend to pay cash dividends on our common stock for the foreseeable future. Any future determination related to
dividend policy will be made at the discretion of our Board of Directors and will depend on, among other factors, our
results of operations, financial condition, capital requirements, contractual restrictions, business prospects and other factors
our Board of Directors may deem relevant.
Stock Performance
The following graph compares cumulative total return of our common stock with the cumulative total return of (i) the
Nasdaq Composite Index, and (ii) the Nasdaq Biotechnology Index. The graph assumes (a) $100 was invested on
December 31, 2015 in each of our common stock, the stocks comprising the Nasdaq Composite Index and the stocks
comprising the Nasdaq Biotechnology Index, and (b) the reinvestment of dividends. The comparisons shown in the
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graph are based on historical data and the stock price performance shown in the graph is not necessarily indicative of, or
intended to forecast, future performance of our stock.
Cumulative Total Return
Cara Therapeutics, Inc.
Nasdaq Biotechnology
Nasdaq Composite
12/31/2015 12/31/2016 12/31/2017 12/31/2018 12/31/2019 12/31/2020
89.74
134.42
257.38
55.10
78.32
107.50
77.11
85.97
132.51
100.00
100.00
100.00
72.60
94.81
137.86
95.55
106.95
179.19
This performance graph shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of
1934, as amended, or the Exchange Act, or incorporated by reference into any filing of ours under the Securities Act,
except as shall be expressly set forth by specific reference to such filing.
Recent Sales of Unregistered Securities
Not applicable.
Purchases of Equity Securities by the Issuer and Affiliated Purchasers
Not applicable.
Use of Proceeds
Not applicable.
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Item 6. Selected Financial Data.
The following selected financial data for the years ended December 31, 2020, 2019 and 2018 and as of December 31,
2020 and 2019 are derived from our audited financial statements included elsewhere in this Annual Report on Form 10-K.
The following selected financial data for the years ended December 31, 2017 and 2016 and as of December 31, 2018, 2017
and 2016 have been derived from our audited financial statements not included in this report. Our historical results for any
prior periods are not necessarily indicative of results to be expected for any future period. The information set forth in the
following table should be read in conjunction with Part II Item 7. Management’s Discussion and Analysis of Financial
Condition and Results of Operations and our financial statements and related notes thereto included elsewhere in this
Annual Report on Form 10-K.
Statement of Operations Data:
Revenue:
License and milestone fees
Collaborative revenue
Clinical compound revenue
Total revenue (1)
Operating expenses:
Research and development
General and administrative
Total operating expenses
Operating income (loss)
Other income, net
Income (loss) before benefit from income
taxes
Benefit from income taxes
Net income (loss)
Net income (loss) per share:
Basic
Diluted
Weighted average shares:
Basic
Diluted
2020
Year Ended December 31,
2018
(in thousands, except share and per share data)
2019
2017
134,439
$
—
643
135,082
19,746
$
—
140
19,886
13,436
$
—
33
13,469
$
530
313
68
911
107,851
21,846
129,697
5,385
2,334
7,719
691
8,410
113,820
17,745
131,565
(111,679)
4,490
(107,189)
816
$ (106,373) $
75,531
15,320
90,851
(77,382)
2,980
48,524
11,872
60,396
(59,485)
1,156
(74,402)
389
(74,013) $
(58,329)
204
(58,125) $
2016
—
—
86
86
49,253
9,233
58,486
(58,400)
652
(57,748)
468
(57,280)
0.18
0.18
$
$
(2.49) $
(2.49) $
(2.06) $
(2.06) $
(1.86) $
(1.86) $
(2.10)
(2.10)
$
$
$
$
47,413,250
47,915,030
42,669,333
42,669,333
35,892,786
35,892,786
31,202,842
31,202,842
27,279,008
27,279,008
2020
2019
As of December 31,
2018
(in thousands)
2017
2016
Balance Sheet Data:
Cash and cash equivalents and marketable securities (2)
Total assets (3)
Deferred revenue (4)
Total liabilities (3)
Total stockholders’ equity
$ 251,490
271,157
22,156
249,001
—
$ 218,165
232,959
22,262
46,246
186,713
$ 182,779
190,823
42,009
57,193
133,630
$ 92,569
97,004
—
10,224
86,780
$ 58,276
63,828
—
13,103
50,725
(1) The changes in revenue for the years ended December 31, 2017 to December 31, 2018, December 31, 2018 to
December 31, 2019 and December 31, 2019 to December 31, 2020 primarily reflect an upfront payment from
VFMCRP related to the license agreement entered into in May 2018 and earned by us as work was performed in 2018,
2019 and 2020. The change in revenue for the year ended December 31, 2019 to December 31, 2020 also reflects an
upfront payment of $150.0 million from Vifor, of which $111.6 million was recorded as revenue, in connection with a
license agreement we entered into in October 2020 (refer to “Item 7. Management’s Discussion and Analysis of
Financial Condition and Results of Operations — Collaboration and License Agreements”, Note 11
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of Notes to Financial Statements, Collaboration and License Agreements, and Note 12 of Notes to Financial
Statements, Revenue Recognition in this Annual Report on Form 10-K).
(2) The increases in cash and cash equivalents and marketable securities from December 31, 2019 to December 31, 2020,
December 31, 2018 to December 31, 2019, December 31, 2017 to December 31, 2018, and from December 31, 2016
to December 31, 2017 reflects the upfront payment from Vifor in connection with a license agreement we entered into
in October 2020, the proceeds from our follow-on offering of our common stock in July 2019 and 2018, respectively,
the upfront payment from VFMCRP related to the license agreement entered into in May 2018, and the proceeds from
our follow-on offering of our common stock in April 2017, respectively, partially offset by cash used in operating
activities for each respective period (refer to Note 9 of Notes to Financial Statements, Stockholders’ Equity, in this
Annual Report on Form 10-K).
(3) On January 1, 2019, we adopted ASC 842, Leases. As a result, we recorded an operating lease right-of-use asset
within total assets and an operating lease liability (current and non-current) within total liabilities as of December 31,
2019 relating to our original lease for office space. In October 2020, we recorded an additional operating lease right-
of-use asset within total assets and an additional operating lease liability (current and non-current) within total
liabilities as of December 31, 2020 for additional office space (refer to Note 2 of Notes to Financial Statements,
Summary of Significant Accounting Policies – Accounting Pronouncements Recently Adopted, and Note 17 of Notes to
Financial Statements, Commitments and Contingencies – Leases, in this Annual Report on Form 10-K.
(4) The changes in deferred revenue from December 31, 2019 to December 31, 2020, December 31, 2018 to December
31, 2019 and December 31, 2017 to December 31, 2018 were due to the upfront payment from VFMCRP related to
the license agreement entered into in May 2018 and earned by us as work was performed in 2018, 2019 and 2020
(refer to Note 12 of Notes to Financial Statements, Revenue Recognition, in this Annual Report on Form 10-K).
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 financial statements and the related notes appearing at the end of this Annual Report on Form 10-K. Some of the
information contained in this discussion and analysis or set forth elsewhere in this Annual Report on Form 10-K, including
information with respect to our plans and strategy for our business and related financing, includes forward-looking
statements that involve risks and uncertainties. You should read “Cautionary Note Regarding Forward-Looking
Statements” and Item 1A. Risk Factors of this Annual Report on Form 10-K for a discussion of important factors that
could cause actual results to differ materially from the results described in or implied by the forward-looking statements
contained in the following discussion and analysis.
Overview
Introduction
We are a clinical-stage biopharmaceutical company focused on developing and commercializing new chemical
entities designed to alleviate pruritus by selectively targeting peripheral kappa opioid receptors, or KORs. We are
developing a novel and proprietary class of product candidates, led by KORSUVA (CR845/difelikefalin), a first-in-class
KOR agonist that targets KORs located in the peripheral nervous system and on immune cells.
In our KALM-1 and KALM-2 Phase 3 trials and two Phase 2 trials, KORSUVA (CR845/difelikefalin) injection
(intravenous formulation) has demonstrated statistically significant reductions in itch intensity and concomitant
improvement in pruritus-related quality of life measures in hemodialysis patients with moderate-to-severe CKD-aP. We
have partnered with VFMCRP, a joint venture between Vifor Pharma Group and Fresenius Medical Care, and Vifor to
commercialize KORSUVA (CR845/difelikefalin) injection in dialysis patients with CKD-aP in the U.S. under profit share
agreements. We have partnered with VFMCRP to commercialize KORSUVA worldwide, excluding Japan (Maruishi/sub-
licensee Kissei), and South Korea (CKDP).
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CR845/difelikefalin has also demonstrated statistically significant pain reduction in clinical trials in patients with
moderate-to-severe acute pain in the post-operative setting, without inducing many of the undesirable side effects typically
associated with currently available opioid pain therapeutics. We retain rights to all KORSUVA/CR845 formulations and
indications worldwide, excluding KORSUVA (CR845/difelikefalin) injection in dialysis patients with CKD-aP under our
agreements with VFMCRP and Vifor for U.S. and certain ex-U.S. territories in Japan (Maruishi/sub-licensee Kissei) and
South Korea (CKDP).
The FDA has conditionally accepted KORSUVA as the trade name for CR845/difelikefalin injection. In December
2020, we submitted a NDA to the FDA for KORSUVA (CR845/difelikefalin) injection for the treatment of moderate-to-
severe pruritus in hemodialysis patients, and in February 2021, the NDA was accepted by the FDA. KORSUVA’s safety
and efficacy have not been fully evaluated by any regulatory authority.
We were incorporated and commenced operations in 2004, and our primary activities to date have been organizing
and staffing our company, developing our product candidates, including conducting preclinical studies and clinical trials of
CR845/difelikefalin-based product candidates and raising capital. To date, we have financed our operations primarily
through sales of our equity and debt securities and payments from license agreements. We have no products currently
available for sale, and substantially all of our revenue to date has been revenue from license agreements, although we have
received nominal amounts of revenue under research grants and the sale of clinical compound.
Collaboration and License Agreements
Vifor (International) Ltd.
On October 15, 2020, we entered into the Vifor Agreement with Vifor under which we granted Vifor an exclusive
license solely in the United States to use, distribute, offer for sale, promote, sell and otherwise commercialize KORSUVA
(CR845/difelikefalin) injection for all therapeutic uses relating to the inhibition, prevention or treatment of itch associated
with pruritus in hemodialysis and peritoneal dialysis patients in the United States. Under the Vifor Agreement, we retain all
rights with respect to the clinical development of, and activities to gain regulatory approvals of, KORSUVA
(CR845/difelikefalin) injection in the United States.
Under the terms of the Vifor Agreement, we received from Vifor an upfront payment of $100.0 million and an
additional payment of $50.0 million for the purchase of an aggregate of 2,939,552 shares of our common stock at a price of
$17.0094 per share, which represents a premium over a pre-determined average closing price of our common stock. Upon
U.S. regulatory approval of KORSUVA (CR845/difelikefalin) injection, we will also be eligible to receive an additional
$50.0 million common stock investment at a 20% premium to the 30-day trailing average price of our common stock as of
such date. In addition, pursuant to the Vifor Agreement, we are eligible to receive payments of up to $240.0 million upon
the achievement of certain sales-based milestones.
The Vifor Agreement provides full commercialization rights in dialysis clinics to Vifor in the United States under a
profit-sharing arrangement. Pursuant to the profit-sharing arrangement, we will generally be entitled to 60% of the net
profits (as defined in the Vifor Agreement) from sales of KORSUVA (CR845/difelikefalin) injection in the United States
(excluding sales to Fresenius Medical Center dialysis clinics, compensation for which is governed by the VFMCRP
Agreement) and Vifor is entitled to 40% of such net profits, subject to potential temporary adjustment in future years based
on certain conditions. Under the Vifor Agreement, in consideration of Vifor’s conduct of the marketing, promotion, selling
and distribution of KORSUVA (CR845/difelikefalin) injection in the United States, we will pay a marketing and
distribution fee to Vifor based on the level of annual net sales. This fee will be deducted from product sales in calculating
the net profits that are subject to the profit-sharing arrangement under the Vifor Agreement.
The Vifor Agreement will continue in effect until its expiration upon the cessation of commercial sale of KORSUVA
(CR845/difelikefalin) injection in the United States by Vifor and its affiliates and sublicensees, or until the earlier
termination of the Vifor Agreement.
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In addition, upon the earlier of: (1) the acceptance for filing of an NDA covering KORSUVA (CR845/difelikefalin)
injection submitted to the FDA; or (2) October 15, 2023, the Vifor Agreement may be terminated by Vifor in its entirety,
with such termination effective upon 12 months’ notice.
In connection with the Vifor Agreement, the parties entered into a separate stock purchase agreement, or the Vifor
Purchase Agreement, governing the issuance of our common stock to Vifor. Pursuant to the Vifor Purchase Agreement,
Vifor will not, and will not cause any direct or indirect affiliate to, during the period beginning on October 15, 2020 and
ending at the close of business on the earlier of (a) October 15, 2022 and (b) the date that we publicly disclose the receipt
of a complete response letter from the FDA with respect to our NDA for KORSUVA (CR845/difelikefalin) injection, or the
Restricted Period, (i) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or
contract to sell, grant any option, right or warrant to purchase, lend, or otherwise transfer or dispose of, directly or
indirectly, any shares of our common stock or any securities convertible into or exercisable or exchangeable for our
common stock (including without limitation, common stock or such other securities which may be deemed to be
beneficially owned by Vifor in accordance with the rules and regulations of the SEC and securities which may be issued
upon exercise of a stock option or warrant) owned by Vifor as of the date hereof or acquired prior to the end of the
Restricted Period (collectively with the common stock, referred to as the Lock-Up Securities, except any such sale, option
or contract by and between Vifor and one of its affiliates (including Vifor Pharma Group Ltd. or VFMCRP), (ii) enter into
any hedging, swap or other agreement or transaction that transfers, in whole or in part, any of the economic consequences
of ownership of the Lock-Up Securities, whether any such transaction described in clause (i) or (ii) above is to be settled by
delivery of Lock-Up Securities, in cash or otherwise, (iii) make any demand for or exercise any right with respect to the
registration of any Lock-Up Securities, or (iv) publicly disclose the intention to do any of the foregoing.
Under the Vifor Purchase Agreement, the parties also agreed that, in certain circumstances, upon the request of Vifor,
the parties will enter into a registration rights agreement prior to the end of the Restricted Period that would provide Vifor
(or its affiliate transferee) customary registration rights with respect to the shares of common stock issued pursuant to the
stock purchase agreement following the expiration of the Restricted Period.
Vifor Fresenius Medical Care Renal Pharma Ltd.
In May 2018, we entered into a license agreement, or the VFMCRP Agreement, with VFMCRP, a joint venture
between Vifor Pharma Group and Fresenius Medical Care, under which we granted VFMCRP a license to seek regulatory
approval to commercialize, import, export, use, distribute, offer for sale, promote, sell and otherwise commercialize
KORSUVA (CR845/difelikefalin) injection for all therapeutic uses to prevent, inhibit or treat itch associated with pruritus
in hemodialysis and peritoneal-dialysis patients worldwide (excluding the United States, Japan and South Korea). We
retain full development and commercialization rights for KORSUVA injection for the treatment of CKD-aP in dialysis
patients in the U.S. except in the dialysis clinics of Fresenius Medical Care North America, or FMCNA, where we and
VFMCRP will promote KORSUVA injection under a profit-sharing arrangement.
Upon entry into the VFMCRP Agreement, VFMCRP made a non-refundable, non-creditable $50 million upfront
payment to us and Vifor purchased 1,174,827 shares of our common stock for $20 million, at a premium for the price of
$17.024 per share. We are eligible to receive from VFMCRP regulatory and commercial milestone payments in the
aggregate of up to $470 million, consisting of up to $30 million in regulatory milestones and up to $440 million in tiered
commercial milestones, all of which are sales-related. We are also eligible to receive tiered double-digit royalty payments
based on annual net sales, as defined, of KORSUVA (CR845/difelikefalin) injection in the licensed territories. In the
United States, we and VFMCRP will promote KORSUVA (CR845/difelikefalin) injection in the dialysis clinics of
FMCNA under a profit-sharing arrangement (subject to the terms and conditions of the VFMCRP Agreement) based on net
FMCNA clinic sales recorded by us.
Maruishi Pharmaceutical Co., Ltd.
In April 2013, we entered into a license agreement with Maruishi, or the Maruishi Agreement, under which we
granted Maruishi an exclusive license to develop, manufacture and commercialize drug products containing
CR845/difelikefalin in Japan in the acute pain and uremic pruritus fields. Maruishi has a right of first negotiation for any
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other indications for which we develop CR845/difelikefalin and, under certain conditions, Maruishi may substitute another
pruritus indication for the uremic pruritus indication originally included in its license from us. If we abandon development
of CR845/difelikefalin and begin development of another kappa opioid receptor agonist that is covered by the claims of the
patents we licensed to Maruishi, such other agonist will automatically be included in the license to Maruishi. Maruishi is
required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory approval for and
commercialize CR845/difelikefalin in Japan. We are required to use commercially reasonable efforts, at our expense, to
develop, obtain regulatory approval for and commercialize CR845/difelikefalin in the United States.
Under the terms of the Maruishi Agreement, we received a non-refundable and non-creditable upfront license fee of
$15.0 million and are eligible to receive up to an aggregate of $10.5 million in clinical development and regulatory
milestones, of which $2.5 million (before contractual foreign currency exchange adjustments) has been received as of
December 31, 2020. In January 2021, we met the milestone criteria, as set forth in the Maruishi Agreement, for Maruishi’s
first initiation of a Phase III trial for uremic pruritus in Japan. As a result, we received a milestone payment of $2.0 million
($1.9 million after contractual foreign currency exchange adjustments) from Maruishi. We are also eligible to receive a
one-time sales milestone of one billion Yen when a certain sales level is attained. We also receive a mid-double-
digit percentage of all non-royalty payments received by Maruishi from its sublicensees, if any. We are also eligible to
receive tiered royalties based on net sales, if any, with minimum royalty rates in the low double digits and maximum
royalty rates in the low twenties. Maruishi’s obligation to pay us royalties continues, on a product-by-product basis, until
the expiration of the last-to-expire licensed patent covering such product or the later expiration of any market exclusivity
period. The Maruishi Agreement continues until terminated. Either we or Maruishi may terminate the Maruishi Agreement
for the other party’s breach of the agreement or bankruptcy. Maruishi may terminate the agreement at any time at will. We
may terminate the agreement as a whole if Maruishi challenges the licensed patent rights, and we may terminate the
agreement with respect to any indication if Maruishi discontinues its development activities. In addition, in connection with
the Maruishi Agreement, Maruishi made an $8.0 million equity investment in our company.
Chong Kun Dang Pharmaceutical Corporation
In April 2012, we entered into a license agreement with CKDP, or the CKDP Agreement, under which we granted
CKDP an exclusive license to develop, manufacture and commercialize drug products containing CR845/difelikefalin in
South Korea. CKDP is required to use commercially reasonable efforts, at its expense, to develop, obtain regulatory
approval for and commercialize CR845/difelikefalin in South Korea. We are required to use commercially reasonable
efforts, at our expense, to develop, obtain regulatory approval for and commercialize CR845/difelikefalin in the United
States.
Under the terms of the CKDP Agreement, we received a non-refundable and non-creditable $0.6 million upfront
payment and are eligible to receive up to an aggregate of $3.8 million in development and regulatory milestones (before
South Korean withholding taxes). In May 2020, we met the milestone criteria, as set forth in the CKDP Agreement, for
completion of a Phase 3 trial for uremic pruritus in the United States. As a result, in June 2020, we received a milestone
payment of $0.6 million (net of South Korean withholding tax) from CKDP. As of December 31, 2020, we have received
$2.3 million (before South Korean withholding tax) of development and regulatory milestones. We are also eligible to
receive a mid-double-digit percentage of all non-royalty payments received by CKDP from its sublicensees, if any, and
tiered royalties ranging from the high single digits to the high teens based on net sales, if any. CKDP’s obligation to pay us
royalties continues, on a product-by-product basis, until the expiration of the last-to-expire licensed patent covering such
product or the later expiration of any market exclusivity period. The CKDP Agreement continues until CKDP no longer
has any obligation to pay us royalties on any product. Either we or CKDP may terminate the CKDP Agreement for the
other party’s breach of the CKDP Agreement or bankruptcy. CKDP may terminate the CKDP Agreement if any of the
licensed patent rights is invalid, unenforceable, is narrowed in scope or is deemed unpatentable, except as a result of a
challenge by CKDP, or a third party commercializes a product containing a compound identical to CR845/difelikefalin
without infringing any of the licensed patent rights in South Korea. We may terminate the CKDP Agreement if CKDP
challenges the licensed patent rights or if a third party in South Korea owns an issued patent that claims
CR845/difelikefalin and CKDP’s sale of products would infringe that patent. In addition, in connection with the CKDP
Agreement, CKDP made a $0.4 million equity investment in our company.
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Manufacturing and License Agreements
Enteris Biopharma, Inc.
In August 2019, we entered into the Enteris License Agreement with Enteris. Pursuant to the Enteris License
Agreement, Enteris granted to us a non-exclusive, royalty-bearing license, including the right to grant sublicenses, under
certain proprietary technology and patent rights related to or covering formulations for oral delivery of peptide active
pharmaceutical ingredients with functional excipients to enhance permeability and/or solubility, known as Enteris’s
Peptelligence® technology, to develop, manufacture and commercialize products using such technology worldwide,
excluding Japan and South Korea.
As consideration for the licensed rights under the Enteris License Agreement, we paid an upfront fee equal to $8.0
million, consisting of $4.0 million in cash and $4.0 million in shares of our common stock pursuant to the Enteris Purchase
Agreement described below. As a result, we recognized $8.0 million of R&D expense related to the Enteris License
Agreement during the year ended December 31, 2019.
We are also obligated, pursuant to the Enteris License Agreement, to pay Enteris (1) milestone payments upon the
achievement of certain development, regulatory and commercial milestones and (2) low-single digit royalty percentages on
net sales of licensed products, subject to reductions in specified circumstances. Until the second anniversary of the entry
into the Enteris License Agreement, we have the right, but not the obligation, to terminate our obligation to pay any
royalties under the Enteris License Agreement in exchange for a lump sum payment in cash, or the Royalty Buyout.
Subject to certain conditions, we may elect to pay 50% of the lump sum due under the Royalty Buyout in shares of our
common stock pursuant to the Enteris Purchase Agreement. During the year ended December 31, 2020, we paid $5.0
million to Enteris for a milestone earned during the year ended December 31, 2020 in relation to the Enteris License
Agreement. As a result, we recognized $5.0 million of R&D expense related to the Enteris License Agreement during the
year ended December 31, 2020.
The Enteris License Agreement will expire on a country-by-country, licensed product-by-licensed product basis upon
the later of (1) the expiration (or invalidation) of all valid claims in licensed patent rights that cover such product in such
country, (2) the end of the calendar quarter in which generic competition (as defined in the Enteris License Agreement)
occurs for such product in such country and (3) ten years from the first commercial sale of such product.
Either party may terminate the Enteris License Agreement upon written notice if the other party has failed to remedy
a material breach within 60 days (or 30 days in the case of a material breach of a payment obligation). Enteris may
terminate the Enteris License Agreement upon 30 days’ written notice to us if we or any of our affiliates formally challenge
the validity of any licensed patent rights or assists a third party in doing so. We may terminate the Enteris License
Agreement for any reason or no reason (a) prior to receipt of first regulatory approval for a licensed product in the United
States for any indication upon 30 days’ prior written notice to Enteris or (b) on or after receipt of first regulatory approval
for a licensed product in the United States for any indication upon 60 days’ prior written notice to Enteris.
In connection with the Enteris License Agreement, in August 2019, we entered into the Enteris Purchase Agreement
with Enteris and its affiliate, EBP Holdco LLC, collectively referred to as Purchaser, pursuant to which we issued and sold
to Purchaser 170,793 shares of our common stock in a private placement. Such shares were issued in satisfaction of the
$4.0 million portion of the upfront fee payable in shares of our common stock pursuant to the Enteris License Agreement
and for no additional consideration, based on a purchase price of $23.42 per share, which was equal to the 30-day volume
weighted average price of our common stock on August 20, 2019. In addition, if we exercise our Royalty Buyout option,
we may elect to make 50% of the payment in stock by issuing additional shares of our common stock valued at the 30-day
volume weighted average price of our common stock as of such exercise. Pursuant to the Purchase Agreement, we effected
the registration and sale of the shares issued and sold to Purchaser thereunder in accordance with the applicable
requirements of the Securities Act of 1933, as amended, or the Securities Act, which included the filing of a registration
statement with the SEC on September 9, 2019. In addition, the Purchase Agreement includes customary representations,
warranties and covenants by us.
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Patheon UK Limited
In July 2019, we entered into an MSA with Patheon UK Limited, or Patheon. The MSA governs the general terms
under which Patheon, or one of its affiliates, will provide non-exclusive manufacturing services to us for the drug products
specified by us from time to time. Pursuant to the MSA, we have agreed to order from Patheon at least a certain percentage
of our commercial requirements for a product under a related Product Agreement. Each Product Agreement that we may
enter into from time to time will be governed by the terms of the MSA, unless expressly modified in such Product
Agreement.
The MSA has an initial term ending December 31, 2023, and will automatically renew after the initial term for
successive terms of two years each if there is a Product Agreement in effect, unless either party gives notice of its intention
to terminate the MSA at least 18 months prior to the end of the then current term.
Either party may terminate the MSA or a Product Agreement upon written notice if the other party (1) has failed to
remedy a material breach within a specified time or (2) is declared insolvent or bankrupt, voluntarily files a petition of
bankruptcy or assigns such agreement for the benefit of creditors. We may terminate a Product Agreement (a) upon
90 days’ prior written notice if any governmental agency takes any action that prevents us from selling the relevant product
in the relevant territory, (b) upon six months’ prior written notice if we do not intend to order manufacturing services due to
a product’s discontinuance in the market, or (c) upon 90 days’ prior written notice if we determine that the manufacture or
supply of a product likely infringes third-party rights. Patheon may terminate the MSA or a Product Agreement (i) upon
six months’ prior written notice if we assign such agreement to an assignee that is unacceptable to Patheon for certain
reasons, or (ii) upon 30 days’ prior written notice if, after the first year of commercial sales, we forecast zero volume for
12 months.
The MSA contains, among other provisions, customary representations and warranties by the parties, a grant to
Patheon of certain limited license rights to our intellectual property in connection with Patheon’s performance of the
services under the MSA, certain indemnification rights in favor of both parties, limitations of liability and customary
confidentiality provisions.
Also in July 2019, we entered into two related Product Agreements under the MSA, one with each of Patheon and
Patheon Manufacturing Services LLC, or Patheon Greenville, to govern the terms and conditions of the manufacture of
commercial supplies of CR845/difelikefalin injection, our lead product candidate. Pursuant to the Product Agreements,
Patheon and Patheon Greenville will manufacture commercial supplies of CR845/difelikefalin injection at the Monza, Italy
and Greenville, North Carolina manufacturing sites, respectively, from active pharmaceutical ingredient supplied by us.
Patheon and Patheon Greenville will be responsible for supplying the other required raw materials and packaging
components, and will also provide supportive manufacturing services such as quality control testing for raw materials,
packaging components and finished product.
Components of Operating Results
Revenue
To date, we have not generated any revenue from product sales. Substantially all of our revenue recognized to date
has consisted of upfront payments under license agreements with Vifor, VFMCRP, Maruishi and CKDP, and milestone and
sub-license payments under license agreements with CKDP and Maruishi for CR845/difelikefalin, some or all of which
was deferred upon receipt, as well as license agreements for CR665, our first-generation drug program for which
development efforts have ceased and clinical compound sales from certain license agreements. Through December 31,
2020, we have earned a total of $6.7 million in clinical development or regulatory milestone payments and clinical
compound sales from certain license agreements. We have not yet received any milestone payments under the Vifor or
VFMCRP agreements or royalties under any of our collaborations.
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Research and Development (R&D)
Our R&D expenses relate primarily to the development of CR845/difelikefalin. R&D expenses consist of expenses
incurred in performing R&D activities, including compensation and benefits for full-time R&D employees, clinical trial
and related clinical manufacturing expenses, third-party formulation expenses, fees paid to CROs and other consultants,
stock-based compensation for R&D employees and consultants and other outside expenses. Our R&D expenses also
included expenses related to preclinical activities for our earlier stage programs in prior periods and may include such
expenses in the future.
R&D costs are expensed as incurred. Non-refundable advance payments for goods or services to be received in the
future for use in R&D activities are deferred and capitalized. The capitalized amounts are expensed as the related goods are
delivered or the services are performed. Most of our R&D costs have been external costs, which we track on a program-by
program basis. Our internal R&D costs are primarily compensation expenses for our full-time R&D employees. We do not
track internal R&D costs on a program-by-program basis.
R&D activities are central to our business model. Product candidates in later stages of clinical development generally
have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and
duration of later-stage clinical trials. Based on our current development plans, we presently expect that our R&D expenses
for 2021 will increase over those for 2020. However, it is difficult to determine with certainty the duration and completion
costs of our current or future nonclinical programs and clinical trials of our product candidates, or if, when or to what
extent we will generate revenues from the commercialization and sale of any of our product candidates that obtain
regulatory approval. We may never succeed in achieving regulatory approval for any of our product candidates.
The duration, costs and timing of clinical trials and development of our product candidates will depend on a variety
of factors including, but not limited to:
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per patient trial costs;
the number of patients that participate in the trials;
the number of sites included in the trials;
the countries in which the trial is conducted;
the length of time required to enroll eligible patients;
the number of doses that patients receive;
the drop-out or discontinuation rates of patients;
potential additional safety monitoring or other studies requested by regulatory agencies;
the duration of patient follow-up; and
the efficacy and safety profile of the product candidate.
In addition, the probability of success for each product candidate will depend on numerous factors, including
competition, manufacturing capability and commercial viability. We will determine which programs to pursue and how
much to fund each program in response to the scientific and clinical success of each product candidate, as well as an
assessment of each product candidate’s commercial potential.
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General and Administrative
General and administrative expenses consist primarily of salaries and other related costs, including stock-based
compensation, for personnel in executive, finance, accounting, legal, business development, information technology and
human resources functions. Other costs include facility costs not otherwise included in R&D expenses, legal fees,
insurance costs, investor relations costs, patent costs and fees for accounting and consulting services.
We anticipate that our general and administrative expenses for 2021 will generally approximate those for 2020 to
support our continued R&D activities and for our product candidates. These expenses will likely include costs related to
the hiring of additional personnel, fees to outside consultants, lawyers, accountants and investor relations firms. In
addition, if Oral CR845/difelikefalin or any future product candidate obtains regulatory approval for marketing, we expect
to incur expenses associated with building a sales and marketing team.
Other Income, Net
Other income, net consists of interest and dividend income earned on our cash, cash equivalents, marketable
securities and restricted cash, realized gains and losses on the sale of marketable securities and property and equipment as
well as accretion of discounts/amortization of premiums on purchases of marketable securities. In the event we record a
credit loss expense on our available-for-sale debt securities, those expenses would be offset against other income.
Benefit from Income Taxes
The benefit from income taxes relates to state R&D tax credits exchanged for cash pursuant to the Connecticut R&D
Tax Credit Exchange Program, which permits qualified small businesses engaged in R&D activities within Connecticut to
exchange their unused R&D tax credits for a cash amount equal to 65% of the value of the exchanged credits.
Results of Operations
Comparison of the years ended December 31, 2020, 2019 and 2018
Revenue
License and milestone fees
Clinical compound revenue
Total revenue
License and milestone fee revenue
2020
Year Ended December 31,
2019
Dollar amounts in thousands
% change
% change
2018
$ 134,439
643
$ 135,082
581 % $ 19,746
359 %
140
579 % $ 19,886
47 % $ 13,436
320 %
33
48 % $ 13,469
License and milestone fees revenue of $134.4 million for the year ended December 31, 2020 was related to license
fees of $111.6 million earned by us in connection with the Vifor Agreement that we entered into in October 2020, license
fees of $22.3 million earned by us in connection with the VFMCRP Agreement, and $0.6 million (net of South Korean
withholding taxes) earned by us for achieving a development milestone under the CKDP Agreement. License and
milestone fees revenue of $19.7 million and $13.4 million for the years ended December 31, 2019 and 2018, respectively,
were related to license fees earned by us during the respective periods in connection with the VFMCRP Agreement (see
Note 11 of Notes to Financial Statements, Collaboration and Licensing Agreements, in this Annual Report on Form 10-K).
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Clinical compound revenue
Clinical compound revenue of $643 thousand for the year ended December 31, 2020 was related to the sales of
clinical compound to VFMCRP for $115 thousand and to Maruishi for $528 thousand. Clinical compound revenue of $140
thousand and $33 thousand for the years ended December 31, 2019 and 2018, respectively, related to the sale of clinical
compound to Maruishi.
Research and Development Expense
Direct clinical trial costs
Consultant services in support of clinical trials
Stock-based compensation
Depreciation and amortization
Other R&D operating expenses
Total R&D expense
2020
Year Ended December 31,
2019
Dollar amounts in thousands
2018
% change
% change
$ 68,937
5,792
8,197
112
24,813
$ 107,851
(14)% $ 80,098
4,470
30 %
5,809
41 %
110
2 %
6 %
23,333
(5)% $ 113,820
41 % $ 56,625
3,406
31 %
4,395
32 %
288
(62)%
116 %
10,817
51 % $ 75,531
For the year ended December 31, 2020 compared to the year ended December 31, 2019, the net decrease in direct
clinical trial costs and related consultant costs primarily resulted from decreases totaling $33.2 million, mainly from
activities related to the KALM-1 Phase 3 efficacy trial and the 52-week open-label extension study of KORSUVA
(CR845/difelikefalin) injection in CKD patients undergoing hemodialysis, the Phase 2 efficacy trial of Oral CR845 in
CKD-aP patients, the KALM-2 Phase 3 efficacy trial of KORSUVA (CR845/difelikefalin) injection in CKD patients
undergoing hemodialysis, the Phase 2 efficacy trial for CLD-aP, costs associated with a supportive Phase 1 study and other
license fees. Those costs were partially offset by an increase of $19.4 million, mainly from the Phase 2 efficacy trial for
pruritus associated with AD, the Phase 2 efficacy and safety trial for pruritus associated with NP, costs associated with a
supportive Phase 1 study, costs associated with the preparation our NDA submission and other general costs. There was
also an increase of $4.1 million in clinical and commercial drug manufacturing costs. The increase in stock-based
compensation expense was primarily the result of additional stock option and restricted stock unit grants to new and
existing employees, as well as additional stock-based compensation expense relating to the vesting of performance-based
restricted stock units that were achieved in 2020 as compared to 2019 by certain executives. The increase in other R&D
operating expenses primarily resulted from a $5.0 million milestone earned by Enteris during the year ended December 31,
2020, as well as increases in payroll and related costs and cost of clinical compound sales, partially offset by the upfront
payment of $8.0 million made to Enteris upon entering the Enteris License Agreement during the year ended December 31,
2019 and decreases in travel and related costs.
For the year ended December 31, 2019 compared to the year ended December 31, 2018, the net increase in direct
clinical trial costs and related consultant costs primarily resulted from increases totaling $32.7 million, mainly from
activities related to the two Phase 3 efficacy trials and up to 12 week Phase 3 safety trial of KORSUVA
(CR845/difelikefalin) injection in CKD patients undergoing hemodialysis, the Phase 2 efficacy trial of Oral CR845 in
CKD-aP patients, the Phase 2 efficacy trial for CLD-aP and the Phase 2 efficacy trial for pruritus associated with AD.
There was also an increase of $1.6 million in drug manufacturing costs. Those costs were partially offset by a decrease of
$9.4 million, mainly from the Phase 2/3 I.V. CR845/difelikefalin adaptive clinical trial in post-operative pain and costs
associated with certain Phase 1 studies. The increase in stock-based compensation expense was primarily the result of
additional stock option grants to R&D employees. The increase in other R&D operating expenses primarily resulted from
the upfront payment of $8.0 million upon entering into the Enteris License Agreement and an increase in payroll and
related costs associated with R&D personnel.
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The following table summarizes our R&D expenses by product candidate for the years ended December 31, 2020,
2019 and 2018:
External research and development expenses:
I.V. CR845 - Pruritus
I.V. CR845 - Pain
Oral CR845 - Pruritus
Oral CR845 - Pain
Internal research and development expenses
Total research and development expenses
General and Administrative Expense
Professional fees and public/investor relations
Stock-based compensation
Depreciation and amortization
Other G&A operating expenses
Total G&A expense
2020
Year Ended December 31,
2019
Dollar amounts in thousands
% change
% change
2018
$ 44,026
100
30,491
23
33,211
$ 107,851
(26)% $ 59,687
(73)%
373
24,475
25 %
33
(32)%
14 %
29,252
(5)% $ 113,820
67 % $ 35,781
6,386
(94)%
15,670
56 %
2,194
(98)%
89 %
15,500
51 % $ 75,531
2020
Year Ended December 31,
2019
Dollar amounts in thousands
2018
% change
% change
$
3,841
6,638
97
11,270
$ 21,846
3,883
(1)% $
6,759
(2)%
88
11 %
61 %
7,015
23 % $ 17,745
34 % $
2,906
19 %
5,700
7 %
82
6 %
6,632
16 % $ 15,320
For the year ended December 31, 2020 compared to the year ended December 31, 2019, the decrease in professional
fees and public/investor relations expenses was primarily the result of a decrease in consultants’ costs, partially offset by
increases in accounting fees. The decrease in stock-based compensation expense was primarily the result of the resignation
of our former Chief Financial Officer in December 2019, a decrease in stock-based compensation expense due to fewer
performance-based restricted stock units vesting during 2020 as compared to 2019, and the issuance of common stock
relating to the consulting agreement that ended in 2019, partially offset by additional stock option grants and restricted
stock unit grants to employees and members of our Board of Directors, including our current CFO beginning in October
2020. The increase in other G&A operating expenses was primarily the result of increases in commercial costs, insurance
costs, and payroll and related costs.
For the year ended December 31, 2019 compared to the year ended December 31, 2018, the increase in professional
fees and public/investor relations expenses was primarily the result of increased consultants’ costs and legal and accounting
fees. The increase in stock-based compensation expense was primarily the result of additional stock option grants to G&A
employees, additional stock-based compensation expense relating to restricted stock units granted to the members of our
Board of Directors in June 2019, and stock-based compensation expense resulting from issuing shares of our common
stock for consulting services performed during the year ended December 31, 2019. The increase in other G&A operating
expenses was primarily the result of an increase in insurance costs and franchise taxes, partially offset by a decrease in rent,
utilities and related costs.
Other Income, Net
Other income, net
2020
Year Ended December 31,
2019
Dollar amounts in thousands
% change
% change
2018
$
2,334
(48)% $
4,490
51 % $
2,980
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For the year ended December 31, 2020 compared to the year ended December 31, 2019, the decrease in other
income, net was primarily due to a decrease in net accretion income and a decrease in interest income resulting from a
lower yield on our lower average balance of our portfolio of investments in the 2020 period, partially offset by a realized
gain of approximately $0.3 million from the sale of our available-for-sale marketable securities in the 2020 period.
For the year ended December 31, 2019 compared to the year ended December 31, 2018, the increase in other income,
net was primarily due to an increase in interest and accretion income resulting from a higher average balance of our
portfolio of investments in the 2019 period.
Benefit from Income Taxes
For the years ended December 31, 2020, 2019 and 2018, pre-tax income (losses) were $7.7 million, $(107.2) million
and $(74.4) million, respectively, and we recognized a benefit from income taxes of $691 thousand, $816 thousand and
$389 thousand, respectively.
The benefit from income taxes relates to state R&D tax credits exchanged for cash pursuant to the Connecticut R&D
Tax Credit Exchange Program, as discussed above. We recognized a full valuation allowance against deferred tax assets at
December 31, 2020, 2019 and 2018.
Liquidity and Capital Resources
Sources of Liquidity
Since our inception and through December 31, 2020, we have raised an aggregate of $774.5 million to fund our
operations, including (1) net proceeds of $446.3 million from the sale of shares of our common stock in five public
offerings, including our initial public offering; (2) proceeds of $73.3 million from the sale of shares of our convertible
preferred stock and from debt financings prior to our initial public offering; (3) payments of $201.9 million under our
license agreements, primarily with Vifor, VFMCRP, Maruishi, CKDP and an earlier product candidate for which
development efforts ceased in 2007; and (4) net proceeds of $53.0 million from the purchase of our common stock in
relation to the license agreements with Vifor and VFMCRP (see Note 11 of Notes to Financial Statements, Collaboration
and Licensing Agreements, in this Annual Report on Form 10-K).
In order to fund our future operations, including our planned clinical trials, we filed the Shelf Registration Statement
(File No. 333-230333), which provides for aggregate offerings of up to $300.0 million of common stock, preferred stock,
debt securities, warrants or any combination thereof and was declared effective on April 4, 2019. The securities registered
under the Shelf Registration Statement include unsold securities that had been registered under our previous Registration
Statement on Form S-3 (File No. 333-216657) that was declared effective on March 24, 2017. To date, we have offered and
sold an aggregate of approximately $145.5 million of securities under this Shelf Registration Statement. We believe that
our Shelf Registration Statement provides us with the flexibility to raise additional capital to finance our operations as
needed.
On July 24, 2019, we entered into an underwriting agreement with J.P. Morgan Securities LLC and Jefferies LLC, as
representatives of the several underwriters named therein, relating to the issuance and sale by us of up to 6,325,000 shares
of our common stock, including 825,000 additional shares of common stock that the underwriters had the option to
purchase, at a public offering price of $23.00 per share. We closed this offering on July 29, 2019, including the full exercise
of the underwriters’ option to purchase additional shares of common stock. We received net proceeds of $136.5 million,
after deducting $9.0 million of underwriting discounts and commissions and offering expenses. This offering was made by
pursuant to the Shelf Registration Statement, and a related prospectus supplement dated July 24, 2019, which was filed
with the SEC on July 25, 2019.
We may offer additional securities under our Shelf Registration Statement from time to time in response to market
conditions or other circumstances if we believe such a plan of financing is in the best interests of our stockholders.
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As of December 31, 2020, we had $251.5 million in unrestricted cash and cash equivalents and available-for-sale
marketable securities. We believe our current unrestricted cash and cash equivalents and available-for-sale marketable
securities will be sufficient to fund our currently anticipated operating expenses and capital expenditures into 2023, without
giving effect to any potential milestone payments or potential product revenue we may receive under our licensing and
collaboration agreements with Vifor, VFMCRP, Maruishi and CKDP. Our anticipated operating expenses include
contractually committed costs as well as non-contractually committed clinical trial costs for trials that may be delayed or
not initiated and other non-committed controllable costs.
Under the Vifor Agreement, we are eligible to receive regulatory and commercial milestone payments in the
aggregate of up to $290.0 million, consisting of a $50.0 million common stock investment for a regulatory milestone and
up to $240.0 million upon the achievement of certain sales-based milestones. As of December 31, 2020, we have not
received any milestone payments under the Vifor Agreement.
Under the VFMCRP Agreement, we are eligible to receive regulatory and commercial milestone payments in the
aggregate of up to $470.0 million, consisting of up to $30.0 million in regulatory milestones and up to $440.0 million in
tiered commercial milestones, all of which are sales-related. We are also eligible to receive tiered double-digit royalty
payments based on annual net sales, as defined in the VFMCRP Agreement, of CR845/difelikefalin injection in the
Licensed Territories. As of December 31, 2020, we have not received any milestone payments under the VFMCRP
Agreement.
Under the Maruishi Agreement, we are also potentially eligible to earn up to an aggregate of $6.0 million in clinical
development milestones and $4.5 million in regulatory milestones, before any foreign exchange adjustment, as well as
tiered royalties, with percentages ranging from the low double digits to the low twenties, based on net sales of products
containing CR845/difelikefalin in Japan, if any, and share in any sub-license fees. As of December 31, 2020, we have
received milestone payments of $2.5 million before contractual foreign currency exchange adjustments under the Maruishi
Agreement. In January 2021, we met the milestone criteria, as set forth in the Maruishi Agreement, for Maruishi’s first
initiation of a Phase III trial for uremic pruritus in Japan. As a result, we received a milestone payment of $2.0 million
($1.9 million after contractual foreign currency exchange adjustments) from Maruishi.
Under the CKDP Agreement, we are potentially eligible to earn up to an aggregate of $2.3 million in clinical
development milestones and $1.5 million in regulatory milestones, before South Korean withholding tax, as well as tiered
royalties with percentages ranging from the high single digits to the high teens, based on net sales of products containing
CR845/difelikefalin in South Korea, if any, and share in any sub-license fees. In May 2020, the criteria for revenue
recognition for a milestone event set forth in the CKDP Agreement was achieved, and we recorded $0.6 million (net of
South Korean withholding tax) as license and milestone fees revenue during the year ended December 31, 2020 relating to
the milestone payment received from CKDP. As of December 31, 2020, $2.3 million (before South Korean withholding
tax) of development and regulatory milestones have been received under the CKDP Agreement.
Our ability to earn these payments and their timing is dependent upon the outcome of I.V. and Oral
CR845/difelikefalin development activities and, potentially, commercialization. However, our receipt of any further such
amounts is uncertain at this time and we may never receive any more of these amounts.
Funding Requirements
Our primary uses of capital have been, and we expect will continue to be, compensation and related expenses, third-
party clinical R&D services and clinical costs. In the past, we have also previously used capital for laboratory and related
supplies.
Since inception, we have incurred significant operating and net losses. We incurred net losses of $106.4 million and
$74.0 million for the years ended December 31, 2019 and 2018, respectively. As of December 31, 2020, we had an
accumulated deficit of $392.3 million. Although we generated net income for the year ended December 31, 2020 as a result
of a commercial license transaction, we expect to continue to incur significant expenses and operating and net losses in the
foreseeable future, as we continue to develop and seek marketing approval for I.V. and Oral CR845/difelikefalin. Our
financial results may fluctuate significantly from quarter to quarter and year to year, depending
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on the timing of our clinical trials, the receipt of additional milestone payments, if any, under our licensing and
collaborations with Vifor, VFMCRP, Maruishi and CKDP, the receipt of payments under any future collaborations and/or
licensing agreements we may enter into, and our expenditures on other R&D activities.
We anticipate that our expenses may increase as we:
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continue the development of KORSUVA (CR845/difelikefalin) injection for CKD-aP in dialysis patients;
continue the development of Oral KORSUVA (CR845/difelikefalin) for CKD-aP and other diseases associated
with pruritus, such as CLD-aP and AD;
explore the potential to further develop I.V. CR845/difelikefalin in the post-operative setting;
conduct R&D of any potential future product candidates;
seek regulatory approvals for I.V. CR845/difelikefalin and any product candidates that successfully complete
clinical trials;
establish a sales, marketing and distribution infrastructure and scale up external manufacturing capabilities to
commercialize any products for which we may obtain regulatory approval;
maintain, expand and protect our global intellectual property portfolio;
hire additional clinical, quality control and scientific personnel; and
add operational, financial and management information systems and personnel, including personnel to support
our drug development and potential future commercialization efforts.
The successful development of any of our product candidates is highly uncertain. As such, at this time, we cannot
reasonably estimate or know the nature, timing and costs of the efforts that will be necessary to complete the development
of I.V. CR845/difelikefalin, Oral CR845/difelikefalin or our other current and future programs. We are also unable to
predict when, if ever, we will generate any further material net cash inflows from CR845/difelikefalin. This is due to the
numerous risks and uncertainties associated with developing medicines, including the uncertainty of:
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successful enrollment in, and completion of clinical trials;
receipt of marketing approvals from applicable regulatory authorities;
establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers;
obtaining and maintaining patent and trade secret protection and regulatory exclusivity for our product
candidates;
launching commercial sales of the products, if and when approved, whether alone or in collaboration with
others;
achieving meaningful penetration in the markets which we seek to serve; and
obtaining adequate coverage or reimbursement by third parties, such as commercial payers and government
healthcare programs, including Medicare and Medicaid.
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A change in the outcome of any of these variables with respect to the development of I.V. CR845/difelikefalin, Oral
CR845/difelikefalin or any of our future product candidates would significantly change the costs and timing associated
with the development of that product candidate. Further, the timing of any of the above may be impacted by the ongoing
COVID-19 pandemic, introducing additional uncertainty.
Because our product candidates are still in clinical development and the outcome of these efforts is uncertain, we
cannot estimate the actual amounts necessary to successfully complete the development and commercialization of all our
product candidates or whether, or when, we may achieve profitability. Until such time, if ever, as we can generate
substantial product revenues, we expect to finance our cash needs through a combination of equity or debt financings and
collaboration arrangements, including our existing licensing and collaboration agreements with Vifor, VFMCRP, Maruishi
and CKDP.
We will require additional capital beyond our current balances of cash and cash equivalents and available-for-sale
marketable securities and anticipated amounts as described above, and this additional capital may not be available when
needed, on reasonable terms, or at all, and our ability to raise additional capital may be adversely impacted by potential
worsening global economic conditions and the recent disruptions to and volatility in the credit and financial markets in the
United States and worldwide resulting from the ongoing COVID-19 pandemic. If we are not able to do so, we could be
required to postpone, scale back or eliminate some, or all, of these objectives. To the extent that we raise additional capital
through the future sale of equity or convertible debt, the ownership interest of our stockholders will be diluted, and the
terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing
common stockholders. If we raise additional funds through the issuance of debt securities, these securities could contain
covenants that would restrict our operations. If we raise additional funds through collaboration arrangements in the future,
we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant
licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt
financings when needed, we may be required to delay, limit, reduce or terminate our drug development or future
commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to
develop and market ourselves.
Outlook
Based on timing expectations and projected costs for our current clinical development plans, which include
conducting supportive Phase 1 trials, Phase 2 trials, and Phase 3 trials of Oral KORSUVA (CR845/difelikefalin) in patients
with pruritus associated with CKD, CLD, AD, and NP, we expect that our existing cash and cash equivalents and available-
for-sale marketable securities as of December 31, 2020 will be sufficient for us to fund our currently anticipated operating
expenses and capital expenditures into 2023, without giving effect to any potential milestone payments or potential product
revenue we may receive under our collaboration agreements with VFMCRP, Maruishi and CKDP. Our anticipated
operating expenses include contractually committed costs as well as non-contractually committed clinical trial costs for
trials that may be delayed or not initiated and other non-committed controllable costs. Because the process of testing
product candidates in clinical trials is costly and the timing of progress in these trials is uncertain, it is possible that the
assumptions upon which we have based this estimate may prove to be wrong, and we could use our capital resources
sooner than we presently expect.
The Tax Cuts and Jobs Act of 2017
On December 22, 2017, the TCJA was enacted in the United States. Under generally accepted accounting principles
in the United States, or GAAP, the effect of a change in tax rates and tax law is recorded discretely as a component of the
income tax provision related to continuing operations in the period of enactment. Under the TCJA, among other provisions,
the maximum Federal corporate tax rate is reduced from 35% to 21% for tax years beginning after December 31, 2017.
Accounting Standards Codification, or ASC, section 740, Income Taxes, requires deferred tax assets and liabilities to
be measured at the enacted tax rate expected to apply when temporary differences are to be realized or settled. Therefore, at
the date of enactment, we reduced deferred tax assets by $25.9 million based on the revised tax rate, which required a re-
assessment of the related valuation allowance. Based on expected net losses into the foreseeable future, we
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will currently continue to record a 100% valuation allowance against our deferred tax assets. The corresponding reduction
in the valuation allowance as a result of the re-measurement of deferred tax assets and liabilities was also recorded to
continuing operations in the tax provision. As of December 31, 2020 and 2019, we did not have any foreign subsidiaries
and the international aspects of the TCJA are not applicable for the respective periods.
In addition, NOLs arising in taxable years beginning after December 31, 2017, can be carried forward indefinitely
but carryback is generally prohibited. The use of such NOL carryforwards for taxable years beginning after 2020 is limited
to 80% of taxable income. NOLs generated before January 1, 2018 will not be subject to the taxable income limitation and
will continue to have a two-year carryback and 20-year carryforward period.
On December 22, 2017, Staff Accounting Bulletin 118, or SAB 118, was issued by the SEC due to the complexities
involved in accounting for the TCJA. SAB 118 requires us to include in our financial statements a reasonable estimate of
the impact of the TCJA on earnings to the extent such estimate has been determined. Accordingly, our U.S. provision for
income tax for 2017 was based on the reasonable estimate guidance provided by SAB 118. We finalized the accounting for
the TCJA as of December 31, 2018, which resulted in insignificant adjustments.
The CARES Act of 2020 and Consolidated Appropriations Act of 2021
On March 27, 2020, President Trump signed into law the Coronavirus Aid, Relief, and Economic Security Act of
2020, or the CARES Act (H.R. 748), which was further expanded with the signing of the Consolidation Appropriations Act
of 2021 (H.R. 133) on December 27, 2020. The CARES Act (and December expansion) includes a variety of economic and
tax relief measures intended to stimulate the economy, including loans for small businesses, payroll tax credits/deferrals,
and corporate income tax relief. Due to our history of tax loss carryforwards and full valuation allowance, the CARES Act
did not have a significant effect to the income tax provision, as the corporate income tax relief was directed towards cash
taxpayers.
Cash Flows
The following is a summary of the net cash flows provided by (used in) our operating, investing and financing
activities for the years ended December 31, 2020, 2019 and 2018:
Year Ended December 31,
2019
Dollar amounts in thousands
$ (5,487) $ (109,225) $ (22,301)
(82,819)
(30,516)
(20,275)
110,813
142,604
39,140
5,693
$
2,863
Net increase in cash, cash equivalents and restricted cash $ 13,378
Net cash used in operating activities
Net cash used in investing activities
Net cash provided by financing activities
2020
2018
$
Net cash used in operating activities
Net cash used in operating activities for the year ended December 31, 2020 consisted primarily of a $7.4 million cash
outflow from net changes in operating assets and liabilities and a $6.5 million cash outflow from net non-cash charges,
partially offset by net income of $8.4 million (which includes $111.6 million of licensing and milestone fees revenue from
the Vifor Agreement). Net non-cash charges primarily consisted of a decrease of $22.3 million in deferred revenue
associated with our VFMCRP Agreement, partially offset by stock-based compensation expense of $14.8 million and the
amortization expense component of lease expense of $0.8 million relating to our Stamford operating leases. The change in
operating assets and liabilities primarily consisted of a cash outflow of $3.2 million from an increase in prepaid expenses,
primarily related to an increase in prepaid clinical costs, a cash outflow of $2.8 million from a decrease in accounts payable
and accrued expenses, and a cash outflow of $1.1 million relating to operating lease liabilities associated with our Stamford
operating leases.
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Net cash used in operating activities for the year ended December 31, 2019 consisted primarily of a net loss of
$106.4 million and a $3.8 million cash outflow from net non-cash charges, partially offset by a $0.9 million cash inflow
from net changes in operating assets and liabilities. Net non-cash charges primarily consisted of a decrease of $19.7 million
in deferred revenue associated with our VFMCRP Agreement and $1.4 million related to accretion of available-for-sale
securities, partially offset by stock-based compensation expense of $12.6 million and a noncash expense of $4.0 million
related to the Enteris License Agreement. The change in operating assets and liabilities primarily consisted of a cash inflow
of $6.0 million from an increase in accounts payable and accrued expenses, partially offset by a cash outflow of $4.1
million from an increase in prepaid expense, primarily related to an increase in prepaid clinical costs and a cash outflow of
$0.9 million from operating lease liability relating to lease payments made for the Stamford Lease as a result of our
adoption of ASC 842: Leases.
Net cash used in operating activities for the year ended December 31, 2018 consisted primarily of a net loss of $74.0
million, partially offset by a $50.5 million cash inflow from net non-cash charges and a $1.2 million inflow from net
changes in operating assets and liabilities. Net non-cash charges primarily consisted of an increase in deferred revenue of
$42.0 million related to the VFMCRP Agreement and stock-based compensation expense of $10.1 million, partially offset
by $1.8 million related to amortization/accretion of available-for-sale securities. The net change in operating assets and
liabilities primarily consisted of a cash inflow of $5.1 million from an increase in accounts payable and accrued expenses,
partially offset by cash outflows of $3.2 million from an increase in prepaid expense, primarily related to an increase in
prepaid clinical costs, and cash outflows of $0.8 million related to an increase in other receivables.
Net cash used in investing activities
Net cash used in investing activities was $20.3 million for the year ended December 31, 2020, which primarily
included cash outflows of $232.9 million for the purchases of available-for-sale marketable securities, partially offset by
cash inflows of $171.4 million from maturities and redemptions of available-for-sale marketable securities and proceeds of
$41.6 million from sales of available-for-sale marketable securities.
Net cash used in investing activities was $30.5 million for the year ended December 31, 2019, which primarily
included cash outflows of $286.1 million for the purchases of available-for-sale marketable securities, partially offset by
$255.6 million from maturities and redemptions of available-for-sale marketable securities.
Net cash used in investing activities was $82.8 million for the year ended December 31, 2018, which primarily
included cash outflows of $337.9 million for the purchase of available-for-sale marketable securities, partially offset by
cash inflows of $175.3 million from maturities of available-for-sale marketable securities and $79.8 million from the sale
of available-for-sale marketable securities.
Net cash provided by financing activities
Net cash provided by financing activities for the year ended December 31, 2020 consisted of proceeds of $38.4
million from the sale of our common stock relating to the Vifor Agreement and $0.7 million received from the exercise of
stock options.
Net cash provided by financing activities for the year ended December 31, 2019 consisted of gross proceeds of
$145.5 million from our issuance and sale of our common stock in July 2019, partially offset by $9.0 million of
underwriting discounts and commissions and offering expenses paid by us during the year ended December 31, 2019, and
proceeds of $6.1 million received from the exercise of stock options.
Net cash provided by financing activities for the year ended December 31, 2018 consisted of gross proceeds of $98.3
million from our issuance and sale of our common stock in July 2018, partially offset by $6.3 million of underwriting
discounts and commissions and offering expenses paid by us during the year ended December 31, 2018, proceeds of $14.6
million from the sale of our common stock relating to the VFMCRP Agreement and $4.2 million received from the
exercise of stock options.
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Contractual Obligations
The following table summarizes our significant contractual obligations as of December 31, 2020 (in thousands):
Stamford operating leases
Payment Due for the Year Ending December 31,
2023
$ 1,992
2022
2024
$
— $
$ 1,921 $ 1,957
2021
2025
— $
Total
5,870
Contractual obligations and commitments at December 31, 2020 also included the Enteris License Agreement, which
we entered into in August 2019, and the MSA we entered into with Patheon in July 2019. However, we have no material
non-cancelable purchase commitments with these contract manufacturers or service providers, as we have generally
contracted on a cancelable purchase order basis. Therefore, these were not included in the table above. Furthermore,
milestone payments potentially owed by us in connection with the Enteris License Agreement were not included in the
table above as these milestone events may or may not be achieved.
See Note 17 of Notes to Financial Statements, Commitments and Contingencies, in this Annual Report on Form 10-K
for details about our contractual obligations and commitments, and Note 7 of Notes to Financial Statements, Restricted
Cash, in this Annual Report on Form 10-K for details about our letter of credit associated with our Stamford operating
leases.
Off-Balance Sheet Arrangements
We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as
defined under SEC rules.
Critical Accounting Policies and Significant Judgments and Estimates
Our management’s discussion and analysis of financial condition and results of operations is based upon our
financial statements, which have been prepared in accordance with GAAP. The preparation of these financial statements
requires us to make estimates, judgments and assumptions that affect the reported amounts of assets and liabilities and
disclosures of contingent assets and liabilities as of the date of the balance sheets and the reported amounts of revenues and
expenses during the reporting periods. We base our estimates on historical experience and on various other assumptions
that we believe to be reasonable under the circumstances at the time such estimates are made. Actual results and outcomes
may differ materially from our estimates, judgments and assumptions. We periodically review our estimates in light of
changes in circumstances, facts and experience. The effects of material revisions in estimates are reflected in the financial
statements prospectively from the date of the change in estimate.
We define our critical accounting policies as those accounting principles generally accepted in the United States that
require us to make subjective estimates and judgments about matters that are uncertain and are likely to have a material
impact on our financial condition and results of operations as well as the specific manner in which we apply those
principles. We believe the critical accounting policies used in the preparation of our financial statements which require
significant estimates and judgments are as follows:
Revenue Recognition
On January 1, 2018, we adopted Accounting Standards Update, or ASU, 2014-09, Revenue from Contracts with
Customers (Topic 606), or ASC 606, as amended by ASU 2016-08, 2016-10, 2016-12 and 2016-20 using the full
retrospective method. Under ASC 606, we recognize revenue in an amount that reflects the consideration to which we
expect to be entitled in exchange for the transfer of promised goods or services to customers. To determine revenue
recognition for contracts with customers that are within the scope of ASC 606, we perform the following steps: (1) identify
the contract with the customer, (2) identify the performance obligations in the contract, (3) determine the transaction price,
(4) allocate the transaction price to the performance obligations in the contract, and (5) recognize revenue when (or as) the
entity satisfies a performance obligation. We concluded that upon adoption of ASC 606, as amended, there was no impact
on our results of operations, financial position or cash flows for any period presented
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from our only two revenue-related contracts, which were in effect at that time: the CKDP Agreement or the Maruishi
Agreement.
We have entered into agreements to license our intellectual property, or IP, related to CR845/difelikefalin to develop,
manufacture and/or commercialize drug products. These agreements typically contain multiple performance obligations,
including licenses of IP and R&D services. Payments to us under these agreements may include nonrefundable license
fees, payments for research activities, payments based upon the achievement of certain milestones and royalties on any
resulting net product sales.
We identify agreements as contracts that create enforceable rights and obligations when the agreement is approved
by the parties, identifies the rights of the parties and the payment terms, has commercial substance and it is probable that
we will collect the consideration to which we will be entitled in exchange for the goods and services that will be transferred
to the customer. The counterparty is considered to be a customer when it has contracted with us to obtain goods and
services that are the output of our ordinary activities (i.e., development of pharmaceutical products) in exchange for
consideration.
A performance obligation is a promise to transfer distinct goods or services to a customer. Performance obligations
that are both capable of being distinct and distinct within the context of the contract are considered to be separate
performance obligations. Performance obligations are capable of being distinct if the counterparty is able to benefit from
the good or service on its own or together with other resources that are readily available to it. Performance obligations are
distinct within the context of the contract when each performance obligation is separately identifiable from each other; i.e.,
we are not using the goods or services as inputs to produce or deliver the combined output or outputs specified by the
customer; one or more of the goods or services does not significantly modify or customize one of the other goods or
services in the contract; and goods or services are not highly interdependent or not highly interrelated. Performance
obligations that are not distinct are accounted for as a single performance obligation over the period that goods or services
are transferred to the customer. The determination of whether performance obligations in a contract are distinct may require
significant judgment.
The transaction price is the amount of consideration that we expect to be entitled to in exchange for transferring
promised goods or services to the customer based on the contract terms at inception of a contract. There is a constraint on
inclusion of variable consideration related to licenses of IP, such as milestone payments or sales-based royalty payments, in
the transaction price if there is uncertainty at inception of the contract as to whether such consideration will be recognized
in the future because it is probable that there will be a significant reversal of revenue in the future when the uncertainty is
resolved. The determination of whether or not it is probable that a significant reversal of revenue will occur in the future
depends on the likelihood and magnitude of the reversal. Factors that could increase the likelihood or magnitude of a
reversal of revenue include (a) the susceptibility of the amount of consideration to factors outside the entity’s influence,
such as the outcome of clinical trials, the timing of initiation of clinical trials by the counterparty and the approval of drug
product candidates by regulatory agencies, (b) situations in which the uncertainty is not expected to be resolved for a long
period of time, and (c) level of our experience in the field. When it becomes probable that events will occur, for which
variable consideration was constrained at inception of the contract, we allocate the related consideration to the separate
performance obligations in the same manner as described below.
At inception of a contract, we allocate the transaction price to the distinct performance obligations based upon their
relative standalone selling prices. Standalone selling price is the price at which an entity would sell a promised good or
service separately to a customer. The best evidence of standalone selling price is an observable price of a good or service
when sold separately by an entity in similar circumstances to similar customers. Since we typically do not have such
evidence, we estimate standalone selling price so that the amount that is allocated to each performance obligation equals
the amount that we expect to receive for transferring goods or services. The methods that we use to make such estimates
include (1) the adjusted market assessment approach, under which we forecast and analyze CR845/difelikefalin in the
appropriate market, the phase of clinical development as well as considering recent similar license arrangements within the
same phase of clinical development, therapeutic area, type of agreement, etc. and (2) the expected cost of satisfying the
performance obligations plus a margin, or the expected cost plus a margin approach.
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We recognize revenue when, or as, we satisfy a performance obligation by transferring a promised good or service to
a customer and the customer obtains control of the good or service. Revenue related to the grant of a license that is a
distinct performance obligation and that is deemed to be functional IP is recognized at the point in time that we have the
right to payment for the license, the customer has legal title to the license and can direct the use of the license (for example,
to grant sublicenses), the customer has the significant risks and rewards of ownership of the license and the customer has
accepted the asset (license) by signing the license agreement.
Recognition of revenue related to R&D services that are a distinct performance obligation or that are combined with
granting of a license as a single performance obligation is deferred at inception of a contract and is recognized as those
services are performed based on the costs incurred as a percentage of the estimated total costs to be incurred to complete
the performance obligation.
Milestone payments are considered to be variable consideration and are not included in the transaction price at
inception of the contract if it is uncertain that the milestone will be achieved. Rather, when it becomes probable that the
milestone will be achieved and, therefore, there will not be a significant reversal of revenue in future periods, the respective
amount to be earned is included in the transaction price, allocated to the distinct performance obligations based on their
relative standalone selling price and recognized as revenue, as described above. Sales milestones and sales-based royalty
payments related to a license of IP are recognized as revenue when the respective sales occur.
See Note 2 of Notes to Financial Statements, Summary of Significant Accounting Policies – Revenue Recognition,
and Note 12 of Notes to Financial Statements, Revenue Recognition, in this Annual Report on Form 10-K for further
details about our critical accounting estimates for revenue recognition for our significant contracts.
Stock-Based Compensation
We grant stock options to employees, non-employee directors and non-employee consultants as compensation for
services performed. Employee and non-employee members of the Board of Directors’ awards of stock-based compensation
are accounted for in accordance with ASC 718, Compensation - Stock Compensation, or ASC 718. ASC 718 requires all
share-based payments to employees and non-employee directors, including grants of stock options, to be recognized in the
Statements of Comprehensive Income (Loss) based on their grant date fair values. The grant date fair value of stock
options is estimated using the Black-Scholes option valuation model. On January 1, 2019, we used the Black-Scholes
option valuation model to remeasure the fair value of all outstanding unvested options that had been granted to non-
employee consultants in accordance with ASU 2018-07, Compensation – Stock Compensation (Topic 718), Improvements
to Non-employee Share-Based Payment Accounting. For all share-based payments granted to employees and non-
employees, compensation cost relating to awards with service-based graded vesting schedules is recognized using the
straight-line method over the requisite service period.
Using this model, fair value is calculated based on (i) the fair value or market price of our common stock on the grant
date; (ii) expected volatility of our common stock price, (iii) the periods of time over which employees and non-employee
directors are expected to hold their options prior to exercise (expected term), (iv) expected dividend yield on our common
stock, and (v) risk-free interest rates.
The assumptions for expected volatility and the expected term of stock options used in computing the fair value of
option awards reflect our best estimates but involve uncertainties related to market and other conditions, many of which are
outside of our control. Changes in any of these assumptions may materially affect the fair value of stock options granted
and the amount of stock-based compensation recognized in future periods.
See Note 2 of Notes to Financial Statements, Summary of Significant Accounting Policies – Stock-Based
Compensation, in this Annual Report on Form 10-K for further details about our critical accounting estimates for stock-
based compensation.
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Accounting Pronouncements Recently Adopted; Recent Accounting Pronouncements Not Yet Adopted
Please refer to Note 2 of Notes to Financial Statements, Summary of Significant Accounting Policies, in this Annual
Report on Form 10-K.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk.
Interest Rate Risk
We invest a majority of our cash reserves in a variety of available-for-sale marketable securities, including
investment-grade debt instruments, principally corporate bonds, commercial paper, municipal bonds and direct obligations
of the U.S. government and U.S. government-sponsored entities, and in cash equivalents. See Note 3 of Notes to Financial
Statements, Available-for-Sale Marketable Securities, in this Annual Report on Form 10-K for details about our available-
for-sale marketable securities.
As of December 31, 2020, we had invested $219.8 million of our cash reserves in such marketable securities. Those
marketable securities include $219.8 million of investment grade debt instruments with a yield of approximately 0.32% and
maturities through December 2023. As of December 31, 2019, we had invested $199.9 million of our cash reserves in such
marketable securities. Those marketable securities include $199.9 million of investment grade debt instruments with a
yield of approximately 2.08% and maturities through December 2021.
We maintain an investment portfolio in accordance with our investment policy, which includes guidelines on
acceptable investment securities, minimum credit quality, maturity parameters, and concentration and diversification. The
primary objectives of our investment policy are to preserve principal, maintain proper liquidity and to meet operating
needs. Our investments are subject to interest rate risk and will decrease in value if market interest rates increase. However,
due to the conservative nature of our investments and relatively short duration, we do not believe we are materially
exposed to changes in interest rates related to our investments. As a result, we do not currently use interest rate derivative
instruments to manage exposure to interest rate changes.
Duration is a sensitivity measure that can be used to approximate the change in the fair value of a security that will
result from a change in interest rates. Applying the duration model, a hypothetical 100 basis point, or 1%, increase in
interest rates as of December 31, 2020 and 2019, would have resulted in immaterial decreases in the fair values of our
portfolio of marketable securities at those dates.
Credit Quality Risk
Although our investments are subject to credit risk, our investment policy specifies credit quality standards for our
investments and limits the amount of credit exposure from any single issue, issuer or type of investment. Nonetheless,
deterioration of the credit quality of an investment security subsequent to purchase may subject us to the risk of not being
able to recover the full principal value of the security. For the year end December 31, 2020, we did not record any charges
to credit loss expense for our available-for-sale securities. For the year ended December 31, 2019, we did not record any
charges for other-than-temporary impairments of our available-for-sale securities. (Refer to Note 2 of Notes to Financial
Statements, Summary of Significant Accounting Policies – Marketable Securities, in this Annual Report on Form 10-K).
As of December 31, 2020 and 2019, we did not have material balances of receivables on our Balance Sheets.
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Item 8. Financial Statements and Supplementary Data.
Cara Therapeutics, Inc.
INDEX TO FINANCIAL STATEMENTS
Reports of Independent Registered Public Accounting Firm
Financial Statements:
Balance Sheets
Statements of Comprehensive Income (Loss)
Statements of Stockholders’ Equity
Statements of Cash Flows
Notes to Financial Statements
100
PAGE
101
104
105
106
107
108
Table of Contents
Report of Independent Registered Public Accounting Firm
To the Shareholders and the Board of Directors of Cara Therapeutics, Inc.
Opinion on the Financial Statements
We have audited the accompanying balance sheets of Cara Therapeutics, Inc. (the Company) as of December 31, 2020 and
2019, the related statements of comprehensive income (loss), stockholders' equity and cash flows for each of the three
years in the period ended December 31, 2020, and the related notes (collectively referred to as the “financial statements”).
In our opinion, the financial statements present fairly, in all material respects, the financial position of the Company at
December 31, 2020 and 2019, and the results of its operations and its cash flows for each of the three years in the period
ended December 31, 2020, in conformity with U.S. generally accepted accounting principles.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United
States) (PCAOB), the Company's internal control over financial reporting as of December 31, 2020, based on criteria
established in Internal Control-Integrated Framework issued by the Committee of Sponsoring Organizations of the
Treadway Commission (2013 framework) and our report dated February 25, 2021 expressed an unqualified opinion
thereon.
Basis for Opinion
These financial statements are the responsibility of the Company's management. Our responsibility is to express an opinion
on the Company’s financial statements based on our audits. We are a public accounting firm registered with the PCAOB
and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the
applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and
perform the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement,
whether due to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the
financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures
included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits
also included evaluating the accounting principles used and significant estimates made by management, as well as
evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our
opinion.
Critical Audit Matter
The critical audit matter communicated below is a matter arising from the current period audit of the financial statements
that was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or
disclosures that are material to the financial statements and (2) involved our especially challenging, subjective or complex
judgments. The communication of the critical audit matter does not alter in any way our opinion on the financial
statements, taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate
opinion on the critical audit matter or on the account or disclosure to which it relates.
Revenue Recognition
Description of the
Matter
As discussed in Notes 11 and 12 to the financial statements, the Company entered into a royalty-free
license agreement with Vifor (International) Ltd. (“Vifor”) on October 15, 2020, whereby the
Company granted Vifor exclusive commercialization rights to its product candidates in the United
States. To determine the revenue to recognize during the period, the Company assessed whether the
obligations, including the intellectual property license and regulatory services, were capable of being
distinct within the context of the license agreement, including whether they would be accounted for
as individual or combined performance obligations.
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Auditing revenue recognition is complex and involves a high degree of subjective auditor judgment
to determine the performance obligations. Changes in the number of performance obligations and the
timing of their fulfillment, could have a significant effect on the amount of revenue recognized in the
period.
How We
Addressed the
Matter in Our
Audit
We obtained an understanding, evaluated the design, and tested the operating effectiveness of controls
that address the risks of a material revenue misstatement, including controls over management’s
review of the terms and conditions of the license agreement and the determination of distinct
performance obligations.
To test the amount of revenue recognized, we evaluated, among other things, whether the identified
performance obligation was properly determined to be distinct. To test the satisfaction of the
performance obligation, our audit procedures included, among others, reviewing management’s
analysis as compared to the underlying contract and evaluating the application of the method for the
recognition of revenue. Our subject matter specialists also assisted us in evaluating the terms of the
license agreement and the interpretation of the related accounting guidance to determine if the
obligations were distinct.
/s/ Ernst & Young LLP
We have served as the Company's auditor since 2006.
Stamford, Connecticut
February 25, 2021
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Report of Independent Registered Public Accounting Firm
To the Shareholders and the Board of Directors of Cara Therapeutics, Inc.
Opinion on Internal Control Over Financial Reporting
We have audited Cara Therapeutics, Inc.’s internal control over financial reporting as of December 31, 2020, based on criteria
established in Internal Control—Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway
Commission (2013 framework) (the COSO criteria). In our opinion, Cara Therapeutics, Inc. (the Company) maintained, in all
material respects, effective internal control over financial reporting as of December 31, 2020, based on the COSO criteria.
We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)
(PCAOB), the balance sheets of the Company as of December 31, 2020 and 2019, the related statements of comprehensive
income (loss), stockholders' equity and cash flows for each of the three years in the period ended December 31, 2020, and the
related notes and our report dated February 25, 2021 expressed an unqualified opinion thereon.
Basis for Opinion
The Company’s management is responsible for maintaining effective internal control over financial reporting and for its
assessment of the effectiveness of internal control over financial reporting included in the accompanying Management’s Report
on Internal Control over Financial Reporting. Our responsibility is to express an opinion on the Company’s internal control over
financial reporting based on our audit. We are a public accounting firm registered with the PCAOB and are required to be
independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and
regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform the
audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in all
material respects.
Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material
weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk, and
performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a
reasonable basis for our opinion.
Definition and Limitations of Internal Control Over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the
reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally
accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures that
(1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions
of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to permit preparation of
financial statements in accordance with generally accepted accounting principles, and that receipts and expenditures of the
company are being made only in accordance with authorizations of management and directors of the company; and (3) provide
reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s
assets that could have a material effect on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate
because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
/s/ Ernst & Young LLP
Stamford, Connecticut
February 25, 2021
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CARA THERAPEUTICS, INC.
BALANCE SHEETS
(amounts in thousands, except share and per share data)
Assets
Current assets:
Cash and cash equivalents
Marketable securities
Income tax receivable
Other receivables
Prepaid expenses
Total current assets
Operating lease right-of-use assets
Marketable securities, non-current
Property and equipment, net
Restricted cash
Total assets
Liabilities and stockholders’ equity
Current liabilities:
Accounts payable and accrued expenses
Operating lease liabilities, current
Current portion of deferred revenue
Total current liabilities
Operating lease liabilities, non-current
Commitments and contingencies (Note 17)
Stockholders’ equity:
Preferred stock; $0.001 par value; 5,000,000 shares authorized at
December 31, 2020 and December 31, 2019, zero shares issued and outstanding
at December 31, 2020 and December 31, 2019
Common stock; $0.001 par value; 100,000,000 shares authorized at
December 31, 2020 and December 31, 2019, 49,872,213 shares and 46,720,225
shares issued and outstanding at December 31, 2020 and December 31, 2019,
respectively
Additional paid-in capital
Accumulated deficit
Accumulated other comprehensive income
Total stockholders’ equity
Total liabilities and stockholders’ equity
See Notes to Financial Statements.
104
December 31, 2020 December 31, 2019
$
$
$
$
31,683
149,242
1,507
557
12,076
195,065
4,279
70,565
840
408
271,157
16,881
1,602
$
$
$
—
18,483
3,673
—
18,305
136,701
816
971
8,863
165,656
3,036
63,159
700
408
232,959
19,665
967
22,262
42,894
3,352
—
—
—
50
641,195
(392,317)
73
249,001
271,157
$
47
587,223
(400,727)
170
186,713
232,959
Table of Contents
CARA THERAPEUTICS, INC.
STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
(amounts in thousands, except share and per share data)
Revenue:
License and milestone fees
Clinical compound revenue
Total revenue
Operating expenses:
Research and development
General and administrative
Total operating expenses
Operating income (loss)
Other income, net
Income (loss) before benefit from income taxes
Benefit from income taxes
Net income (loss)
Net income (loss) per share:
Basic
Diluted
Weighted average shares:
Basic
Diluted
Other comprehensive income (loss), net of tax of $0:
Change in unrealized gains (losses) on available-for-sale marketable
securities
Total comprehensive income (loss)
2020
Year Ended December 31,
2019
2018
134,439
643
135,082
107,851
21,846
129,697
5,385
2,334
7,719
691
8,410
0.18
0.18
$
$
$
$
$
19,746
140
19,886
113,820
17,745
131,565
(111,679)
4,490
(107,189)
816
(106,373) $
13,436
33
13,469
75,531
15,320
90,851
(77,382)
2,980
(74,402)
389
(74,013)
(2.49) $
(2.49) $
(2.06)
(2.06)
$
$
$
$
47,413,250
47,915,030
42,669,333
42,669,333
35,892,786
35,892,786
(97)
8,313
$
284
(106,089) $
(44)
(74,057)
$
See Notes to Financial Statements.
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CARA THERAPEUTICS, INC.
STATEMENTS OF STOCKHOLDERS’ EQUITY
(amounts in thousands, except share and per share data)
Balance at December 31, 2017
Sale of common stock under license agreement
Sale of common stock in a follow-on public
offering ($19.00 per share), net of underwriting
discounts and commissions and offering
expenses of $6,262
Stock-based compensation expense
Modification of equity awards
Shares issued upon vesting of restricted stock
units
Shares issued upon exercise of stock options
Net loss
Other comprehensive loss
Balance at December 31, 2018
Sale of common stock in a follow-on public
offering ($23.00 per share), net of underwriting
discounts and commissions and offering
expenses of $8,977
Issuance of common stock upon entry into
License Agreement with Enteris Biopharma,
Inc. ($23.42 per share)
Stock-based compensation expense
Shares issued upon exercise of stock options
Shares issued upon vesting of restricted stock
units
Shares issued for consulting services
Net loss
Other comprehensive income
Balance at December 31, 2019
Sale of common stock under license agreement
Stock-based compensation expense
Shares issued upon exercise of stock options
Shares issued upon vesting of restricted stock
units
Net income
Other comprehensive loss
Balance at December 31, 2020
Common Stock
Amount
Additional
Paid-in
Capital
$
33
1
$
307,158
14,555
$
Shares
32,662,255
1,174,827
Deficit
(220,341)
$
—
Accumulated
Other
Accumulated Comprehensive
Income (Loss)
Total
Stockholders’
Equity
5,175,000
—
—
5
—
—
83,791
451,685
—
—
39,547,558
—
—
—
—
39
92,058
7,785
616
1,693
4,194
—
—
428,059
—
—
—
—
—
(74,013)
—
(294,354)
(70)
$
—
86,780
14,556
—
—
—
—
—
—
(44)
(114)
92,063
7,785
616
1,693
4,194
(74,013)
(44)
133,630
6,325,000
7
136,491
—
—
136,498
170,793
—
555,847
110,832
10,195
—
—
46,720,225
2,939,552
—
55,852
156,584
—
—
$
49,872,213
—
—
1
—
—
—
—
47
3
—
—
4,000
10,587
6,105
1,784
197
—
—
587,223
38,446
12,486
691
—
—
—
$
50
2,349
—
—
$
641,195
—
—
—
—
—
(106,373)
—
(400,727)
—
—
—
—
8,410
—
$
(392,317)
See Notes to Financial Statements.
106
—
—
—
—
—
—
284
170
—
—
—
—
—
(97)
73
$
4,000
10,587
6,106
1,784
197
(106,373)
284
186,713
38,449
12,486
691
2,349
8,410
(97)
249,001
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CARA THERAPEUTICS, INC.
STATEMENTS OF CASH FLOWS
(in thousands)
Operating activities
Net income (loss)
Adjustments to reconcile net income (loss) to net cash used in operating
activities:
Stock-based compensation expense
Modification of equity awards
Depreciation and amortization
Amortization expense component of lease expense
Noncash expense related to oral formulation license agreement
Amortization/(accretion) of available-for-sale marketable securities,
net
Realized loss (gain) on sale of available-for-sale marketable securities
Deferred rent costs
Deferred revenue
Changes in operating assets and liabilities:
Income tax receivable
Other receivables
Prepaid expenses
Accounts payable and accrued expenses
Operating lease liabilities
Net cash used in operating activities
Investing activities
Proceeds from maturities of available-for-sale marketable securities
Proceeds from redemptions of available-for-sale marketable securities,
at par
Proceeds from sale of available-for-sale marketable securities
Purchases of available-for-sale marketable securities
Purchases of property and equipment
Net cash used in investing activities
Financing activities
Year Ended December 31,
2020
2019
2018
$
8,410
$
(106,373)
$ (74,013)
14,835
—
209
806
—
12,568
—
198
601
4,000
154
(272)
—
(1,381)
—
—
(22,262)
(19,747)
(691)
414
(3,213)
(2,784)
(1,093)
(5,487)
(152)
(45)
(4,058)
6,043
(879)
(109,225)
9,478
616
370
—
—
(1,820)
5
(156)
42,009
67
(803)
(3,170)
5,116
—
(22,301)
144,320
253,584
175,300
27,035
41,600
(232,881)
(349)
(20,275)
2,000
—
(286,082)
(18)
(30,516)
—
79,808
(337,854)
(73)
(82,819)
Proceeds from the sale of common stock under license agreement
Proceeds from the sale of common stock in a follow-on public offering,
net of issuance costs
Proceeds from the exercise of stock options
Net cash provided by financing activities
Net increase in cash, cash equivalents and restricted cash
Cash, cash equivalents and restricted cash at beginning of period
Cash, cash equivalents and restricted cash at end of period
Noncash investing and financing activities
Shares of common stock issued in connection with oral formulation
license agreement
Shares of common stock issued in exchange for consulting services
$
$
$
38,449
—
14,556
—
691
39,140
13,378
18,713
32,091
$
136,498
6,106
142,604
2,863
15,850
18,713
— $
— $
4,000
197
92,063
4,194
110,813
5,693
10,157
15,850
—
—
$
$
$
See Notes to Financial Statements.
107
Table of Contents
1. Business
CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Cara Therapeutics, Inc., or the Company, is a clinical-stage biopharmaceutical corporation formed on July 2, 2004.
The Company is focused on developing and commercializing new chemical entities designed to alleviate pruritus by
selectively targeting peripheral kappa opioid receptors. The Company’s primary activities to date have been organizing and
staffing the Company, developing its product candidates and raising capital.
As of December 31, 2020, the Company has raised aggregate net proceeds of approximately $519,600 from several
rounds of equity financing, including its initial public offering, or IPO, which closed in February 2014 and four follow-on
public offerings of common stock, which closed in July 2019, July 2018, April 2017 and August 2015, respectively, and
the issuance of convertible preferred stock and debt prior to the IPO. The Company had also received approximately
$201,893 under its license agreements for CR845/difelikefalin, primarily with Vifor (International) Ltd., or Vifor, Vifor
Fresenius Medical Care Renal Pharma Ltd., or VFMCRP, Maruishi Pharmaceutical Co. Ltd., or Maruishi, and Chong Kun
Dang Pharmaceutical Corp., or CKDP, and an earlier product candidate for which development efforts ceased in 2007.
Additionally, in October 2020, the Company received net proceeds of $38,449 from the issuance and sale of 2,939,552
shares of the Company’s common stock to Vifor in connection with the Company’s license agreement with Vifor.
Furthermore, in May 2018, the Company received net proceeds of $14,556 from the issuance and sale of 1,174,827 shares
of the Company’s common stock to Vifor in connection with the Company’s license agreement with VFMCRP (see
Note 11, Collaboration and Licensing Agreements).
As of December 31, 2020, the Company had unrestricted cash and cash equivalents and marketable securities of
$251,490 and an accumulated deficit of $392,317. The Company has incurred substantial net losses and negative cash
flows from operating activities in nearly every fiscal period since inception and expects this trend to continue for the
foreseeable future. The Company recognized net income of $8,410 and had net cash used in operating activities of $5,487
for the year ended December 31, 2020.
The Company is subject to risks common to other life science companies including, but not limited to, uncertainty of
product development and commercialization, lack of marketing and sales history, development by its competitors of new
technological innovations, dependence on key personnel, market acceptance of products, product liability, protection of
proprietary technology, ability to raise additional financing, and compliance with the Food and Drug Administration, or
FDA, and other government regulations. If the Company does not successfully commercialize any of its product
candidates, it will be unable to generate recurring product revenue or achieve profitability.
2. Summary of Significant Accounting Policies
Use of Estimates
The preparation of financial statements in conformity with generally-accepted accounting principles in the United
States or GAAP, requires the Company to make estimates and assumptions that affect the reported amounts of assets and
liabilities, and disclosure of contingent assets and liabilities, as of the date of the financial statements as well as the
reported amounts of revenues and expenses during the reporting period. The more significant estimates include the fair
value of marketable securities that are classified as level 2 of the fair value hierarchy, the periods over which certain
revenues will be recognized, including licensing and collaborative revenue recognized from non-refundable up-front and
milestone payments, the determination of prepaid research and development, or R&D, clinical costs and accrued research
projects, the amount of non-cash compensation costs related to share-based payments to employees and non-employees and
the periods over which those costs are expensed, the incremental borrowing rate used in lease calculations and the
likelihood of realization of deferred tax assets.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The ongoing COVID-19 pandemic has interrupted business operations across the globe. Estimates and assumptions
about future events and their effects cannot be determined with certainty and therefore require the exercise of judgment. As
of the date of issuance of these financial statements, the Company is not aware of any specific event or circumstance that
would require the Company to update its estimates, assumptions and judgments or revise the reported amounts of assets
and liabilities or the disclosure of contingent assets and liabilities. These estimates, however, may change as new events
occur and additional information is obtained, and are recognized in the financial statements as soon as they become known.
Actual results could differ materially from the Company’s estimates and assumptions.
Concentrations of Credit Risk
Financial instruments, which potentially subject the Company to significant concentrations of credit risk consist
primarily of cash equivalents and marketable securities. The Company invests its cash reserves in money market funds or
high-quality marketable securities in accordance with its investment policy. The stated objectives of its investment policy
are to preserve capital, provide liquidity consistent with forecasted cash flow requirements, maintain appropriate
diversification and generate returns relative to these investment objectives and prevailing market conditions. The
Company’s investment policy includes guidelines on acceptable investment securities, limits interest-bearing security
investments to certain types of debt and money market instruments issued by the U.S. government and institutions with
investment grade credit ratings and places restrictions on maturities and concentration by asset class and issuer. The
Company’s cash and cash equivalents and marketable securities are held by four major financial institutions. In accordance
with the Company’s policies, the Company monitors exposure with its counterparties. The Company also maintains
deposits in federally insured financial institutions in excess of federally insured limits. The Company has not experienced
any losses in such accounts and management believes that the Company is not exposed to significant credit risk due to the
financial position of the depository institutions in which those deposits are held.
Cash and Cash Equivalents
Cash and cash equivalents include cash on hand, demand deposits, deposits with banks and highly liquid money
market funds with holdings of cash and other investments with original maturities of three months or less.
Marketable Securities
On January 1, 2020, the Company adopted Accounting Standards Update, or ASU, No. 2016-13, Financial
Instruments—Credit Losses (Topic 326), Measurement of Credit Losses on Financial Instruments, or ASU 2016-13, which
replaces the incurred loss impairment methodology in prior GAAP that delays recognition of a credit loss until it is
probable that such loss has been incurred, with a methodology that reflects expected credit losses and requires
consideration of a broader range of reasonable and supportable information to inform credit loss estimates.
The Company deems certain of its investments to be marketable securities if the investment, or in the case of money
market funds, the securities underlying the money market fund, meet the definition of a debt security in Accounting
Standards Codification, or ASC, section 320-10-20. The Company considers its marketable securities to be available-for-
sale, which are its only financial instruments that are within the scope of ASU 2016-13 as of December 31, 2020. The
Company’s investments in marketable securities, including U.S. Treasury securities, U.S. government agency obligations,
corporate bonds, commercial paper, and municipal bonds are highly rated by Moody’s and S&P and have maturities
primarily of less than one year but no longer than three years. Accordingly, credit risk associated with the Company’s
available-for-sale debt security portfolio is mitigated.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
ASU 2016-13 modifies the prior other-than-temporary impairment model for available-for-sale debt securities by
requiring (1) estimating expected credit losses (the portion of the amortized cost basis of a financial asset that the Company
does not expect to collect) only when the fair value is below the amortized cost of the asset; (2) recording a credit loss
without regard to the length of time a security has been in an unrealized loss position; (3) limiting the measurement of the
credit loss to the difference between the security’s amortized cost basis and its fair value; and (4) presenting credit losses as
an allowance rather than as a write-down, which will allow the Company to record reversals of credit losses in current
period net income, a practice that was previously prohibited.
The Company reviews each of its available-for-sale marketable securities for unrealized losses (declines in fair value
below its amortized cost basis) at each balance sheet date presented in its financial statements and whenever events or
changes in circumstances indicate that the amortized cost basis of an asset may not be recoverable. In accordance with the
adoption of ASU 2016-13, the Company is required to determine whether any portion of the unrealized loss for any
available-for-sale debt security is due to a credit loss, and if so, to measure the amount of the credit loss.
The Company will rely on both qualitative and quantitative factors to determine whether the unrealized loss for each
available-for-sale debt security at any balance sheet date is due to a credit loss.
Qualitative factors may include a credit downgrade, severity of the decline in fair value below amortized cost and
other adverse conditions related specifically to the security, as well as the intent to sell the security, or whether the
Company will more likely than not be required to sell the security before recovery of its amortized cost basis. The
Company’s assessment of whether a security is impaired could change in the future due to new developments or changes in
assumptions related to any particular security. If material qualitative factors indicate that a credit loss has occurred, the
Company will determine the magnitude of that credit loss using a discounted cash flow model or other quantitative method.
If the Company intends to sell the security or it is more likely than not that the Company will be forced to sell the
security before recovery of the amortized cost of the security, the entire unrealized loss is deemed to be a credit loss, which
is recognized in net income (loss). Otherwise, the portion of the unrealized loss that is due to a credit loss will be recorded
as an allowance for credit loss, which will offset the balance of marketable securities and as credit loss expense within
other income, net. The portion of the unrealized loss that is not due to a credit loss as well as all unrealized gains will be
recorded in Accumulated Other Comprehensive Income (Loss). There was no cumulative effect adjustment as a result of
the adoption of ASU 2016-13 on January 1, 2020 (see Note 3, Available-for-Sale Marketable Securities, and Note 10, Fair
Value Measurements).
Accrued interest receivables are excluded from the Company’s amortized cost bases for its available-for-sale
marketable securities and are included within other receivables. The Company’s policy is to not measure an allowance for
credit losses on accrued interest receivable balances at each reporting period since it elects to write off uncollectible
accrued interest receivable balances as credit loss expense in a timely manner, which is by maturity date for all categories
of its debt securities.
Fair Value of Financial Instruments
The Company applies fair value accounting for all financial assets and liabilities that are recognized or disclosed at
fair value in the financial statements on a recurring basis. The Company defines fair value as the price that would be
received from selling an asset or paid to transfer a liability in an orderly transaction between market participants at the
measurement date. When determining the fair value measurements for assets and liabilities which are required to be
recorded at fair value, the Company considers the principal or most advantageous market in which it would transact and the
market-based risk measurements or assumptions that market participants would use in pricing the asset or liability, such as
risks inherent in valuation techniques, transfer restrictions and credit risks.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company’s financial instruments consist of cash, cash equivalents, available-for-sale marketable securities,
prepaid expenses, restricted cash, accounts payable and accrued liabilities. The fair values of cash, cash equivalents,
prepaid expenses, restricted cash, accounts payable and accrued liabilities approximate their carrying values due to the
short-term nature of these financial instruments. Available-for-sale marketable securities are reported as marketable
securities at their fair values, based upon pricing of securities with the same or similar investment characteristics as
provided by third-party pricing services, as described below.
The valuation techniques used by the Company are based on observable and unobservable inputs. Observable inputs
reflect readily obtainable data from independent sources, while unobservable inputs reflect the Company’s assumptions
about the inputs that market participants would use in pricing the asset or liability and are developed based on the best
information available in the circumstances.
The Company classifies its investments in a fair value hierarchy that is intended to increase consistency and
comparability in fair value measurements and related disclosures. The fair value hierarchy is divided into three levels based
on the source of inputs as follows:
●
●
●
Level 1 – Observable inputs – quoted prices in active markets for identical assets and liabilities.
Level 2 – Observable inputs other than the quoted prices in active markets for identical assets and liabilities –
such as quoted prices for similar instruments, quoted prices for identical or similar instruments in inactive
markets, or other inputs that are observable or can be corroborated by observable market data.
Level 3 – Unobservable inputs – includes amounts derived from valuation models where one or more
significant inputs are unobservable and require the Company to develop relevant assumptions.
The Company records transfers between levels in the hierarchy by assuming that the transfer occurred at the end of
the quarter or year-to-date period.
Valuation Techniques - Level 2 Inputs
The Company estimates the fair values of its financial instruments categorized as level 2 in the fair value hierarchy,
including U.S. Treasury securities, U.S. government agency obligations, corporate bonds, commercial paper and municipal
bonds, by taking into consideration valuations obtained from third-party pricing services. The pricing services use industry
standard valuation models, including both income- and market-based approaches, for which all significant inputs are
observable, either directly or indirectly, to estimate fair value. These inputs include reported trades of and broker/dealer
quotes on the same or similar securities, benchmark yields, issuer credit spreads, benchmark securities, and other
observable inputs. The Company obtains a single price for each financial instrument and does not adjust the prices obtained
from the pricing service.
The Company validates the prices provided by its third-party pricing services by reviewing their pricing methods,
obtaining market values from other pricing sources and comparing them to the share prices presented by the third-party
pricing services. After completing its validation procedures, the Company did not adjust or override any fair value
measurements provided by its pricing services as of December 31, 2020 or December 31, 2019.
Property and Equipment, net
Property and equipment (consisting of computer, office and laboratory equipment, furniture and fixtures and
leasehold improvements) are stated at cost, net of accumulated depreciation and amortization of leasehold improvements.
Depreciation and amortization are calculated using the straight-line method over the estimated useful
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
lives of the respective assets. Leasehold improvements are amortized over the lesser of their useful lives or the life of the
lease.
Asset Category
Computer and office equipment
Short-term laboratory equipment
Furniture and fixtures
Leasehold improvements
Useful Lives
5 years
2 years
7 years
lesser of useful life of asset or life of lease
(Stamford - 7 years)
The Company reviews the recorded values of property and equipment for impairment whenever events or changes in
business circumstances indicate that the carrying amount of an asset or group of assets may not be fully recoverable.
Revenue Recognition
On January 1, 2018, the Company adopted ASU 2014-09, Revenue from Contracts with Customers (Topic 606), or
ASC 606, as amended by ASU 2016-08, 2016-10, 2016-12 and 2016-20 using the full retrospective method. Under ASC
606, the Company recognizes revenue in an amount that reflects the consideration to which it expects to be entitled in
exchange for the transfer of promised goods or services to customers. To determine revenue recognition for contracts with
customers that are within the scope of ASC 606, the Company performs the following steps: (1) identifies the contract with
the customer, (2) identifies the performance obligations in the contract, (3) determines the transaction price, (4) allocates
the transaction price to the performance obligations in the contract, and (5) recognizes revenue when (or as) the entity
satisfies a performance obligation. The Company concluded that upon adoption of ASC 606, as amended, there was no
impact on its results of operations, financial position or cash flows for any period presented from its only two revenue-
related contracts, which were in effect at that time: the CKDP Agreement or the Maruishi Agreement (see Note 11,
Collaboration and Licensing Agreements and Note 12, Revenue Recognition).
The Company has entered into agreements to license its intellectual property, or IP, related to CR845/difelikefalin to
develop, manufacture and/or commercialize drug products. These agreements typically contain multiple performance
obligations, including licenses of IP and R&D services. Payments to the Company under these agreements may include
nonrefundable license fees, payments for research activities, payments based upon the achievement of certain milestones
and royalties on any resulting net product sales.
The Company identifies agreements as contracts that create enforceable rights and obligations when the agreement is
approved by the parties, identifies the rights of the parties and the payment terms, has commercial substance and it is
probable that the Company will collect the consideration to which it will be entitled in exchange for the goods and services
that will be transferred to the customer. The counterparty is considered to be a customer when it has contracted with the
Company to obtain goods and services that are the output of the Company’s ordinary activities (i.e., development of
pharmaceutical products) in exchange for consideration.
A performance obligation is a promise to transfer distinct goods or services to a customer. Performance obligations
that are both capable of being distinct and distinct within the context of the contract are considered to be separate
performance obligations. Performance obligations are capable of being distinct if the counterparty is able to benefit from
the good or service on its own or together with other resources that are readily available to it. Performance obligations are
distinct within the context of the contract when each performance obligation is separately identifiable from each other; i.e.,
the Company is not using the goods or services as inputs to produce or deliver the combined output or outputs specified by
the customer; one or more of the goods or services does not significantly modify or customize one of the other goods or
services in the contract; and goods or services are not highly interdependent or not highly interrelated. Performance
obligations that are not distinct are accounted for as a single performance obligation over the period that
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
goods or services are transferred to the customer. The determination of whether performance obligations in a contract are
distinct may require significant judgment.
The transaction price is the amount of consideration that the Company expects to be entitled to in exchange for
transferring promised goods or services to the customer based on the contract terms at inception of a contract. There is a
constraint on inclusion of variable consideration related to licenses of IP, such as milestone payments or sales-based royalty
payments, in the transaction price if there is uncertainty at inception of the contract as to whether such consideration will
be recognized in the future because it is probable that there will be a significant reversal of revenue in the future when the
uncertainty is resolved. The determination of whether or not it is probable that a significant reversal of revenue will occur
in the future depends on the likelihood and magnitude of the reversal. Factors that could increase the likelihood or
magnitude of a reversal of revenue include (a) the susceptibility of the amount of consideration to factors outside the
entity’s influence, such as the outcome of clinical trials, the timing of initiation of clinical trials by the counterparty and the
approval of drug product candidates by regulatory agencies, (b) situations in which the uncertainty is not expected to be
resolved for a long period of time, and (c) level of the Company’s experience in the field. When it becomes probable that
events will occur, for which variable consideration was constrained at inception of the contract, the Company allocates the
related consideration to the separate performance obligations in the same manner as described below.
At inception of a contract, the Company allocates the transaction price to the distinct performance obligations based
upon their relative standalone selling prices. Standalone selling price is the price at which an entity would sell a promised
good or service separately to a customer. The best evidence of standalone selling price is an observable price of a good or
service when sold separately by an entity in similar circumstances to similar customers. Since the Company typically does
not have such evidence, it estimates standalone selling price so that the amount that is allocated to each performance
obligation equals the amount that the Company expects to receive for transferring goods or services. The methods that the
Company uses to make such estimates include (1) the adjusted market assessment approach, under which the Company
forecasts and analyzes CR845/difelikefalin in the appropriate market, the phase of clinical development as well as
considering recent similar license arrangements within the same phase of clinical development, therapeutic area, type of
agreement, etc. and (2) the expected cost of satisfying the performance obligations plus a margin, or the expected cost plus
a margin approach.
The Company recognizes revenue when, or as, it satisfies a performance obligation by transferring a promised good
or service to a customer and the customer obtains control of the good or service. Revenue related to the grant of a license
that is a distinct performance obligation and that is deemed to be functional IP is recognized at the point in time that the
Company has the right to payment for the license, the customer has legal title to the license and can direct the use of the
license (for example, to grant sublicenses), the customer has the significant risks and rewards of ownership of the license
and the customer has accepted the asset (license) by signing the license agreement.
Recognition of revenue related to R&D services that are a distinct performance obligation or that are combined with
granting of a license as a single performance obligation is deferred at inception of a contract and is recognized as those
services are performed based on the costs incurred as a percentage of the estimated total costs to be incurred to complete
the performance obligation.
Milestone payments are considered to be variable consideration and are not included in the transaction price at
inception of the contract if it is uncertain that the milestone will be achieved. Rather, when it becomes probable that the
milestone will be achieved and, therefore, there will not be a significant reversal of revenue in future periods, the respective
amount to be earned is included in the transaction price, allocated to the distinct performance obligations based on their
relative standalone selling price and recognized as revenue, as described above. Sales milestones and sales-based royalty
payments related to a license of IP are recognized as revenue when the respective sales occur.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Research and Development (R&D) Expenses
R&D costs are charged to expense as incurred. Costs incurred under agreements with third parties are charged to
expense as incurred in accordance with the specific contractual performance terms of such agreements. R&D expenses
include, among other costs, compensation and other personnel-related costs, including consultant costs, and costs to
conduct clinical trials using clinical research organizations, or CRO’s, which include upfront, milestone and monthly
expenses as well as reimbursement for pass through costs. The amount of clinical trial expense recognized in any period
varies depending on the duration and progress of each clinical trial, including the required level of patient enrollment, the
rate at which patients actually enroll in and drop-out of the clinical trial, and the number of sites involved in the trial as
well as the activities to be performed by the sites each period. R&D costs also include costs to manufacture product
candidates and clinical supplies, laboratory supplies costs, facility-related costs and stock-based compensation for R&D
personnel. Non-refundable R&D advance payments are deferred and capitalized as prepaid R&D expense. The capitalized
amounts are expensed as the related goods are delivered or services are performed. As of December 31, 2020 and 2019, the
Company recorded $11,286 and $8,498 as prepaid R&D expense, respectively.
Income Taxes
The Company accounts for income taxes using the asset and liability method. Under this method, deferred tax assets
and liabilities are determined based on differences between the financial reporting and tax bases of assets and liabilities and
are measured using the enacted tax rates and laws that will be in effect when the differences are expected to reverse.
Deferred income tax assets are reduced, as necessary, by a valuation allowance when management determines it is more
likely than not that some or all of the tax benefits will not be realized.
There were no material uncertain tax positions taken as of December 31, 2020 and December 31, 2019. The
Company does not have any interest or penalties accrued related to tax positions as it does not have any unrecognized tax
benefits. In the event the Company determines that accrual of interest or penalties are necessary in the future, the amount
will be presented as a component of interest expense.
Stock-Based Compensation
The Company grants stock options to employees, non-employee members of the Company’s Board of Directors and
non-employee consultants as compensation for services performed. All share-based payments, including grants of stock
options, are recognized based on their grant date fair values. The grant date fair value of stock options is estimated using
the Black-Scholes option valuation model.
Using this model, fair value is calculated based on assumptions with respect to (i) the fair value or market price of
the Company’s common stock on the grant date; (ii) expected volatility of the Company’s common stock price, (iii) the
periods of time over which employees and members of the Company’s Board of Directors or non-employee consultants are
expected to hold their options prior to exercise (expected term), (iv) expected dividend yield on the Company’s common
stock, and (v) risk-free interest rates.
The Company’s common stock has been traded on a public exchange only since January 31, 2014. Since that time,
exercises of stock options have been limited due to various factors, including fluctuations in the Company’s stock price to
below the exercise prices of awards and blackout periods during which exercises are not allowed, among others. Therefore,
the Company believes that as of December 31, 2020, it does not have sufficient company-specific information available to
determine the expected term based on its historical data. As a result, the expected term of stock options granted is
determined using the average of the vesting period and term (6.25 years), an accepted method for the Company’s option
grants under the SEC’s Staff Accounting Bulletin No. 110, Share-Based Payment.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
During the period from January 31, 2014 to December 31, 2018, the Company’s stock had not traded on a public
exchange for a sufficient period of time to approximate its expected term (as noted above). Therefore, the Company
calculated the volatility for stock options granted using an analysis of guideline companies for the year ended December
31, 2018. Volatility calculated in this manner was in the range of 83% - 93% for stock options granted during the year
ended December 31, 2018.
Beginning on January 1, 2019, the Company determined that it had sufficient company-specific trading activity of its
common stock available to use that activity exclusively to calculate the volatility of the Company’s common stock.
Volatility calculated in this manner was in the range of 72% - 75% for stock options granted during the year ended
December 31, 2020, and 71% - 75% for stock options granted during the year ended December 31, 2019. Volatility of the
Company’s common stock from January 31, 2014 to December 31, 2018 was 75%, which was determined to be
comparable to the method using guideline companies during the year ended December 31, 2018.
The expected dividend yield is zero as the Company has never paid dividends and does not currently anticipate
paying any in the foreseeable future. Risk-free interest rates are based on quoted U.S. Treasury rates for securities with
maturities approximating the option’s expected term.
Prior to January 1, 2019, the Company accounted for stock options granted to non-employee consultants under ASC
505-50, Equity-Based Payments to Non-Employees. As such, the Company estimated the fair value of each option to non-
employees using the Black-Scholes model, with the expected term of stock options granted to non-employees initially
equal to the options’ maximum contractual life of ten years, at issuance. On each subsequent reporting date until
performance was complete, the Company revalued all outstanding options granted to non-employee consultants during the
vesting period of each tranche. Under ASC 505-50, upon re-measurement of each award, income or expense was
recognized during its vesting term.
On January 1, 2019, the Company adopted ASU 2018-07, Compensation – Stock Compensation (Topic 718),
Improvements to Non-employee Share-Based Payment Accounting, or ASU 2018-07, which expanded the scope of ASC
718 to include share-based payment transactions for acquiring goods and services from non-employees. As a result, the fair
value of all outstanding unvested stock options that had been granted to non-employees as of January 1, 2019 was
remeasured on that date. The adoption of ASU 2018-07 did not have a material effect on the Company’s results of
operations, financial position or cash flows because grants of stock options to nonemployees have been insignificant.
Compensation cost for all share-based payments granted with service-based graded vesting schedules is recognized
using the straight-line method over the requisite service period.
Income (Loss) Per Share
The Company computes basic net income (loss) per share by dividing net income (loss) by the weighted average
number of shares of common stock outstanding. Diluted net income (loss) per share includes the potential dilutive effect of
common stock equivalents as if such securities were converted or exercised during the period, when the effect is dilutive.
Common stock equivalents may include outstanding stock options and restricted stock units, which are included under the
treasury stock method when dilutive. For the quarter and year ended December 31, 2020, the Company included the effects
of dilutive shares that were outstanding in the denominator as their inclusion was dilutive due to the Company’s net income
for the period. For each of the years ended December 31, 2019 and 2018, the Company excluded the effects of potentially
dilutive shares that were outstanding during those respective periods from the denominator as their inclusion would have
been anti-dilutive due to the Company’s net losses for those periods.
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Segment Reporting
CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Operating segments are identified as components of an enterprise about which separate discrete financial information
is available for evaluation by the chief operating decision-maker in making decisions regarding resource allocation and
assessing performance. The Company views its operations and manages its business as one operating segment, which
includes all activities related to the discovery and development of novel therapeutics to treat serious medical conditions,
including pruritus and pain.
Leases
Prior to January 1, 2019, the Company recognized rent expense for operating leases on a straight-line basis over the
term of the lease, beginning on the date the Company took possession of the property. Rent expense included the base
amounts stated in the lease agreement as well as the effect of reduced or free rent and rent escalations. At lease inception,
the Company determined the lease term by assuming the exercise of those renewal options that are reasonably assured
because of the significant economic penalty that exists for not exercising those options. The exercise of renewal options is
at the Company’s sole discretion. The expected lease term was one of the factors used to determine whether a lease was
classified as operating or capital and was used to calculate the straight-line rent expense. The difference between the cash
paid to the landlord and the amount recognized as rent expense on a straight-line basis was included in deferred rent and
classified within long-term liabilities. Lease incentives made by landlords to or on behalf of the Company for leasehold
improvements were recorded as deferred rent and classified as long-term liabilities. Deferred rent related to landlord
incentives was amortized using the straight-line method over the lease term as an offset to rent expense for the year ended
December 31, 2018.
On January 1, 2019, the Company adopted ASC 842, Leases, or ASC 842, under which it elected not to adjust prior
comparative periods, which are reported under ASC 840. In addition, the Company elected to adopt both the practical
expedient to use hindsight when determining the lease term and the package of practical expedients available under ASC
842, including:
● No re-evaluation of whether a contract is or contains a lease (embedded lease);
● Lease classification is grandfathered
● No reassessment of initial direct costs
Upon adoption of ASC 842, the Company had only one lease, the Stamford Lease (see Note 17, Commitments and
Contingencies: Leases), which is included in operating lease right-of-use assets, or ROU assets, operating lease liabilities –
current and operating lease liabilities – non-current.
In general, the Company determines if a contract, at its inception, is a lease or contains a lease based on whether the
contract conveys the right to control the use of identified property, plant, or equipment (an identified asset) for a period of
time in exchange for consideration. To determine whether a contract conveys the right to control the use of an identified
asset for a period of time, the Company assesses whether, throughout the period of use, it has both the right to obtain
substantially all of the economic benefits from use of the identified asset, and the right to direct the use of the identified
asset. Both of these criteria are met by the Stamford Lease.
Under ASC 842, the Company determines the amount of the operating lease liability based on the present value of
the future minimum lease payments over the remaining lease term. The amount of the operating lease ROU asset is equal
to the amount of the lease liability, less accrued rent and lease incentives received from the landlord. Initial direct costs
were deemed to be immaterial.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Since the Stamford Lease does not provide an implicit interest rate, the Company used an annual incremental
borrowing rate of 7% based on the information available at the date of adoption for the purpose of determining the lease
liability during the term of the lease.
As noted above, upon adoption of ASC 842, the Company used hindsight in determining the term of the Stamford
Lease. Although the Stamford Lease is renewable for one five-year term, upon inception of the lease the renewal term was
not included in the lease term since it was not reasonably certain that the Company will exercise that option. Accordingly,
the lease term of the Stamford Lease was not adjusted upon adoption of ASC 842 to determine the operating lease ROU
asset and operating lease liability.
The Stamford Lease contains both a lease and non-lease component which are accounted for separately. The
Company allocates the consideration to the lease and the non-lease component on a relative standalone price basis. Lease
expense under ASC 842 is recognized on a straight-line basis over the lease term in the Statement of Comprehensive
Income (Loss).
There was no cumulative effect adjustment as a result of the adoption of ASC 842 on January 1, 2019, which reflects
the difference between the amount of lease expense under ASC 842 that would have been recognized from inception of the
Stamford Lease through December 31, 2018 and the amount of rent expense actually recognized under ASC 840 during
that same period.
In June 2020, the Company entered into an amendment to the Stamford Lease to add additional office space, or the
Lease Amendment. The term of the Lease Amendment began when renovation of the additional space was completed and
the Company took possession of the additional space in October 2020, or the Amendment Commencement Date, and ends
on December 31, 2023. The Lease Amendment is also renewable for one five-year term, although this renewable period is
not included as part of the lease term as defined in ASC 842 since it is not reasonably certain that the Company will
exercise that option. The Lease Amendment contains both a lease and non-lease component which are accounted for
separately. The Company allocates the consideration to the lease and non-lease component on a relative standalone price
basis. The rent for the Lease Amendment is at market rate as of the signing of the Lease Amendment. The Lease
Amendment requires monthly lease payments, including rent escalations, during the lease term. The Company began
paying rent for the Lease Amendment on the Amendment Commencement Date.
The Company accounted for the terms and conditions of the Lease Amendment as a lease modification, as defined in
ASC 842, because it grants an additional right-of-use to an underlying asset (the new additional space). Under ASC 842, a
lease modification can result in either a new lease that is accounted for separately from the original lease or as a single
modified lease. The Lease Amendment is accounted for separately from the original Stamford Lease because the Lease
Amendment grants the right-of-use to additional space and the price of the additional right-of-use is commensurate with its
standalone price as no discounts were provided to the Company. Furthermore, there were no material changes to the
original Stamford Lease.
As of the Amendment Commencement Date, the Company recorded the lease liability for the Lease Amendment as
the sum of the present value of the future minimum lease payments over the term for the new lease. Since the Lease
Amendment does not provide an implicit interest rate, the Company used an incremental borrowing rate of 7%, which is
based on the rate that the Company could obtain in the market for a fully collateralized loan equal to the term of the Lease
Amendment. The Company also recorded a ROU asset equal to the amount of the lease liability, as no lease incentives
were identified in the Lease Amendment. During the term of the Lease Amendment, interest expense will be calculated
using the effective interest method and the ROU asset will be amortized on a straight-line basis over the lease term, and
both will be recorded as lease expense.
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Litigation Reserves
CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
From time to time, the Company may become subject to arbitration, litigation or claims arising in the ordinary course
of its business. Accruals are recorded when it is probable that a liability has been incurred and the amount of the liability
can be reasonably estimated. The Company reviews these reserves at least quarterly and adjusts these reserves to reflect
current law, progress of each case, opinions and views of legal counsel and other advisers, the Company’s experience in
similar matters and intended response to the litigation. The Company expenses amounts for administering or litigating
claims as incurred. Accruals for legal proceedings, if any, are included in accounts payable and accrued expenses.
Accounting Pronouncements Recently Adopted
On January 1, 2020, the Company adopted ASU 2016-13 which replaces the incurred loss impairment methodology
in prior GAAP that delays recognition of a credit loss until it is probable that such loss has been incurred, with a
methodology that reflects expected credit losses and requires consideration of a broader range of reasonable and
supportable information to inform credit loss estimates (see Note 2, Summary of Significant Accounting Policies:
Marketable Securities).
On January 1, 2020, the Company adopted ASU 2019-08, Compensation – Stock Compensation (Topic 718) and
Revenue from Contracts with Customers (Topic 606), or ASU 2019-08, which requires the Company to measure and
classify share-based payment awards granted to a customer by applying the guidance in Topic 718. The amount recorded as
a reduction to the transaction price is required to be measured on the basis of the grant-date fair value of the share-based
payment award in accordance with Topic 718. The grant date is the date at which a grantor (supplier) and a grantee
(customer) reach a mutual understanding of the key terms and conditions of a share-based payment award. The
classification and subsequent measurement of the award are subject to the guidance in Topic 718 unless the share-based
payment award is subsequently modified and the grantee is no longer a customer. The adoption of ASU 2019-08 did not
have a material effect on its results of operations, financial position or cash flows since the Company has not historically
granted share-based payment awards to customers.
On January 1, 2020, the Company adopted ASU No. 2018-18, Collaborative Arrangements (Topic 808): Clarifying
the Interaction between Topic 808 and Topic 606, or ASU 2018-18, which clarifies the interaction between Topic 808 and
Topic 606 by (1) clarifying that certain transactions between collaborative arrangement participants should be accounted
for under Topic 606; (2) adding unit-of-account guidance in Topic 808 to align with the guidance in Topic 606; and
(3) clarifying presentation guidance for transactions with a collaborative arrangement participant that are not accounted for
under Topic 606. The adoption of ASU 2018-18 did not have any effect on its financial position, results of operations or
cash flows since all three of its collaboration and licensing agreements are accounted for under Topic 606 (see Note 10,
Collaboration and Licensing Agreements and Note 11, Revenue Recognition).
On January 1, 2020, the Company adopted ASU No. 2018-13, Fair Value Measurement (Topic 820): Disclosure
Framework – Changes to the Disclosure Requirements for Fair Value Measurement, or ASU 2018-13, which modifies the
disclosure requirements on fair value measurements in Topic 820 to remove the amount of and reasons for transfers
between Level 1 and Level 2 of the fair value hierarchy, the policy for timing of transfers between levels, and the valuation
processes for Level 3 fair value measurements. ASU 2018-13 also amends Topic 820 to clarify that the measurement
uncertainty disclosure is to communicate information about the uncertainty in measurement as of the reporting date. ASU
2018-13 also requires additional disclosure for changes in unrealized gains and losses for the period included in other
comprehensive income (loss) for recurring Level 3 fair value measurements held at the end of the reporting period as well
as the range and weighted average of significant unobservable inputs used to develop Level 3 fair value measurements.
Upon adoption of ASU 2018-13, the Company did not have any assets or liabilities that are
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
included in Level 3 fair value measurements and no retrospective treatment was applicable. As a result, the adoption of
ASU 2018-13 did not have a material effect on its results of operations, financial position or cash flows.
Recent Accounting Pronouncements Not Yet Adopted
In December 2019, the FASB issued ASU 2019-12, Income Taxes (Topic 740), or ASU 2019-12, which removes
specific exceptions to the general principles in Topic 740. ASU 2019-12 eliminates the need for an organization to analyze
whether the following apply in a given period: (1) exception to the incremental approach for intra-period tax allocation; (2)
exceptions to accounting for basis differences when there are ownership changes in foreign investments; and (3) exception
to the general methodology for calculating income taxes in an interim period when a year-to-date loss exceeds the
anticipated loss. ASU 2019-12 also simplifies the accounting for income taxes for: (i) franchise taxes that are partially
based on income; (ii) transactions with a government that result in a step up in the tax basis of goodwill; (iii) separate
financial statements of legal entities that are not subject to tax; and (iv) enacted changes in tax laws in interim periods. The
amendments in ASU 2019-12 are effective for fiscal years, and interim periods within those fiscal years, beginning after
December 15, 2020. Early adoption of the amendments is permitted. An entity that elects to early adopt the amendments in
an interim period should reflect any adjustments as of the beginning of the annual period that includes that interim period
and must adopt all the amendments in the same period. The amendments in ASU 2019-12 related to separate financial
statements of legal entities that are not subject to tax should be applied on a retrospective basis for all periods presented.
The amendments related to changes in ownership of foreign equity method investments or foreign subsidiaries should be
applied on a modified retrospective basis through a cumulative-effect adjustment to retained earnings as of the beginning of
the fiscal year of adoption. The amendments related to franchise taxes that are partially based on income should be applied
on either a retrospective basis for all periods presented or a modified retrospective basis through a cumulative-effect
adjustment to retained earnings as of the beginning of the fiscal year of adoption. All other amendments should be applied
on a prospective basis. As such, the Company will adopt ASU 2019-12 on January 1, 2021 and determined that the
adoption will not have a material effect on its results of operations, financial position and cash flows due to the full
valuation allowance recorded.
3. Available-for-Sale Marketable Securities
As of December 31, 2020 and 2019, the Company’s available-for-sale marketable securities consisted of debt
securities issued by the U.S. Treasury, U.S. government-sponsored entities and investment grade institutions as well as
municipal bonds.
The following tables summarize the Company’s available-for-sale marketable securities by major type of security as
of December 31, 2020 and 2019:
As of December 31, 2020
Type of Security
Amortized Cost
Gains
Losses
Gross Unrealized
U.S. Treasury securities
U.S. government agency obligations
Corporate bonds
Commercial paper
Municipal bonds
Total available-for-sale marketable securities
$
$
20,710
22,125
49,080
116,139
11,680
219,734
$
$
41
4
61
5
12
123
$
$
Estimated Fair
Value
(1)
(1)
(23)
(17)
(8)
(50)
$
$
20,750
22,128
49,118
116,127
11,684
219,807
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
As of December 31, 2019
Type of Security
Amortized Cost
Gains
Losses
Gross Unrealized
U.S. Treasury securities
U.S. government agency obligations
Corporate bonds
Commercial paper
Municipal bonds
Total available-for-sale marketable securities
$
$
16,052
25,803
115,788
38,547
3,500
199,690
$
$
31
14
125
27
—
197
$
$
Estimated Fair
Value
(2)
(1)
(23)
(1)
—
(27)
$
$
16,081
25,816
115,890
38,573
3,500
199,860
The following tables summarize the fair value and gross unrealized losses of the Company’s available-for-sale
marketable securities by investment category and disaggregated by the length of time that individual debt securities have
been in a continuous unrealized loss position as of December 31, 2020 and 2019:
As of December 31, 2020
U.S. Treasury securities
U.S. government agency obligations
Corporate bonds
Commercial paper
Municipal bonds
Total
As of December 31, 2019
U.S. Treasury securities
U.S. government agency obligations
Corporate bonds
Commercial paper
Total
$
$
$
$
Less than 12 Months
Fair
Value
12,682
2,500
23,553
68,897
6,259
113,891
Gross
Unrealized
Losses
$
$
(1) $
(1)
(23)
(17)
(8)
(50) $
12 Months or Greater
Gross
Unrealized
Losses
Fair
Value
Total
Fair
Value
12,682
— $
2,500
—
23,553
—
68,897
—
—
6,259
— $ 113,891
Gross
Unrealized
Losses
$
$
(1)
(1)
(23)
(17)
(8)
(50)
— $
—
—
—
—
— $
Less than 12 Months
Fair
Value
3,185
2,400
28,895
4,264
38,744
Gross
Unrealized
Losses
$
$
(2) $
(1)
(23)
(1)
(27) $
12 Months or Greater
Gross
Unrealized
Losses
Fair
Value
— $
—
—
—
— $
— $
—
—
—
— $
Total
Fair
Value
3,185
2,400
28,895
4,264
38,744
Gross
Unrealized
Losses
$
$
(2)
(1)
(23)
(1)
(27)
As of December 31, 2020 and 2019, respectively, no allowance for credit losses were recognized on the Company’s
available-for-sale debt securities as no portion of the unrealized losses associated with those securities were due to credit
losses. The information that the Company considered in reaching the conclusion that an allowance for credit losses was not
necessary for the following categories of securities is as follows:
As of December 31, 2020 and 2019, the Company held a total of 30 out of 59 positions and 16 out of 81 positions,
respectively, that were in an unrealized loss position, none of which had been in an unrealized loss position for
120
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
12 months or greater. Unrealized losses individually and in aggregate were not considered to be material for each
respective period. Based on the Company’s review of these securities, the Company believes that the cost basis of its
available-for-sale marketable securities is recoverable.
U.S. Treasury and U.S. government agency obligations. The unrealized losses on the Company’s investments in
direct obligations of the U.S. Treasury and government agencies were due to changes in interest rates and non-credit related
factors. The contractual terms of these investments do not permit the issuer to repay principal at a price less than the
amortized cost bases of the investments, which is equivalent to the par value on the maturity date. The Company expects to
recover the entire amortized cost bases of these securities on the maturity date. The Company does not intend to sell these
investments, and it is not more likely than not that the Company will be required to sell these investments before recovery
of their amortized cost bases. The Company held 3 out of 6 positions for its U.S Treasury securities, and 1 out of 6
positions for its U.S. government agency obligations, that were in unrealized loss positions as of December 31, 2020.
Corporate bonds, commercial paper, and municipal bonds. The unrealized losses on the Company’s investments
in corporate bonds, commercial paper and municipal bonds were due to changes in interest rates and non-credit related
factors. The credit ratings of these investments in the Company’s portfolio have not been downgraded below investment
grade status. The contractual terms of these investments do not permit the issuer to repay principal at a price less than the
amortized cost bases of the investments, which is equivalent to the par value on the maturity date. The Company expects to
recover the entire amortized cost bases of these securities on the maturity date. The Company does not intend to sell these
investments, and it is not more likely than not that the Company will be required to sell these investments, before recovery
of their amortized cost bases. The Company held 8 out of 18 positions for its corporate bonds, 15 out of 22 positions for its
commercial paper, and 3 out of 7 positions for its municipal bonds, that were in unrealized loss positions as of December
31, 2020.
The Company classifies its marketable debt securities based on their contractual maturity dates. As of December 31,
2020, the Company’s marketable debt securities mature at various dates through December 2023. The amortized cost and
fair values of marketable debt securities by contractual maturity were as follows:
Contractual maturity
Less than one year
One year to three years
Total
As of December 31, 2020
As of December 31, 2019
Amortized Cost
Fair Value
Amortized Cost
Fair Value
$
$
149,164
70,570
219,734
$
$
149,242
70,565
219,807
$
$
136,565
63,125
199,690
$
$
136,701
63,159
199,860
All available-for-sale marketable securities are classified as Marketable securities, current or Marketable securities,
non-current depending on the contractual maturity date of the individual available-for-sale security. Other income, net
includes interest and dividends, accretion/amortization of discounts/premiums, realized gains and losses on sales of
securities and credit loss expense due to declines in the fair value of securities, if any. The cost of securities sold is based
on the specific identification method.
During the year ended December 31, 2020, the Company sold certain shares of its available-for-sale debt securities
with a total fair value of $41,600, which resulted in realized gains of $272. There were no sales of available-for-sale
marketable securities during the year ended December 31, 2019.
As of December 31, 2020 and 2019, accrued interest receivables on our available-for-sale debt securities were $311
and $971, respectively.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
4. Accumulated Other Comprehensive Income (Loss)
The following table summarizes the changes in accumulated other comprehensive income (loss), net of tax, from
unrealized gains (losses) on available-for-sale marketable securities, the Company’s only component of accumulated other
comprehensive income (loss), for the years ended December 31, 2020, 2019 and 2018.
Balance, December 31, 2017
Other comprehensive loss before reclassifications
Amount reclassified from accumulated other comprehensive loss
Net current period other comprehensive loss
Balance, December 31, 2018
Other comprehensive income before reclassifications
Amount reclassified from accumulated other comprehensive loss
Net current period other comprehensive income
Balance, December 31, 2019
Other comprehensive income before reclassifications
Amount reclassified from accumulated other comprehensive income
Net current period other comprehensive loss
Balance, December 31, 2020
Total Accumulated
Other Comprehensive
Income (Loss)
(70)
(49)
5
(44)
(114)
284
—
284
170
175
(272)
(97)
73
$
$
$
$
Amounts reclassified out of accumulated other comprehensive income (loss) into net income (loss) are determined
by specific identification. The reclassifications out of accumulated other comprehensive income (loss) and into net income
(loss) were as follows:
Component of Accumulated Other
Comprehensive Income (Loss)
Unrealized gains (losses) on available-for- sale
marketable securities
Realized gains (losses) on sale of securities
5. Prepaid Expenses
Year Ended December 31,
2019
2018
2020
Affected Line Item in the
Statements of
Comprehensive Income (Loss)
$
$
272
$
—
$
272
— $
—
— $
(5) Other income, net
— Benefit from income taxes
(5)
As of December 31, 2020, the amount of prepaid expenses was $12,076, consisting of $11,286 of prepaid R&D
clinical costs, $223 of prepaid insurance and $567 of other costs. As of December 31, 2019, the amount of prepaid
expenses was $8,863, consisting of $8,498 of prepaid R&D clinical costs, $181 of prepaid insurance and $184 of other
costs.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
6. Property and Equipment, net
Property and equipment, net consists of the following:
Computer and office equipment
Laboratory equipment
Furniture and fixtures
Leasehold improvements
Less accumulated depreciation and amortization
Property and equipment, net
December 31,
2020
2019
$
$
$
211
628
330
1,212
2,381
1,541
840
$
$
$
211
628
61
1,132
2,032
1,332
700
Depreciation and amortization expense included in R&D expense and general and administrative, or G&A, expense
was $209, $198 and $370 for the years ended December 31, 2020, 2019 and 2018, respectively.
There were no gains or losses on sales of property and equipment during the years ended December 31, 2020, 2019
and 2018.
7. Restricted Cash
The Company is required to maintain a stand-by letter of credit as a security deposit under its leases for its office
space in Stamford, Connecticut (refer to Note 17, Commitments and Contingencies: Leases). The fair value of the letter of
credit approximates its contract value. The Company’s bank requires the Company to maintain a restricted cash balance to
serve as collateral for the letter of credit issued to the landlord by the bank. As of December 31, 2020, the restricted cash
balance for the Stamford Lease was invested in a commercial money market account.
The letter of credit balance for the Stamford lease was required to remain at $769 through May 2019 and thereafter,
upon request from the Company, was eligible to be reduced to $408 through the end of the lease term in December 2023.
The reduction in the balance of the letter of credit for the Stamford lease was contingent upon the Company not being in
default of any provisions of that lease prior to request for the reduction. In July 2019, the Company was granted the
reduction in the balance of the letter of credit. As of December 31, 2020 and 2019, the Company had $408 of restricted
cash related to the Stamford lease in long-term assets.
The following table provides a reconciliation of cash, cash equivalents and restricted cash reported within the
Balance Sheets that sum to the total of the same such amounts shown in the Statements of Cash Flows.
Cash and cash equivalents
Restricted cash, long-term assets
December 31, 2020 December 31, 2019
18,305
408
31,683
408
$
$
Total cash, cash equivalents, and restricted cash shown in the Statements of Cash
Flows
$
32,091
$
18,713
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
8. Accounts Payable and Accrued Expenses
Accounts payable and accrued expenses consist of the following:
Accounts payable
Accrued research projects
Accrued professional fees
Accrued compensation and benefits
Total
9. Stockholders’ Equity
$
$
December 31, 2020 December 31, 2019
9,100
6,637
635
3,293
19,665
4,893
6,194
839
4,955
16,881
$
$
The Company’s Board of Directors has authorized 100,000,000 shares of the Company’s common stock, par value
$0.001 per share, and 5,000,000 shares of undesignated preferred stock, par value $0.001 per share, that may be issued
from time to time by the Board of Directors of the Company in one or more series. As of December 31, 2020, there were
49,872,213 shares of common stock and no shares of preferred stock issued and outstanding.
Each share of common stock entitles the holder to one vote on all matters submitted to a vote of the Company’s
stockholders. Common stockholders are entitled to dividends when and if declared by the Board of Directors, subject to the
preferential rights of the holders of preferred stock, if any.
In December 2020, as a result of the achievement of a performance target, an aggregate of 36,750 restricted stock
units of various executive officers vested and were settled in shares of the Company’s common stock (see Note 13, Stock-
Based Compensation).
In October 2020, the Company issued 2,939,552 shares of its common stock to Vifor in connection with the license
agreement entered into with Vifor (see Note 11, Collaboration and Licensing Agreements).
Pursuant to the stock purchase agreement with Vifor, or the Vifor Purchase Agreement, Vifor will not, and will not
cause any direct or indirect affiliate to, during the period beginning on October 15, 2020 and ending at the close of business
on the earlier of (a) October 15, 2022 and (b) the date that the Company publicly discloses the receipt of a complete
response letter from the FDA with respect to the Company’s NDA for CR845/difelikefalin injection, or the Restricted
Period, (i) offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell,
grant any option, right or warrant to purchase, lend, or otherwise transfer or dispose of, directly or indirectly, any shares of
common stock of the Company or any securities convertible into or exercisable or exchangeable for common stock of the
Company (including without limitation, common stock or such other securities which may be deemed to be beneficially
owned by Vifor in accordance with the rules and regulations of the SEC and securities which may be issued upon exercise
of a stock option or warrant) owned by Vifor as of the date hereof or acquired prior to the end of the Restricted Period
(collectively with the common stock, referred to as the Lock-Up Securities), except any such sale, option or contract by and
between Vifor and one of its affiliates (including Vifor Pharma Group Ltd. or VFMCRP), (ii) enter into any hedging, swap
or other agreement or transaction that transfers, in whole or in part, any of the economic consequences of ownership of the
Lock-Up Securities, whether any such transaction described in clause (i) or (ii) above is to be settled by delivery of Lock-
Up Securities, in cash or otherwise, (iii) make any demand for or exercise any right with respect to the registration of any
Lock-Up Securities, or (iv) publicly disclose the intention to do any of the foregoing.
Under the Vifor Purchase Agreement, the parties also agreed that, in certain circumstances, upon the request of Vifor,
the parties will enter into a registration rights agreement prior to the end of the Restricted Period that would
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
provide Vifor (or its affiliate transferee) customary registration rights with respect to the shares of common stock issued
pursuant to the Vifor Purchase Agreement following the expiration of the Restricted Period.
In June 2020, as a result of the completion of the one-year vesting period, an aggregate of 24,000 restricted stock
units of members of the Board of Directors vested and were settled in shares of the Company’s common stock (see Note
13, Stock-Based Compensation).
In April and June 2020, as a result of the achievement of certain performance targets, an aggregate of 95,834
restricted stock units of various executive officers vested and were settled in shares of the Company’s common stock (see
Note 13, Stock-Based Compensation).
In December 2019, as a result of the achievement of a clinical performance target, restricted stock units of various
executive officers vested and were converted into 36,666 shares of the Company’s common stock (see Note 13, Stock-
Based Compensation).
In August 2019, the Company entered into a Non-Exclusive License Agreement, or the Enteris License Agreement,
with Enteris Biopharma, Inc., or Enteris (see Note 17, Commitments and Contingencies for additional information
regarding the Enteris License Agreement). As consideration for the licensed rights under the Enteris License Agreement,
the Company paid an upfront fee equal to $8,000, consisting of $4,000 in cash and $4,000 in shares of the Company’s
common stock. In connection with the Enteris License Agreement, in August 2019, the Company entered into a Common
Stock Purchase Agreement, or the Enteris Purchase Agreement, with Enteris and its affiliate, EBP Holdco LLC,
collectively referred to as Purchaser, pursuant to which the Company issued and sold to Purchaser 170,793 shares of its
common stock in a private placement in satisfaction of the $4,000 portion of the upfront fee payable in shares of the
Company’s common stock pursuant to the Enteris License Agreement, and for no additional consideration, based on a
purchase price of $23.42 per share, which was equal to the 30-day volume weighted average price of the Company’s
common stock on August 20, 2019. In addition, if the Company exercises its right, but not obligation, to terminate its
obligation to pay any royalties under the Enteris License Agreement in exchange for a lump sum payment in cash, it may
elect to make 50% of the payment in stock by issuing additional shares of the Company’s common stock valued at the 30-
day volume weighted average price of the Company’s common stock as of such exercise. Pursuant to its obligations under
the Enteris Purchase Agreement, the Company effected the registration and sale of the shares issued and sold to Purchaser
thereunder in accordance with the applicable requirements of the Securities Act of 1933, as amended, or the Securities Act,
through the filing of an automatic shelf registration statement on Form S-3ASR (File No. 333-233666) with the SEC on
September 9, 2019. In addition, the Enteris Purchase Agreement includes customary representations, warranties and
covenants by the Company (see Note 17, Commitments and Contingencies).
In July 2019, the Company entered into an underwriting agreement with J.P. Morgan Securities LLC and Jefferies
LLC, as representatives of the several underwriters named therein, relating to the issuance and sale by the Company of
6,325,000 shares of its common stock, which included the exercise of the underwriters’ option to purchase 825,000
additional shares of common stock, at a public offering price of $23.00 per share. The Company closed this offering on
July 29, 2019, including the full exercise of the underwriters’ option to purchase 825,000 additional shares of common
stock. The Company received net proceeds of $136,498, after deducting $8,977 of underwriting discounts and
commissions and offering expenses.
This offering was made pursuant to the Company’s Shelf Registration Statement on Form S-3 (File No. 333-230333),
or the Shelf Registration Statement, filed with the SEC on March 15, 2019 and declared effective on April 4, 2019, and a
related prospectus supplement dated July 24, 2019, which was filed with the SEC on July 25, 2019. The Shelf Registration
Statement provides for aggregate offerings of up to $300,000 of common stock, preferred stock, debt securities, warrants or
any combination thereof. The securities registered under the Shelf Registration Statement include
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
unsold securities that had been registered under the Company’s previous shelf registration statement (File No. 333-216657)
that was declared effective on March 24, 2017.
In May 2019, as a result of the achievement of a clinical performance target, an aggregate of 74,166 restricted stock
units of various executive officers vested and were settled in shares of the Company’s common stock (see Note 13, Stock-
Based Compensation).
In March 2019, the Company entered into a consulting agreement with an existing stockholder. In accordance with
the agreement, the stockholder provided various consulting services to the Company in exchange for 10,195 unregistered
shares of the Company’s common stock. The closing price of the Company’s common stock on March 20, 2019, or the
Effective Date of the consulting agreement, was $19.37 per share. The services provided by the consultant were performed
during the six-month period following the Effective Date. During the year ended December 31, 2019, stock-based
compensation expense of $197 was recognized in the Statements of Comprehensive Income (Loss), all of which related to
G&A expense.
In December 2018, as a result of the achievement of a clinical performance target, an aggregate of 83,791 restricted
stock units of various executive officers vested and were settled in shares of the Company’s common stock (see Note 13,
Stock-Based Compensation).
In July 2018, the Company entered into an underwriting agreement with Jefferies LLC and Merrill Lynch, Pierce,
Fenner & Smith Incorporated, as representatives of the several underwriters named therein, relating to the issuance and sale
by the Company of up to 5,175,000 shares of its common stock, including 675,000 shares of common stock the
underwriters had the option to purchase, at a public offering price of $19.00 per share. This offering was made pursuant to
the Company’s Registration Statement on Form S-3 (File No. 333-216657), filed with the SEC on March 13, 2017 and
declared effective on March 24, 2017, and a related prospectus dated March 24, 2017 and prospectus supplement dated
July 18, 2018, which was filed with the SEC on July 20, 2018.
On July 23, 2018, the Company closed the offering, including the full exercise of the underwriters’ option to
purchase 675,000 additional shares of common stock. The Company received net proceeds of $92,063, after deducting
$6,262 relating to underwriting discounts and commissions and offering expenses.
In May 2018, the Company issued 1,174,827 shares of its common stock to Vifor in connection with the license
agreement entered into with VFMCRP (refer to Note 11, Collaboration and Licensing Agreements).
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
10. Fair Value Measurements
The following tables summarize the Company’s financial assets measured at fair value on a recurring basis as of
December 31, 2020 and 2019 and by level within the fair value hierarchy:
Fair value measurement as of December 31, 2020:
Financial assets
Type of Instrument
Total
Quoted prices in
active markets for
identical assets
(Level 1)
Significant other
observable
inputs
(Level 2)
Significant
unobservable
inputs
(Level 3)
Cash and cash equivalents:
Money market funds and checking accounts
Available-for-sale marketable securities:
U.S. Treasury securities
U.S. government agency obligations
Corporate bonds
Commercial paper
Municipal bonds
Restricted cash:
Commercial money market account
Total financial assets
Fair value measurement as of December 31, 2019:
$ 31,683
$
31,683
$
— $
20,750
22,128
49,118
116,127
11,684
—
—
—
—
—
20,750
22,128
49,118
116,127
11,684
408
$ 251,898
$
408
32,091
$
—
$
219,807
—
—
—
—
—
—
—
—
Financial assets
Type of Instrument
Total
Quoted prices in
active markets for
identical assets
(Level 1)
Significant other
observable
inputs
(Level 2)
Significant
unobservable
inputs
(Level 3)
Cash and cash equivalents:
Money market funds and checking accounts
Available-for-sale marketable securities:
U.S. Treasury securities
U.S. government agency obligations
Corporate bonds
Commercial paper
Municipal bonds
Restricted cash:
Commercial money market account
Total financial assets
$ 18,305
$
18,305
$
— $
16,081
25,816
115,890
38,573
3,500
—
—
—
—
—
16,081
25,816
115,890
38,573
3,500
408
$ 218,573
$
408
18,713
$
—
$
199,860
—
—
—
—
—
—
—
—
There were no purchases, sales or maturities of Level 3 financial assets and no unrealized gains or losses related to
Level 3 available-for-sale marketable securities for the years ended December 31, 2020, 2019 and 2018. There were no
transfers of financial assets between Levels 1, 2, or 3 classifications during the years ended December 31, 2020 and 2019.
127
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
11. Collaboration and Licensing Agreements
Vifor (International) Ltd.
In October 2020, the Company entered into a license agreement with Vifor, or the Vifor Agreement, under which the
Company granted Vifor an exclusive license solely in the United States to use, distribute, offer for sale, promote, sell and
otherwise commercialize CR845/difelikefalin injection for all therapeutic uses relating to the inhibition, prevention or
treatment of itch associated with pruritus in hemodialysis and peritoneal dialysis patients in the United States. Under the
Vifor Agreement, the Company retains all rights with respect to the clinical development of, and activities to gain
regulatory approvals of, CR845/difelikefalin injection in the United States. The Joint Commercialization Committee, or
JCC, have the responsibility for overall coordination and oversight of Vifor (and any affiliates or sublicensees). The
Company’s membership on the JCC is at its sole discretion and is not its obligation.
The Vifor Agreement provides full commercialization rights in dialysis clinics to Vifor in the United States under a
profit-sharing arrangement. Pursuant to the profit-sharing arrangement, the Company will generally be entitled to 60% of
the net profits (as defined in the Vifor Agreement) from sales of CR845/difelikefalin injection in the United States
(excluding sales to Fresenius Medical Center dialysis clinics, compensation for which is governed by the VFMCRP
Agreement) and Vifor is entitled to 40% of such net profits, subject to potential temporary adjustment in future years based
on certain conditions. Under the Vifor Agreement, in consideration of Vifor’s conduct of the marketing, promotion, selling
and distribution of CR845/difelikefalin injection in the United States, the Company will pay a marketing and distribution
fee to Vifor based on the level of annual net sales. This fee will be deducted from product sales in calculating the net profits
that are subject to the profit-sharing arrangement under the Vifor Agreement.
The Company has identified one performance obligation under ASC 606: granting of the license to Vifor. No other
performance obligations were identified in the Vifor Agreement (see Note 12, Revenue Recognition).
Under the terms of the Vifor Agreement, the Company received from Vifor an upfront payment of $100,000 and an
additional payment of $50,000 for the purchase of an aggregate of 2,939,552 shares of the Company’s common stock at a
price of $17.0094 per share, which represents a premium over a pre-determined average closing price of the Company’s
common stock. The purchase of the Company’s common stock was governed by a separate stock purchase agreement. The
excess of the stock purchase price over the cost of the Vifor shares at the closing price of the Company’s common stock on
the purchase date of $11,551 was added to the upfront payment for accounting purposes
Upon U.S. regulatory approval of CR845/difelikefalin, the Company will also be eligible to receive an additional
$50,000 common stock investment at a 20% premium to the 30-day trailing average price of the Company’s common stock
as of such date. In addition, pursuant to the Vifor Agreement, the Company is eligible to receive payments of up to
$240,000 upon the achievement of certain sales-based milestones.
At inception of the Vifor Agreement, the transaction price of $111,551 was allocated entirely to the one performance
obligation, as described above, and was recorded as license and milestone fees revenue during the year ended December
31, 2020. Any future sales milestones are constrained from the transaction price at inception since there is a significant
uncertainty as to whether these milestones would be achieved. These sales milestones will be recognized as revenue if, and
when, such sales transactions occur in the future.
The license also requires Vifor to promote and take orders for Licensed Products throughout the United States,
including coordinating with VFMCRP promotional activities to FMC U.S. Dialysis Clinics which are subject to the
Company’s rights under the VFMCRP Agreement. The license also allows Vifor to grant sub-licenses, which, in certain
cases, requires the Company’s prior written consent. The Company retains the rights to import, distribute, promote, sell
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
and otherwise commercialize the Licensed Product on an exclusive basis outside of the Field either in or outside of the
United States.
The Company retains the rights to make and have made the Licensed Product, on a non-exclusive basis, in the United
States for commercial sale of the Licensed Product for use in the Field anywhere in the world and for supply of Licensed
Product to Vifor under the terms of a supply agreement, or the Vifor Supply Agreement. The supply price will be the
Company’s cost of goods sold, as calculated under U.S. GAAP, plus an agreed upon margin. The Vifor Supply Agreement
will co-terminate with the Vifor Agreement. In regards to a supply agreement, the Vifor Agreement only includes a
requirement for the Company to negotiate in good faith with Vifor. After the execution of the Vifor Agreement, a separate
agreement to supply them with the Licensed Product would be entered into, although the Company has no obligation to
execute a supply agreement.
The Vifor Supply Agreement will be accounted for as a customer option that is not a material right because the
selling price of the Licensed Product under the Vifor Supply Agreement is the Company’s cost of goods sold plus an
agreed upon margin, which is commensurate with the “cost of goods sold plus” model that the Company would charge
other parties under similar agreements (the standalone selling price) and not at a discount. Therefore, the sale of clinical
compound to Vifor is not a performance obligation under the Vifor Agreement but rather the Vifor Supply Agreement is a
separate agreement from the Vifor Agreement. The only performance obligation under the Vifor Supply Agreement is the
delivery of the Licensed Product to Vifor for commercialization. Revenue from the sale of the Licensed Product to Vifor
will be recognized in the Company’s Statements of Comprehensive Income (Loss) as sales of the Licensed Product occur.
As of December 31, 2020, no supply agreement has been entered into between the Company and Vifor.
The Vifor Agreement will continue in effect until its expiration upon the cessation of commercial sale of
CR845/difelikefalin injection in the United States by Vifor and its affiliates and sublicensees, or until the earlier
termination of the Vifor Agreement.
In addition, upon the earlier of: (1) the acceptance for filing of an NDA covering CR845/difelikefalin injection
submitted to the FDA; or (2) October 15, 2023, the Vifor Agreement may be terminated by Vifor in its entirety, with such
termination effective upon 12 months’ notice.
The Vifor Agreement may also be terminated earlier by either party for material breach that is not cured within 60
days, bankruptcy by either party and by both parties upon mutual written consent. The Company may terminate the Vifor
Agreement if Vifor challenges the validity of any licensed patent rights, except if such patent challenge results from the
Company’s action against Vifor for infringement of any licensed patent in the United States. In addition, upon the earlier of
(1) the acceptance for filing of an NDA covering Licensed Product filed with the FDA (after completion of the Phase 3
program) or (2) the third anniversary of the Effective Date, the Vifor Agreement may be terminated by Vifor in its entirety
upon written notice to the Company. Such termination will be effective twelve months following the date of such notice
Vifor Fresenius Medical Care Renal Pharma Ltd.
In May 2018, the Company entered into a license agreement, or the VFMCRP Agreement, with VFMCRP under
which the Company granted VFMCRP an exclusive, royalty-bearing license, or the VFMCRP License, to seek regulatory
approval to commercialize, import, export, use, distribute, offer for sale, promote, sell and otherwise commercialize
CR845/difelikefalin injection, or the Licensed Product, for all therapeutic uses to prevent, inhibit or treat itch associated
with pruritus in hemodialysis and peritoneal-dialysis patients, or the Field, worldwide (excluding the United States, Japan
and South Korea), or the Territory. VFMCRP cannot perform development activities on their own unless specifically
allocated to VFMCRP by the Joint Development Committee, or JDC, and Joint Steering Committee, or JSC. The
Company’s membership on the JSC or JDC is at its sole discretion and is not its obligation.
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company is responsible, at its own cost, to undertake clinical and non-clinical development, or the R&D
services. The Company is also responsible to provide all content and subject matter expertise required for registration with
the European Medicines Agency, or EMA, in the European Union, or the EU, that will be needed by VFMCRP for such
registration, including participation in regulatory meetings, as needed. If third-party costs incurred by the Company with
respect to its clinical development for the EMA registration exceed $20,000, such excess costs will be shared equally by
the Company and VFMCRP. VFMCRP will contribute, at its own cost, its clinical development expertise as reasonably
useful for such development activities, such as preparing the clinical results that the Company presents to it in a format
acceptable to the EMA to obtain marketing approval in the EU.
The Company has identified two performance obligations under ASC 606: (1) granting of the VFMCRP License and
(2) the R&D services. The Company has determined that these two performance obligations are not capable of being
distinct (i.e., do not have standalone value for VFMCRP) because VFMCRP cannot benefit (derive potential cash flows)
from either one on its own or together with other resources that are readily available to it since VFMCRP is relying on the
Company’s expertise in investigating chronic kidney disease-associated pruritus, or CKD-aP, and its know-how obtained
from multiple years of pre-clinical and clinical development, and years of interactions with the FDA which other
companies or CROs would not have. The VFMCRP License does not provide benefit to VFMCRP until and unless the
Company conducts the pivotal clinical trials and other supportive trials in CKD-aP to gather sufficient clinical data for
VFMCRP to obtain marketing approval in the Territory. Furthermore, VFMCRP does not have the right to perform
development activities on its own unless specifically allocated by the JDC or JSC.
The two identified performance obligations are also not distinct within the context of the contract, (i.e., are not
separately identifiable from each other) because of the nature of the promise within the context of the contract. The nature
of the promise is to transfer a combined deliverable to VFMCRP based on the agreement (to support the ability of
VFMCRP to commercialize the Licensed Product) and the Company determined that the VFMCRP License and the R&D
services are inputs rather than a transfer of each of these goods and services individually. In addition, the two identified
performance obligations are highly interrelated and interdependent because satisfaction of both performance obligations is
required for VFMCRP to derive benefit from the VFMCRP Agreement for commercialization of the Licensed Product in
the Territory. Therefore, the two performance obligations are not distinct from each other and are accounted for as a single
performance obligation.
Upon entry into the VFMCRP Agreement, VFMCRP made a non-refundable, non-creditable $50,000 upfront
payment to the Company and Vifor purchased 1,174,827 shares of the Company’s common stock, or the Vifor Shares, for
$20,000 at a price of $17.024 per share, which represents a premium over a pre-determined average closing price of the
Company’s common stock. The purchase of the Company’s common stock was governed by a separate stock purchase
agreement. The excess of the stock purchase price over the cost of the Vifor Shares at the closing price of the Company’s
common stock on the purchase date of $5,444 was added to the upfront payment for accounting purposes.
The Company is eligible to receive from VFMCRP regulatory and commercial milestone payments in the aggregate
of up to $470,000, consisting of up to $30,000 in regulatory milestones and up to $440,000 in tiered commercial
milestones, all of which are sales related. The Company is also eligible to receive tiered double-digit royalty payments
based on annual net sales, as defined in the VFMCRP Agreement, of CR845/difelikefalin injection in the Licensed
Territories. The Company retains full commercialization rights for CR845/difelikefalin injection for the treatment of CKD-
aP in the United States except in the dialysis clinics of Fresenius Medical Care North America, or FMCNA, where
VFMCRP and the Company will promote CR845/difelikefalin injection under a profit-sharing arrangement (subject to the
terms and conditions of the VFMCRP Agreement) based on net FMCNA clinic sales recorded by the Company.
At inception of the VFMCRP Agreement, there was significant uncertainty as to whether marketing approval would
be obtained in the Territory for the Licensed Product. Therefore, at that time, there was a significant probability
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
that any potential revenue from sales of the Licensed Product that would be included in the transaction price would be
reversed when the uncertainty is resolved. Consequently, any sales royalties and sales milestones are constrained from the
transaction price at inception of the VFMCRP Agreement and will be recognized as revenue if, and when, such sales
transactions occur in the future.
At inception of the VFMCRP Agreement, the transaction price of $55,444 was allocated entirely to the one
combined performance obligation, as described above, and was initially recorded as deferred revenue. License and
milestone revenue will be recognized proportionately as the R&D services are conducted (i.e., prior to submission of an
NDA).
The license also requires VFMCRP to promote and take orders in the U.S. for sale by the Company to FMC U.S.
Dialysis Clinics and allows VFMCRP to grant sub-licenses, which, in certain cases, requires the Company’s prior written
consent. The Company retains the rights to import, distribute, promote, sell and otherwise commercialize the Licensed
Product outside of the Field and outside of the Territory.
The Company retains the rights to make and have made the Licensed Product in the Territory for commercial sale by
VFMCRP in the Field in or outside the Territory and for supply of Licensed Product to VFMCRP under the terms of a
supply agreement, or the VFMCRP Supply Agreement, which was executed in May 2020. The supply price is the
Company’s cost of goods sold, as calculated under U.S. GAAP, plus an agreed upon margin. The VFMCRP Supply
Agreement will co-terminate with the VFMCRP Agreement.
The VFMCRP Supply Agreement is accounted for as a customer option that is not a material right because the
selling price of the Licensed Product under the VFMCRP Supply Agreement is the Company’s cost of goods sold plus an
agreed upon margin, which is commensurate with the “cost of goods sold plus” model that the Company would charge
other parties under similar agreements (the standalone selling price) and not at a discount. Therefore, the sale of clinical
compound to VFMCRP is not a performance obligation under the VFMCRP Agreement but rather the VFMCRP Supply
Agreement is a separate agreement from the VFMCRP Agreement. The only performance obligation under the VFMCRP
Supply Agreement is the delivery of the Licensed Product to VFMCRP for commercialization. Revenue from the sale of
the Licensed Product to VFMCRP will be recognized in the Company’s Statements of Comprehensive Income (Loss) as
sales of the Licensed Product occur. During the year ended December 31, 2020, the Company recognized clinical
compound revenue of $115 from the sale of clinical compound to VFMCRP and as a result, the Company incurred R&D
expense of $108 during this period.
The VFMCRP Agreement terminates upon the expiration of all royalty terms with respect to the Licensed Products,
which expire on a Product-by-Product and country-by-country basis, at the latest of (a) the expiration of all patent rights
licensed to VFMCRP covering such Licensed Product; (b) the expiration of all regulatory and data exclusivity applicable to
such Licensed Product in such country and (c) the tenth anniversary of the first commercial sale of such Product in such
country.
The VFMCRP Agreement may be terminated earlier by either party for material breach that is not cured within
60 days, bankruptcy by either party and by both parties upon mutual written consent. The Company may terminate the
VFMCRP Agreement if VFMCRP challenges the validity of any licensed patent rights, except if such patent challenge
results from the Company’s action against VFMCRP for infringement of any licensed patent in the Territory. In addition,
upon the earlier of (1) the acceptance for filing of an NDA covering Licensed Product filed with the FDA (after completion
of the Phase 3 program) or (2) the third anniversary of the Effective Date, the VFMCRP Agreement may be terminated by
VFMCRP in its entirety or with respect to any countries within the Territory upon written notice to the Company. Such
termination will be effective twelve months following the date of such notice.
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
If the VFMCRP Agreement terminates early for any reason stated above, VFMCRP’s licenses will terminate,
VFMCRP’s rights to use the Company’s confidential information and the Company’s know-how will revert to the
Company and VFMCRP will assign and transfer to the Company all right, title and interest in all regulatory applications
(IND’s and NDA’s), regulatory approval applications and regulatory approvals in the Territory covering Licensed Product.
Maruishi Pharmaceutical Co., Ltd.
In April 2013, the Company entered into a license agreement with Maruishi, or the Maruishi Agreement, under
which the Company granted Maruishi an exclusive license to develop, manufacture, and commercialize drug products
containing CR845/difelikefalin for acute pain and/or uremic pruritus in Japan. Maruishi has the right to grant sub-licenses
in Japan, which entitles the Company to receive sub-license fees, net of prior payments made by Maruishi to the Company.
Under the Maruishi Agreement, the Company and Maruishi are required to use commercially reasonable efforts, at their
own expense, to develop, obtain regulatory approval for and commercialize CR845/difelikefalin in the United States and
Japan, respectively. In addition, the Company provided Maruishi specific clinical development services for
CR845/difelikefalin used in Maruishi’s field of use.
Under the Maruishi Agreement, the Company identified two performance obligations in accordance with ASC 606:
(1) the license; and (2) the R&D services specific to the uremic pruritus field of use (specified as Phase 1 and proof-of-
concept clinical trials), both of which were determined to have standalone value. The Company determined that these
performance obligations had standalone value due to the fact that Maruishi obtained the right to develop the compound on
its own and the Company was specifically contracted to perform specific R&D services as noted above. The Company
believes that these early stage R&D services performed by the Company did not require any specific expertise or know-
how, but rather could have been completed by outside third parties, therefore providing standalone value to Maruishi.
Under the terms of the Maruishi Agreement, the Company is eligible to receive milestone payments upon the
achievement of defined clinical and regulatory events as well as tiered, low double-digit royalties with respect to any sales
of the licensed product sold in Japan by Maruishi, if any, and share in any sub-license fees.
During the years ended December 31, 2020, 2019 and 2018, the Company recognized clinical compound revenue of
$528, $140 and $33, respectively, from the sale of clinical compound to Maruishi.
The Company incurred R&D expense related to the Maruishi Agreement of $476, $126 and $30 (all related to the
cost of clinical compound sold to Maruishi) during the years ended December 31, 2020, 2019 and 2018, respectively.
Chong Kun Dang Pharmaceutical Corporation
In April 2012, the Company entered into a license agreement, or the CKDP Agreement, with Chong Kun Dang
Pharmaceutical Corporation, or CKDP, in South Korea, under which the Company granted CKDP an exclusive license to
develop, manufacture and commercialize drug products containing CR845/difelikefalin in South Korea. The Company and
CKDP are each required to use commercially reasonable efforts, at their respective expense, to develop, obtain regulatory
approval for and commercialize CR845/difelikefalin in the United States and South Korea, respectively. The Company
identified the granting of the license as its only performance obligation under the CKDP Agreement.
Under the terms of the CKDP Agreement, the Company is eligible to receive milestone payments upon the
achievement of defined clinical and regulatory events as well as tiered royalties, with percentages ranging from the high
single digits to the high teens, based on net sales of products containing CR845/difelikefalin in South Korea, if any, and
share in any sub-license fees.
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12. Revenue Recognition
CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The Company currently recognizes revenue in accordance with ASC 606, as amended, for the Vifor, VFMCRP,
Maruishi and CKDP agreements (see Note 11, Collaboration and Licensing Agreements). Under each of these agreements,
the Company has recognized revenue from upfront payments and, under the Maruishi and CKDP agreements, from clinical
development milestone payments. The Company has also recognized revenue from a sub-license payment earned under the
Maruishi Agreement. Under the Maruishi and CKDP agreements, the Company may earn additional future milestone
payments upon the achievement of defined clinical events, and under the Vifor, VFMCRP, Maruishi and CKDP agreements
upon the achievement of defined regulatory events and, under the Vifor, VFMCRP and Maruishi agreements, from sales
milestones. The Company may also recognize revenue in the future from royalties on net sales under the VFMCRP,
Maruishi and CKDP agreements. In addition, the Company has recognized revenue upon the delivery of clinical compound
to VFMCRP and Maruishi in accordance with separate supply agreements.
Contract balances
As of December 31, 2020, there were no material balances of receivables, and no other assets or deferred revenue
related to the Vifor, VFMCRP, Maruishi and CKDP agreements. As of December 31, 2019, the Company had deferred
revenue, current of $22,262 related to the performance obligations from the VFMCRP Agreement and had no balances of
receivables, other assets or deferred revenue, non-current related to the VFMCRP Agreement. There were no balances of
receivables, other assets or deferred revenue relating to the Maruishi and CKDP agreements as of December 31, 2019.
Performance obligations
Under the Vifor Agreement, the Company’s only performance obligation is granting a license to allow Vifor to
commercialize CR845/difelikefalin in the United States, which occurred at inception of the contract in October 2020 (see
Note 11, Collaboration and Licensing Agreements).
Under the VFMCRP Agreement, the Company’s performance obligations of granting a license to allow VFMCRP to
commercialize CR845/difelikefalin injection worldwide, except in the United States, Japan and South Korea, which
occurred at inception of the contract in May 2018, and performing R&D services by the Company to obtain sufficient
clinical data which will be shared with VFMCRP to allow them to receive regulatory approval to sell CR845/difelikefalin
in the licensed territory, are not distinct, and are accounted for as a single performance obligation during the period that the
R&D services are rendered (see Note 11, Collaboration and Licensing Agreements).
The Company’s distinct performance obligations under the Maruishi Agreement include transfer of the license to the
Company’s IP, which allowed Maruishi to develop and commercialize CR845/difelikefalin, for acute pain and uremic
pruritus indications in Japan, which occurred at inception of the contract in 2013, and performance of R&D services, which
occurred from 2013 to 2015, as those services were rendered. The Company agreed to conduct limited work on an oral
tablet formulation of CR845/difelikefalin and to conduct Phase 1 and proof-of-concept Phase 2 clinical trials of an
intravenous formulation of CR845/difelikefalin to be used to treat patients with uremic pruritus. The Company agreed to
transfer the data and information from such development to Maruishi for its efforts to obtain regulatory approval in Japan.
These activities are referred to as R&D services.
The Company’s only performance obligation under the supply agreement with Maruishi is to deliver clinical
compound to Maruishi in accordance with the receipt of purchase orders. The Company’s only performance obligation
under the VFMCRP Supply Agreement is to deliver CR845/difelikefalin injection to VFMCRP in accordance with the
receipt of purchase orders.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Under the CKDP Agreement, the Company’s only performance obligation is to transfer the license to the Company’s
IP related to CR845/difelikefalin, which occurred at inception of the contract in 2012.
Upon execution of the Vifor, VFMCRP, Maruishi and CKDP agreements, the Company received a single fixed
payment from each counterparty in exchange for granting the respective licenses and performing its other obligations (if
applicable). In addition, each of the counterparties made an equity investment in the Company’s common stock.
Transaction price allocated to the remaining performance obligations
At inception of the Vifor Agreement, the entire transaction price of $111,551 was allocated to the one performance
obligation, as described above. For the year ended December 31, 2020, the entire $111,551 was recognized as license and
milestone fees revenue as the license was granted to Vifor in October 2020. As of December 31, 2020, there were no
remaining performance obligations under the Vifor Agreement. The Company is eligible to receive milestone payments in
the future.
At inception of the VFMCRP Agreement, the entire transaction price of $55,444 was allocated to the one combined
performance obligation, as described above. For the year ended December 31, 2020, $22,262 was recognized as license and
milestone fees revenue based on the percentage of R&D services that were completed during the period. As of
December 31, 2020, there were no remaining performance obligations and the entire $55,444 has been recognized as
license and milestone fees revenue based on the percentage of R&D services that has been completed since the inception of
the VFMCRP Agreement. The Company is eligible to receive milestone payments and sales royalties in the future.
As of December 31, 2020, there were no remaining performance obligations under either the Maruishi Agreement or
the CKDP Agreement, although the Company is eligible to receive milestone payments and sales royalties in the future.
Significant judgments
In applying ASC 606, as amended, to its four contracts, the Company made the following judgments that
significantly affect the timing and amount of revenue recognition:
1. Determination of the number of distinct performance obligations in a contract
The VFMCRP Agreement contains one combined performance obligation, which includes the Company’s two
performance obligations to grant a license to VFMCRP and conduct R&D services. Both of those performance obligations
are inputs to the promise, within the context of the contract, to transfer a combined output for which VFMCRP has
contracted (the ability of VFMCRP to commercialize the Licensed Product) (see Note 11, Collaboration and Licensing
Agreements, for further discussion).
The Maruishi Agreement contains two distinct performance obligations: the granting of the license and the promise
to deliver defined R&D services. Under the Maruishi Agreement, the license and the R&D services represent distinct
goods or services from each other because Maruishi is able to benefit from the license on its own or together with other
resources that are readily available to it (i.e., capable of being distinct). Maruishi’s ability to benefit from the license
without the R&D services is indicated by its ability to conduct clinical trials of CR845/difelikefalin on its own and by the
provision in the Maruishi Agreement whereby if the Company suspends or discontinues its development activity, the
Company will provide information regarding its development efforts up to that point so that Maruishi may continue
development and commercialization of the product in Japan. Therefore, the R&D services do not significantly affect
Maruishi’s ability to use and benefit from the license.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
In addition, the Company’s promise in the Maruishi contract to transfer the license is separately identifiable from the
promise to provide defined R&D services (i.e., distinct within the context of the contract) because the Company is not
using the goods or services as inputs to produce or deliver the combined output or outputs specified by the customer. The
combined output specified by Maruishi is its right to conduct development activities related to CR845/difelikefalin in
Japan, which could result in regulatory approval in Japan. That right is derived from the Company’s grant of the license.
Maruishi is conducting clinical trials on its own and does not require the R&D services provided by the Company.
Furthermore, the R&D services do not significantly modify or customize the license and vice versa. Finally, the license and
R&D services are not highly interdependent or highly interrelated because the Company is able to fulfill its promise to
transfer the initial license independently from its promise to subsequently provide the R&D services, which Maruishi can
obtain on its own.
The only performance obligation in the Vifor and CKDP agreements is the granting of the license.
2. Determination of the transaction price, including whether any variable consideration is included at inception of
the contract
The transaction price is the amount of consideration that the Company expects to be entitled to in exchange for
transferring promised goods or services to the customer. The transaction price must be determined at inception of a contract
and may include amounts of variable consideration. However, there is a constraint on inclusion of variable consideration,
such as milestone payments or sales-based royalty payments, in the transaction price related to licenses of IP, if there is
uncertainty at inception of the contract as to whether such consideration will be recognized in the future (see Note 2,
Significant Accounting Policies: Revenue Recognition).
The decision as to whether or not it is probable that a significant reversal of revenue will occur in the future, depends
on the likelihood and magnitude of the reversal and is highly susceptible to factors outside the entity’s influence (for
example, the Company cannot determine the outcome of clinical trials; the Company cannot determine if or when they or
the counterparty will initiate or complete clinical trials; and the Company’s ability to obtain regulatory approval is
difficult). In addition, the uncertainty is not expected to be resolved for a long period of time (in the order of years) and
finally, the Company has limited experience in the field.
Therefore, at inception of the Vifor, VFMCRP, Maruishi and CKDP agreements, milestones and sales-based royalty
payments were not included in the transaction price based on the factors noted above.
Under the Vifor Agreement, the one performance obligation was satisfied when the license was granted to Vifor in
October 2020, and as a result, $111,551 (including the upfront payment of $100,000 and the premium on the common stock
purchased by Vifor of $11,551) was recognized as license and milestone fees revenue during the year ended December 31,
2020. The remaining potential consideration was considered to be variable consideration and was constrained at inception
of the contract, which includes regulatory and sales milestones (see Note 11, Collaboration and Licensing Agreements).
Under the VFMCRP Agreement, the single combined performance obligation was satisfied as the R&D services
were rendered and the transaction price (including the upfront payment of $50,000 and the premium on the common stock
purchased by VFMCRP of $5,444) was recognized as revenue as the R&D services were performed based on the costs
incurred as a percentage of the estimated total costs to be incurred to complete the performance obligation. The remaining
potential consideration was considered to be variable consideration and was constrained at inception of the contract, which
includes regulatory and sales milestones and sales royalties (see Note 11, Collaboration and Licensing Agreements).
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
All performance obligations under the Maruishi Agreement and the CKDP Agreement were satisfied by the end of
2015. In the future, any milestone event will be recognized in accordance with Note 2, Significant Accounting Polices:
Revenue Recognition, as milestone and license fee revenue and collaboration revenue based upon the relative standalone
selling prices of the two performance obligations at inception of the Maruishi Agreement, and as milestone and license fee
revenue under the CKDP Agreement.
Under the Maruishi Agreement, the transaction price includes only the non-refundable and non-creditable upfront
license fee of $15,337, including the premium of $337 from the sale of Company stock to Maruishi, that was paid to the
Company at inception of the contract. The remaining potential consideration was considered to be variable consideration
and was constrained at inception of the contract, including an aggregate of up to $10,500, which the Company is eligible to
receive upon achievement of clinical development and regulatory milestones, a one-time sales milestone of one billion Yen
when a certain sales level is attained; a mid-double-digit percentage of all non-royalty payments received by Maruishi from
its sub-licensees, if any; and tiered royalties based on net sales of products containing CR845/difelikefalin in Japan, if any,
with minimum royalty rates in the low double digits and maximum royalty rates in the low twenties.
Under the CKDP Agreement, the transaction price includes only the non-refundable and non-creditable upfront
license fee of $646, including the premium of $83 from the sale of Company stock to CKDP, that was paid to the Company
at inception of the contract. The remaining consideration was considered to be variable consideration and was constrained
at inception of the contract, including an aggregate of up to $3,750, which the Company is eligible to earn upon
achievement of clinical development and regulatory milestones. The Company is also eligible to receive a mid-double-
digit percentage of all non-royalty payments received by CKDP from its sub-licensees, if any, and tiered royalties ranging
from the high single digits to the high teens based on net sales of products containing CR845/difelikefalin in South Korea,
if any.
3. Determination of the estimate of the standalone selling price of performance obligations
In order to recognize revenue under ASC 606, as amended, for contracts for which more than one distinct
performance obligation has been identified, the Company must allocate the transaction price to the performance obligations
based upon their standalone selling prices. The best evidence of standalone selling price is an observable price of a good or
service when sold separately by an entity in similar circumstances to similar customers. If such evidence is not available,
standalone selling price should be estimated so that the amount that is allocated to each performance obligation equals the
amount that the entity expects to receive for transferring goods or services. The Company has identified more than one
performance obligation only in the Maruishi Agreement. Since evidence based on observable prices is not available for the
performance obligations under the Maruishi Agreement, the Company considered market conditions and entity-specific
factors, including those contemplated in negotiating the agreements, as well as certain internally developed estimates.
At inception of the Maruishi Agreement, the Company determined the estimate of standalone selling price for the
license performance obligation by using the adjusted market assessment approach. Under this method, the Company
forecasted and analyzed CR845/difelikefalin in the Japanese market, the phase of clinical development as well as
considered recent similar license arrangements within the same phase of clinical development, therapeutic area, type of
agreement, etc. To estimate the standalone selling price of the R&D services, the Company forecasted its expected costs of
satisfying that performance obligation and added a margin for that service.
4. Determination of the method of allocation of the transaction price to the distinct performance obligations
At inception of the Maruishi Agreement, the Company allocated the transaction price of $15,337 between the two
performance obligations based on their relative standalone selling prices, determined as described above. The Company
determined that the license and the R&D services had estimated standalone selling prices of $10,200 and $6,200,
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
respectively. The resulting percentage allocations were applied to the $15,337 of total transaction price, which resulted in
$9,637 being allocated to the license performance obligation, which was recognized immediately as license revenue, while
$5,700 was allocated to the R&D services performance obligation. The amount allocated to the R&D services performance
obligation was initially recorded as deferred revenue and was recognized as collaborative revenue as the R&D services
were provided through July 2015.
Since the Vifor, VFMCRP and CKDP agreements each contain only one distinct performance obligation, at the
inception of each of those agreements, the entire transaction price was allocated to the respective performance obligation.
5. Determination of the timing of revenue recognition for contracts
Revenue should be recognized when, or as, an entity satisfies a performance obligation by transferring a promised
good or service to a customer; i.e., when the customer obtains control of the good or service. The licenses granted to Vifor,
Maruishi and CKDP are being accounted for as distinct performance obligations. As discussed below, the licenses relate to
functional IP for which revenue is recognized at a point in time – in the case of these three license agreements, the point in
time is at inception of the contract because the customer obtained control of the license at that point.
The licenses grant Vifor, Maruishi and CKDP the right to use the Company’s IP relating to CR845/difelikefalin as it
existed at the point in time that the licenses were granted. That IP has significant standalone functionality as it provides the
customer with the ability to perform a function or task, such as to manufacture CR845/difelikefalin, conduct clinical trials,
or commercialize CR845/difelikefalin, and is considered to be functional IP.
During the license periods, the Company is continuing to develop and advance CR845/difelikefalin by conducting
clinical trials. Those development efforts are for its own benefit and do not substantively change the significant standalone
functionality of the licensed IP granted to Vifor, Maruishi or CKDP. Therefore, the Company’s ongoing development
efforts do not significantly affect the IP’s utility to which Vifor, Maruishi or CKDP have rights. Furthermore, if the
Company abandons its development efforts, Vifor, Maruishi or CKDP may still continue to develop CR845/difelikefalin in
their respective countries.
The R&D services performance obligation under the Maruishi Agreement represents a separate performance
obligation. The R&D services were provided to Maruishi by the Company from inception of the agreement in 2013
through the third quarter of 2015, at which time the Company had fulfilled its promise related to the R&D services.
Revenue related to the R&D services performance obligation was recognized as services were performed based on the
costs incurred as a percentage of the estimated total costs to be incurred to complete the performance obligation.
Similarly, under the VFMCRP Agreement, revenue related to the single distinct performance obligation, which
includes both granting of the license and performance of the R&D services, was recognized as the R&D services were
performed, based on the costs incurred as a percentage of the estimated total costs to be incurred to complete the
performance obligation. As of December 31, 2020, there is no remaining amount of the transaction price to be recognized
as license and milestone fees revenue.
6. Determination of consideration as variable consideration, including factors related to inclusion in the
transaction price at inception of the contract and timing of recognition as revenue.
The Vifor, VFMCRP, Maruishi and CKDP agreements contain potential payments related to achievement of defined
milestone events and royalties (excluding Vifor) upon net sales of future products, which are considered to be variable
consideration because of the uncertainty of occurrence of any of those events specified in those agreements at
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
inception of the agreements. Therefore, those potential payments were not included in the transaction price at the inception
of the agreements.
Revenue related to achievement of milestone events is recognized when the Company has determined that it is
probable that a milestone event will be achieved and there will not be a significant reversal of revenue in future periods.
Upon probability of achievement of a milestone event, the most likely amount of variable consideration is included in the
transaction price. Subsequent changes to the transaction price, after contract initiation, are allocated to the performance
obligations in the contract on the same basis as at contract inception. Revenue for variable consideration is recognized in
the same manner (point in time or over time) as for the performance obligations to which the payment amounts were
allocated.
The Maruishi Agreement and the CKDP Agreement specify that certain development milestones will be achieved at
pre-specified defined phases of a clinical trial (such as initiation or completion or other pre-specified time during a clinical
trial as specified in the agreements).
During the year ended December 31, 2020, the criteria for revenue recognition for a milestone event set forth in the
CKDP Agreement was achieved, and the Company recorded $626 (net of South Korean taxes) as license and milestone
fees revenue. No milestone events were probable of occurrence or achieved during the years ended December 31, 2019 and
2018.
Sublicense payments
Vifor’s, VFMCRP’s, Maruishi’s and CKDP’s right to grant sub-licenses is explicitly stated in their respective license
agreements. The amount of any potential sub-license fees to be received by the Company, which is based on a formula if
applicable to that respective agreement, is considered to be variable consideration and is constrained from inclusion in the
transaction price at inception of the contract since at that time it was probable that there would be a reversal of such
revenue in the future because the Company did not know if a sublicense would be granted in the future.
Sales-based Royalty Payments
The VFMCRP Agreement, CKDP Agreement and Maruishi Agreement each allow the Company to earn sales-based
royalty payments in exchange for a license of intellectual property. In that case, the Company will recognize revenue for a
sales-based royalty only when (or as) the later of the following events occurs:
a.
b.
The subsequent sale or usage occurs.
The performance obligation to which some or all of the sales-based royalty has been allocated has been
satisfied (or partially satisfied).
Since the sale (item a, above) occurs after the license was delivered (item b, above), the sales-based royalty
exception, to exclude such royalty payments from the transaction price, applies to the overall revenue stream. Therefore,
sales-based royalty payments are recognized as revenue when the customer’s sales occur. To date, no royalties have been
earned or were otherwise due to the Company.
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
13. Stock-Based Compensation
2019 Inducement Plan
In October 2019, the Company’s Board of Directors adopted the 2019 Inducement Plan, or the 2019 Plan, which is a
non-stockholder approved stock plan adopted pursuant to the “inducement exception” provided under Nasdaq Listing Rule
5635(c)(4), or Rule 5635, for the purpose of awarding (i) non-statutory stock options, (ii) restricted stock awards, (iii)
restricted stock unit awards, (iv) other stock awards (collectively, the Inducement Awards) to new employees of the
Company, as inducement material to such new employees entering into employment with the Company. On November 20,
2019, the Company filed a Registration Statement on Form S-8 with the SEC covering the offering of up to 300,000 shares
of its common stock, par value $0.001, pursuant to the Company’s 2019 Plan. No stock options were granted under the
2019 Inducement Plan during the year ended December 31, 2020. During the year ended December 31, 2019, the Company
granted 47,500 stock options under the 2019 Plan to new employees. Initial grants of Inducement Awards made to
employees vest as to 25% on the first anniversary of the date of grant and the balance ratably over the next 36 months and
subsequent grants vest monthly over a period of four years from the grant date.
2014 Equity Incentive Plan
The Company’s 2014 Equity Incentive Plan, or the 2014 Plan, is administered by the Company’s Board of Directors
or a duly authorized committee thereof, referred to as the Plan administrator. The 2014 Plan provides for the grant of
incentive stock options, non-statutory stock options, restricted stock awards, restricted stock unit awards, stock
appreciation rights, performance stock awards and other forms of equity compensation, collectively referred to as Stock
Awards. Additionally, the 2014 Plan provides for the grant of performance cash awards. Incentive stock options may be
granted only to employees. All other awards may be granted to employees, including officers, non-employee directors, and
consultants. No incentive stock options may be granted under the 2014 Plan after the tenth anniversary of the effective date
of the 2014 Plan. Stock Awards granted under the 2014 Plan vest at the rate specified by the Plan administrator. Initial
grants of Stock Awards made to employees and non-employee consultants generally vest as to 25% on the first anniversary
of the date of grant and the balance ratably over the next 36 months and subsequent grants vest monthly over a period of
four years from the grant date. Stock options initially granted to members of the Company’s Board of Directors vest over a
period of three years in equal quarterly installments from the date of the grant, subject to the option holder’s continued
service as a Director through such date. Subsequent grants to Directors that are made automatically at Annual Meetings of
Stockholders vest fully on the first anniversary of the date of grant. The Plan administrator determines the term of Stock
Awards granted under the 2014 Plan up to a maximum of ten years.
The aggregate number of shares of the Company’s common stock reserved for issuance under the 2014 Plan has
automatically increased on January 1 of each year, beginning on January 1, 2015 and will continue to increase on January 1
of each year through and including January 1, 2024, by 3% of the total number of shares of the Company’s capital stock
outstanding on December 31 of the preceding calendar year, or a lesser number of shares determined by the Company’s
Board of Directors. On January 1, 2021, the aggregate number of shares of common stock that may be issued pursuant to
Stock Awards under the 2014 Plan automatically increased from 7,488,513 to 8,984,679. The maximum number of shares
that may be issued pursuant to the exercise of incentive stock options under the 2014 Plan is 30,000,000 shares.
Restricted Stock Units
Pursuant to the Company’s non-employee director compensation policy, an aggregate of 36,000 restricted stock units
were granted to non-employee directors on June 4, 2020, the date of the Company’s 2020 Annual Meeting of Stockholders,
under the 2014 Plan with a grant date fair value of $15.62 per share. The restricted stock units will vest on the earlier of
(i) June 4, 2021 and (ii) immediately prior to the Company’s next Annual Meeting of Stockholders
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
following the grant date, subject to the recipient’s continued service through such date. As a result, the Company will
recognize compensation expense associated with these restricted stock units ratably over the one-year vesting period
following the grant date. For the year ended December 31, 2020, $323 of stock compensation expense relating to these
restricted stock units was recognized in G&A expense. None of the 36,000 restricted stock units vested and were settled in
shares of the Company’s common stock as of December 31, 2020.
In February 2020, the Compensation Committee of the Company’s Board of Directors approved and granted a total
of 138,000 restricted stock units to executive officers under the 2014 Plan with a grant date fair value of $16.36 per share.
Vesting of the restricted stock units is contingent on the achievement of certain performance targets related to the results of
ongoing clinical trials, NDA filing and FDA approval as well as the recipient’s continuous service through each
performance target. At the date of grant, the Company concluded that the probability of achievement of the performance
targets could not be determined until the various milestones were probable of being achieved. Recognition of compensation
expense associated with these awards begins when, and to the extent, the performance criteria have been achieved and
therefore, the restricted stock units are earned and vesting has occurred. As a result of the achievement of a performance
target relating to its NDA filing in December 2020, the Company recognized $601 of stock compensation expense, with
$196 recorded in R&D expense and $405 in G&A expense. As of December 31, 2020, 36,750 of the 138,000 restricted
stock units vested and were settled in shares of the Company’s common stock.
Additionally in February 2020, the Compensation Committee of the Company’s Board of Directors also approved
and granted a total of 98,000 time-based restricted stock units to executive officers under the 2014 Plan with a grant date
fair value of $16.36 per share. The restricted stock units vest in three equal installments annually from the date of the grant.
As a result, the Company recognizes compensation expense associated with these restricted stock units ratably over the
three-year vesting period following the grant date. For the year ended December 31, 2020, the Company recognized $455
of stock compensation expense, with $149 recorded in R&D expense and $306 in G&A expense. None of the 98,000
restricted stock units vested or were settled in shares of the Company’s common stock as of December 31, 2020.
Pursuant to the terms of the Company’s non-employee director compensation policy, an aggregate of 24,000
restricted stock units were granted to non-employee directors on June 4, 2019, the date of the Company’s 2019 Annual
Meeting of Stockholders, under the 2014 Plan with a grant date fair value of $20.47 per share. The restricted stock units
vested on the earlier of (i) June 4, 2020 and (ii) immediately prior to the Company’s next Annual Meeting of Stockholders
following the grant date, subject to the recipient’s continued service through such date. As a result, the Company
recognized compensation expense associated with these restricted stock units ratably over the one-year vesting period
following the grant date. For the years ended December 31, 2020 and 2019, the Company recognized $205 and $287,
respectively, of stock compensation expense relating to these restricted stock units in G&A expense. As of December 31,
2020, all of the 24,000 restricted stock units vested and were settled in shares of the Company’s common stock.
In March 2019, the Compensation Committee of the Company’s Board of Directors approved and granted a total of
215,000 restricted stock units to executive officers under the 2014 Plan with a grant date fair value of $16.10 per share.
Vesting of the restricted stock units was contingent on the achievement of certain performance targets related to the results
of ongoing clinical trials, subject to the recipient’s continuous service through the vesting events. At the date of grant, the
Company concluded that the probability of achievement of the performance targets could not be determined until the
milestones were probable of being achieved, and accordingly, the Company would recognize compensation expense
associated with these awards when, and to the extent, the restricted stock units vested in accordance with achievement of
the performance targets. In December 2019 and May 2019, performance targets relating to 36,666 and 74,166 restricted
stock units, respectively, had been achieved and thus such restricted stock units vested and the awards were settled in
shares of common stock. Also in December 2019, 8,334 restricted stock units were forfeited. In April and June 2020,
performance targets relating to 65,834 and 30,000 restricted stock units, respectively, had been achieved and
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
thus such restricted stock units vested and the awards were settled in shares of common stock. During the year ended
December 31, 2020, the Company recognized $1,543 of stock compensation expense relating to the vesting of these
restricted stock units, with $1,087 recorded in R&D expense and $456 in G&A expense. During the year ended December
31, 2019, the Company recognized $1,784 of stock compensation expense relating to the vesting of these restricted stock
units, with $1,180 recorded in G&A expense and $604 in R&D expense. As of December 31, 2020, all of the 215,000
restricted stock units either vested and were settled in shares of the Company’s common stock or were forfeited.
In September 2018, the Company granted a total of 83,791 restricted stock units to executive officers under the 2014
Plan with a grant date fair value of $20.21 per share. Vesting of the restricted stock units was contingent on the
achievement of certain performance targets through the first quarter of 2019, subject to the recipient’s continuous service
through the vesting events. At the date of grant, the Company concluded that the probability of achievement of the
performance targets could not be determined until they were achieved, and accordingly, the Company would recognize
compensation expense associated with these awards when, and to the extent, the restricted stock units vested in accordance
with achievement of the performance targets. As of December 31, 2018, all of the performance targets had been achieved
and, consequently, all of the restricted stock units had vested. As a result, $1,693 of stock compensation expense relating to
the vesting of restricted stock units was recognized for the year ended December 31, 2018, with $1,217 recorded in G&A
expense and $476 in R&D expense. In addition, all of the 83,791 restricted stock units vested and were settled in shares of
the Company’s common stock as of December 31, 2018.
Stock Options
A summary of the Company’s stock option activity related to employees, non-employee members of the Board of
Directors and non-employee consultants for the 2019 Plan and the 2014 Plan as of and for the year ended December 31,
2020 is as follows:
Outstanding, December 31, 2019
Granted
Exercised
Expired
Forfeited
Outstanding, December 31, 2020
Weighted average remaining contractual life as of December 31, 2020 (in
years)
Options exercisable, December 31, 2020
Weighted average remaining contractual life as of December 31, 2020 (in
years)
Options vested and expected to vest as of December 31, 2020
Weighted average remaining contractual life as of December 31, 2020 (in
years)
Weighted
Average Exercise
Price
Aggregate
Intrinsic
Value
$
$
$
$
14.73
15.88
12.37
14.06
16.55
15.02
$
8,441
13.96
$
7,589
15.02
$
8,441
Number of
Shares
4,450,517
1,377,850
(55,852)
(175,971)
(127,151)
5,469,393
7.26
3,192,128
6.23
5,469,393
7.26
The total fair value of options vested during the years ended December 31, 2020, 2019 and 2018 was $12,819,
$10,074, and $9,023, respectively. The intrinsic value of options exercised during the years ended December 31, 2020,
2019 and 2018 was $152, $5,741, and $3,893, respectively.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
During the years ended December 31, 2020, 2019 and 2018, the Company granted 1,377,850, 1,324,000 and
1,197,500 stock options, respectively, to employees and non-employee members of the Board of Directors. There were no
options granted to nonemployee consultants during the years ended December 31, 2020, 2019 and 2018. The fair values of
the stock options granted to those groups were estimated using the Black-Scholes option valuation model with the
following ranges of assumptions (see Note 2, Summary of Significant Accounting Policies – Stock-Based Compensation):
Risk-free interest rate
Expected volatility
Expected dividend yield
Expected life of employee and Board options (in years)
2020
Year Ended December 31,
2019
0.35% - 1.57 % 1.55% - 2.62 % 2.51% - 3.09 %
71.8% - 74.8 % 71.1% - 75.2 % 82.6% - 92.8 %
%
0
6.25
0
6.25
0
6.25
%
%
2018
The weighted average grant date fair value of options granted to employees and non-employee members of the Board
of Directors for their Board service during the years ended December 31, 2020, 2019 and 2018 was $10.33, $11.67, and
$11.99, respectively.
On January 1, 2019, the Company used the Black Scholes option valuation model to remeasure the fair value of all
outstanding unvested options that had been granted to non-employee consultants in accordance with ASU 2018-07. At the
end of each fiscal quarter during the year ended December 31, 2018, the Company used the Black-Scholes option valuation
model to re-measure the fair value of all outstanding options that had been granted to non-employee consultants during the
vesting period of each tranche in accordance with ASC 505-50. The range of assumptions used by the Company on January
1, 2019 and during the year ended December 31, 2018 are as follows:
Risk-free interest rate
Expected volatility
Expected dividend yield
Expected life of non-employee options (in years)
Year Ended
December 31, 2018
January 1, 2019
2.59% - 2.62%
1.82% - 3.02%
58.9% - 84.6% 58.2% - 101.0%
0%
0.81 - 8.19
0%
0.25 - 8.94
The weighted average fair value of outstanding options that had been granted to nonemployee consultants, as re-
measured during the vesting period of each tranche during the year ended December 31, 2018, was $8.74.
During the years ended December 31, 2020, 2019 and 2018, the Company recognized compensation expense relating
to stock options as follows:
Research and development
General and administrative
Total stock option expense
$
2020
6,765
4,943
$ 11,708
Year Ended December 31,
2019
5,206
5,094
$ 10,300
$
$
$
2018
3,919
4,482
8,401
The following were excluded from the table above as they are not related to stock options: compensation expense for
i) the vesting of executives’ restricted stock units for $1,432, $604 and $476 in R&D expense for the years ended
December 31, 2020, 2019 and 2018, respectively, and $1,167, $1,180 and $1,217 in G&A expense for the years ended
December 31, 2020, 2019 and 2018, respectively; ii) compensation expense relating to the Board of Directors’ restricted
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NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
stock units for $528 and $287 in G&A expense for the years ended December 31, 2020 and 2019, respectively; and iii) the
issuance of common stock relating to the consulting agreement for $197 in G&A expense for the year ended December 31,
2019.
During the year ended December 31, 2018, the Company recognized additional compensation expense of $616
relating to modifications of outstanding Stock Awards for the former Chief Medical Officer and former Chief Financial
Officer. This included expense based on marking to market the fair value of the modified Stock Awards in accordance with
ASC 505-50, which is included within R&D expense in the total compensation table above for the year ended December
31, 2018. The Company determined that the acceleration of vesting for Stock Awards that would have vested based on their
original vesting terms through the term of the consulting services were Type 1 modifications pursuant to ASC 718,
Compensation – Stock Compensation, because those Stock Awards would have vested whether or not the vesting of those
Stock Awards had been accelerated. However, acceleration of vesting for the remaining Stock Awards was a Type 3
modification pursuant to ASC 718 because absent the modification terms, those Stock Awards would have been forfeited
as of the last day that the former Chief Medical Officer and Chief Financial Officer provided continuous service as a
consultant.
As of December 31, 2020, the total compensation expense relating to unvested options granted to employees and
non-employee members of the Board of Directors that had not yet been recognized was $23,110, which is expected to be
realized over a weighted average period of 2.54 years. The Company will issue shares upon exercise of options from
common stock reserved.
The Company does not expect to realize any tax benefits from its stock option activity or the recognition of stock-
based compensation expense because the Company currently has net operating losses and has a full valuation allowance
against its deferred tax assets. Accordingly, no amounts related to excess tax benefits have been reported in cash flows
from operations or cash flows from financing activities for the years ended December 31, 2020, 2019 and 2018.
14. Income Taxes
The Company’s benefit from income taxes is as follows:
Current:
Federal
State
Deferred:
Federal
State
Benefit from income taxes
2020
December 31,
2019
2018
$
— $
— $
(691)
(691)
(816)
(816)
—
—
—
(691) $
—
—
—
(816) $
$
—
(389)
(389)
—
—
—
(389)
The Company’s tax benefits relate to state R&D tax credits exchanged for cash. The State of Connecticut provides
companies with the opportunity to exchange certain R&D credit carryforwards for cash in exchange for foregoing the
carryforward of the R&D credit. The program provides for such exchange of the R&D credits at a rate of 65% of the
annual R&D credit, as defined.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
A reconciliation of income taxes computed using the U.S. federal statutory rate to that reflected in operations is as
follows:
Income taxes using U.S. federal statutory rate
State income taxes, net of federal benefit
Tax Cuts and Jobs Act
Impact of R&D tax credit on effective tax rate
Stock option shortfalls and cancellations
Permanent items and other
Change in valuation allowance
Provision to return
Non-taxable revenue
December 31,
2019
2018
2020
21.00 % 21.00 % 21.00 %
6.82 %
(1.99)%
(58.68)%
0.00 %
0.00 %
0.00 %
3.48 %
4.34 %
(52.06)%
(0.43)%
(0.17)%
0.35 %
(5.08)%
(0.15)%
0.36 %
84.61 % (22.76)% (31.76)%
0.03 %
(0.02)%
1.54 %
0.00 %
0.53 %
0.76 %
0.92 %
0.00 %
(8.94)%
Significant components of the Company’s deferred tax assets and liabilities are as follows:
Valuation allowance
Net operating loss carryforwards
Federal and state tax credits
Deferred revenue
Stock-based compensation expense
Other
Deferred tax assets
Other
Deferred tax liabilities:
Net deferred tax asset:
December 31,
2020
2019
$ (120,666) $ (114,136)
93,507
19,982
—
6,732
2,414
122,635
(1,969)
(1,969)
84,608
16,624
5,994
4,481
3,409
115,116
(980)
(980)
$
— $
—
A 100% valuation allowance has been recorded on the deferred tax asset as of December 31, 2020 and 2019 because
management believes it is more likely than not that the asset will not be realized. The change in the valuation allowance
during 2020 and 2019 was an increase of $6,530 and $24,321, respectively.
The financial statements reflect expected future tax consequences of such positions presuming the taxing authorities
possess full knowledge of the position and all relevant facts. As of December 31, 2020 and 2019, the Company had no
unrecognized tax benefits or related interest and penalties accrued. In the event the Company determines that accrual of
interest or penalties are necessary in the future, the amount will be presented as a component of income tax expense.
At December 31, 2020, the Company had federal and state net operating loss carryforwards of $368,237 and
$273,041, respectively. The federal and state tax loss carryforwards will begin to expire in 2026 and 2027, respectively,
unless previously utilized. The federal net operating losses arising in taxable years beginning in 2018 and forward have an
unlimited carryforward period, and, in the case of such federal net operating losses arising in taxable years beginning
before 2021, may be carried back five years due to the Coronavirus Aid, Relief, and Economic Security Act of 2020, or
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
the CARES Act. The federal losses may also be subject to limitation pursuant to Internal Revenue Code section 382. The
Company also had federal and state R&D tax credit carryforwards of $18,358 and $1,795, respectively. The federal credits
will begin expiring in 2025 unless previously utilized. The Connecticut credit carryforwards have no expiration period.
Because of the net operating loss and research credit carryforwards, tax years 2006 through 2020 remain open to U.S.
federal and state tax examinations.
On March 27, 2020, President Trump signed into law the CARES Act (H.R. 748), which was further expanded with
the signing of the Consolidation Appropriations Act of 2021 (H.R. 133) on December 27, 2020. The CARES Act (and
December expansion) includes a variety of economic and tax relief measures intended to stimulate the economy, including
loans for small businesses, payroll tax credits/deferrals, and corporate income tax relief. Due to the Company’s history of
tax loss carryforwards and full valuation allowance, the CARES Act did not have a significant effect to the income tax
provision, as the corporate income tax relief was directed towards cash taxpayers.
On December 22, 2017, the United States enacted the Tax Cuts and Jobs Act, or the TCJA. The TCJA, which is also
commonly referred to as “U.S. tax reform”, significantly changes U.S. corporate income tax laws by, among other
provisions, reducing the maximum U.S. corporate income tax rate from 35% to 21% starting in 2018. As of December 31,
2020 and 2019, the Company did not have any foreign subsidiaries and the international aspects of the TCJA were not
applicable.
On December, 22, 2017, Staff Accounting Bulletin 118, or SAB 118, was issued by the SEC due to the complexities
involved in accounting for the TCJA. SAB 118 requires the Company to include in its financial statements a reasonable
estimate of the impact of the TCJA on earnings to the extent such estimate has been determined. The Company finalized its
accounting for the TCJA as of December 31, 2018, which resulted in insignificant adjustments.
15. Net Income (loss) per Share
The Company computes net income (loss) per share in accordance with ASC 260-10, Earnings per Share (see
Note 2, Significant Accounting Policies – Income (Loss) per Share).
The denominators used in the net income (loss) per share computations are as follows:
Basic:
Weighted average common shares outstanding
Diluted:
Weighted average common shares outstanding - Basic
Common stock equivalents*
Denominator for diluted net income (loss) per share
Year Ended December 31,
2019
2018
2020
47,413,250 42,669,333 35,892,786
47,413,250 42,669,333 35,892,786
—
47,915,030 42,669,333 35,892,786
501,780
—
*
For the year end December 31, 2020, common stock equivalents include dilutive stock options and restricted stock
units. For the years ended December 31, 2019 and 2018, no amounts were considered as their effects would have been
anti-dilutive due to net losses for those periods.
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Basic and diluted net income (loss) per share is computed as follows:
Net income (loss) - basic and diluted
$
2020
Year Ended December 31,
2019
(106,373) $
$
8,410
2018
(74,013)
Weighted-average common shares outstanding - basic
47,413,250
42,669,333
35,892,786
Effect of dilutive securities:
Stock options
Restricted stock units
Weighted-average common shares outstanding - diluted
Net income (loss) per share:
Basic
Diluted
481,254
20,526
47,915,030
—
—
42,669,333
—
—
35,892,786
$
$
0.18
0.18
$
$
(2.49) $
(2.49) $
(2.06)
(2.06)
As of December 31, 2020, 5,469,393 stock options and 235,250 restricted stock units were outstanding, which could
potentially dilute basic earnings per share in the future. 481,254 of these outstanding stock options and 20,526 of these
restricted stock units were considered dilutive and included in the computation of diluted net income per share for the year
ended December 31, 2020.
In addition, the Company entered into the Vifor Agreement in October 2020. The Company will be eligible to
receive an additional $50,000 common stock investment upon U.S. regulatory approval of CR845/difelikefalin at a 20%
premium to the 30-day trailing average price of the Company’s common stock as of such date, which could potentially
dilute basic earnings per share in the future (see Note 11, Collaboration and Licensing Agreements).
As of December 31, 2019, 4,450,517 stock options and 119,834 restricted stock units were outstanding, which could
potentially dilute basic earnings per share in the future, but were not included in the computation of diluted net loss per
share because to do so would have been anti-dilutive as a result of the net loss for the period.
As of December 31, 2018, 4,004,422 stock options were outstanding, which could potentially dilute basic earnings
per share in the future, but were not included in the computation of diluted net loss per share because to do so would have
been anti-dilutive as a result of the net loss for the period.
16. Employee Benefit Plan
In February 2006, the Company adopted a defined contribution retirement plan that complies with Section 401(k) of
the Internal Revenue Code. All employees over the age of 21 are eligible to participate in the plan at the beginning of the
calendar quarter after three consecutive months of service. Employees are able to defer a portion of their pay into the plan
on the first day of the quarter on or after the day all age and service requirements have been met. All eligible employees
receive an employer contribution equal to 3% of their salary up to the annual IRS limit. During the years ended
December 31, 2020, 2019 and 2018, employer contributions to the plan were $349, $279 and $198, respectively.
146
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
17. Commitments and Contingencies
License Agreement with Enteris Biopharma, Inc.
In August 2019, the Company entered into the Enteris License Agreement, pursuant to which Enteris granted to the
Company a non-exclusive, royalty-bearing license, including the right to grant sublicenses, under certain proprietary
technology and patent rights related to or covering formulations for oral delivery of peptide active pharmaceutical
ingredients with functional excipients to enhance permeability and/or solubility, known as Enteris’s Peptelligence®
technology, to develop, manufacture and commercialize products using such technology worldwide, excluding Japan and
South Korea.
As consideration for the licensed rights under the Enteris License Agreement, the Company paid an upfront fee equal
to $8,000, consisting of $4,000 in cash and $4,000 in shares of the Company’s common stock pursuant to the Enteris
Purchase Agreement (see Note 9, Stockholders’ Equity). As a result, the Company recognized R&D expense of $8,000
related to the Enteris License Agreement during the year ended December 31, 2019.
The Company is also obligated, pursuant to the Enteris License Agreement, to pay Enteris (1) milestone payments
upon the achievement of certain development, regulatory and commercial milestones and (2) low-single digit royalty
percentages on net sales of licensed products, subject to reductions in specified circumstances. Until the second anniversary
of the entry into the Enteris License Agreement, the Company has the right, but not the obligation, to terminate its
obligation to pay any royalties under the Enteris License Agreement in exchange for a lump sum payment in cash, or the
Royalty Buyout. Subject to certain conditions, the Company may elect to pay 50% of the lump sum due under the Royalty
Buyout in shares of the Company’s common stock pursuant to the Purchase Agreement. During the year ended December
31, 2020, the Company paid $5,000 to Enteris for a milestone earned during the year ended December 31, 2020 in relation
to the Enteris License Agreement. As a result, the Company recognized $5,000 of R&D expense related to the Enteris
License Agreement during the year ended December 31, 2020.
The Enteris License Agreement will expire on a country-by-country, licensed product-by-licensed product basis upon
the later of (1) the expiration (or invalidation) of all valid claims in licensed patent rights that cover such product in such
country, (2) the end of the calendar quarter in which generic competition (as defined in the Enteris License Agreement)
occurs for such product in such country and (3) ten years from the first commercial sale of such product.
Either party may terminate the Enteris License Agreement upon written notice if the other party has failed to remedy
a material breach within 60 days (or 30 days in the case of a material breach of a payment obligation). Enteris may
terminate the Enteris License Agreement upon 30 days’ written notice to the Company if the Company or any of its
affiliates formally challenge the validity of any licensed patent rights or assists a third party in doing so. The Company may
terminate the Enteris License Agreement for any reason or no reason (a) prior to receipt of first regulatory approval for a
licensed product in the United States for any indication upon 30 days’ prior written notice to Enteris or (b) on or after
receipt of first regulatory approval for a licensed product in the United States for any indication upon 60 days’ prior written
notice to Enteris.
Manufacturing Agreement with Patheon UK Limited
In July 2019, the Company entered into a Master Manufacturing Services Agreement, or MSA, with Patheon UK
Limited, or Patheon. The MSA governs the general terms under which Patheon, or one of its affiliates, will provide non-
exclusive manufacturing services to the Company for the drug products specified by the Company from time to time.
Pursuant to the MSA, the Company has agreed to order from Patheon at least a certain percentage of its commercial
requirements for a product under a related Product Agreement. Each Product Agreement that the Company may enter into
from time to time will be governed by the terms of the MSA, unless expressly modified in such Product Agreement.
147
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
The MSA has an initial term ending December 31, 2023, and will automatically renew after the initial term for
successive terms of two years each if there is a Product Agreement in effect, unless either party gives notice of its intention
to terminate the MSA at least 18 months prior to the end of the then current term.
Either party may terminate the MSA or a Product Agreement upon written notice if the other party (1) has failed to
remedy a material breach within a specified time or (2) is declared insolvent or bankrupt, voluntarily files a petition of
bankruptcy or assigns such agreement for the benefit of creditors. The Company may terminate a Product Agreement
(a) upon 90 days’ prior written notice if any governmental agency takes any action that prevents the Company from selling
the relevant product in the relevant territory, (b) upon six months’ prior written notice if it does not intend to order
manufacturing services due to a product’s discontinuance in the market, or (c) upon 90 days’ prior written notice if it
determines that the manufacture or supply of a product likely infringes third-party rights. Patheon may terminate the MSA
or a Product Agreement (i) upon six months’ prior written notice if the Company assigns such agreement to an assignee
that is unacceptable to Patheon for certain reasons, or (ii) upon 30 days’ prior written notice if, after the first year of
commercial sales, the Company forecasts zero volume for 12 months.
The MSA contains, among other provisions, customary representations and warranties by the parties, a grant to
Patheon of certain limited license rights to the Company’s intellectual property in connection with Patheon’s performance
of the services under the MSA, certain indemnification rights in favor of both parties, limitations of liability and customary
confidentiality provisions.
Also in July 2019, the Company entered into two related Product Agreements under the MSA, one with each of
Patheon and Patheon Manufacturing Services LLC, or Patheon Greenville, to govern the terms and conditions of the
manufacture of commercial supplies of CR845/difelikefalin injection, the Company’s lead product candidate. Pursuant to
the Product Agreements, Patheon and Patheon Greenville will manufacture commercial supplies of CR845/difelikefalin
injection at the Monza, Italy and Greenville, North Carolina manufacturing sites, respectively, from active pharmaceutical
ingredient supplied by the Company. Patheon and Patheon Greenville will be responsible for supplying the other required
raw materials and packaging components and will also provide supportive manufacturing services such as quality control
testing for raw materials, packaging components and finished product.
Leases
In December 2015, the Company entered into a lease agreement, or the Stamford Lease, for office space in Stamford,
Connecticut, or the Premises, for the purpose of relocating its headquarters. The initial term of the Stamford Lease
commenced in May 2016, or the Commencement Date, and ends in December 2023 and is renewable for one five-year
term.
The Stamford Lease requires monthly lease payments, including rent escalations and rent holidays, during the initial
lease term. The Company began to make rental payments from the Commencement Date. Prior to January 1, 2019, the
Company recorded monthly rent expense on a straight-line basis from March 2016, upon taking possession of the
Premises, through December 31, 2018. Total rent expense under the Stamford Lease was $974 for the year ended
December 31, 2018. As of the Commencement Date, the Stamford Lease landlord had made tenant improvements of
$1,094 to the leased premises which was included in Property and equipment, net.
In connection with the signing of the Stamford Lease, the Company entered into a standby letter of credit agreement
which serves as a security deposit for the Premises. The standby letter of credit is automatically renewed annually through
November 2023. This standby letter of credit is secured with restricted cash in a money market account (refer to Note 7,
Restricted Cash).
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
On January 1, 2019, the Company adopted ASC 842 (see Note 2 – Summary of Significant Accounting Policies -
Leases). Under ASC 842, since the Company adopted the practical expedients not to re-evaluate whether a contract is or
contains a lease and to maintain the lease classification under ASC 840, the Stamford Lease continues to be accounted for
as an operating lease.
Upon adoption of ASC 842, the Company established an operating lease ROU asset and operating lease liability for
the Stamford Lease. In establishing the ROU asset, the operating lease liability of $5,198 was reduced by lease incentives
relating to tenant improvements of $698 and deferred lease obligation of $864, which were outstanding on December 31,
2018.
In June 2020, the Company entered into an amendment to the Stamford Lease to add additional office space, or the
Lease Amendment. The term of the Lease Amendment began when renovation of the additional space was completed and
the Company took possession of the additional space in October 2020, or the Amendment Commencement Date, and ends
on December 31, 2023. The Lease Amendment is also renewable for one five-year term (see Note 2 - Summary of
Significant Accounting Policies – Leases).
The rent for the Lease Amendment is at market rate as of the signing of the Lease Amendment. The Lease
Amendment requires monthly lease payments, including rent escalations, during the lease term. The Company began
paying rent for the Lease Amendment on the Amendment Commencement Date.
In October 2020, the Company recorded an operating lease liability of $1,934 for the Lease Amendment as the sum
of the present value of the future minimum lease payments over the term for the new lease. The Company also recorded a
corresponding ROU asset of $1,934, as no lease incentives were identified in the Lease Amendment.
Under ASC 842, lease expenses on the Stamford lease and Lease Amendment are recognized on a straight-line basis
over the lease term. As a result, $1,116 and $937 of operating lease cost, or lease expense, was recognized for the years
ended December 31, 2020 and 2019, respectively, consisting of $781 relating to R&D lease expense and $335 relating to
G&A lease expense for the 2020 period, and $656 relating to R&D lease expense and $281 relating to G&A lease expense
for the 2019 period.
Other information related to the Stamford Lease and Lease Amendment was as follows:
Cash paid for amounts included in the measurement of lease liabilities:
Operating cash outflows relating to operating leases
ROU assets obtained in exchange for new operating lease liabilities
Remaining lease term - operating leases (years)
Discount rate - operating leases
Year Ended December 31,
2019
2020
$
$
$
$
1,403
1,934
3.0
7.0 %
1,215
3,636
3.9
7.0 %
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
Future minimum lease payments under the non-cancellable operating leases for the Stamford lease and the Lease
Amendment, as well as a reconciliation of these undiscounted cash flows to the operating lease liability as of December 31,
2020, were as follows:
Year Ending December 31,
2021
2022
2023
Total future minimum lease payments, undiscounted
Less imputed interest
Total
Operating lease liabilities reported as of December 31, 2020:
Operating lease liabilities - current
Operating lease liabilities - non-current
Total
18. Legal Matters
$
$
$
$
1,921
1,957
1,992
5,870
(595)
5,275
1,602
3,673
5,275
From time to time, the Company may become subject to arbitration, litigation or claims arising in the ordinary course
of its business. The Company is not currently a party to any arbitration or legal proceeding that, if determined adversely to
the Company, would have a material adverse effect on its business, operating results or financial condition. The results of
any future claims or proceedings cannot be predicted with certainty, and regardless of the outcome, litigation can have an
adverse impact on the Company because of defense and settlement costs, diversion of management resources and other
factors.
19. Quarterly Results of Operations (Unaudited)
The following tables contain selected financial data for each quarter of the years ended December 31, 2020 and 2019.
The Company believes that the following information reflects all normal recurring adjustments necessary for a fair
presentation of the information for each quarter of the years ended December 31, 2020 and 2019. The operating results for
any period are not necessarily indicative of results for any future periods.
Revenues
Operating expenses
Net income (loss) - Basic and Diluted
Income (loss) per share - Basic
Income (loss) per share - Diluted
First
Quarter
8,093
$
$
38,094
$ (28,922)
(0.62)
$
(0.62)
$
Year Ended December 31, 2020
Second
Quarter
5,634
$
$
31,518
$ (25,068)
(0.54)
$
(0.54)
$
Third
Quarter
9,266
$
$
26,286
$ (16,509)
(0.35)
$
(0.35)
$
Fourth
Quarter
$ 112,089 (a)
33,799
$
78,909
$
$
$
1.60 (b)
1.59 (c)
(a) Revenues for the fourth quarter of 2020 include $111,551 relating to the Vifor Agreement (see Note 12, Revenue
Recognition).
(b) The difference between the sum of net income (loss) per share – basic of $0.09, as calculated on a quarterly basis
for 2020, and net income per share – basic of $0.18 for the year ended December 31, 2020, is due to the
denominator used for the year ended December 31, 2020, which weights shares outstanding on a cumulative
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CARA THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(amounts in thousands, except share and per share data)
basis and reflects the issuance of 2,939,552 shares of the Company’s common stock during the year ended
December 31, 2020 (see Note 9, Stockholders’ Equity).
(c) The difference between the sum of net income (loss) per share – diluted of $0.08, as calculated on a quarterly
basis for 2020, and net income per share – diluted of $0.18 for the year ended December 31, 2020, is due to: i) the
issuance of shares of the Company’s common stock as described in b) above; and ii) first, second and third
quarter diluted per share amounts did not include stock options and restricted stock units that were dilutive in
those periods as those periods were in a net loss position; however, those same stock options and restricted stock
units were included in the annual diluted per share amounts since the Company had net income for the year ended
December 31, 2020.
Revenues
Operating expenses
Net loss - Basic and Diluted
Loss per share - Basic and Diluted
First
Quarter
4,382
$
$
27,516
$ (21,960)
(0.56)
$
Year Ended December 31, 2019
Second
Quarter
5,208
29,350
(22,960)
(0.58)
$
$
$
$
Third
Quarter
5,785
40,218
(32,842)
(0.74)
$
$
$
$
Fourth
Quarter
4,511
34,481
(28,611)
(0.61)
$
$
$
$
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Table of Contents
Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.
None.
Item 9A. Controls and Procedures.
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of our Chief Executive Officer and Chief Financial Officer, has evaluated
the effectiveness of our disclosure controls and procedures (as such term is defined in Rules 13a-15(e) and 15d-15(e) under
the Exchange Act) as of December 31, 2020. Based on such evaluation, our Chief Executive Officer and Chief Financial
Officer have concluded that, as of December 31, 2020, our disclosure controls and procedures were effective to provide
reasonable assurance that information required to be disclosed by us in the reports that we file or submit under the
Exchange Act is (1) recorded, processed, summarized, and reported within the time periods specified in the rules and forms
of the SEC, and (2) accumulated and communicated to our management, including our principal executive officer and
principal 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 adequate internal control over financial reporting as
defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act. Our 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. 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.
Our management utilized the criteria established in the Internal Control – Integrated Framework (2013) issued by the
Committee of Sponsoring Organizations of the Treadway Commission (COSO) to conduct an assessment of the
effectiveness of our internal control over financial reporting as of December 31, 2020. Based on the assessment,
management has concluded that, as of December 31, 2020, our internal control over financial reporting was effective.
Ernst & Young LLP, an independent registered public accounting firm, has audited the effectiveness of our internal
control over financial reporting as of December 31, 2020, as stated in their attestation report, which is included in Part II
Item 8 of this Annual Report.
Changes in Internal Control Over Financial Reporting
Beginning January 1, 2020, we implemented ASU 2016-13, Financial Instruments—Credit Losses (Topic 326),
Measurement of Credit Losses on Financial Instruments, or ASU 2016-13. Although ASU 2016-13 did not have a material
impact on our results of operations, financial position or cash flows upon adoption, we did revise our internal controls and
procedures to review qualitative and quantitative factors to determine whether the unrealized loss for each available-for-
sale debt security at any balance sheet date is due to a credit loss during the year ended December 31, 2020.
There was no other change in our internal control over financial reporting that occurred during the quarter ended
December 31, 2020 that has materially affected, or is reasonably likely to materially affect, our internal control over
financial reporting.
Limitations on Controls and Procedures
Management, including our Chief Executive Officer and Chief Financial Officer, recognizes that any controls and
procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives
and management necessarily applies its judgment in evaluating the cost benefit relationship of possible
152
Table of Contents
controls and procedures. Because of the inherent limitations in all control systems, no evaluation of controls and
procedures can provide absolute assurance that all control issues and instances of fraud, if any, within Cara have been
detected.
Item 9B. Other Information.
None.
Item 10. Directors, Executive Officers and Corporate Governance.
PART III
The information required by this item will be set forth under the captions “Executive Officers and Directors of Cara”
and “Board of Directors and Corporate Governance” in our Definitive Proxy Statement with respect to our 2021 Annual
Meeting of Stockholders and is incorporated herein by reference.
Item 11. Executive Compensation.
The information required by this item will be set forth under the captions “Executive Compensation” and “Board of
Directors and Corporate Governance” in our Definitive Proxy Statement with respect to our 2021 Annual Meeting of
Stockholders and is incorporated herein by reference.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.
The information required by this item will be set forth under the captions “Security Ownership of Certain Beneficial
Owners and Management” and “Securities Authorized for Issuance under Equity Compensation Plans” in our Definitive
Proxy Statement with respect to our 2021 Annual Meeting of Stockholders and is incorporated by reference.
Item 13. Certain Relationships and Related Transactions and Director Independence.
The information required by this item will be set forth under the captions “Transactions with Related Persons” and
“Board of Directors and Corporate Governance” in our Definitive Proxy Statement with respect to our 2021 Annual
Meeting of Stockholders and is incorporated herein by reference.
Item 14. Principal Accountant Fees and Services.
The information required by this item will be set forth under the caption “Independent Registered Public Accounting
Firm’s Fees” in our Definitive Proxy Statement with respect to our 2021 Annual Meeting of Stockholders and is
incorporated herein by reference.
153
Table of Contents
PART IV
Item 15. Exhibits, Financial Statement Schedules.
(a) We have filed the following documents as part of this Annual Report on Form 10-K:
(1) Financial Statements of Cara Therapeutics, Inc.
INDEX TO FINANCIAL STATEMENTS
Reports of Independent Registered Public Accounting Firm
Financial Statements:
Balance Sheets
Statements of Comprehensive Income (Loss)
Statements of Stockholders’ Equity
Statements of Cash Flows
Notes to Financial Statements
(2) Financial Statement Schedules
PAGE
101
104
105
106
107
108
All schedules for which provision is made in the applicable accounting regulations of the SEC which are not
included with this additional financial data have been omitted because they are not applicable or the required information is
shown in the Financial Statements or Notes included in Item 8. Financial Statements and Supplementary Data.
(3) List of Exhibits
Exhibit
No.
3.1
3.2
4.1
4.2#
4.3
4.4†#
10.1+
10.2+
Form
File No.
Incorporated by Reference
Date Filed
Exhibit No.
8-K
8-K
001-36279
001-36279
S-1/A
333-192230
S-3ASR
333-233666
3.1
3.2
4.1
4.3
February 7, 2014
February 7, 2014
January 17, 2014
September 9, 2019
Description of Exhibit
Amended and Restated Certificate
of Incorporation.
Amended and Restated Bylaws.
Form of Common Stock
Certificate.
Common Stock Purchase
Agreement, dated August 20,
2019, by and among the
Registrant, Enteris Biopharma,
Inc. and EBP Holdco LLC.
Description of Securities.
10-K
001-36279
4.3
February 27, 2020
Securities Purchase Agreement,
dated October 15, 2020, by and
between the Registrant and Vifor
(International) Ltd.
Form of Indemnity Agreement.
S-1/A
333-192230
2004 Stock Incentive Plan, as
amended, and forms of Stock
Option Agreement thereunder.
S-1
333-192230
10.1
10.2
January 17, 2014
November 8, 2013
154
Table of Contents
10.3+
2014 Equity Incentive Plan.
10.3.1
10.3.2
10.4
10.5*
10.6*
10.7
10.8+
10.9+
Form of Stock Option Agreement
under 2014 Equity Incentive Plan.
Form of Restricted Stock Unit
Award under 2014 Equity
Incentive Plan.
Fourth Amended and Restated
Investors Rights Agreement dated
April 25, 2013 among the
Registrant and certain of its
stockholders, as amended.
License Agreement dated April 4,
2013 by and between the
Registrant and Maruishi
Pharmaceutical Co., Ltd.
License and API Supply
Agreement effective as of April
16, 2012 by and between the
Registrant and Chong Kun Dang
Pharmaceutical Corp.
Amendment to License and API
Supply Agreement effective as of
May 1, 2012 by and between the
Registrant and Chong Kun Dang
Pharmaceutical Corp.
Employment Agreement with
Derek Chalmers.
Employment Agreement with
Frédérique Menzaghi.
S-1/A
S-1/A
333-192230
10.3
January 17, 2014
333-192230
10.3.1
January 17, 2014
S-1/A
333-192230
10.3.2
January 17, 2014
S-1
333-192230
10.5
November 8, 2013
S-1
333-192230
10.7
November 8, 2013
S-1
333-192230
10.8
November 8, 2013
S-1
333-192230
10.9
November 8, 2013
8-K
8-K
001-36279
10.1
February 7, 2014
001-36279
10.2
February 7, 2014
10.10+
Employment Agreement with
Joana Goncalves.
10-K
001-36279
10.11
March 12, 2019
10.11+
10.12+
10.13
10.14
Employment Agreement with
Thomas Reilly
Amended and Restated Non-
Employee Director Compensation
Policy.
Lease Agreement dated December
21, 2015 between the Registrant
and Four Stamford Plaza Owner
L.L.C.
Amendment to Lease Agreement
between the Registrant and Four
Stamford Plaza Owner L.L.C.
Stamford Lease, dated June 23,
2020.
8-K
001-36279
10.1
October 1, 2020
10-Q
001-36279
10.1
May 11, 2020
8-K
001-36279
10.1
December 23, 2015
10-Q
001-36279
10.2
August 10, 2020
155
Table of Contents
10.15*
10.16#
10.17#
License Agreement by and
between Cara Therapeutics, Inc.
and Vifor Fresenius Medical Care
Renal Pharma Ltd.
Master Manufacturing Services
Agreement between the Registrant
and Patheon UK Limited and
related Product Agreements
Non-Exclusive License
Agreement, dated August 20,
2019, between the Registrant and
Enteris Biopharma, Inc.
10.18+
2019 Inducement Plan.
10.19
10.20
10.21†#
23.1†
24.1†
31.1†
31.2†
32.1†**
Form of Stock Option Grant
Notice under 2019 Inducement
Plan
Form of Restricted Stock Unit
Notice under 2019 Inducement
Plan
License Agreement, dated October
15, 2020, by and between Cara
Therapeutics, Inc. and Vifor
(International) Ltd.
Consent of Ernst & Young, LLP,
independent registered public
accounting firm.
Power of Attorney (included on
signature page).
Certification of Chief Executive
Officer of Cara Therapeutics, Inc.
pursuant to Rule 13a-14(a)/15d-
14(a) of the Securities Exchange
Act of 1934.
Certification of Chief Financial
Officer of Cara Therapeutics, Inc.
pursuant to Rule 13a-14(a)/15d-
14(a) of the Securities Exchange
Act of 1934.
Certifications of Chief Executive
Officer and Chief Financial Officer
of Cara Therapeutics, Inc. pursuant
to 18 U.S.C. Section 1350, as
adopted pursuant to Section 906 of
the Sarbanes-Oxley Act of 2002.
101.CAL†
Inline XBRL Taxonomy Extension
Calculation Linkbase.
101.INS†
Inline XBRL Instance Document.
10-Q
001-36279
10.1
August 7, 2018
10-Q
001-36279
10.2
August 7, 2019
10-Q
001-36279
10.1
November 5, 2019
8-K
8-K
001-36279
001-36279
10.1
10.2
November 20, 2019
November 20, 2019
8-K
001-36279
10.3
November 20, 2019
156
Table of Contents
101.LAB†
Inline XBRL Taxonomy Extension
Label Linkbase.
101.PRE†
Inline XBRL Taxonomy Extension
Presentation Linkbase.
101.SCH†
Inline XBRL Taxonomy Extension
Schema Linkbase.
101.DEF†
Inline XBRL Taxonomy Extension
Definition Linkbase Document.
104†
Cover page interactive data file
(formatted as Inline XBRL and
contained in Exhibit 101).
+
indicates management contract or compensatory plan.
* 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 (indicated by asterisks) have been omitted because the Registrant has determined they are not
material and would likely cause competitive harm to the Registrant if publicly disclosed.
Filed herewith.
** This certification is deemed not filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended,
or otherwise subject to the liability of that section, nor shall it 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.
157
Table of Contents
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly
caused this report to be signed on its behalf by the undersigned, thereunto duly authorized on this 25th day of
February 2021.
CARA THERAPEUTICS, INC.
/s/ DEREK CHALMERS
By:
Name: Derek Chalmers, Ph.D., D.Sc.
Title:
President and Chief Executive Officer
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes
and appoints Derek Chalmers, Ph.D., D.Sc. and Scott Terrillion, and each of them, as his true and lawful attorneys-in-fact
and agents, with full power of substitution for him, and in his name in any and all capacities, to sign any and all
amendments to this Annual Report on Form 10-K, and to file the same, with exhibits thereto and other documents in
connection therewith, with the U.S. Securities and Exchange Commission, granting unto said attorneys-in-fact and agents,
and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be
done therewith, as fully to all intents and purposes as he might or could do in person, hereby ratifying and confirming all
that said attorneys-in-fact and agents, and either of them, his substitute or substitutes, may lawfully do or cause to be done
by virtue hereof.
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the
following persons on behalf of the registrant and in the capacities and on the dates indicated.
Signature
Title
Date
/s/ DEREK CHALMERS
Derek Chalmers, Ph.D., D.Sc.
President, Chief Executive Officer and Director
(Principal Executive Officer)
February 25, 2021
/s/ THOMAS REILLY
Thomas Reilly
Chief Financial Officer
(Principal Financial and Accounting Officer)
February 25, 2021
/s/ MARTIN VOGELBAUM
Martin Vogelbaum
/s/ HARRISON M. BAINS, JR.
Harrison M. Bains, Jr.
/s/ JEFFREY IVES
Jeffrey Ives, Ph.D.
/s/ CHRISTOPHER POSNER
Christopher Posner
/s/ SUSAN SHIFF
Susan Shiff, Ph.D.
Director
Director
Director
Director
Director
158
February 25, 2021
February 25, 2021
February 25, 2021
February 25, 2021
February 25, 2021
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
Exhibit 4.4
CARA THERAPEUTICS, INC.
SECURITIES PURCHASE AGREEMENT
THIS SECURITIES PURCHASE AGREEMENT (the “Agreement”) is made as of October 15, 2020 by and between
CARA THERAPEUTICS, INC., a corporation organized and existing under the laws of Delaware and having an office located at
offices at 4 Stamford Plaza,107 Elm Street, 9th Floor Stamford, CT 06902, USA (the “Company”), and VIFOR (INTERNATIONAL)
LTD., a corporation organized and existing under the laws of Switzerland and having an office located at Rechenstrasse 37, CH-9014 St.
Gallen, Switzerland (“Purchaser”). The Company and Purchaser may be referred to herein individually as a “Party” and, collectively, as
the “Parties.”
RECITALS
WHEREAS, in connection with that certain License Agreement entered into by the Company and Vifor Pharma Group Ltd.
(“Vifor”) concurrently with this Agreement (the “License Agreement”), the Company desires to enter into this agreement to sell and
issue to Purchaser, and Purchaser desires to purchase and acquire, equity securities of the Company, on the terms and conditions
hereinafter set forth.
NOW, THEREFORE, IT IS AGREED between the Parties as follows:
AGREEMENT
1. Purchase and Sale of Securities. Purchaser hereby agrees to purchase and acquire from the Company, and the Company hereby
agrees to sell and issue to Purchaser:
(a) On the date hereof, an aggregate of 2,939,552 shares of the Company’s common stock, par value $0.001 per share (the
“Common Stock”) at a price per share of $17.0094, for an aggregate purchase price of fifty million U.S. dollars ($50,000,000). The
closing of such purchase and sale of the Common Stock pursuant to this clause (a) (the “Initial Closing”), including payment for and
delivery of the Common Stock, shall occur simultaneously with the execution of this Agreement on the date hereof at the offices of the
Company, or at such other time and place as the Parties may mutually agree (including remotely via the exchange of electronic
signatures).
(b) Upon the achievement of the Approval Milestone as set forth in Section 6.3(a) of the License Agreement (the “Approval
Milestone”), an additional number of shares of Common Stock equal to an aggregate purchase price of fifty million U.S. dollars
($50,000,000) divided by a purchase price per share equal to 120% of the average of the closing trading price of the Company’s Common
Stock on the primary trading market for the 30 trading day period ending on the date immediately prior to the achievement of the
Approval Milestone. The closing of such purchase and sale of the Common Stock pursuant to this clause (b) (the “Additional Closing”
and the Initial Closing, each a “Closing”), including payment for and delivery of the Common Stock, shall occur at the offices of the
Company within five business days following the later of (i) the achievement of the Approval Milestone and (ii) if required by applicable
law, the expiration or
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvement Act of 1976 (the “HSR Act”) applicable to the
consummation of the Additional Closing, or at such other time and place as the Parties may mutually agree. The Common Stock to be
sold and issued in accordance with the terms of this Agreement at each Closing is referred to herein as the “Securities.” The purchase
price for the Securities shall be payable in cash by wire transfer of immediately available funds.
(c) At each Closing, the Company shall issue or deliver to the Purchaser evidence of a book entry position evidencing the
Securities purchased by the Purchaser hereunder, registered in the name of the Purchaser, representing the Securities to be purchased by
the Purchaser at the Closing against payment of the purchase price for the Securities.
2. Limitations on Transfer. Purchaser shall not assign, hypothecate, donate, encumber or otherwise dispose of any interest in the
Securities except in compliance with applicable securities laws. Purchaser hereby agrees that, without the prior written consent of the
Company, Purchaser will not, and will not cause any direct or indirect affiliate of Purchaser to, during the period beginning on the date of
this Agreement and ending at the close of business on the earlier of October 15, 2022 or the date that the Company publicly discloses the
receipt of a complete response letter from the U.S. Federal Drug Administration with respect to the Company’s new drug application of
CR-845 in I.V. form (such period, the “Restricted Period”), (1) offer, pledge, sell, contract to sell, sell any option or contract to
purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, lend, or otherwise transfer or dispose of,
directly or indirectly, any shares of Common Stock or any securities convertible into or exercisable or exchangeable for Common Stock
(including without limitation, Common Stock or such other securities which may be deemed to be beneficially owned by the undersigned
in accordance with the rules and regulations of the Securities and Exchange Commission and securities which may be issued upon
exercise of a stock option or warrant) owned by the undersigned as of the date hereof or acquired prior to the end of the Restricted Period
(collectively with the Common Stock, “Lock-Up Securities”), except any such sale, option or contract by and between Purchaser and
one of its affiliates (including Vifor or Vifor Fresenius Medical Care Renal Pharma Ltd.), (2) enter into any hedging, swap or other
agreement or transaction that transfers, in whole or in part, any of the economic consequences of ownership of the Lock-Up Securities,
whether any such transaction described in clause (1) or (2) above is to be settled by delivery of Lock-Up Securities, in cash or otherwise,
(3) make any demand for or exercise any right with respect to the registration of any Lock-Up Securities, or (4) publicly disclose the
intention to do any of the foregoing.
3. Restrictive Legends. All certificates and/or transfer agent book entry positions representing the Securities initially shall have
endorsed thereon legends in substantially the following forms (in addition to any other legend which may be required by other
agreements between the Parties hereto):
THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE SECURITIES ACT
OF 1933 AS AMENDED. THEY MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED OR HYPOTHECATED IN THE
ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT AS TO THE SECURITIES UNDER SAID
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
2
ACT OR A CUSTOMARY OPINION OF COUNSEL REASONABLY SATISFACTORY TO THE COMPANY THAT SUCH
REGISTRATION IS NOT REQUIRED.
4. Company Representations. In connection with the purchase and sale of the Securities, the Company represents and warrants to
Purchaser, as of the date hereof, the following:
(a) The Company is a corporation duly incorporated, validly existing and in good standing under the laws of the State of
Delaware and is duly qualified to do business in each jurisdiction where it conducts business and has all necessary corporate power and
authority to carry on its business as now conducted and to own and operate its assets, properties and business.
(b) The Company has all necessary power and authority to execute and deliver this Agreement and to carry out its
provisions. All action on the Company’s part required for the lawful execution and delivery of this Agreement has been taken. Upon its
execution and delivery, this Agreement will be a valid and binding obligation of the Company, enforceable in accordance with its terms,
except (i) as limited by applicable bankruptcy, insolvency, reorganization, moratorium or other laws of general application affecting
enforcement of creditors’ rights and (ii) as limited by general principles of equity that restrict the availability of equitable remedies.
(c) The execution, delivery and performance of this Agreement and the sale of the Securities by the Company do not violate
any (i) federal, state or local law, statute, ordinance, rule, regulation or published guidelines promulgated by, or any order, decree or
judgement issued by, any governmental or regulatory authority to which the Company or any of the assets owned or used by the
Company is subject, (ii) any of the provisions of the Company’s organizational documents or any resolution adopted by the Company’s
Board of Directors (or any committee thereof) or stockholders, or (iii) any material agreement or other instrument or arrangement to
which the Company is subject. No consent, order, authorization, approval, declaration or filing, including with or to any governmental or
regulatory authority, is required on the part of the Company for or in connection with the execution, delivery or performance of this
Agreement, other than (i) the filing of a Current Report on Form 8-K pursuant to Items 1.01 and/or 3.02 thereof and a Notice of Sale of
Securities on Form D with the Securities and Exchange Commission (the “SEC”), and (ii) such consents, orders, authorizations,
approvals, declarations or filings as have been already been made or obtained.
(d) There are no pending actions, suits, proceedings, arbitrations, writs, judgments, decrees, injunctions or similar orders of
any governmental or regulatory authority (in each case whether preliminary or final), hearings, assessments with respect to fines or
penalties or litigation (whether civil, criminal, administrative, investigative or informal) commenced, brought, conducted or heard by or
before any governmental or regulatory authority (collectively, “Actions”), and, to the knowledge of the Company, no natural person,
corporation, general partnership, limited partnership, limited liability company, proprietorship, other business association, trust, union,
association or other governmental or regulatory authority has threatened to commence any Action, in each case that challenges, or has
the effect of preventing, making illegal or otherwise materially interfering with, the issuance of the Securities to Purchaser as
contemplated by this Agreement.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
3
(e) The Company has not retained any broker in connection with the issuance of the Securities to Purchaser contemplated
by this Agreement. Purchaser has no, and will have no, obligation to pay any brokers’, finders’, investment bankers’, financial advisors’
or similar fees in connection with the issuance of the Securities to Purchaser pursuant to this Agreement by reason of any action taken by
or on behalf of the Company.
(f) The Common Stock has been duly authorized and will, when issued in accordance with the provisions of this
Agreement, be validly issued, fully paid and non-assessable, free and clear of all liens, charges, claims, security interests, encumbrances,
preemptive rights, rights of first refusal or similar restrictions. Assuming the accuracy of the representations and warranties of Purchaser
in this Agreement, the Securities will be issued in compliance with all applicable federal and state securities laws.
(g) The authorized capitalization of the Company consists of 5,000,000 shares of Preferred Stock, par value $0.001, of
which no shares are issued and outstanding, and 100,000,000 shares of Common Stock, par value $0.001, of which 46,864,405 shares
were issued and outstanding as of June 30, 2020. The Company has not issued any capital stock since the date it filed its Quarterly
Report on Form 10-Q for the quarterly period ended June 30, 2020 (the “Most Recent 10-Q”), other than in connection with the exercise
of options or the vesting of restricted stock awards or similar securities, in each case to the extent disclosed in the footnotes to the
financial statements included in the Most Recent 10-Q or awarded in the ordinary course of business since June 30, 2020. Other than the
options, restricted stock awards or similar securities to the extent disclosed in the footnotes to the financial statements included in the
Most Recent 10-Q or awarded in the ordinary course of business since June 30, 2020, the Company has no outstanding options, restricted
stock awards or other rights to subscribe for, or securities convertible into or exchangeable for, shares of Common Stock (or securities
convertible into or exchangeable therefor). Except for the Investors’ Rights Agreement, the Company is not a party to any stockholders
or stock voting agreement with any other person.
(h) Since January 1, 2019, the Company has filed all reports, schedules, forms, statements and other documents required to
have been filed by it under the Securities Exchange Act of 1934, as amended (the “Exchange Act”), including pursuant to Section 13(a)
or 15(d) thereof (the foregoing materials, including the exhibits thereto and documents incorporated by reference therein, the “SEC
Reports”) on a timely basis or has received a valid extension of such time of filing and has filed any such SEC Reports prior to the
expiration of any such extension. As of their respective filing dates, or to the extent corrected by a subsequent restatement, the SEC
Reports complied in all material respects with the requirements of the Exchange Act and the rules and regulations of the SEC
promulgated thereunder, and none of the SEC Reports, when filed, contained any untrue statement of a material fact or omitted to state a
material fact required to be stated therein or necessary in order to make the statements therein, in light of the circumstances under which
they were made, not misleading.
(i) The financial statements of the Company included in the SEC Reports comply in all material respects with applicable
accounting requirements and the rules and regulations of the SEC with respect thereto as in effect at the time of filing (or to the extent
corrected by a subsequent
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
4
restatement). Such financial statements have been prepared in accordance with U.S. generally accepted accounting principles (“GAAP”)
applied on a consistent basis during the periods involved, except as may be otherwise specified in such financial statements or the notes
thereto and except that unaudited financial statements may not contain all footnotes required by GAAP, and fairly present in all material
respects the financial position of the Company as of and for the dates thereof and the results of operations and cash flows for the periods
then ended, subject, in the case of unaudited statements, to normal and recurring year-end audit adjustments.
(j) Except as specifically disclosed in the SEC Reports filed prior to the date hereof, (i) since the date of the Most
Recent 10-Q, there have been no events, occurrences or developments that have had or would reasonably be expected to have, either
individually or in the aggregate, a Material Adverse Effect (as defined below), and (ii) the Company has not incurred any material
liabilities other than (A) trade payables and accrued expenses incurred in the ordinary course of business consistent with the Company’s
past practice and (B) liabilities not required to be reflected in the Company’s financial statements pursuant to GAAP or disclosed in
filings made with the SEC.
For purposes of this Agreement, the term “Material Adverse Effect” means any change, event or occurrence that, individually or in the
aggregate, has had or is reasonably likely to have (i) a material adverse effect on the business, condition (financial or otherwise), assets,
liabilities or results of operations of the Company and its subsidiaries, taken as a whole, or (ii) a material adverse effect on the
Company’s ability to timely perform its obligations under, or timely consummate any of the transactions contemplated by, this
Agreement or the License Agreement, except to the extent that any such change, event or occurrence results from or arises out of
changes occurring after the filing date of the Most Recent 10-Q in general legal, regulatory, political, economic or business conditions or
changes in GAAP or interpretations thereof occurring after such date that, in each case, generally affect the biotechnology or
biopharmaceutical industries and have not had or would not be reasonably likely to have a disproportionate effect on the Company and
its subsidiaries compared to other participants in the biotechnology or biopharmaceutical industries.
5. Investment Representations. In connection with the purchase and sale of the Securities, Purchaser represents and warrants to
the Company, as of the date hereof and each Closing, the following:
(a) Purchaser has all necessary power and authority to execute and deliver this Agreement and to carry out its provisions.
All action on Purchaser’s part required for the lawful execution and delivery of this Agreement has been taken. Upon its execution and
delivery, this Agreement will be a valid and binding obligation of Purchaser, enforceable in accordance with its terms, except (i) as
limited by applicable bankruptcy, insolvency, reorganization, moratorium or other laws of general application affecting enforcement of
creditors’ rights and (ii) as limited by general principles of equity that restrict the availability of equitable remedies.
(b) Purchaser understands that the Securities have not been and will not be registered under the Securities Act of 1933, as
amended (the “Securities Act”). Purchaser also understands
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
5
that the Securities are being offered and sold pursuant to an exemption from registration contained in the Securities Act based in part
upon Purchaser’s representations contained in the Agreement. Purchaser hereby represents and warrants, as of the date hereof, as
follows:
(i) Purchaser has substantial experience in evaluating and investing in private placement transactions of
securities in companies similar to the Company so that it is capable of evaluating the merits and risks of its investment in the Company
and has the capacity to protect its own interests. Purchaser must bear the economic risk of this investment indefinitely unless the
Securities are registered for resale pursuant to the Securities Act, or an exemption from registration is available. Purchaser understands
that the Company has no present intention of registering the resale of the Securities on behalf of Purchaser or any other person.
Purchaser also understands that there is no assurance that any exemption from registration under the Securities Act will be available and
that, even if available, such exemption may not allow Purchaser to transfer all or any portion of the Securities under the circumstances, in
the amounts or at the times Purchaser might propose. Purchaser acknowledges that Purchaser has no need for liquidity in connection
with Purchaser’s purchase hereunder.
towards any distribution of the Securities.
(ii) Purchaser is acquiring the Securities for its own account for investment only, and not with a view
(iii) Purchaser represents that by reason of its business or financial experience, Purchaser has the capacity
to protect its own interests in connection with the transactions contemplated in this Agreement. Purchaser recognizes that purchase of
the Securities involves a substantial degree of risk and may result in the total loss of investment. Further, Purchaser is aware of no
publication of any advertisement in connection with the transactions contemplated in this Agreement.
Securities Act.
(iv) Purchaser represents that it is an “accredited investor” within the meaning of Regulation D under the
(v) Purchaser has received and read materials that describe the Company’s presently proposed business
and products and the markets therefore and has had an opportunity to discuss the Company’s business, management and financial affairs
with directors, officers and management of the Company and has had the opportunity to review the Company’s operations and facilities.
Purchaser has also had the opportunity to ask questions of and receive answers from the Company and its management regarding the
terms and conditions of this investment.
(vi) Purchaser acknowledges and agrees that the Securities constitute “restricted securities” as defined in
Rule 144 promulgated under the Securities Act as in effect from time to time and must be held indefinitely unless it is subsequently
registered under the Securities Act or an exemption from such registration is available. Purchaser has been advised or is aware of the
provisions of Rule 144, which permits limited resale of shares purchased in a private placement subject to the satisfaction of certain
conditions, including, among other things: the availability of certain current public information about the Company, the resale occurring
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
6
following the required holding period under Rule 144 and the number of shares being sold during any three-month period not exceeding
specified limitations.
(vii) Neither Purchaser nor any of its Rule 506(d) Related Parties is subject to a “bad actor” disqualifying
event described in Rule 506)(d)(1)(i)-(viii) of the Securities Act. For purposes of this Agreement, “Rule 506(d) Related Party” shall
mean a person or entity covered by the “Bad Actor disqualification” provision of Rule 506(d) of the Securities Act.
6. Registration Rights. In the event that the Purchaser holds Registrable Securities (as such term is defined in the form of
registration rights agreement attached hereto as Exhibit A) as of October 15, 2022, at the request of the Purchaser, the Company and the
Purchaser shall enter into a registration rights agreement, in the form attached hereto as Exhibit A.
7. Facilitation of Sales Pursuant to Rule 144. The Company shall (a) make and keep public information available, as those terms
are understood and defined in Rule 144, at all times after the date hereof, (b) use commercially reasonable efforts to file in a timely
manner all SEC Reports required to be filed by it, and (c) furnish to Purchaser, so long as Purchaser holds any Common Stock, upon
Purchaser’s request (i) a written statement by the Company that it has complied with the reporting requirements of Rule 144, the
Securities Act of 1933, as amended and the Exchange Act and (ii) such other information as may be reasonably requested in availing
Purchaser of any rule or regulation of the SEC that permits the selling of any Company securities without registration.
8. Regulatory Approvals. If required by applicable law, the Company and the Purchaser shall cooperate with each other and use
(and shall cause their respective affiliates to use) their respective reasonable best efforts to take or cause to be taken all actions, and do or
cause to be done all things, reasonably necessary, proper or advisable on its part under this Agreement to consummate and make effective
the transactions contemplated by this Agreement, including the Additional Closing, as soon as practicable, including preparing and filing
as promptly as practicable all documentation to effect all necessary notices, reports and other filings and to obtain as promptly as
practicable all consents, registrations, approvals, permits and authorizations necessary or advisable to be obtained from any governmental
entity in order to consummate the transactions contemplated by this Agreement, including, within [***] after receiving the Approval
Milestone, filing a Notice and Report Form with the Federal Trade Commission and the Antitrust Division of the Department of Justice
pursuant to the HSR Act.
9. Successors and Assigns. This Agreement shall inure to the benefit of the successors and assigns of the Company and, subject to
the restrictions on transfer herein set forth, be binding upon Purchaser, Purchaser’s successors, and assigns. Subject to compliance with
all securities laws and regulations, it is agreed that Purchaser may transfer the Securities to its affiliate Vifor or to Vifor Fresenius
Medical Care Renal Pharma Ltd., provided that, in connection with such transfer. Purchaser must assign this Agreement to Vifor or Vifor
Fresenius Medical Care Renal Pharma Ltd. (as applicable), and Vifor or Vifor Fresenius Medical Care Renal Pharma Ltd. (as applicable)
must agree in a writing provided to the Company that Vifor or Vifor Fresenius Medical Care Renal
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
7
Pharma Ltd. (as applicable) accepts such assignment and is bound by the obligations of this Agreement as the Purchaser.
10. Governing Law; Venue. This Agreement shall be governed by and construed in accordance with the laws of the State of New
York. The Parties agree that any action brought by either Party to interpret or enforce any provision of this Agreement shall be brought
in, and each Party hereby submits to the jurisdiction and venue of, the New York State Supreme Court or the federal district court, in
each case sitting in the Borough of Manhattan, and each of the Parties hereby consents to the jurisdiction of such courts (and of the
appropriate appellate courts therefrom).
11. Waiver of Jury Trial. EACH PARTY HEREBY WAIVES, TO THE FULLEST EXTENT PERMITTED BY LAW, ANY
RIGHT TO TRIAL BY JURY OF ANY CLAIM, DEMAND, ACTION OR CAUSE OF ACTION (A) ARISING UNDER THIS
AGREEMENT OR (B) IN ANY WAY CONNECTED WITH OR RELATED OR INCIDENTAL TO THE DEALINGS OF THE
PARTIES IN RESPECT OF THIS AGREEMENT OR ANY OF THE TRANSACTIONS CONTEMPLATED HEREBY, IN EACH
CASE WHETHER IN CONTRACT, TORT, EQUITY OR OTHERWISE. EACH PARTY AGREES AND CONSENTS THAT ANY
SUCH CLAIM, DEMAND, ACTION OR CAUSE OF ACTION WILL BE DECIDED BY A COURT TRIAL WITHOUT A JURY,
AND THAT THE PARTIES TO THIS AGREEMENT MAY FILE A COPY OF THIS AGREEMENT WITH ANY COURT AS
WRITTEN EVIDENCE OF THE CONSENT OF THE PARTIES HERETO TO THE WAIVER OF THEIR RIGHT TO TRIAL BY
JURY.
12. Notices. Any notice, demand or request given by either Party pursuant to this Agreement shall be in writing and shall be deemed
given when delivered in accordance with Section 12.3 of the License Agreement.
13. Further Execution. The Parties agree to take all such further action(s) as may reasonably be necessary to carry out and
consummate this Agreement as soon as practicable, and to take whatever steps may be necessary to obtain any governmental approval in
connection with or otherwise qualify the issuance of the securities that are the subject of this Agreement.
14. Limitations on Liability. THE COMPANY WILL NOT BE LIABLE TO PURCHASER OR ANY AFFILIATE OF
PURCHASER FOR ANY INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, EXEMPLARY OR PUNITIVE DAMAGES,
INCLUDING LOST PROFITS, ARISING FROM OR RELATING TO THIS AGREEMENT, REGARDLESS OF ANY NOTICE OF
SUCH DAMAGES. Further, the maximum liability of the Company to Purchaser or any of its affiliates with respect to any breach of
any warranty or other obligation of Company under this Agreement shall not exceed [***] in the aggregate.
15. Entire Agreement; Amendment. This Agreement, together with the License Agreement, constitutes the entire agreement
between the Parties with respect to the subject matter hereof and supersedes and merges all prior agreements or understandings, whether
written or oral. This
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
8
Agreement may not be amended, modified or revoked, in whole or in part, except by an agreement in writing signed by each of the
Parties hereto.
16. Severability. If one or more provisions of this Agreement are held to be unenforceable under applicable law, the Parties agree to
renegotiate such provision in good faith. In the event that the Parties cannot reach a mutually agreeable and enforceable replacement for
such provision, then (i) such provision shall be excluded from this Agreement, (ii) the balance of the Agreement shall be interpreted as if
such provision were so excluded and (iii) the balance of the Agreement shall be enforceable in accordance with its terms.
17. Counterparts. This Agreement may be executed and delivered (including by facsimile or portable document format (“.pdf”)) in
two or more counterparts, each of which shall be deemed an original and all of which together shall constitute one instrument.
IN WITNESS WHEREOF, the Parties hereto have executed this Securities Purchase Agreement as of the day and year first
above written.
CARA THERAPEUTICS, INC.
By: /s/ Derek Chalmers
Name: Derek Chalmers
Title: Chief Executive Officer
PURCHASER:
VIFOR (INTERNATIONAL) LTD.
By: /s/ Stefan Schulze
Name: Stefan Schulze
Title: Chief Executive Officer
By: /s/ Dr. Christoph Springer
Name: Dr. Christoph Springer
Title: Chief Strategy Officer
[Signature Page to Cara Therapeutics, Inc.—Securities Purchase Agreement]
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
9
EXHIBIT A
FORM OF REGISTRATION RIGHTS AGREEMENT
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
REGISTRATION RIGHTS AGREEMENT
THIS REGISTRATION RIGHTS AGREEMENT (“Agreement”) is made as of the [__]th day of [_____], 202[_], by and
between Cara Therapeutics, Inc., a Delaware corporation (the “Company”), and Vifor (International) Ltd., an entity formed under the
laws of Switzerland, located at Rechenstrasse 34, 9014 t. Gallen, Switzerland (including any permitted transferee pursuant to Section
2.14, the “Investor”).
WHEREAS, the Investor has acquired Common Stock of the Company pursuant to a Securities Purchase Agreement, dated
as of October 15, 2020 (the “SPA”); and
WHEREAS, as an inducement to the Investor to complete the transaction contemplated by the SPA, the Company has
agreed that, under certain circumstances, the Company shall upon request of the Investor enter into this agreement to provide certain
registration rights in respect of the Registrable Securities.
NOW, THEREFORE, in consideration of the mutual covenants and agreements set forth herein and for good and valuable
consideration, the receipt and sufficiency of which is hereby acknowledged by each party hereto, the parties hereto agree as follows:
1. Definitions. For purposes of this Agreement:
1.1 “Affiliate” means, with respect to any specified Person, any other Person who or which, directly or indirectly, controls,
is controlled by, or is under common control with such specified Person, including without limitation any partner, officer, director,
manager, member or committee member or employee of such Person and any venture capital fund now or hereafter existing that is
controlled by or under common control with one or more general partners or managing members of, or shares the same management
company with, such Person. Company and Investor acknowledge and agree that Vifor Fresenius Medical Care Renal Pharma Ltd.
(“VFMCRP”) shall be considered an “Affiliate” of Investor for the purposes of this Agreement so long as it meets the definition set forth
in this Section 1.1 and/or Investor retains at least a 50% interest in the income of VFMCRP.
1.2 “Common Stock” means shares of the Company’s common stock, par value $0.001 per share.
1.3 “Damages” means any loss, claim, damage, or liability (joint or several) to which a party hereto may become subject
under the Securities Act, the Exchange Act, or other federal or state law, insofar as such loss, claim, damage, or liability (or any action in
respect thereof) arises out of or is based upon (i) any untrue statement or alleged untrue statement of a material fact contained in any
registration statement of the Company, including any preliminary prospectus or final prospectus contained therein or any amendments or
supplements thereto; (ii) an omission or alleged omission to state therein a material fact required to be stated therein, or necessary to
make the statements therein not misleading; or (iii) any violation or alleged violation by any other party hereto of the Securities Act, the
Exchange Act, any state securities law, or any rule or regulation promulgated under the Securities Act, the Exchange Act, or any state
securities law.
1.4 “Exchange Act” means the Securities Exchange Act of 1934, as amended, and the rules and regulations promulgated
thereunder.
1.5 “Excluded Registration” means a registration relating either to the sale of securities to employees of the Company
pursuant to a stock option, stock purchase, or similar plan or to an SEC Rule 145 transaction; a registration on any form that does not
include substantially the same information as would be required to be included in a registration statement covering the sale of the
Registrable Securities; or a registration in which the only Common Stock being registered is Common Stock issuable upon conversion of
debt securities that are also being registered.
1.6 “Form S-3” means such form under the Securities Act as in effect on the date hereof or any registration form under the
Securities Act subsequently adopted by the SEC that permits incorporation of substantial information by reference to other documents
filed by the Company with the SEC.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
1
1.7 “License Agreement” means that certain License Agreement entered into between the Company and Investor as of
October 15, 2020.
1.8 “Person” means any individual, corporation, partnership, trust, limited liability company, association or other entity.
1.9 “Register,” “registered,” and “registration” refer to a registration effected by preparing and filing a registration
statement or similar document in compliance with the Securities Act, and the declaration or ordering of effectiveness of such registration
statement or document.
1.10 “Registrable Securities” means (i) the Common Stock issued pursuant to the SPA; (ii) any securities issued or
issuable, directly or indirectly, with respect to, on account of or in exchange for the shares referenced in clause (i) above, whether by
stock split, stock dividend, recapitalization, merger, consolidation or other reorganization, charter amendment or otherwise; and (iii) any
securities issued as (or issuable upon the conversion or exercise of any warrant, right, or other security that is issued as) a dividend or
other distribution with respect to, or in exchange for or in replacement of, the securities referenced in clauses (i) and (ii) above, excluding
in all cases, however, any Registrable Securities sold by the Investor in a transaction in which the rights under Section 2 hereof are not
assigned or any securities for which registration rights have terminated pursuant to Section 2.16 hereof. In addition, securities shall cease
to be considered Registrable Securities at such time as the Investor may freely sell such securities pursuant to SEC Rule 144 without
regard to the volume limitations, public information requirement and manner of sale provisions thereof.
1.11 “Restated Certificate” means the Company’s Amended and Restated Certificate of Incorporation dated February 5,
2014.
1.12 “Restricted Period” means the period beginning on the date of this Agreement and ending on the earlier of (i) October
15, 2022 and (ii) the date that the Company publicly discloses the receipt of a complete response letter from the U.S. Federal Drug
Administration with respect to the Company’s new drug application of CR-845 in I.V. form; provided, however, that the Company may
waive such Restricted Period at any time.
1.13 “Restricted Securities” means the securities of the Company required to bear the legend set forth in Section 2.15(b)
hereof.
1.14 “SEC” means the Securities and Exchange Commission.
1.15 “SEC Rule 144” means Rule 144 promulgated by the SEC under the Securities Act.
1.16 “SEC Rule 145” means Rule 145 promulgated by the SEC under the Securities Act.
1.17 “Securities Act” means the Securities Act of 1933, as amended, and the rules and regulations promulgated thereunder.
1.18 “Selling Expenses” means all underwriting discounts, selling commissions, and stock transfer taxes applicable to the
sale of Registrable Securities, and fees and disbursements of counsel for the Investor, except as provided in Section 2.8.
2. Registration Rights.
The Company covenants and agrees as follows:
2.1 Demand Registration.
(a) If at any time after the Restricted Period or the waiver thereof, the Company receives a request from the
Investor that the Company effect a registration with respect to all or a part of the Registrable Securities owned by the Investor, then the
Company shall (i) as soon as practicable, and in any event within [***]
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
2
after the date such request is given by the Investor, file a registration statement under the Securities Act and (ii) use its commercially
reasonable efforts to effect, at the earliest practicable date, such registration as would permit or facilitate the disposition (in accordance
with the intended methods of disposition) of all of the Investor’s Registrable Securities as are specified in such request, subject to the
limitations in Section 2.1(b).
(b) Notwithstanding the foregoing obligations, if the Company furnishes to the Investor a certificate signed by the
Company’s chief executive officer stating that in the good faith judgment of the Company’s Board of Directors it would be materially
detrimental to the Company and its stockholders for the applicable registration statement to become effective at such time because such
action would (i) materially interfere with a significant acquisition, corporate reorganization, or other similar transaction involving the
Company; (ii) require premature disclosure of material information that the Company has a bona fide business purpose for preserving as
confidential; or (iii) render the Company unable to comply with requirements under the Securities Act or Exchange Act, then the
Company shall have the right to defer the filing of such registration statement for a period of not more than [***] after the request of the
Investor is given; provided, however, that the Company may not invoke this right more than [***] period; and provided further that the
Company shall not register any securities for its own account or that of any other stockholder during such [***] period other than
pursuant to an Excluded Registration.
(c) The Company shall not be obligated to effect any registration pursuant to this Section 2.1 (i) if the shares of
Registrable Securities proposed to be registered for resale on behalf of the Investor may be immediately registered on Form S-3 pursuant
to a request made pursuant to Section 2.3; (ii) if the Investor proposes to sell Registrable Securities at an aggregate price to the public
(net of Selling Expenses) of less than [***]; (iii) if the Company has, within the [***] period preceding the date of such request, already
effected [***] registrations for the Investor pursuant to this Section 2.1 and/or Section 2.3.
(d) A registration shall not be counted as “effected” for purposes of this Section 2.1 (i) if the applicable
registration statement is withdrawn without becoming effective; provided, however, that if such withdrawal was at the request of the
Investor and the Investor elects not to pay the registration expenses therefor and forfeits its right to [***] demand registration statement
pursuant to Section 2.8, such withdrawn registration statement shall be counted as “effected” for purposes of this Section 2.1 and Section
2.3; (ii) if the registration statement does not remain effective in compliance with the provisions of the Securities Act and the laws of any
state or other jurisdiction applicable to the disposition of the Registrable Securities covered by such registration statement for the period
required pursuant to Section 2.6(a); (iii) if, after it has become effective, such registration statement is subject to any stop order,
injunction or other order or requirement of the SEC or other governmental or regulatory agency or court for any reason other than a
violation of applicable law solely by the Investor and has not thereafter become effective; or (iv) if the Company does not include in the
applicable registration statement all Registrable Securities held by the Investor that are required by the terms of this Section 2.1 to be
included in such registration statement.
2.2 [Reserved].
2.3 Form S-3 Registration.
(a) If at any time after the Restricted Period or the waiver thereof, the Company qualifies to use Form S-3 for the
registration of the resale of its Common Stock on behalf of a selling stockholder and the Company receives a request from the Investor
that the Company effect a registration with respect to all or a part of the Registrable Securities owned by the Investor, then the Company
shall (i) as soon as practicable, and in any event within [***] after the date such request is given by the Investor, file a registration
statement on Form S-3 under the Securities Act and (ii) use its commercially reasonable efforts to effect, at the earliest practicable date,
such registration as would permit or facilitate the disposition (in accordance with the intended methods of disposition) of all of the
Investor’s Registrable Securities as are specified in such request, subject to the limitations in Section 2.3(b).
(b) Notwithstanding the foregoing obligations, if the Company furnishes to the Investor a certificate signed by the
Company’s chief executive officer stating that in the good faith judgment of the Company’s Board of Directors it would be materially
detrimental to the Company and its stockholders for the applicable
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
3
registration statement to become effective at such time because such action would (i) materially interfere with a significant acquisition,
corporate reorganization, or other similar transaction involving the Company; (ii) require premature disclosure of material information
that the Company has a bona fide business purpose for preserving as confidential; or (iii) render the Company unable to comply with
requirements under the Securities Act or Exchange Act, then the Company shall have the right to defer the filing of such registration
statement for a period of not more than [***] after the request of the Investor is given; provided, however, that the Company may not
invoke this right more than [***] in any [***] period; and provided further that the Company shall not register any securities for its own
account or that of any other stockholder during such [***] period other than pursuant to an Excluded Registration.
(c) The Company shall not be obligated to effect any registration pursuant to this Section 2.3 (i) if Form S-3 is not
then available for such offering by the Investor; (ii) if the Investor proposes to sell Registrable Securities at an aggregate price to the
public (net of Selling Expenses) of less than [***]; (iii) if the Company has, within the [***] period preceding the date of such request,
already effected [***] registrations for the Investor pursuant to this Section 2.3 and/or Section 2.1.
(d) A registration shall not be counted as “effected” for purposes of this Section 2.3 (i) if the applicable
registration statement is withdrawn without becoming effective; provided, however, that if such withdrawal was at the request of the
Investor and the Investor elects not to pay the registration expenses therefor and forfeits its right to [***] demand registration statement
pursuant to Section 2.8, such withdrawn registration statement shall be counted as “effected” for purposes of this Section 2.3 and Section
2.1; (ii) if the registration statement does not remain effective in compliance with the provisions of the Securities Act and the laws of any
state or other jurisdiction applicable to the disposition of the Registrable Securities covered by such registration statement for the period
required pursuant to Section 2.6(a); (iii) if, after it has become effective, such registration statement is subject to any stop order,
injunction or other order or requirement of the SEC or other governmental or regulatory agency or court for any reason other than a
violation of applicable law solely by the Investor and has not thereafter become effective; or (iv) if the Company does not include in the
applicable registration statement all Registrable Securities held by the Investor that are required by the terms of this Section 2.3 to be
included in such registration statement.
2.4 [Reserved].
2.5 [Reserved].
2.6 Obligations of the Company. Whenever required under this Section 2 to effect the registration of any Registrable
Securities, the Company shall:
(a) as expeditiously as reasonably possible, prepare and file with the SEC a registration statement with respect to
such Registrable Securities and use its commercially reasonable efforts to cause such registration statement to become effective and,
upon the request of the Investor, keep such registration statement effective for a period of up to [***] or, if earlier, until the distribution
contemplated in the registration statement has been completed; provided, however, that (i) such [***] period shall be extended for a
period of time equal to the period the Investor refrains, at the request of an underwriter of Common Stock (or other securities) of the
Company, from selling any securities included in such registration, (ii) in the case of any registration of Registrable Securities on Form
S-3 that are intended to be offered on a continuous or delayed basis, subject to compliance with applicable SEC rules, such [***] period
shall be extended for up to [***] (or such longer period as may be requested by the Investor, if necessary, to keep the registration
statement effective until all such Registrable Securities are sold, and (iii) such [***] period shall be extended for a period of time equal to
the duration of any Suspension Period pursuant to Section 2.10;
(b) as expeditiously as reasonably possible, prepare and file with the SEC such amendments and supplements to
such registration statement, and the prospectus used in connection with such registration statement, as may be necessary to comply with
the Securities Act in order to enable the disposition of all securities covered by such registration statement;
amendment or supplement thereto (including any documents incorporated by reference therein), or
(c) (i) at least [***] prior to the anticipated filing of a registration statement or any related prospectus or any
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
4
before using any issuer free writing prospectus, furnish to the Investor and the Investor’s counsel, copies of all such documents proposed
to be filed, (ii) use its commercially reasonable efforts to address in each such document prior to being so filed with the SEC such
comments as the Investor or its counsel reasonably shall propose within [***] of receipt of such copies by the Investor and (iii) not file
any registration statement or any related prospectus or any amendment or supplement thereto containing information regarding the
Investor to which the Investor objects;
(d) furnish to the Investor such numbers of copies of a prospectus, including a preliminary prospectus, as required
by the Securities Act, and such other documents as the Investor may reasonably request in order to facilitate its disposition of its
Registrable Securities;
(e) use its commercially reasonable efforts to register and qualify the securities covered by such registration
statement under such other securities or blue-sky laws of such jurisdictions as shall be reasonably requested by the Investor; provided
that the Company shall not be required to qualify to do business or to file a general consent to service of process in any such states or
jurisdictions, unless the Company is already subject to service in such jurisdiction and except as may be required by the Securities Act;
under an underwriting agreement, in usual and customary form, with the managing underwriter(s) of such offering;
(f) in the event of any underwritten public offering of Registrable Securities, enter into an perform its obligations
(g) use its commercially reasonable efforts to cause all such Registrable Securities covered by such registration
statement to be listed on a national securities exchange or trading system and each securities exchange and trading system (if any) on
which similar securities issued by the Company are then listed;
provide a CUSIP number for all such Registrable Securities, in each case not later than the effective date of such registration;
(h) provide a transfer agent and registrar for all Registrable Securities registered pursuant to this Agreement and
(i) promptly make available for inspection by the Investor, any managing underwriter participating in any
disposition pursuant to such registration statement, and any attorney or accountant or other agent retained by any such underwriter or
selected by the Investor, all financial and other records, pertinent corporate documents, and properties of the Company, and cause the
Company’s officers, directors, employees, and independent accountants to supply all information reasonably requested by the Investor or
any such underwriter, attorney, accountant, or agent in connection with any such registration statement; and
(j) as promptly as reasonably practicable, notify the Investor: (i)(A) when a registration statement, any
amendments and supplements to such registration statement, any prospectus or any prospectus supplement used in connection with such
registration statement, or any free writing prospectus is proposed to be filed; (B) when the SEC notifies the Company whether there will
be a “review” of such registration statement and whenever the SEC comments on such registration statement (in which case the
Company shall provide true and complete copies thereof and all written responses thereto to the Investor, other than information that the
Company determines in good faith would constitute material non-public information that is not already in the possession of the Investor);
and (C) of the time when such registration statement, or any post-effective amendment thereto, has been declared effective or a
supplement to any prospectus forming a part of such registration statement has been filed; (ii) of any request by the SEC that the
Company amend or supplement such registration statement or prospectus; (iii) of the issuance by the SEC or any other governmental or
regulatory authority of any stop order, injunction or other order or requirement suspending the effectiveness of a registration statement
covering any or all of the Registrable Securities or the initiation of any proceedings for that purpose; (iv) of the receipt by the Company
of any notification with respect to the suspension of the qualification or exemption from qualification of any of the Registrable Securities
for sale in any jurisdiction, or the initiation or threatening of any proceeding for such purpose; (v) if the representations and warranties of
the Company in any applicable underwriting agreement or similar agreement cease to be true and correct in all material respects as of the
date such representations and warranties are made; and (vi) of the occurrence of any event that makes any statement made in such
registration statement or prospectus or any document incorporated or deemed to be incorporated therein by reference untrue in any
material respect or if, as a result of such event or the
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
5
passage of time, such registration statement, prospectus or other document requires revisions so that, in the case of such registration
statement or the prospectus, as the case may be, it will not contain any untrue statement of a material fact or omit to state any material
fact required to be stated therein or necessary to make the statements therein (in the case of the prospectus, in the light of the
circumstances under which they were made) not misleading, or when any issuer free writing prospectus includes information that may
conflict with the information contained in such registration statement or prospectus, or if, for any other reason, it shall be necessary
during such time period to amend or supplement such registration statement or prospectus in order to comply with the Securities Act,
which shall correct such misstatement or omission or effect such compliance.
2.7 Furnish Information. It shall be a condition precedent to the obligations of the Company to take any action pursuant to
this Section 2 with respect to the Registrable Securities of the Investor that the Investor shall furnish to the Company such information
regarding itself, the Registrable Securities held by it, and the intended method of disposition of such securities as is reasonably required
to effect the registration of Investor’s Registrable Securities.
2.8 Expenses of Registration. All expenses (other than Selling Expenses) incurred in connection with registrations, filings,
or qualifications pursuant to Section 2, including all registration, filing, and qualification fees; printers’ and accounting fees; fees and
disbursements of counsel for the Company; and the reasonable fees and disbursements, not to exceed [***], of one counsel for the
Investor, shall be borne and paid by the Company; provided, however, that the Company shall not be required to pay for any expenses of
any registration proceeding begun pursuant to Section 2.1 or Section 2.3 if the registration request is subsequently withdrawn at the
request of the Investor (in which case the Investor shall bear such expenses), unless the Investor elects to forfeit its right to one
registration pursuant to Section 2.1 and Section 2.3; provided further that if, at the time of such withdrawal, the Investor has learned of a
material adverse change in the condition, business, or prospects of the Company from that known to the Investor at the time of its request
and has withdrawn the request with reasonable promptness after learning of such information, then the Investor shall not be required to
pay any of such expenses and shall not forfeit its right to one registration pursuant to Section 2.1 and Section 2.3. All Selling Expenses
relating to Registrable Securities registered pursuant to this Section 2 shall be borne and paid by the Investor.
2.9 Delay of Registration. The Investor shall have no right to obtain or seek an injunction restraining or otherwise
delaying any registration pursuant to this Agreement as the result of any controversy that might arise with respect to the interpretation or
implementation of this Section 2.
2.10 Suspension Period. Notwithstanding any other provision of this Section 2, (i) if an event occurs as a result of which a
registration statement covering Registrable Securities and any related prospectus as then supplemented would include any untrue
statement of a material fact or omit to state any material fact necessary to make the statements therein in the light of the circumstances
under which they were made at such time not misleading, or if it shall be necessary to amend the registration statement, file a new
registration statement or supplement any related prospectus to comply with the Securities Act or the Exchange Act or the respective rules
thereunder; (ii) upon issuance by the SEC of a stop order suspending the effectiveness of any registration statement with respect to
Registrable Securities or the initiation of proceedings with respect to such registration statement under Section 9(d) or 8(e) of the
Securities Act; (iii) if the Company furnishes to the Investor a certificate signed by the Company’s chief executive officer stating that in
the good faith judgment of the Company’s Board of Directors it would be materially detrimental to the Company and its stockholders for
such registration statement to remain effective at such time because such action would (A) materially interfere with a significant
acquisition, corporate reorganization, or other similar transaction involving the Company; (B) require premature disclosure of material
information that the Company has a bona fide business purpose for preserving as confidential; or (C) otherwise render the Company
unable to comply with requirements under the Securities Act or Exchange Act; or (iv) if the Company is actively employing in good faith
commercially reasonable efforts to pursue a primary underwritten offering of capital stock of the Company pursuant to a registration
statement, then the Company shall have the right to suspend the use by the Investor of any such registration statement for a period of not
more than [***] (the “Suspension Period”); provided, however, that the Company may not invoke this right more than [***] in any
[***] period; and provided further that the Company shall not effect any new registration of securities for its own account or that of any
other stockholder during such Suspension Period other than pursuant to an Excluded Registration.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
6
2.11 Indemnification. If any Registrable Securities are included in a registration statement under this Section 2:
(a) To the extent permitted by law, the Company will indemnify and hold harmless the Investor, and the partners,
members, officers, directors, and stockholders of the Investor; legal counsel and accountants for the Investor; any underwriter (as defined
in the Securities Act) for the Investor; and each Person, if any, who controls the Investor or such underwriter within the meaning of the
Securities Act or the Exchange Act, against any Damages, and the Company will pay to the Investor, and each such underwriter,
controlling Person, or other aforementioned Person any legal or other expenses reasonably incurred thereby in connection with
investigating any matter or defending any proceeding from which Damages may result, as such expenses are incurred; provided,
however, that the indemnity agreement contained in this Section 2.11(a) shall not apply to amounts paid in settlement of any such
investigation or proceeding if such settlement is effected without the consent of the Company, which consent shall not be unreasonably
withheld, nor shall the Company be liable for any Damages to the extent that they arise out of or are based upon actions or omissions
made in reliance upon and in conformity with written information furnished by or on behalf of the Investor, any such underwriter,
controlling Person, or other aforementioned Person expressly for use in connection with such registration.
(b) To the extent permitted by law, the Investor, severally and not jointly, will indemnify and hold harmless the
Company, and each of its directors, each of its officers who has signed the registration statement, each Person (if any), who controls the
Company within the meaning of the Securities Act, legal counsel and accountants for the Company, any underwriter (as defined in the
Securities Act), and any controlling Person of any such underwriter, against any Damages, in each case only to the extent that such
Damages arise out of or are based upon actions or omissions made in reliance upon and in conformity with written information furnished
by or on behalf of the Investor expressly for use in connection with such registration; and the Investor will pay to the Company and each
other aforementioned Person any legal or other expenses reasonably incurred thereby in connection with investigating any investigation
or defending any proceeding from which Damages may result, as such expenses are incurred; provided, however, that the indemnity
agreement contained in this Section 2.11(b) shall not apply to amounts paid in settlement of any such investigation or proceeding if such
settlement is effected without the consent of the Investor, which consent shall not be unreasonably withheld; and provided further that in
no event shall any indemnity under this Section 2.11(b) exceed the proceeds from the offering (net of any Selling Expenses) received by
the Investor, except in the case of fraud or willful misconduct by the Investor.
(c) Promptly after receipt by an indemnified party under this Section 2.11 of notice of the commencement of any
action (including any governmental action) for which a party may be entitled to indemnification hereunder, such indemnified party will,
if a claim in respect thereof is to be made against any indemnifying party under this Section 2.11, give the indemnifying party notice of
the commencement thereof. The indemnifying party shall have the right to participate in such action and, to the extent the indemnifying
party so desires, participate jointly with any other indemnifying party to which notice has been given, and to assume the defense thereof
with counsel mutually satisfactory to the parties; provided, however, that an indemnified party (together with all other indemnified
parties that may be represented without conflict by one counsel) shall have the right to retain one separate counsel, with the fees and
expenses to be paid by the indemnifying party, if representation of such indemnified party by the counsel retained by the indemnifying
party would be inappropriate due to actual or potential differing interests between such indemnified party and any other party represented
by such counsel in such action. The failure to give notice to the indemnifying party within a reasonable time of the commencement of
any such action shall relieve such indemnifying party of any liability to the indemnified party under this Section 2.11, to the extent that
such failure materially prejudices the indemnifying party’s ability to defend such action. The failure to give notice to the indemnifying
party will not relieve it of any liability that it may have to any indemnified party otherwise than under this Section 2.11.
(d) The foregoing indemnity agreements of the Company and the Investor are subject to the condition that,
insofar as they relate to any Damages arising from any untrue statement or alleged untrue statement of a material fact contained in, or
omission or alleged omission of a material fact from, a preliminary prospectus (or necessary to make the statements therein not
misleading) that has been corrected in the form of prospectus included in the registration statement at the time it becomes effective, or
any amendment or supplement thereto filed with the
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
7
SEC pursuant to Rule 424(b) under the Securities Act (the “Final Prospectus”), such indemnity agreement shall not inure to the benefit
of any Person if a copy of the Final Prospectus was furnished to the indemnified party and such indemnified party failed to deliver, at or
before the confirmation of the sale of the shares registered in such offering, a copy of the Final Prospectus to the Person asserting the
loss, liability, claim, or damage in any case in which such delivery was required by the Securities Act.
(e) To provide for just and equitable contribution to joint liability under the Securities Act in any case in which
either (i) any party otherwise entitled to indemnification hereunder makes a claim for indemnification pursuant to this Section 2.11 but it
is judicially determined (by the entry of a final judgment or decree by a court of competent jurisdiction and the expiration of time to
appeal or the denial of the last right of appeal) that such indemnification may not be enforced in such case, notwithstanding the fact that
this Section 2.11 provides for indemnification in such case, or (ii) contribution under the Securities Act may be required on the part of
any party hereto for which indemnification is provided under this Section 2.11, then, and in each such case, such parties will contribute to
the aggregate losses, claims, damages, liabilities, or expenses to which they may be subject (after contribution from others) in such
proportion as is appropriate to reflect the relative fault of the each of indemnifying party and the indemnified party in connection with the
statements, omissions, or other actions that resulted in such loss, claim, damage, liability, or expense, as well as to reflect any other
relevant equitable considerations. The relative fault of the indemnifying party and of the indemnified party shall be determined by
reference to, among other things, whether the untrue or allegedly untrue statement of a material fact, or the omission or alleged omission
of a material fact, relates to information supplied by the indemnifying party or by the indemnified party and the parties’ relative intent,
knowledge, access to information, and opportunity to correct or prevent such statement or omission; provided, however, that, in any such
case, (x) the Investor will not be required to contribute any amount in excess of the public offering price of all such Registrable Securities
offered and sold by the Investor pursuant to such registration statement, and (y) no Person guilty of fraudulent misrepresentation (within
the meaning of Section 11(f) of the Securities Act) will be entitled to contribution from any Person who was not guilty of such fraudulent
misrepresentation; and provided further that in no event shall the Investor’s liability pursuant to this Section 2.11(e), when combined
with the amounts paid or payable by the Investor pursuant to Section 2.11(b), exceed the proceeds from the offering (net of any Selling
Expenses) received by the Investor, except in the case of willful misconduct or fraud by the Investor.
(f) Notwithstanding the foregoing, to the extent that the provisions on indemnification and contribution
contained in the underwriting agreement entered into in connection with an underwritten public offering are in conflict with the
foregoing provisions, the provisions in the underwriting agreement shall control.
(g) Unless otherwise superseded by an underwriting agreement entered into in connection with the underwritten
public offering, the obligations of the Company and the Investor under this Section 2.11 shall survive the completion of any offering of
Registrable Securities in a registration under this Section 2, and otherwise shall survive the termination of this Agreement.
2.12 Reports Under Exchange Act. With a view to making available to the Investor the benefits of SEC Rule 144 and any
other rule or regulation of the SEC that may at any time permit the Investor to sell securities of the Company to the public without
registration or pursuant to a registration on Form S-3, the Company shall:
all times;
(a) make and keep public information available, as those terms are understood and defined in SEC Rule 144, at
(b) use commercially reasonable efforts to file with the SEC in a timely manner all reports and other documents
required of the Company under the Securities Act and the Exchange Act (at any time after the Company has become subject to such
reporting requirements); and
(c) furnish to any the Investor, so long as the Investor owns any Registrable Securities, forthwith upon request (i)
a written statement by the Company that it has complied with the reporting requirements of SEC Rule 144, the Securities Act, and the
Exchange Act (at any time after the Company has become subject to such reporting requirements), or that it qualifies as a registrant
whose securities may be resold pursuant to Form S-3 (at any time after the Company so qualifies); (ii) a copy of the most recent annual
or quarterly report of the Company and
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
8
such other reports and documents so filed by the Company; and (iii) such other information as may be reasonably requested in availing
the Investor of any rule or regulation of the SEC that permits the selling of any such securities without registration or pursuant to such
Form S-3 (at any time the Company so qualifies to use such form).
2.13 [Reserved].
2.14 Assignment of Registration Rights. The rights to cause the Company to register Registrable Securities pursuant to this
Section 2 may be assigned (but only with all related obligations) by the Investor to a transferee of such Registrable Securities that is an
Affiliate of the Investor (including Vifor Fresenius Medical Care Renal Pharma Ltd.); provided, however, that (x) the Company is, within
a reasonable time after such transfer, furnished with written notice of the name and address of such transferee and the Registrable
Securities with respect to which such registration rights are being transferred; and (y) such transferee agrees in writing to be bound by
and subject to the terms and conditions of this Agreement, including the provisions of this Section 2.14.
2.15 Restrictions on Transfer.
(a) The Registrable Securities shall not be sold, pledged, or otherwise transferred, and the Company shall not
recognize any such sale, pledge, or transfer, except upon the conditions specified in this Agreement and the SPA, which conditions are
intended to ensure compliance with the provisions of the Securities Act. Upon transfer, the Investor will cause any proposed purchaser,
pledgee, or transferee of the Registrable Securities held by the Investor to agree to take and hold such securities subject to the provisions
and upon the conditions specified in this Agreement.
(b) Each certificate representing the Registrable Securities (unless otherwise permitted by the provisions of
Section 2.15(c)) be stamped or otherwise imprinted with a legend in the following form:
THE SECURITIES REPRESENTED BY THIS CERTIFICATE HAVE NOT BEEN REGISTERED UNDER THE
SECURITIES ACT OF 1933 AS AMENDED. THEY MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED OR
HYPOTHECATED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT AS TO THE SECURITIES
UNDER SAID ACT OR A CUSTOMARY OPINION OF COUNSEL REASONABLY SATISFACTORY TO THE
COMPANY THAT SUCH REGISTRATION IS NOT REQUIRED.
The Investor consents to the Company making a notation in its records and giving instructions to any transfer agent of the Restricted
Securities in order to implement the restrictions on transfer set forth in this Section 2.15.
(c) The holder of each certificate representing Restricted Securities, by acceptance thereof, agrees to comply in all
respects with the provisions of this Section 2. Before any proposed sale, pledge, or transfer of any Restricted Securities, unless there is in
effect a registration statement under the Securities Act covering the proposed transaction, the Investor shall give notice to the Company
of the Investor’s intention to effect such sale, pledge, or transfer. Each such notice shall describe the manner and circumstances of the
proposed sale, pledge, or transfer in sufficient detail and, if reasonably requested by the Company, shall be accompanied at the Investor’s
expense by either (i) a written opinion of legal counsel who shall, and whose legal opinion shall, be reasonably satisfactory to the
Company, addressed to the Company, to the effect that the proposed transaction may be effected without registration under the Securities
Act; (ii) a “no action” letter from the SEC to the effect that the proposed sale, pledge, or transfer of such Restricted Securities without
registration will not result in a recommendation by the staff of the SEC that action be taken with respect thereto; or (iii) any other
evidence reasonably satisfactory to counsel to the Company to the effect that the proposed sale, pledge, or transfer of the Restricted
Securities may be effected without registration under the Securities Act, whereupon the Investor shall be entitled to sell, pledge, or
transfer such Restricted Securities in accordance with the terms of the notice given by the Investor to the Company. The Company will
not require such a legal opinion or “no action” letter (x) in any transaction in compliance with Rule 144 or (y) in any transaction in which
the Investor transfers Restricted Securities to an Affiliate of the Investor for no consideration;
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
9
provided that each transferee agrees in writing to be subject to the terms of this Section 2.15(c). Each certificate evidencing the
Restricted Securities transferred as above provided shall bear, except if such transfer is made pursuant to Rule 144, the appropriate
restrictive legend set forth in Section 2.15(b), except that such certificate shall not bear such restrictive legend if, in the opinion of
counsel for the Investor and the Company, such legend is not required in order to establish compliance with any provisions of the
Securities Act.
2.16 Termination of Registration Rights. The right of the Investor to request registration or inclusion of Registrable
Securities in any registration pursuant to Section 2.1 or Section 2.3 shall terminate upon the closing of a Deemed Liquidation Event, as
such term is defined in the Restated Certificate, or the date that the Investor no longer holds Registrable Securities.
3. Miscellaneous.
3.1 Successors and Assigns. The Investor hereby agrees that it shall not, and may not, assign any of its rights and
obligations hereunder, unless such rights and obligations are assigned by the Investor to any Person to which Registrable Securities are
transferred by the Investor pursuant to Section 2.14; provided that such assignment of rights shall be contingent upon the assignee
providing a written instrument to the Company notifying the Company of such assignment and agreeing in writing to be bound by the
terms of this Agreement. The terms and conditions of this Agreement inure to the benefit of and are binding upon the respective
successors and permitted assignees of the parties. Nothing in this Agreement, express or implied, is intended to confer upon any party
other than the parties hereto or their respective successors and permitted assignees any rights, remedies, obligations or liabilities under or
by reason of this Agreement, except as expressly provided herein.
3.2 Governing Law. This Agreement shall be governed by and construed in accordance with the General Corporation Law
of the State of Delaware as to matters within the scope thereof, and as to all other matters shall be governed by and construed in
accordance with the internal laws of the State of New York, without regard to its principles of conflicts of laws.
3.3 Counterparts. This Agreement may be executed in two or more counterparts, each of which shall be deemed an
original, but all of which together shall constitute one and the same instrument. This Agreement may also be executed and delivered by
facsimile signature and in two or more counterparts, each of which shall be deemed an original, but all of which together shall constitute
one and the same instrument.
3.4 Titles and Subtitles. The titles and subtitles used in this Agreement are for convenience only and are not to be
considered in construing or interpreting this Agreement.
3.5 Notices. All notices, requests, and other communications given or made pursuant to this Agreement shall be in writing
and shall be deemed effectively given (i) upon personal delivery to the party to be notified; (ii) when sent by confirmed electronic mail or
facsimile if sent during normal business hours of the recipient, and if not so confirmed, then on the next business day; (iii) five (5) days
after having been sent by registered or certified mail, return receipt requested, postage prepaid; or (iv) one (1) day after deposit with a
nationally recognized overnight courier, specifying next-day delivery, with written verification of receipt. All communications shall be
sent to the Company and the Investor at the addresses specified in Section 12.3 of the License Agreement.
3.6 Amendments and Waivers. Any term of this Agreement may be amended and the observance of any term of this
Agreement may be waived (either generally or in a particular instance, and either retroactively or prospectively) only with the written
consent of the Company and the Investor; provided that the Company may in its sole discretion waive compliance with Section 2.15(c)
(and the Company’s failure to object promptly in writing to a proposed assignment allegedly in violation of Section 2.15(c) shall be
deemed to be a waiver). No waivers of or exceptions to any term, condition, or provision of this Agreement, in any one or more
instances, shall be deemed to be or construed as a further or continuing waiver of any such term, condition, or provision.
3.7 Severability. In case any one or more of the provisions contained in this Agreement is for any reason held to be
invalid, illegal or unenforceable in any respect, such invalidity, illegality, or unenforceability shall not affect
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
10
any other provision of this Agreement, and such invalid, illegal, or unenforceable provision shall be reformed and construed so that it
will be valid, legal, and enforceable to the maximum extent permitted by law.
3.8 [Reserved].
3.9 Entire Agreement. This Agreement (including any Schedules and Exhibits hereto) constitutes the full and entire
understanding and agreement between the parties with respect to the subject matter hereof, and any other written or oral agreement
relating to the subject matter hereof existing between the parties is expressly canceled.
3.10 Dispute Resolution. Any unresolved controversy or claim arising out of or relating to this Agreement, except (i) as
otherwise provided in this Agreement, or (ii) for any such controversies or claims arising out of either party’s intellectual property rights
for which a provisional remedy or equitable relief is sought, shall be submitted to arbitration by one arbitrator mutually agreed upon by
the parties, and if no agreement can be reached within [***] after names of potential arbitrators have been proposed by [***], then by
[***] arbitrator having reasonable experience in corporate finance transactions of the type provided for in this Agreement and who [***]
chosen by [***]. The arbitration shall take place in [***], in accordance with [***] rules then in effect, and judgment upon any award
rendered in such arbitration will be binding and may be entered in any court having jurisdiction thereof. There shall be limited discovery
prior to the arbitration hearing as follows: [***]. Depositions shall be conducted in accordance with [***], the [***] shall be required to
provide in writing to the parties the basis for the award or order of such arbitrator, and a court reporter shall record all hearings, with such
record constituting the official transcript of such proceedings. Each party will bear its own costs in respect of any disputes arising under
this Agreement.
3.11 Delays or Omissions. No delay or omission to exercise any right, power, or remedy accruing to any party under this
Agreement, upon any breach or default of any other party under this Agreement, shall impair any such right, power, or remedy of such
nonbreaching or nondefaulting party, nor shall it be construed to be a waiver of or acquiescence to any such breach or default, or to any
similar breach or default thereafter occurring, nor shall any waiver of any single breach or default be deemed a waiver of any other
breach or default theretofore or thereafter occurring. All remedies, whether under this Agreement or by law or otherwise afforded to any
party, shall be cumulative and not alternative.
[Remainder of Page Intentionally Left Blank]
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
11
IN WITNESS WHEREOF, the parties have executed Registration Rights Agreement as of the date first written above.
CARA THERAPEUTICS, INC.
VIFOR (INTERNATIONAL) LTD.
By:
Name:
Date:
By:
Name:
Title:
12
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
Exhibit 10.21
Execution Version
LICENSE AGREEMENT
BY AND BETWEEN
CARA THERAPEUTICS, INC.
AND
VIFOR (International) LTD.
October 15, 2020
LICENSE AGREEMENT
This LICENSE AGREEMENT (the “Agreement”) is entered into as of October 15, 2020 (the
“Effective Date”), by and between Cara Therapeutics, Inc., a corporation organized and existing under the laws
of Delaware and having an office located at offices at 4 Stamford Plaza, 107 Elm Street, 9th Floor Stamford, CT
06902 (“Cara”), and Vifor (International) Ltd., a corporation organized and existing under the laws of
Switzerland and having an office located at Rechenstrasse 37, CH-9014 St. Gallen, Switzerland (“Vifor”).
INTRODUCTION
1. Cara is a biopharmaceutical company focused on, among other things, the discovery, research and
development of novel drugs to address unmet medical needs.
2. Vifor is a pharmaceutical company focused on, among other health conditions, renal care and it has
expertise and resources relating to, among other things, promotion, marketing, sale and distribution of
pharmaceutical products useful in treating patients with renal diseases.
3. Cara has developed expertise, technology and intellectual property relating to its drug candidate
referred to as CR-845, in intravenous (or I.V.) form, and wishes to license such drug candidate (solely in I.V. form,
except as otherwise provided per Section 2.7 below) on an exclusive basis for marketing, promotion and sale for
use in the Field (as defined below) in the United States (with certain limitations on such license rights with respect
to dialysis clinics in the United States owned by Fresenius Medical Care (or its affiliate), as further specified
below).
4. Vifor desires to obtain such license rights in accordance with the terms of this Agreement.
5. Vifor Fresenius Medical Care Renal Pharma Ltd. (“VFMCRP”), an affiliate of Vifor, previously
entered into a license agreement with Cara covering the grant to VFMCRP of certain license rights to
commercialize CR-845 in I.V. form in the Field in certain territories and to certain markets, and the Parties hereto
intend that this Agreement is consistent with the terms of that prior agreement.
NOW, THEREFORE, in consideration of the mutual covenants contained herein, and other good and
valuable consideration, the receipt of which is hereby acknowledged, Cara and Vifor agree as follows:
ARTICLE I
DEFINITIONS
Unless specifically set forth to the contrary herein, the following capitalized terms, when used in this
Agreement and whether used in the singular or plural, shall have the respective meanings set forth below:
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
1
1.1 “Accounting Standards” means, with respect to either Party or its Affiliates, United States
generally accepted accounting principles (GAAP), consistently applied, as such standards exist from time to time,
consistently applied throughout the applicable entity or organization.
1.2 “Affiliate” means, with respect to an entity, any corporation or other business entity controlled by,
controlling, or under common control with the first entity, with term “controlling” (with correlative meanings for
the terms “controlled by” and “under common control with”) meaning that the applicable entity has direct or
indirect beneficial ownership of more than 50% of the voting stock of, or the actual ability (direct or indirect) to
direct and control the management and business policies of, the applicable other entity. The Parties acknowledge
and agree that VFMCRP shall be considered an “Affiliate” of Vifor for the purposes of this Agreement so long as
it meets the definition set forth in this Section 1.2 and/or Vifor retains at least a 50% interest in the income of
VFMCRP. Notwithstanding the foregoing, the “Affiliates” of Vifor will not include, FMC or any member of the
FMC Group.
1.3 “API” means active pharmaceutical ingredient, which is also commonly referred to as drug
substance.
1.4 “Applicable Law” means all laws, statutes, rules, codes, regulations, orders, judgments or
ordinances applicable to a Party in connection with the applicable activities of such Party as contemplated under
this Agreement.
1.5 “Business Day” means a day that is not a Saturday, Sunday or a day on which national banking
institutions in Stamford, Connecticut and in Zurich, Switzerland are authorized by Law to remain closed.
1.6 “Bundle” means a treatment protocol for which CMS has either (a) issued a final ruling to include
a Licensed Product in the bundled payment under the End-Stage Renal Disease Prospective Payment System for
renal dialysis services, or (b) provided written confirmation that CMS considers the Licensed Product to be
included as part of the bundled payment under such End-Stage Renal Disease Prospective Payment System.
1.7 “Bundled Product” means one or more Licensed Products together with one or more other
products that are either (a) packaged together for sale or shipment as a single unit or sold at a single price or
(b) marketed or sold collectively as a single product.
1.8 “Calendar Quarter” means any of the respective periods of three (3) consecutive calendar months
ending on March 31, June 30, September 30 or December 31.
1.9 “Calendar Year” means any successive period of twelve (12) consecutive months commencing on
a January 1 and ending on the following December 31.
1.10 “Cara Product Technology” means all Licensed Patent Rights and Licensed Know-How.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
2
1.11 “CMS” means Center for Medicaid & Medicare Services.
1.12 “COGS” means the actual cost of goods sold for Licensed Product sold in the U.S. hereunder, as
agreed by the Parties from time-to-time in accordance with US GAAP.
1.13 “Combination Product” means any Licensed Product that is comprised of two or more APIs, at
least one of which is the Licensed Compound.
1.14 “Commercialization Plan” means the plan developed by Vifor and as approved by the JCC, as set
forth in Section 3.3, that sets forth the Commercialization activities to be undertaken by (or on behalf of) Vifor
with respect to Licensed Product in the U.S., and as such plan may be amended, updated or modified in writing by
the JCC or the Parties, as provided in this Agreement.
1.15 “Commercially Reasonable Efforts” means, with respect to particular efforts to be expended by a
Party with respect to any objective, including, without limitation, Development, seeking Regulatory Approval or
Reimbursement Approval, Commercialization and manufacturing of the Licensed Products under the Agreement,
those efforts and resources commonly used and applied by a similarly situated pharmaceutical company to
conduct similar tasks or obligations for compounds or pharmaceutical products at a similar stage of research,
development, commercialization and which are of similar market potential as the Licensed Product and (if
applicable) at a similar stage of product life, in each case taking into account the Relevant Factors in effect at the
time such efforts are expended.
1.16 “Commercialization” or “Commercialize” means any activity directed to obtaining pricing or
reimbursement approvals, manufacturing, marketing, promoting, distributing, importing, offering to sell or selling
a Licensed Product.
1.17 “Compound” means the kappa opioid receptor agonist compound of Cara known as “CR-845”,
having the chemical structure set forth in Exhibit 1.17 of this Agreement, including any salt, known pro-drug (i.e.,
a chemically modified form of such agonist compound that is designed and intended to be metabolized in a human
to become such agonist compound), freebase, partially protonated or deprotonated form, or crystal form of such
compound or a stereoisomer thereof.
1.18 “Competing Product” means any pharmaceutical product, other than the Licensed Product, that is
an agonist of the kappa-opioid receptor and is directed to the inhibition, prevention or treatment of uremic
pruritus.
1.19 “Confidential Information” means, with respect to a Party, any and all data, results and other
Know-How, which may include scientific, pre-clinical, clinical, regulatory, manufacturing, marketing, financial
and commercial results, data and other information, that is or was provided or disclosed by such Party (or its
Affiliate) to the other Party (or its Affiliate), whether communicated in writing or orally or by any other method,
in connection with this Agreement and including all such information that was or is provided or disclosed under
or in
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
3
connection with the VFMCRP Agreement. Notwithstanding the foregoing, the term “Confidential Information”
excludes particular information that, in each case as demonstrated by competent written documentation:
(a) is publicly disclosed and made generally available to the public, either before or after it
becomes known to the receiving Party, and other than through any act or omission of the receiving Party or its
Affiliates in breach of this Agreement;
(b) was known to the receiving Party or its Affiliate, without obligation to a Third Party to keep
it confidential, prior to the date of first disclosure by the disclosing Party to the receiving Party;
(c) is subsequently disclosed to the receiving Party or its Affiliate by a Third Party lawfully in
possession thereof without obligation to keep it confidential and without a breach of such Third Party’s
obligations of confidentiality; or
(d) has been independently developed by the receiving Party or its Affiliate without the aid,
application or use of the disclosing Party’s Confidential Information (the competent written proof of which must
be contemporaneous with such independent development).
1.20 “Control” means, with respect to any item of or right under Patent Rights or Know-How, that the
applicable Party owns or has a license (or sublicense, as applicable) under (other than a license granted by the
other Party pursuant to this Agreement) such items or right, and has the actual rights to grant the other Party
access to and/or a license or sublicense (as applicable) under such item or right, as provided for in this Agreement,
without violating the terms of any agreement or other arrangement with any Third Party existing at the time such
Party would be required hereunder to grant the other Party such access or license or sublicense.
1.21 “Cover” means (with correlative meanings for the terms “Covering” or “Covered”), with respect
to a compound, composition of matter, formulation, apparatus, article of manufacture, product, technology,
process or method (collectively, “Compositions or Technology”) that, in the absence of ownership of or a license
granted under a particular Valid Claim, the manufacture, use, offer for sale, sale or importation of such
Compositions or Technology would infringe such Valid Claim, or, in the case of a Valid Claim that has not yet
issued, would infringe such Valid Claim if it were to issue.
1.22 “Default” means, with respect to a Party, that (a) any material representation and warranty of such
Party set forth in this Agreement shall have been untrue in any material respect when made, or (b) such Party shall
have materially failed to perform any material obligation of such Party set forth in this Agreement.
1.23 “Development” or “Develop” means all internal and external research, development prior to
receipt of Regulatory Approval in the applicable country, including (as applicable): research, preclinical testing,
test method development and stability testing, toxicology, formulation, process development, manufacturing
scale-up, development-stage
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
4
manufacturing, quality assurance/quality control procedure development and performance with respect to clinical
materials, statistical analysis and report writing and clinical studies, regulatory affairs, and all other pre-
Regulatory Approval activities. “Development” will also include development and regulatory activities for
additional forms, formulations or indications for a Licensed Product after Regulatory Approval of such Licensed
Product, and clinical trials initiated following receipt of Regulatory Approval, or to be conducted after a
Regulatory Approval, that was mandated by the applicable Regulatory Authority as a condition of such
Regulatory Approval with respect to an approved indication. When used as a verb, “Develop” means to engage in
Development.
1.24 “Dollars” or “$” means the legal tender of the U.S.
1.25 “FDA” or “Food and Drug Administration” means the United States Food and Drug
Administration, or any successor agency thereto.
1.26 “Field” means all therapeutic uses relating to the inhibition, prevention or treatment of itch
associated with pruritus in hemodialysis and peritoneal dialysis patients in the United States using the Licensed
Product.
1.27 “First Commercial Sale” means, as to a particular Licensed Product in the United States, on a
Licensed Product-by-Licensed Product basis, the first sale of such Licensed Product in a bona fide arms-length
transaction by or on behalf of Vifor or its Affiliate or Sublicensee to a Third Party in the United States in exchange
for cash or some equivalent to which value can be assigned after such Licensed Product has been granted all
necessary Regulatory Approvals by a Regulatory Authority having jurisdiction for such country. First Commercial
Sale excludes any sale or other distribution for use in a clinical trial or other Development activity, or for
compassionate or named-patient use sold at or below seller’s costs.
1.28 “FMC Group” means FMC and FMC’s Affiliates and FMC US Dialysis Clinics, which for
purposes of this Agreement are not considered to be Affiliates of Vifor.
1.29 “FMC” means Fresenius Medical Care Holdings Inc., a New York corporation, which for purposes
of this Agreement is not considered to be an Affiliate of Vifor.
1.30 “FMC US Dialysis Clinics” means mean Majority Owned Clinics and Formulary Clinics (in each
case, as defined below), and home hemodialysis and peritoneal-dialysis programs administered through Majority
Owned Clinics or Formulary Clinics.
For the purposes of this Agreement: (i) “Majority Owned Clinics” shall mean all dialysis clinics and home
dialysis programs in the U.S. that are Affiliates of FMC; and (ii) “Formulary Clinics” shall mean, except as
otherwise provided below, all dialysis clinics (including home dialysis programs) in the U.S. that purchase
pharmaceutical products under FMC’s or FMC’s Affiliates’ formulary guidelines and all dialysis clinics
(including home dialysis programs) for which FMC or its Affiliates provide management or administrative
services that include the purchase of pharmaceutical products. For clarity,
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
5
the Majority Owned Clinics and Formulary Clinics existing on the Effective Date are all listed by name
and address on the “List of FMC US Dialysis Clinics” document provided to Cara as of just prior to the
effective date of the VFMCRP Agreement. Notwithstanding the foregoing, the term “Formulary Clinics”
expressly excludes (except as otherwise agreed by the Parties in writing) all dialysis clinics and home
dialysis programs owned or operated by any of the five dialysis providers listed on Exhibit 1.30 of this
Agreement or any affiliate of any such provider (and, for clarity, any sales of Licensed Product by Cara (or
its Affiliate) to any such clinics or programs shall not be included in Net Sales or in the calculation of “Net
Profit/Non-FMC Customers” hereunder).
1.31 “Generic Product” means, with respect to a Licensed Product, any other product sold by a Third
Party in the United States that (a) contains the same active ingredient (and no other active ingredient(s)) and has
regulatory approval for the same use as the Licensed Product, (b) has received marketing approval in the United
States by reference to any Regulatory Approval in the United States for the Licensed Product (or any data therein)
and (c) is sold in in the United States by a Third Party that is not a sublicensee of Licensee or its Affiliates and did
not purchase such product in a chain of distribution that included Licensee, its Affiliates or sublicensees.
1.32 “Good Manufacturing Practices” or “GMP” means the then-current good manufacturing
practice standards, practices and procedures promulgated or endorsed by the applicable Regulatory Authority as
set forth in the guidelines imposed by such Regulatory Authority, as may be updated from time to time.
1.33 “Governmental Authority” means any United States federal, state or local government agency or
authority, or any governmental agency or authority of a country or jurisdiction in the United States outside the
United States, or political subdivision thereof, or any multinational organization or authority in the United States,
or any authority, agency or commission entitled to exercise any administrative, executive, judicial, legislative,
police, regulatory or taxing authority or power, any court or tribunal (or any department, bureau or division
thereof), or any governmental arbitrator or arbitral body.
1.34 “Improvement” means any data, results and other Know-How, including any improvements,
enhancements or modifications to Compound, Licensed Product, and/or Cara Product Technology, patented or not,
that are conceived, reduced to practice or otherwise discovered, generated, invented or developed during the Term
by or on behalf of Vifor or its Affiliate or Sublicensee, alone or in collaboration with a Third Party (which
includes, for clarity, all clinical and study data and results of research or Development conducted by any such
party on Compound or Licensed Product), provided, however, that an Improvement will not include any Invention
directed towards any compound (excluding, for clarity, the Compound) that is proprietary to Licensee or any
Affiliate of Licensee or that is developed by or on behalf of Licensee or any Affiliate of Licensee outside of the
scope of this Agreement.
1.35 “Invention” means any new and useful method, process, article of manufacture, compound,
composition of matter, formulation, apparatus, discovery or finding, or any improvement thereof, that is or may be
patentable in the United States.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
6
1.36 “Investigator-Sponsored Studies” (ISS) shall mean research efforts in which the investigator
designs and implements the study and the investigator or his/her institution acts as the study sponsor. As the
sponsor, the investigator assumes all responsibilities for complying with applicable regulatory requirements. ISS
may be supported by Cara, Vifor, or VFMCRP in the form of investigational product, funding, and/or technical
input, all as provided in the VFMCRP License Agreement or as otherwise agreed by the Parties.
1.37 “Joint Commercialization Committee” or “JCC” means the committee formed by the Parties as
provided in Section 3.3, to supervise and oversee the Commercialization of the Licensed Products by Vifor in the
United States under this Agreement.
1.38 “Joint Know-How” means any Know-How that is jointly made, identified, discovered or created
during the Term by at least one employee of Cara or its Affiliate or person contractually required to assign or
license such Know-How to Cara and at least one employee of Vifor or its Affiliate or person contractually
required to assign such Know-How to Vifor, but excluding any Improvements.
1.39 “Joint Patents” mean all Patent Rights claiming Inventions in Joint Know-How.
1.40 “Joint Technology” means Joint Know-How and Joint Patents
1.41 “Know-How” means (a) any scientific or technical results, data and other information of any type
whatsoever, in any tangible or intangible form whatsoever, that is not in the public domain, which may include
databases, practices, methods, techniques, specifications, formulations, formulae, protein sequences, DNA
sequences, knowledge, know-how, skill, experience, test data including pharmacological, medicinal chemistry,
biological, chemical, biochemical, toxicological and clinical test data, analytical and quality control data, stability
data, studies and procedures, and manufacturing process and development information, results and data, (b) any
biological, chemical, or physical material that is not in the public domain or otherwise generally available to the
public and (c) any dosage regimens, control assays, product specifications, analytical and quality control data,
marketing, pricing, distribution cost and sales data or descriptions that are not in the public domain or otherwise
generally available to the public, and including, for clarity, all Inventions.
1.42 “Licensed Know-How” means all Know-How that (a) is Controlled by Cara as of the Effective
Date or during the Term and (b) is related to the marketing or use of Licensed Product in the Field in the United
States.
1.43 “Licensed Patent Rights” means all Patent Rights in the United States that (a) are Controlled by
Cara as of the Effective Date or during the Term, and (b) Cover Licensed Product or its manufacture or method of
use in the Field (which includes Cara’s rights in applicable Joint Patents in the United States).
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
7
1.44 “Licensed Product” means any intravenous (I.V.) pharmaceutical drug product, including any
appropriate IV preparation, formulation, or dosage form thereof, that includes the Compound as at least one API
therein.
1.45 “Marketing/Distribution Fee” shall have the meaning ascribed to such term in Section 6.4 of this
Agreement.
1.46 “NDA” means a New Drug Application filed with the FDA, but excluding Reimbursement
Approval applications.
1.47 “Net Sales” means the gross amount invoiced for sales (during the applicable period) of Licensed
Product in the United States by Vifor or its Affiliates or Sublicensees to unaffiliated Third Parties, or (as
applicable) for sales of Licensed Product for use in the Field by Cara, including to FMC US Dialysis Clinics based
on orders taken by Vifor or VFMCRP (or its Sublicensee, if applicable) from such FMC US Dialysis Clinics for
such Licensed Products, less the following deductions from such amount to the extent actually allowed or incurred
with respect to such sales: [***];
such deductions, in each case, to the extent allowable in calculating net sales in accordance with the Accounting
Standards, consistently applied through the selling party’s corporate organization.
Net Sales will be determined from books and records of sellers, maintained in accordance with the Accounting
Standards, as consistently applied, with respect to sales of any Licensed Product.
[***].
Net Sales will not include [***].
Each of the foregoing deductions shall be permitted if incurred in the ordinary course of business in type and
amount consistent with good industry practice and in accordance with the Accounting Standards on a basis
consistent with Vifor’s audited consolidated financial statements.
If Licensed Product is sold other than for cash, the Net Sales on such sale shall be calculated by [***].
In the event that a Licensed Product is sold as part of a Combination Product (which Combination Product has
been approved by the Parties, as required in Section 2.1), the Net Sales from such sale of the Combination
Product, for the purposes of determining royalty payments, will be determined (a) [***]. In such event, Licensee
will in good faith make a determination of the respective fair market values of the Licensed Product and all other
API(s) included in the Combination Product, or (b) as otherwise agreed in writing by the Parties.
If a Licensed Product is sold as part of a Bundled Product, then the Seller will [***].
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
8
1.48 “Net Sales/Non-FMC Customers” means, for any applicable time period, the Net Sales occurring
during such period for sales of Licensed Product in the U.S. under this Agreement to all customers and purchasers
other than to FMC US Dialysis Clinics.
1.49 “Non-FMC Net Profit” means, for any particular period, the amount equal to: [***].
1.50 “Party” means Vifor or Cara individually, and “Parties” means Vifor and Cara collectively.
1.51 “Patent Rights” means patents, patent applications or provisional patent applications, utility
models and utility model applications, petty patents, innovation patents, patents of addition, divisionals,
continuations, continuation-in-part applications, continued prosecution applications, requests for continued
examinations, reissues, renewals, reexaminations and extensions and supplementary protection certificates granted
in relation thereto, in any country of the world.
1.52 “Product Trademark” means the trademark of Cara set forth in Exhibit 1.52 of this Agreement.
1.53 “Prosecution” means, with respect to a Patent Right, the preparation, filing, prosecution and
maintenance of such Patent Right (and all directly related activities), as well as all activities relating to post grant
review proceedings, reexaminations, reissues and the like with respect to such Patent Right, together with the
conduct of interferences, the defense of oppositions and other similar proceedings with respect to the particular
Patent Right; the term “Prosecute” shall have the correlative meaning.
1.54 “Regulatory Approval” means, with respect to a particular Licensed Product in the United States,
obtaining the technical, medical and scientific licenses, registrations, authorizations and approvals (including
approvals of NDAs and labeling approvals), in each case as necessary under Applicable Law for the promotion or
sale of such Licensed Product in in the United States.
1.55 “Regulatory Authority” means any applicable Government Authority involved in granting
approvals, registrations or licenses for the manufacturing, marketing, selling, reimbursement or pricing of a
Licensed Product in the United States or any portion thereof, including but not limited to the FDA, and any
successor governmental authority having substantially the same function.
1.56 “Reimbursement Approval” means an approval, agreement, determination or other decision by
the applicable Governmental Authority and/or Regulatory Authority that establishes prices charged to end-users
for biopharmaceutical products that a Licensed Product will be reimbursed by the Governmental Authorities
and/or Regulatory Authorities in the United States.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
9
1.57 “Relevant Factors” means, with respect to a particular activity or obligation of a Party under this
Agreement relating to the Reimbursement Approval, Commercialization or manufacturing of a Licensed Product,
the applicable (in the judgement of an independent unbiased pharma industry expert) of the following factors that
likely apply to or affect such activity or obligation (without taking into account any other product or products that
such Party may be developing, manufacturing or commercializing): material issues of safety, efficacy or stability;
product profile (including product modality, category and mechanism of action); stage of development or life
cycle status; material projected costs of the applicable development, Regulatory Approval, manufacturing or
Commercialization activities (without taking into account any payments under this Agreement); material issues
regarding the ability to manufacture or have manufactured any Licensed Product; the likelihood of obtaining
Regulatory Approvals and the timing of such Regulatory Approvals; the labeling and anticipated labeling of such
Licensed Product; present and future market potential of such Licensed Product; existing or projected pricing,
sales, reimbursement and profitability of such Licensed Product; pricing or reimbursement changes in the relevant
country in the United States; and proprietary position, strength and duration of patent protection and anticipated
exclusivity of such Licensed Product.
1.58 “Senior Executive” means (a) in the case of Cara, the Chief Executive Officer of Cara (or a senior
executive officer designated by the Chief Executive Officer of Cara), and (b) in the case of Vifor, the Chief
Executive Officer of Vifor, or such individual’s nominated designee who is a member of the applicable Party’s
senior management with appropriate decision making authority.
1.59 “Sublicensee” means any Third Party or other entity that is granted a sublicense under the license
rights granted in Section 2.1, 2.2 or 2.3 of this Agreement in compliance with Section 2.4.
1.60 “Supply Agreement” means a supply agreement covering manufacture and supply of Licensed
Product to Vifor, to be negotiated and entered into by the Parties as provided in Section 5.4.
1.61 “Term” means the term of this Agreement, as defined in Section 10.1 of this Agreement.
1.62 “Third Party” means an entity or person other than Cara, Vifor and their respective Affiliates.
1.63 “U.S.” or “the United States” means the United States of America, including all its territories.
1.64 “Valid Claim” means: (a) a claim of an issued patent that has not expired or been abandoned, and
has not been revoked, held invalid or unenforceable by a patent office, court or other governmental agency of
competent jurisdiction in a final judgment from which no further appeal can be taken, or (b) a claim within a
pending patent application which application has not been pending for more than seven (7) years from the date of
its priority filing date and which claim
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
10
has not been irretrievably revoked, irretrievably cancelled, irretrievably withdrawn, held invalid or abandoned by
a patent office, court or other governmental agency of competent jurisdiction in a final judgment from which no
further appeal can be taken, or finally determined to be unallowable in a decision from which an appeal cannot or
can no longer be taken. For clarity, a claim of an issued patent that ceased to be a Valid Claim before it issued
because it had been pending too long, but subsequently issues and is otherwise described by clause (a), shall again
be considered to be a Valid Claim once it issues. The same principle shall apply in similar circumstances such as
if, for example (but without limitation), a final rejection of a claim is overcome. “Valid Claim” does not include
any claim in any issued and unexpired Cara Patent in the Territory Covering (i) an alternative manufacturing
process to produce the Compound or the Licensed Product, including its components (i.e., a manufacturing
process other than the manufacturing process used by or on behalf of Cara or its Affiliate to produce the
Compound or the Licensed Product as of the applicable time) or (ii) an Improvement made solely by one or more
employees of Licensee or its Affiliates or persons contractually required to assign or license such Improvement
(or Patent Covering such Improvement) to Licensee or an Affiliate of Licensee.
1.65 “VFMCRP Agreement” means that certain License Agreement between VFMCRP and Cara,
entered into effective as of May 17, 2018.
1.66 “Vifor Product Technology” means all Improvements and all Patent Rights and other intellectual
property rights that claim or cover or otherwise relate to any Improvements.
1.67 Additional Definitions. Each of the following definitions is set forth in the section of this
Agreement indicated below:
Defined Term
Additional I.V. Indications
Bankruptcy Code
Breach Notice
Cara Indemnitees
Defaulting Party
Dispute
Field Infringement
Initiating Party
Jointly-Owned Patent Rights
Knowledge
Losses
Mark Infringement
Non-Defaulting Party
Patent Challenge
Records
SEC Filing
Supply Agreement
Supply Price
Taxes
Section
2.10
2.8
10.2(a)
9.5
10.2(a)
11.1
7.4(b)
7.6(d)
7.2
9.2
9.5
7.7
10.2(a)
10.2(d)
4.5
8.3(c)
5.7
5.7
6.10
11
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
Defined Term
Third Party Claim
Vifor Indemnitees
Section
9.5
9.6
1.68 Interpretation. (a) Whenever any provision of this Agreement uses the term “including” (or
“includes”), such term will be deemed to mean “including without limitation” and “including but not limited to”
(or “includes without limitations” and “includes but is not limited to”) regardless of whether the words “without
limitation” or “but not limited to” actually follow the term “including” (or “includes”); (b) “herein,” “hereby,”
“hereunder,” “hereof” and other equivalent words will refer to this Agreement in its entirety and not solely to the
particular portion of this Agreement in which any such word is used; (c) all definitions set forth herein will be
deemed applicable whether the words defined are used herein in the singular or the plural; (d) wherever used
herein, any pronoun or pronouns will be deemed to include both the singular and plural and to cover all genders;
(e) the recitals set forth at the start of this Agreement, along with the schedules and exhibits to this Agreement,
and the terms and conditions incorporated in such recitals and schedules and exhibits will be deemed integral parts
of this Agreement and all references in this Agreement to this Agreement will encompass such recitals and
schedules and exhibits and the terms and conditions incorporated in such recitals and schedules and exhibits;
provided that in the event of any conflict between the terms and conditions of this Agreement and any terms and
conditions set forth in the recitals, schedules or exhibits, the terms of this Agreement will control; (f) in the event
of any conflict between the terms and conditions of this Agreement and any terms and conditions that may be set
forth on any order, invoice, verbal agreement or otherwise, the terms and conditions of this Agreement will
govern; (g) this Agreement will be construed as if both Parties drafted it jointly, and will not be construed against
either Party as principal drafter; (h) unless otherwise provided, all references to Sections, Articles and Schedules
in this Agreement are to Sections, Articles and Schedules of and to this Agreement; (i) any reference to any
federal, national, state, local or foreign statute or law will be deemed to also refer to all rules and regulations
promulgated thereunder, unless the context requires otherwise; (j) wherever used, the word “shall” and the word
“will” are each understood to be imperative or mandatory in nature and are interchangeable with one another; (k)
the word “or” will not be exclusive; (l) references to a particular person include such person’s successors and
assigns to the extent not prohibited by this Agreement and (m) the section headings and captions used herein are
inserted for convenience of reference only and will not be construed to create obligations, benefits or limitations.
ARTICLE II
GRANTS OF RIGHTS; LIMITATIONS
2.1 Commercialization Licenses to Vifor in U.S.. Subject to the terms and conditions of this
Agreement, and to the rights granted to VFMCRP pursuant to the VFMCRP License Agreement, Cara hereby
grants to Vifor an exclusive (even as to Cara, but subject to Cara’s retained rights hereunder), royalty-bearing
license solely in the U.S., with the right to grant
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
12
sublicenses as provided in Section 2.4 below, under the Cara Product Technology and its interest in the Joint
Technology solely to:
(a) import solely into the U.S., use, distribute, offer for sale, promote, sell and otherwise
Commercialize the Licensed Product solely for use in the Field in the U.S, and subject to Section 2.3.
Notwithstanding the above license, Vifor covenants and agrees that it and its Affiliates and Sublicensees
shall not Develop or Commercialize any Combination Product except as agreed by the Parties in writing.
2.2 Limitation on Promotion License Rights to Vifor Regarding FMC Clinics.
(a) Vifor acknowledges and agrees that Cara has previously granted VMFCRP certain rights in
the U.S. to promote the Licensed Product to FMC US Dialysis Clinics and to take orders for the Licensed
Products solely for sale by Cara to FMC US Dialysis Clinics for use in treating their customers in the Field.
Vifor thus acknowledges and agrees that any of its license rights in Section 2.1 with respect to FMC US Dialysis
Clinics are subject to such VFMCRP pre-existing license rights and that Vifor shall and may only conduct
promotion and sale of Licensed Product to such FMC US Dialysis Clinics under express authority of VFMCRP.
Notwithstanding the foregoing and as approved by VFMCRP, the Parties acknowledge and agree that Vifor shall
take orders for Licensed Products for sale to FMC US Dialysis Clinics (subject only to Cara’s rights under the
VFMCRP Agreement).
(b) Notwithstanding the license grants to Vifor in Section 2.1 above, Cara retains and shall
retain the rights to promote Licensed Products in the U.S., in compliance with the relevant Commercialization
Plan(s) as approved by the JCC.
2.3 License to Product Trademark. Subject to the other terms and conditions of this Agreement,
Cara hereby grants to Vifor an exclusive (even as to Cara, but subject to the rights granted VFMCRP under the
VFMCRP License Agreement), royalty-free license in the U.S., with the right to grant sublicenses as provided in
Section 2.4 below, under the Product Trademark solely to promote and otherwise Commercialize the Licensed
Product in the U.S. in accordance with this Agreement. In exercising the foregoing license, Vifor shall comply
with all reasonable and typical restrictions and obligations (as provided in writing by Cara) regarding use of the
Product Trademark, and quality of the finished Licensed Product (or related promotional or advertising materials)
that bear the Product Trademark. Cara shall have the right to inspect samples of Finished Licensed Product (and
related promotional or advertising materials) that bear the Product Trademark, to ensure compliance with such
restrictions, and Vifor agrees to provide such samples on reasonable request, for such purposes.
2.4 Sublicenses.
(a) Subject to the terms of this Agreement, Vifor shall have the right to grant sublicenses
through multiple tiers, under the rights granted in Section 2.1 and 2.3 to its Affiliates
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
13
and to Third Party sub-licensees, with Cara’s prior written consent, which shall not be unreasonably withheld,
delayed or conditioned, provided that Cara’s prior consent shall not be required for Vifor to grant such sublicenses
to the following entities:
(i) Vifor's Affiliates in existence on the Effective Date, as listed in Exhibit 2.4(a) of the
Agreement.
(b) With respect to any such sublicenses granted, the sublicense agreement must be expressly
subject to and comply with all terms of this Agreement, and Vifor is and shall remain fully responsible for the
compliance by all Sublicensees with all terms of the Agreement and for any breach of such terms by any
Sublicensee.
2.5 Grantback License to Cara. Vifor hereby grants to Cara a worldwide, royalty-free, perpetual,
irrevocable, non-exclusive license, with full rights to grant sublicenses through multiple tiers, under the Vifor
Product Technology and its interest in the Joint Technology: (a) to research, Develop, use, import, offer for sale,
sell and have sold and export Compound and Licensed Products anywhere in the world, and (b) to make and have
made Licensed Products worldwide.
2.6 [***].
2.7 Rights Retained by the Parties; License Limitations.
(a) Except as expressly set forth in this Agreement, neither Party shall be granted, acquire or
retain any license or other intellectual property interest, by implication or otherwise, in any Confidential
Information of the other Party or under any Patent Right or proprietary Know-How in which such other Party or
its Affiliates has rights. Without limiting the generality of the foregoing, any of Cara’s rights to Cara Product
Technology that is not specifically licensed to Vifor shall be retained by Cara.
(b) Without limiting the generality of Section 2.7(a) above, Cara retains and shall retain the
rights under the Cara Product Technology (i) to make and have made Licensed Products, on a non-exclusive basis
(but subject to Section 5.6), in the United States for commercial sale of the Licensed Product for use in the Field
anywhere in the world (in compliance with the terms of this Agreement), (ii) to supply Licensed Products to Vifor
under the terms of the Supply Agreement (in compliance with the terms of the Supply Agreement) and (iii) to
import, distribute promote, sell and otherwise Commercialize the Licensed Product on an exclusive basis outside
of the Field either in or outside of the United States.
(c) Vifor covenants and agrees that, unless otherwise agreed by Cara in writing, Vifor shall not
assign or otherwise sell or transfer to any Third Party any of the Cara Product Technology and shall not practice or
use the Cara Product Technology (including to use, offer for sale or sell Licensed Product for use outside the
Field) except as permitted in the license rights (including the rights to sublicense, subject to Section 2.5) expressly
granted in Sections 2.1, 2.2, 2.3 and 2.4.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
14
(d) Cara covenants and agrees that, unless otherwise agreed by Vifor in writing, Cara shall not
assign or otherwise sell or transfer to any Third Party any of the Vifor Product Technology and shall not practice
or use the Vifor Product Technology except as permitted in the license rights (including the rights to sublicense)
expressly granted in Section 2.5.
2.8 Section 365(n) of the Bankruptcy Code. All rights and licenses granted under or pursuant to any
section of this Agreement are and will otherwise be deemed to be for purposes of Section 365(n) of the United
States Bankruptcy Code (Title 11, U.S. Code), as amended (the “Bankruptcy Code”) or any comparable Law
outside the United States, licenses of rights to “intellectual property” as defined in Section 101(35A) of the
Bankruptcy Code. Each of the Parties will retain and may fully exercise all of its respective rights and elections
under the Bankruptcy Code and any comparable Law outside the United States. Each Party agrees that the other
Party, as licensee of such rights under this Agreement, will retain and may fully exercise all of its rights and
elections under the Bankruptcy Code or any other provisions of Applicable Law outside the United States that
provide similar protection for “intellectual property.” The Parties further agree that, in the event of the
commencement of a bankruptcy proceeding by or against a Party under the Bankruptcy Code or analogous
provisions of Applicable Law outside the United States, the other Party will be entitled to a complete copy of (or
complete access to, as appropriate) such intellectual property and all embodiments of such intellectual property,
which, if not already in such other Party’s possession, will be promptly delivered to it upon such other Party’s
written request thereof.
2.9 Exclusivity.
(a) Exclusive Efforts in the Field. During the Term, and for [***] thereafter, neither Party
nor any of its Affiliates will directly, or indirectly through the grant of rights to any Third Party, promote, sell,
offer for sale or otherwise commercialize any Competing Product in the Field in the United States, without the
prior written consent of the other Party, provided that the foregoing provisions of this Section 2.9(a) shall have no
force or effect (a) if, and to the extent that, in the United States such provisions contravene any applicable antitrust
or antimonopoly law, and (b) with respect to any future Affiliate of either Party that becomes an Affiliate through
acquisition (or similar change of control transaction) of such Party, as to any compound or product that is in a
development or commercialization program of such Affiliate that exists prior to such acquisition or similar
transaction closes.
2.10 Off-Label Sales. If Cara or its Affiliates Commercialize, or grant a license to Third Party to
Commercialize, either (a) a Licensed Product for an Additional I.V. Indication and/or (b) a commercial product
that is an oral formulation of the Compound in the United States, then the Parties shall agree in good faith on an
effective mechanism to (i) seek to prevent off-label sales in each other’s respective field (for Vifor, in the Field,
and for Cara (and its Affiliates and Third Party licensees), outside the Field) in the Licensed Territory of such
Licensed Product and (ii) provide adequate compensation to the other Party for off-label sales in its respective
field in the Licensed Territory of such Licensed Product. If such an agreement is not reached, the matter will be
resolved as provided under Section 11.4. As used herein, an “Additional I.V. Indication” means a therapeutic
use of an I.V. Licensed Product relating to the prevention or treatment of acute pain in hospital settings.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
15
ARTICLE III
GOVERNANCE – JCC
3.1 Formation of Joint Commercialization Committee. As of the Effective Date, the Parties
establish a Joint Commercialization Committee, which shall have the responsibilities for overall coordination and
oversight of the activities of Vifor (and its Affiliates and Sublicensees) under this Agreement and (as applicable)
the Supply Agreement with respect to the promotion, marketing, selling and other Commercialization of Licensed
Products in the Field in the United States, including (i) discussing and agreeing on the Commercialization Plan
prepared by Vifor, and annual (or interim, as needed) updates thereto; (ii) exchanging appropriate information
about the Commercialization of the Licensed Products in the Field in the United States; (iii) overseeing the
Commercialization of Licensed Product in the United States in the Field, including coordination of Vifor efforts
with those of VFMCRP with respect to FMC US Dialysis Clinics; and (iv) otherwise reviewing and discussing
each Party’s activities under this Agreement as needed to ensure efficient and effective progress towards achieving
the goals and intention of the Agreement. The JCC can establish one or more sub-committees as it deems
necessary to manage the business under the Agreement, which committees shall have the responsibilities and
authority as designated in writing by the JCC and shall be subject to the direct oversight and control of the JCC.
The JCC may also have such other authority or make such other decisions as may be delegated to the JCC by
written agreement of the Parties.
3.2 JCC Membership and Decisions. Promptly after the Effective Date, each Party shall designate,
in its sole discretion, at least three (3) employees to serve as members of the JCC, each with the requisite
experience and seniority to make decisions on behalf of the Parties with respect to issues falling within the
responsibility of the JCC. The JCC shall meet at least once per Calendar Quarter (in person, or by teleconference,
if requested by a Party), or as otherwise agreed by the Parties. Promptly following formation of the JCC, each
Party shall nominate one of its JCC members as a co-chair of the JCC. The co-chairpersons shall be responsible
for agreeing on and circulating to all members of the JCC (a) an agenda for each meeting, at least [***] before
each meeting, which agenda shall include all agenda items requested by any member. The co-chairpersons shall
also be responsible, on an alternating basis, for preparing reasonably detailed accurate written minutes of each
meeting of the JCC, setting forth in reasonable detail all matters discussed and all decisions made and actions
taken by the JCC at the meeting, within [***] after the meeting. Each Party may invite a reasonable number of
non-voting representatives to attend JCC meetings; provided that such Party provides advance notice to the other
Party of such attendance, and such representatives are bound by the confidentiality provisions of this Agreement.
The JCC shall make decisions or take actions only with the unanimous consent of the Parties with each Party
having collectively one (1) vote. The members of the JCC shall use reasonable efforts to reach agreement on all
matters requiring a decision or action by the JCC. If, despite such efforts, agreement on a particular matter cannot
be reached by the JCC within [***] after the JCC first considers such matter (or such shorter time as may be
reasonable in the circumstances), then either Party shall have the right to refer such issue to the Senior Executives
of each Party for discussion
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
16
and resolution by good faith negotiations during a period of [***]. Any final decision mutually agreed to by the
Senior Executives shall be conclusive and binding on the Parties. If such issue has not been resolved by the
Senior Officers within such [***] period, then:
(a) subject to Section (b) below, Vifor shall have the final decision making authority to the
extent that such particular matter relates to the day-to-day implementation of the Commercialization of the
Licensed Product in the Field in the United States, provided such decisions shall be commercially reasonable and
are in accordance with the Commercialization Plan;
(b) If the JCC cannot reach agreement on approving the Commercialization Plan for the
Licensed Product and including any amendment, modification or update thereto, and if it shall be deadlocked as to
any issue relating thereto, then neither Party shall have final decision-making authority with respect to such failure
to agree or approve, and such dispute shall be resolved in accordance with the procedures set forth in Article 11.
Without limiting the foregoing, the Parties hereby agree that matters explicitly reserved to the consent, approval or
other decision-making authority of one or both Parties, as expressly provided in this Agreement, are outside the
jurisdiction and authority of the JCC or any subcommittee thereof, including amendment, modification or waiver
of compliance with this Agreement.
For clarity, the JCC shall not have any authority to amend, modify or waive the provisions of this Agreement.
3.3 Commercialization Plan. While Vifor shall be responsible for preparing the Commercialization
Plan, the JCC (using appropriate experts within each Party’s organization) shall have the right and be responsible
for discussing and approving the initial Commercialization Plan, which sets forth in reasonable detail the tasks,
timeline and budget for Commercialization activities for the Licensed Product in the Field in the United States,
and for discussing, and approving on an annual basis (or, if needed, on an interim basis) all subsequent updates,
amendments and modifications to the Commercialization Plan, as reasonably needed or appropriate for the
Commercialization of Licensed Product in the Field in the United States consistent with this Agreement. Vifor
(and its applicable Affiliates and Sublicensees) shall conduct Commercialization activities for the Licensed
Product in the Field in the United States in accordance with the approved Commercialization Plan. The
Commercialization Plan shall set forth the tasks to be undertaken by (or on behalf of) Vifor for Commercialization
activities for the Licensed Product in the Field in the United States (including coordination with VFMCFP
promotional activities to FMC US Dialysis Clinics), including budgets for all such Commercialization activities,
the marketing and advertising plans, the specific commitments for the numbers of “Primary Detail Equivalents”
for the Vifor (or VFMCRP, as applicable) sales representatives to conduct on Licensed Product in the applicable
calendar year, and annual projections for Net Sales of Licensed Products in the U.S. for the coming year. From
time to time, either Party may propose amendments or modifications to the Commercialization Plan as needed
based on the progress or results of the Commercialization of Licensed Products, and/or changes in the U.S. market
for Licensed Products in the Field, and in such case the JCC shall review in good
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
17
faith and comment on the proposed amendments or modifications, and if the JCC agrees, shall subject the agreed
amendments or modifications to the JCC for review and comment and, if acceptable, approval.
3.4 Formation of Supply Chain Committee. Within 120 days of the Effective Date, the Parties shall
establish a Supply Chain Committee (the “SCC”), which shall have the responsibilities for overall coordination
and oversight of the manufacturing and supply of Licensed Product for use in sales in the United States under this
Agreement, including (i) coordinating communication and operations regarding manufacturing of Licensed
Products, and resolving supply chain issues; and (ii) exchanging appropriate information about manufacture and
supply chain, both in and outside the United States. The SCC shall be subject to the direct oversight and control
of the JCC. The SCC shall coordinate fully and reasonably with the Supply Chain Committee formed under the
VFMCRP License Agreement.
3.5 SCC Membership, Meetings and Decisions. Within 120 days of the Effective Date, each Party
shall designate, in its sole discretion, two (2) employees to serve as members of the SCC, each with the requisite
experience and seniority to make decisions on behalf of the Parties with respect to the manufacturing, supply
chain and quality matters and issues falling within the responsibility of the SCC. The SCC shall meet at least
once per Calendar Quarter (in person, or by teleconference, if requested by a Party), or as otherwise agreed by the
Parties. Each Party may invite a reasonable number of non-voting representatives to attend SCC meetings;
provided that such Party provides advance notice to the other Party of such attendance, and such representatives
are bound by the confidentiality provisions of this Agreement. The SCC shall elect a Chair, who shall be
responsible for circulating to all members of the SCC (a) an agenda for each meeting, at least [***] before each
meeting, which agenda shall include all agenda items requested by any member, and (b) the accurate minutes of
each meeting of the SCC, setting forth in reasonable detail all matters discussed and all decisions made and
actions taken by the JDC at the meeting, within [***] after the meeting. The SCC shall make decisions or take
actions only with the unanimous consent of its members. The members of the SCC shall use reasonable efforts to
reach agreement on all matters requiring a decision or action by the SCC. If, despite such efforts, agreement on a
particular matter cannot be reached by the SCC within [***] after the SCC first considers such matter (or such
shorter time as may be reasonable in the circumstances), then the matter shall be referred to the JCC for discussion
and resolution in accordance with Section 3.2.
3.6 Discontinuation of Participation on a Committee. For clarity, Cara’s membership in the JCC or
SCC shall be at its sole discretion, as a matter of right and not obligation, for the sole purpose of participation in
governance, decision-making, and information exchange with respect to activities within the jurisdiction of the
Committee. Cara shall have the right to withdraw, at any time, from membership on any of the JCC or SCC upon
[***] prior written notice to Vifor, which notice shall be effective upon the expiration of such [***] period.
Following the issuance of such notice: (a) Cara’s membership in such committee shall be terminated and (b) each
Party shall have the obligation to provide and the right to continue to receive the information it would otherwise
be required to provide and entitled to receive under the Agreement and to participate directly with the other Party
in discussions, reviews and approvals currently allocated to such committee pursuant to this Article 3. If, at any
time following issuance of such a
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
18
withdrawal notice, Cara wishes to resume participation in the committee, Cara shall notify Vifor in writing and,
thereafter, Cara’s representatives to the committee shall be entitled to attend any subsequent meeting of the
committee and to participate in the activities of, and decision-making by, the committee as provided in this
Article 3 as if such withdrawal notice had not been issued by Cara pursuant to this Section 3.8. If the JCC or SCC
is disbanded, then any data and information of the nature intended to be shared within such committee hereunder
shall thereafter be provided by each Party directly to the other Party.
ARTICLE IV
CLINICAL AND REGULATORY MATTERS
4.1 General. It is understood and agreed that Cara retains all rights, in its discretion, with respect to
clinical development of, and activities to gain Regulatory Approvals of, the Licensed Products in the U.S., subject
only to the applicable terms of the VFMCRP License Agreement.
4.2 Regulatory Matters.
(a) As between the Parties, Cara shall be responsible for the regulatory strategy for the
Licensed Product in the United States, and shall keep the JCC reasonably informed of the strategy and progress of
its efforts to obtain Regulatory Approval of Licensed Product in the U.S. for use in the Field.
(b) Cara shall be the holder of all Regulatory Approvals for the Licensed Products in the United
States and shall maintain such Regulatory Approvals. Vifor, or its applicable Affiliate or Sublicensee, shall be
responsible for the registration and maintenance of all NDC codes for Licensed Product for use in the Field in the
United States, at its own cost. Vifor shall keep Cara fully informed of the progress and results of all efforts to
register such NDC codes for Licensed Products in the United States for use in the Field and shall provide to Cara
copies of all relevant regulatory filings and material correspondence relating thereto, and shall provide Cara final
copies of all document reflecting such registered NDC codes.
(c) Information Rights Granted to Licensee. Cara will provide access to all relevant
Licensed Know-How in the United States that are Controlled by Cara and are necessary or reasonably useful to
Vifor in support of Vifor’s preparation for and activities relating to Commerialization of Licensed Product for use
in the Field in the United States in accordance with this Agreement.
(d) FDA Filing of Promotional Materials. As Cara’s agent, Vifor will be responsible for
submission to, and receiving comments from, the FDA for all applicable Promotional Materials. Vifor will keep
Cara fully informed of all such submission and related
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
19
activities. Cara will file general correspondence with the FDA informing them that Cara is appointing Vifor as
agent for the purposes of form 2253.
(e) Other Regulatory Responsibilities. Vifor shall be responsible for all U.S. and state
government price reporting, entering into any required agreements required by the U.S. or state government (e.g.,
Medicaid Drug Rebate Act or VHCA/FSS contracting), and for performing all other filings, registrations and
reporting obligations of the NDC code holder.
4.3 Changes to Applicable Laws. In the event that following the Effective Date there is a change in
the Applicable Laws existing as of the Effective Date with respect to any import or export of pharmaceutical
products from Canada into the US, the Parties shall promptly meet and discuss in good faith the consequences of
such new Applicable Laws or changes to current Applicable Laws as they relate to the Parties’ respective rights
and obligations under the Agreement and endeavor to find a mutual agreement on how to address these
consequences (by amendment to this agreement or otherwise) in a manner designed to preserve each Party’s
respective rights and obligations as such rights and obligations existed prior to the relevant change in Applicable
Laws. In the event that the Parties cannot reach a mutual agreement to address such consequences, after using
reasonable good faith efforts, then Section 11 shall apply to the issue.
4.4 Adverse Drug Events. The Parties will, within 90 days after the Effective Date, finalize and enter
into a reasonable and customary Safety Data Exchange Agreement. Such Safety Data Exchange Agreement will
provide for the exchange by the Parties of any information that a Party becomes aware of in the United States
concerning any adverse event in or involving a research patient or subject or, in the case of non-clinical studies, an
animal in a toxicology study, and the seriousness thereof, whether or not determined to be attributable to the
Compound or any Licensed Product, including any such safety information received by either Party from a Third
Party (subject to receipt of any required consents from such Third Party) (such information, the “Safety Data”),
and such agreement shall be consistent with and coordinate with the similar Safety Data Exchange Agreement
under the VFMCRP License Agreement. Cara will own all of the Safety Data, and the Safety Data Exchange
Agreement will include provisions requiring the establishment of a global safety database owned and maintained
by Cara. It is understood that each Party and its Affiliates or licensees/sublicensees will have the right to disclose
such information if such disclosure is reasonably necessary to comply with applicable laws and regulations and
requirements of Regulatory Authorities within its respective territory with respect to its filings and activities
related to the Compound and the Licensed Products.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
20
ARTICLE V
COMMERCIALIZATION OF LICENSED PRODUCTS
5.1 Responsibility for Commercialization in the United States.
(a) Except as otherwise provided in Sections 2.1 and 2.2, Vifor shall have the responsibility
and obligation, at its sole expense and using Commercially Reasonable Efforts, for the Commercialization (other
than manufacturing, to the extent Cara is supplying Licensed Product under the Supply Agreement) of Licensed
Products for use in the Field throughout the United States, subject to the payment and other relevant obligations
under this Agreement, and subject to VFMCRP’s rights and obligations with respect to FMC US Dialysis Clinics
under the VFMCRP License Agreement. Vifor shall conduct, and is responsible for ensuring that its applicable
Affiliates and Sublicensees conduct, all such responsibilities and activities subject to and in compliance with the
other terms of this Agreement and all Applicable Law. In particular, but without limiting the foregoing, Vifor is
solely responsible, at its sole cost, for the following activities on Licensed Products in the United States: (i)
executing a commercial launch and pre-launch plan for Licensed Product Commercialization in the United States,
which would be reviewed and approved by the JCC and shall be consistent with the Commercialization Plan, (ii)
marketing and promotion activities consistent with the Commercialization Plan; (iii) conducting all Licensed
Product detailing activities in the Field in the U.S., consistent with the “primary detail equivalents” requirements
of the Commercialization Plan; (iv) booking sales and distributing Licensed Product in the U.S. and performing
related activities; (iv) handling all aspects of order processing, invoicing and collection, inventory and receivables;
and (v) providing customer support to all customers and end users in the United States.
5.2 Vifor Responsibility for Promotion to FMC US Dialysis Clinics in U.S. It is understood that,
under the VFMCRP License Agreement, VFMCRP has the rights and responsibility to promote sales of Licensed
Product to FMC US Dialysis Clinics in U.S. for use in the Field. However, the Parties acknowledge that Vifor
shall be compensated, pursuant to the terms of Section 6.4, for the marketing, promotion and sale of Licensed
Products in the Field throughout the U.S. In consideration of such compensation, Vifor hereby agrees that it shall
ensure that the marketing and promotion of Licensed Products to, and the solicitation of orders for Licensed
Products by, FMC US Dialysis Clinics in U.S. shall be conducted by or on behalf of VFMCRP (including by
using Vifor sales representatives, as appropriate) in accordance with the Commercialization Plan, including using
all Commercially Reasonable Efforts to promote sales of Licensed Product to the FMC US Dialysis Clinics and to
obtain orders for purchase of the Licensed Product from the FMC US Dialysis Clinics; such orders shall then be
fulfilled and Licensed Product be supplied and sold by Vifor.
5.3 Marketing Efforts. All marketing, advertising, promotion and order-taking efforts for Licensed
Product by or on behalf of Vifor (and its Affiliates and Sublicensees) shall be consistent with Applicable Law and
the applicable aspects of the Commercialization Plan. Vifor shall be responsible for booking and fulfilling sales
of Licensed Product based on orders received by Vifor (or its Affiliate or its Sublicensee) from customers in the
U.S. (subject to the applicable
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
21
terms of the VFMCRP Agreement). The Parties acknowledge and agree to use Commercially Reasonable Efforts
to work together in good faith to establish appropriate market access for Licensed Product throughout the U.S.,
including Medicare reimbursement (as a part of the Bundle or otherwise) and reimbursement by other federal or
state government payor programs. Cara shall be responsible for leading discussions with federal or state
government payors, including but not limited to CMS, regarding reimbursement for Licensed Product sold in the
U.S, and Cara and Vifor will work collaboratively on all such efforts, and provided that such overall
reimbursement strategy shall be consistent with the strategy in the Commercialization Plan.
5.4 Progress Reports and Reporting. Until the First Commercial Sale of a Licensed Product in the
United States, Cara shall provide to Vifor, within [***] after the end of each [***] period, a reasonable summary
report that provides reasonable summaries of the activities undertaken in the prior [***] to Develop the Licensed
Products and seek Regulatory Approval in the U.S. and the results and progress of all such activities and efforts.
In addition, Vifor shall promptly disclose fully to Cara the discovery, development, invention or creation of any
Improvements and other Vifor Product Technology and shall transfer copies of such Improvements and other
VFCRP Product Technology.
5.5 Global Brand Plan; Promotional Materials. Within [***] after the Effective Date, Vifor will
submit to the JCC, for its review, discussion and approval, a global brand plan, including the key positioning and
messaging strategy, for commercialization of the Licensed Product in the Field (the “Global Brand Plan”), and
Vifor shall update such plan annually. Vifor will provide Cara with copies of all its promotional materials and
information for the Licensed Product for use in the United States, for Cara’s review and written approval prior to
first use. For the avoidance of doubt, if Cara does not provide its approval or consent and/or comments for any
particular promotional material or information for Licensed Product, provided by Vifor for review, within [***]
after receipt for review, then such particular promotional material or information for Licensed Product shall be
deemed approved by Cara. All promotional, advertising or other marketing materials used by Vifor or its Affiliate
or Sublicensee in the US shall comply with all Applicable Law and shall include the Cara corporate logo in a
fashion reasonably acceptable to Cara.
5.6 Trademark Usage. Vifor will Commercialize Licensed Products in the U.S. under the Product
Trademarks and under the trade dress selected by Cara and approved by FDA.
5.7 Manufacture and Supply of Licensed Product to Vifor. No later than 60 days after the Effective
Date of this Agreement, the Parties will discuss and use good faith efforts to agree on the material terms to be
included in the Supply Agreement. No later than 60 days before the filing of the NDA for Licensed Product in the
United States, the Parties will enter into a supply agreement for the commercial supply to Vifor of the Licensed
Products that contains standard and customary terms for commercial supply arrangements (the “Supply
Agreement”), which Supply Agreement will include those material terms on which the Parties have agreed
pursuant to this Section. The supply price for the Licensed Products supplied by Cara to Vifor pursuant to the
Supply Agreement will be equal to Cara’s COGS (calculated according to U.S. GAAP) plus [***] (but without
allocation of idle costs)) (the “Supply Price”) and the term of the Supply Agreement
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
22
will be coterminous with the Term of the Agreement. The Parties acknowledge and agree that they shall discuss
in good faith the best solution for the supply chain, taking into account the interests of both Parties (which likely
shall include the supply of bulk products and the right for Vifor to package and label the Licensed Products for the
United States). The Supply Agreement shall provide that, after the end of the Term (other than due to early
termination of the Agreement), Cara shall continue to supply Vifor with Licensed Product (on a non-exclusive
basis) under the terms of the Supply Agreement to ensure supply continuity until Vifor has either set up its own
manufacturing capacity or the Parties have agreed on terms for continued supply by Cara after the Term. For
clarity, Vifor shall not exercise the manufacturing license under Section 2.2, unless the Parties fail to enter into the
Supply Agreement, or as otherwise provided in the Supply Agreement with respect to failure of Cara to supply on
a timely basis material amounts of Compound or Licensed Product ordered under the Supply Agreement. The
Parties will also enter into a reasonable and customary Quality Agreement. Such Quality Agreement will
establish each Party’s manufacturing activities as well as responsibilities relating to recalls and withdrawals of
Licensed Products.
The Parties acknowledge and agree that the Supply Agreement shall include the terms reasonably
consistent with the following:
(i) Vifor shall be entitled to receive [***] the damage suffered by Vifor for any Late
Delivery (as defined below) of Licensed Product ordered by Vifor in accordance with the Supply Agreement,
unless such delay is caused by an event of Force Majeure. If there is such a Late Delivery of such ordered
Licensed Product, such damage compensation (which shall be Vifor’s exclusive remedy for any such Late
Delivery) shall be equal to: [***]; provided that the total amount of any such compensation shall not in any event
exceed [***] for such amount of Licensed Product that was subject to the Late Deliver. At Vifor’s sole discretion,
Vifor shall be entitled to set-off the referred penalty fee as credit against any outstanding invoices. For clarity, this
non-compensatory penalty fee provision shall be Vifor’s sole and exclusive remedy for any damages or harm due
to a delay in supply under the Supply Agreement; for clarity, notwithstanding the foregoing, the Supply
Agreement will provide Vifor a back-up right to manufacture Licensed Product and/or to obtain Licensed Product
from a Third Party in the event of a Failure of Supply (as defined in the Supply Agreement). As used herein, a
“Late Delivery” means that more than [***] of the amount of Licensed Product ordered by Vifor in a purchase
order submitted by Vifor under the Supply Agreement is actually delivered by (or on behalf of) Cara more than
[***] the date that such ordered Licensed Product was required to be delivered under the Supply Agreement
delivery terms.
(ii) in the event that there is a Failure of Supply under the Supply Agreement, and in
connection therewith Vifor purchases from a Third Party replacement Licensed Product in the amount of Licensed
Product that Cara failed to deliver in such Failure of Supply, then Cara will have the obligation under the Supply
Agreement, to pay to Vifor an amount equal to [***], provided that Vifor has taken all commercially reasonable
efforts to minimize such purchase price from the Third Party for such replacement Licensed Product.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
23
ARTICLE VI
PAYMENTS; PROFIT SHARING AND REPORTS
6.1 Initial License Payment. Within five (5) days upon execution of this Agreement, Vifor shall
make a non-refundable, non-creditable cash payment of one hundred million U.S. dollars (USD $100,000,000) to
Cara.
6.2 Purchase of Cara Equity. As part consideration for the rights granted hereunder, Vifor is
purchasing, for fifty million U.S. dollars (USD $50,000,000), shares of Cara common stock pursuant to the Stock
Purchase Agreement entered into by Cara and Vifor concurrently with this Agreement. The Parties agree that the
rights granted by Cara to Vifor under this Agreement are contingent upon closing of such equity purchase by Vifor
under such Stock Purchase Agreement.
6.3 Milestone Payments. Subject to Section 6.5, Vifor shall pay to Cara the milestone payment
amounts set forth in the tables below within [***] after the achievement of the corresponding milestone event.
Each such payment shall be made by wire transfer of immediately available funds into an account designated by
Cara. Except as set forth in Section 6.5, each such payment is nonrefundable and non-creditable against any other
payments due hereunder. For the avoidance of doubt, each such payment will only be payable one time upon the
occurrence of the indicated event in the United States unless otherwise indicated, and Vifor will not be obligated
to pay any milestone payment more than once unless otherwise indicated.
(a) Approval Milestone.
Milestone Event
Milestone Payments
First Regulatory Approval of the Licensed Product
by the FDA for the DD-CKD indication
Fifty million U.S. dollars (USD $50,000,000), by Vifor
purchasing fifty million U.S. dollars (USD
$50,000,000) in Cara common stock, pursuant to the
terms of the Stock Purchase Agreement entered into by
Cara and Vifor concurrently with this Agreement, at the
purchase price as set in that agreement
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
24
(b) Sales Milestones in the United States.
Milestone Event
Milestone Payment
(i) Annual Net Sales/Non-FMC Customers exceed [***]
in the United States
(ii) Annual Net Sales/Non-FMC Customers exceed [***]
in the United States
[***]
[***]
For the avoidance of doubt, all sales made in the U.S. during a particular Calendar Year, excluding to FMC
US Dialysis Clinics, shall be included in the calculation of Annual Net Sales/Non-FMC Customers.
6.4 Marketing/Distribution Fees to Vifor. In consideration of Vifor’s conduct of the marketing,
promotion, undertaking medical activities, selling and distribution of Licensed Products in the U.S. in accordance
with the Commercialization Plan and the other applicable obligations and terms of this Agreement, Vifor shall be
entitled to retain, from the Net Sales/Non-FMC Customers (i.e., Net Sales generated by sales of Licensed Product
in the Field in the U.S., excluding sales to FMC US Dialysis Clinics) on a Calendar Year basis, an amount (the
“Marketing/Distribution Fee”) determined based on the total Net Sales/Non-FMC Customers during such year,
where such Marketing/Distribution Fee amount, for a particular Calendar Year, is determined according the
following provisions (as such provisions may be adjusted by written agreement of the Parties):
(a) If total Net Sales/Non-FMC Customers in a Calendar Year are less than or equal to [***], the
Marketing/Distribution Fee on such Net Sales/Non-FMC Customers in the Calendar Year (i.e., up to [***] in such
Net Sales) shall be: [***];
(b) If Net Sales/Non-FMC Customers in a Calendar Year exceed [***], the Marketing/Distribution Fee
shall equal: [***], where such percentage is determined according to the following schedule:
Total Net Sales/Non-FMC Customers in Calendar Year
Percentage
[***]
[***]
[***]
[***]
[***]
[***]
[***]
[***]
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
25
The following examples demonstrate the application of the foregoing provisions to assumed amounts of total Net
Sales/Non-FMC Customers in a Calendar Year, to calculate the Marketing/Distribution Fee for such Calendar
Year for such assumed amounts of total Net Sales/Non-FMC Customers:
Example 1:
total Net Sales/Non-FMC Customers in Calendar Year = [***]
Marketing/Distribution Fee = [***]
Example 2:
total Net Sales/Non-FMC Customers in Calendar Year = [***]
Marketing/Distribution Fee = [***]
Example 3:
total Net Sales/Non-FMC Customers in Calendar Year = [***]
Marketing/Distribution Fee = [***]
Example 4:
total Net Sales/Non-FMC Customers in Calendar Year = [***]
Marketing/Distribution Fee = [***]
Example 5:
total Net Sales/Non-FMC Customers in Calendar Year = [***]
Marketing/Distribution Fee = [***]
(c) Quarterly Determination of Marketing Fees. Promptly after the end of each Calendar
Quarter in which Licensed Products are sold in the U.S., the appropriate finance employee of each Party shall
meet (by teleconference) to review the applicable sales records and agree on the total Net Sales/Non-FMC
Customers for such Calendar Quarter. Based on such agreed amount of Net Sales/Non-FMC Customers for such
Calendar Quarter (and including, if applicable, the agreed amounts of Net Sales/Non-FMC Customers for
previous Calendar Quarters in the same Calendar Year), the Parties (through such employees) shall agree on the
amount of Marketing/Distribution Fee for such Calendar Quarter, which amount shall be equal to: [***]. Each
such Marketing/Distribution Fee amount for a particular Calendar Quarter shall be: (i) agreed to by the Parties no
later than [***] after the end of each such Calendar Quarter, (ii) used in determining Non-FMC Net Profit under
Section 6.6 below, and (iii) retained by Vifor out of the Net Sales/Non-FMC Customers for the applicable
Calendar Quarter.
6.5 Vifor Payment of Share of Net Profits to VFMCRP and Cara. Subject to Section 6.7 (if
applicable), for all sales of Licensed Products to FMC Dialysis Clinics, during a Calendar Year, Vifor shall pay to
VFMCRP 50% of the Net Profit (as such term is defined and calculated in accordance with Section 6.6 of the
VFMCRP Agreement, such Net Profit amount after the deduction in the following proviso) resulting from such
sales to FMC Dialysis Clinics,
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
26
and shall pay to Cara 50% of such Net Profit in accordance with the payment terms of the VFMCRP Agreement
(with Vifor performing payment on behalf of Cara, and such Net Profit amount after the deduction in the
following proviso), provided that prior to any such payment of the share of Net Profit owed, Vifor shall be able to
deduct, from such amount of Net Profit, an amount equal to [***] of the actual Net Sales of Licensed Products to
FMC Dialysis Clinics that was used in calculating the applicable Net Profit amount.
6.6 Vifor Payment of Share of Non-FMC Net Profit to Cara. Subject to Section 6.7 (if applicable),
for all sales of Licensed Products to customers in the U.S. hereunder, other than sales to FMC Dialysis Clinics
(compensation for which is addressed in the VFMCRP License Agreement), during a Calendar Quarter, Vifor
shall pay to Cara 60% of the Non-FMC Net Profit resulting from such sales. Such share of Non-FMC Net Profit
shall be paid to on a Calendar Quarter basis, according to the following:
(a) Quarterly Payments to Cara. No later than [***] after the end of each Calendar Quarter
in which Licensed Products are sold in the U.S, the Parties shall meet and agree on the amount of Non-FMC Net
Profit for such Calendar Quarter. Such Non-FMC Net Profit amount shall be equal to: [***]. By the date [***]
after the end of each such Calendar Quarter, Vifor shall pay to Cara an amount equal sixty percent (60%) of the
Non-FMC Net Profit for such Calendar Quarter, as determined in the foregoing.
6.7 [***]
6.8 Reports. Within [***] after the end of each Calendar Quarter during which there are sales of
Licensed Product in the United States, Vifor shall submit to Cara a report listing the total Net Sales (including
listing the deductions taken from gross sales to arrive at Net Sales) for Licensed Product in the United States for
such Calendar Quarter and the total Net Sales/Non-FMC Customers within such Net Sales.
6.9 Books and Records; Audit Rights.
(a) Vifor shall keep and shall cause its applicable Affiliates and Sublicensees to keep complete,
true and accurate books and records in accordance with Accounting Standards in sufficient detail to determine the
amounts due to Cara under Section 6.5.
(b) Cara shall have the right, once annually at its own expense, to have an independent,
certified public accounting firm of nationally recognized standing, selected by Cara and reasonably acceptable to
Vifor, review (i) the applicable records of Vifor and such Affiliates and Sublicensees, in the location(s) where
such records are maintained by the audited party, upon reasonable notice (which shall be no less than [***] prior
notice) and during regular business hours and under obligations of confidence, for the sole purpose of verifying
the accuracy of, and determine any discrepancies in, the amounts paid and payable to Cara under this Agreement.
The report of such accounting firm shall be limited to: a certificate stating whether any report made or invoice or
payment submitted by Vifor during such period is accurate or inaccurate, the actual amounts of payments owed
under this Agreement, and the amount of any Net Sales, Net Profit or
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
27
other payment discrepancy, and a reasonable summary of the factual basis for any such discrepancy. Vifor shall
receive a copy of each such report concurrently with receipt by Cara. Should such inspection lead to the
discovery of a discrepancy to Cara’s detriment, Vifor shall pay the amount of the within [***] after its receipt
from the accounting firm of the certificate showing the amount of the discrepancy. Cara shall pay the full cost of
the review unless the audit determined an underpayment of amounts owed hereunder, for the inspected period,
that is greater than [***] of the amount actually due for the period audited, in which case Vifor shall pay the costs
charged by such accounting firm for such review. Any overpayment by Vifor revealed by an inspection shall be
creditable against future payments of amounts owed to Cara under this Article 6.
6.10 Taxes. All payments under or in connection with this Agreement shall be inclusive of any taxes,
and each Party shall be responsible for its own taxes assessed by a tax or other authority except as otherwise set
forth in this Agreement. “Taxes” mean all present and future taxes, import deposits assessments, and other
governmental charges and any related penalties and interest not attributable to the fault or delay of a Party.
6.11 Payment Method. Except as otherwise provided herein, all payments due to a Party hereunder
shall be due and payable on the date specified to be owed, and shall be paid via a bank wire transfer to such bank
account as such Party shall designate.
6.12 Late Payments. Any payment not made within [***] after the due date for such payment pursuant
to the terms of this Agreement shall bear interest at a rate of the thirty-day U.S. dollar LIBOR rate effective for the
date that payment was due (as published in The Wall Street Journal, Eastern Edition) plus [***]. Calculation of
interest will be made for the exact number of days the payment was past due based on a year of 360 days (actual
days/360).
ARTICLE VII
PATENT MATTERS
7.1 Ownership.
(a) As between the Parties, each Party shall exclusively own all Know-How (including
Inventions), Patent Rights, and other intellectual property rights conceived, created, made, discovered, generated
or invented solely by employees, agents and consultants of such Party or its Affiliates either prior to the Effective
Date, or thereafter either pursuant activities conducted independent of, or under and in connection with this
Agreement, but in each case subject to the licenses granted to the other Party under Article 2, as applicable.
(b) The Parties will jointly own (i.e., each Party shall own an undivided one-half interest in and
to) the entire rights, title and interests in and to all Joint Technology (except as may otherwise be agreed by the
Parties under Section 7.2). The Parties will promptly disclose to
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
28
each other any Joint Technology conceived or reduced to practice no later than [***] after the Intellectual Property
or Legal Department of the Party receives a written disclosure of such conception or reduction to practice. Except
to the extent either Party is restricted by the licenses granted to the other Party under this Agreement, each Party
shall be entitled to practice, license, assign, and otherwise exploit its interests in the Joint Technology without a
duty of accounting to or seeking consent from the other Party.
(c) The Parties intend that this Agreement is a joint research agreement under the provisions of
pre-AIA 35 U.S.C. 103(c) and AIA 35 U.S.C. 102(c). The Parties further agree to cooperate and to take
reasonable actions to maximize the protections available under the safe harbor provisions of 35 U.S.C. 100 et seq.
for U.S. Patent Rights.
7.2 Prosecution and Maintenance of Joint Patents. With respect to any Inventions in the Joint
Know-How, Cara and Vifor shall discuss reasonably and endeavor to agree on the Prosecution of any Joint Patents
claiming potentially patentable Inventions within the Joint Know-How. All such Joint Patents shall be jointly-
owned by the Parties (i.e., each Party shall own [***] in and to the entire rights, title and interests in and to the
Joint Patents), absent a written agreement of the Parties otherwise, in appropriate countries throughout the world.
Absent agreement of the Parties otherwise, Vifor shall be responsible for the Prosecution of any such Joint
Patents in the United States, at its sole expense, and Cara shall be responsible for the Prosecution of any such Joint
Patents in countries and jurisdictions outside the United States, at its sole expense, provided that Cara and Vifor
shall discuss reasonably and endeavor to agree on all filings and responses in the United States. Each Party shall
keep the other fully informed regarding the filing, prosecution, defense and maintenance of the Joint Patents being
prosecuted by such Party (including in any case, a detailed update at least once per Calendar Quarter). If
reasonably requested by either Party, the other Party shall provide reasonable assistance and support to such Party
in the above Prosecution and Maintenance, provided that any reasonable out-of-pocket costs of such assistance
(including appearances at any compelled hearings or preparation or attendance at discovery responses) shall be
paid for by the Party providing assistance.
7.3 Prosecution and Maintenance of Licensed Patent Rights. Cara shall have the sole right (except
as otherwise provided below and be responsible for the Prosecution of the Licensed Patent Rights in the United
States, at its own expense (except as provided below) and at its reasonable discretion. Vifor (or VFMCRP,
according to their separate agreement) shall reimburse Cara for [***] of annual maintenance fee costs for
Licensed Patents in the United States, based on invoices submitted. Cara shall keep Vifor fully informed
regarding the filing, prosecution, defense and maintenance of such Licensed Patent Rights (including in any case,
a detailed update at least once per Calendar Year). If reasonably requested by Cara, Vifor shall provide reasonable
assistance and support to Cara in the above Prosecution and Maintenance.
7.4 Vifor’s rights. If Cara decides that it shall no longer continue the Prosecution of a particular
Licensed Patent Right in the United States during the Term, then it will promptly advise Vifor of this decision at
least [***] in advance of any Prosecution filing or response deadline that would result in the loss of such Licensed
Patent Right. Thereafter Vifor (or VFMCRP, in accordance with their separate agreement) may, upon written
notice to Cara, assume the
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
29
Prosecution of such Licensed Patent Right in the United States at its sole expense and discretion. Upon such
written notice, Cara will grant to Vifor (or VFMCRP, as applicable) the right to conduct the Prosecution, on Cara’s
behalf, of such Licensed Patent Right, and shall transfer copies of all documents relating directly to Cara’s prior
Prosecution of same, at Vifor’s cost. Following such grant, such Licensed Patent Right will remained licensed to
Vifor under the license grants hereunder. Cara will reasonably cooperate, upon Vifor’s reasonable request and at
its expense, in connection with the prosecution of all patent applications included within such Licensed Patent
Right, including providing (at Vifor’s expense) reasonable and related technical expertise, technical data,
prosecution history and other relevant expertise, to the extent required for Vifor to conduct such Prosecution. For
clarity, the foregoing is subject to the rights of VFMCRP under Section 7.4 of the VFMCRP Agreement
7.5 Patent Term Extensions. The Party prosecuting a Licensed Patent Right or Joint Patent will be
solely responsible for making all decisions regarding patent term extensions, including supplementary protection
certificates and any other extensions, that are now available or become available in the future, that are applicable
to such Licensed Patent Right or jointly-owned Patent Right and that become available directly as a result of the
Regulatory Approval of a Licensed Product by Vifor or any of its Affiliates or sublicensees; provided that the
prosecuting Party will consult the other Party with respect to such decisions and will consider the comments and
concerns of the other Party in good faith, and further provided that, Cara will consult with Vifor with respect to
such decisions (including selection of the patent(s) for patent term extension, supplementary protection certificates
or any other extensions) as a result of the first Regulatory Approval in territory of any product containing the
Compound, even if outside the Field and even if not by Vifor or any of its Affiliates or sublicensees and that the
patent(s) selected for patent term extension, supplementary protection certificates or any other extensions in a
territory within the United States shall Cover the Licensed Product.
7.6 Third Party Infringement.
(a) Notice. Each Party shall promptly report in writing to the other Party any known or
reasonably suspected (i) infringement of any Licensed Patent Right, Vifor Product Technology Patent or Joint
Patent, or (ii) unauthorized use or misappropriation of any of the Licensed Know-How or Joint Know-How in the
United States, of which such Party becomes aware and shall provide the other Party with all material evidence in
its possession regarding such known or suspected infringement or unauthorized or use misappopriation (to the
extent able to be disclosed). Vifor and Cara shall thereafter consult and cooperate to discuss and seek to
determine a course of action, which may include (subject to the following provisions of this Section 7.6) the
commencement of legal action by either or both of Cara and Vifor to terminate any Infringement of the Licensed
Patent Rights, Vifor Product Technology Patent or Joint Patent.
(b) Initial Right to Enforce. Except as may be otherwise agreed by the Parties in writing with
respect to a particular Field Infringement (as defined below), Cara shall have the first right, but not the obligation,
to initiate a lawsuit or take other reasonable action to enforce the applicable Licensed Patent Rights or Joint Patent
with respect to an infringement by a Third Party by making, using, importing or selling in the United States a
product that contains a Compound or
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
30
otherwise competes or likely would compete with Licensed Product or a misappropriation or other violation of the
Licensed Know-How (in each case, a “Field Infringement”). Cara shall consult with Vifor and give good faith
consideration to any reasonable objection from Vifor regarding Cara’s proposed course of action prior to initiating
any such lawsuit or other enforcement action asserting any such Licensed Patent Rights or Joint Patent against a
Field Infringement in the United States. Vifor shall reasonably cooperate in the prosecution of any such suit or
other action against a Field Infringement as may be reasonably requested by Cara, including joining any action as
party-plaintiff at Cara’s request if needed for Cara to have standing to bring such suit; provided, that Cara shall
promptly reimburse all out-of-pocket expenses (including reasonable counsel fees and expenses) incurred at
Cara’s request and actually incurred by Vifor in connection with such cooperation. Cara shall keep Vifor
reasonably informed regarding the prosecution and results of any such enforcement suit or action (including in
any case, a detailed update at least once per Calendar Quarter). For clarity, the foregoing is subject to the rights of
VFMCRP under Section 7.6 of the VFMCRP Agreement.
(c) ANDA Para IV Actions. In case of an ANDA Para IV notification (under the Drug Price
Competition and Patent Term Restoration Act of 1984) with respect to a generic product of Licensed Product that
provides such a notification as to a Licensed Patent that claims a Licensed Product, it shall be Cara’s
responsibility to initiate the law suit (within [***] following the ANDA Para IV notification date) if any Licensed
Patent Rights, Vifor Product Technology Patent or Joint Patent listed in the Orange Book would be infringed or
suspected to be infringed by the Third Party that submits such ANDA notification. Cara and Vifor shall
immediately consult and cooperate to seek to determine a course of action, which may include the commencement
of legal action by Cara (and/or Vifor, if agreed by Cara in writing) to terminate any Infringement of the Licensed
Patent Rights, Vifor Product Technology Patent or Joint Patent by such ANDA filer, provided that Cara shall have
control of any such action. Vifor shall actively provide full cooperate in the prosecution of any such ANDA Para
IV suit or legal action. The Parties shall share all out-of-pocket costs and expenses of conducting such suits or
actions (including all the pre-ANDA legal costs (ANDA dispute preparation), ANDA legal costs (costs associated
with the ANDA litigation law firm (litigation counsel), appointed experts, experts reports, analytical tests) and full
fact discovery costs, with Cara bearing [***] of such costs and expenses and Vifor bearing [***] thereof. Cara
and Vifor shall create a Joint ANDA Para IV Defense team to coordinate the selection of the Patent Litigation
Firm (litigation counsel) and coordinate the defense strategy with the appointed Patent Litigation Firm including
patent settlement discussions. Vifor and Cara shall bear their own respective internal and out-of-pocket costs
incurred by their activities and support provided under the Joint ANDA Para IV Defense team and any such
ANDA suit preparation activities. The Joint ANDA Para IV Defense team shall be created by the Parties no later
than [***] after the first FDA marketing approval of Licensed Product.
(d) Step-In Right. With the exception of the ANDA Para IV disputes, if Cara does not initiate
a lawsuit or take other reasonable action intended to cause a Field Infringement of Licensed Patent Rights or
jointly-owned Patent Rights occurring in the United States to cease and obtain remedies for the harm resulting
therefrom, pursuant to Section 7.6(b), within [***] of actual notice provided under Section 7.6(a) with respect to
any such Field Infringement, then Vifor shall have the right, but not the obligation, to initiate such lawsuit or take
such other action, after
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
31
providing [***] notice to Cara and giving good faith consideration to the Cara’s reason(s) for not initiating a
lawsuit or taking other action. For this purpose, Cara shall cooperate in the prosecution of such suit as may be
reasonably requested by Vifor, including joining any action as party-plaintiff at Vifor’s request if required for
Vifor to have standing to bring such suit; provided, that Vifor shall promptly reimburse all out-of-pocket expenses
(including reasonable counsel fees and expenses) of Cara incurred in connection with such cooperation.
(e) Conduct of Certain Actions; Costs. The Party initiating legal action against a Field
Infringement shall have the sole and exclusive right to select counsel for any suit initiated by it pursuant to
Section 7.4(b) or 7.4(c) (the “Initiating Party”). The Initiating Party shall bear its own internal and out-of-pocket
costs incurred in any such legal action, including the fees and expenses of the counsel selected by it. The other
Party shall have the right to participate and be represented in any such legal action (in cases where such other
Party has standing) by its own counsel at its own expense, provided that the Initiating Party shall in any event
have the final say about the strategy and decisions in the suit and any settlement.
(f) Recoveries. Any amount recovered in any action or settlement of any such action against a
Field Infringement in the United States shall be allocated first to reimburse on a pro-rata basis each Party’s actual
out-of-pocket costs (including reasonable attorneys’ fees and expenses) incurred in such action and any amount
remaining shall be allocated as follows: (i) if Cara is the Initiating Party, then Cara shall provide to Vifor [***] of
the net amount remaining, and (ii) if Vifor is the Initiating Party, with respect to any remaining portion of such
recovery, then Vifor shall pay Cara [***] of such net amounts remaining. For clarity, Cara shall retain any
amounts it recovers from enforcing all Cara Patent Rights, the Joint Patents or its rights in any Cara Know-How
outside the United States, and Cara retains the sole and exclusive rights to enforce Cara Patent Rights, the Joint
Patents or its rights in any Cara Know-How outside the United States, subject only to the applicable terms of the
VFMCRP Agreement.
(g) Responsibility for Third Party Licenses. At any time during the Term, if Cara believes it
is necessary or advisable to seek to acquire or obtain a license from any Third Party in order to avoid infringement
in the United States of Patents owned or controlled by such Third Party during the exercise of the rights herein
granted, whether or not there has been the institution of any infringement claim, Cara will have the sole right, but
not the obligation, to negotiate and acquire or obtain a license under such Patents from such Third Party. Cara will
be responsible for the amounts payable to such Third Party assignor, licensor or grantor of rights pursuant to such
agreement to the extent such payments arise out of or relate to the research, Development, use, import, offer for
sale or sale of the Licensed Products (including Combination Products and Bundled Products) in the United States
by Vifor or its Affiliates or Sublicensee. This section will not be interpreted as placing on either Party a duty of
inquiry regarding Third Party intellectual property rights. Each Party will keep the other Party informed of the
status of any Third Party claim of infringement.
7.7 Enforcement of Product Trademark. Cara shall have the sole initial rights to initiate lawsuits
and/or take any other action to enforce the Product Trademark against any infringement, dilution or other violation
(a “Mark Infringement”) anywhere in the world. Vifor
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
32
shall reasonably cooperate in the prosecution of any such suit or other action brought by Cara against such Mark
Infringement as may be reasonably requested by Cara, including joining any action as party-plaintiff at Cara’s
request if needed for Cara to have standing to bring such suit; provided, that Cara shall promptly reimburse all
out-of-pocket expenses (including reasonable counsel fees and expenses) incurred at Cara’s request and actually
incurred by Vifor in connection with such cooperation. Cara shall keep Vifor reasonably informed regarding the
prosecution and results of any such enforcement suit. If Cara does not initiate a lawsuit or take other reasonable
action intended to cause a Mark Infringement in the United States to cease and obtain remedies for the harm
resulting therefrom, pursuant to this Section 7.5, within [***] of actual notice with respect to any such Mark
Infringement, then Vifor shall have the right, but not the obligation, to initiate such lawsuit or take such other
action, after providing [***] notice to Cara and giving good faith consideration to the Cara’s reason(s) for not
initiating a lawsuit or taking other action, and shall keep Cara reasonably informed of the progress and results of
such action. The Party that conducts an action against a Mark Infringement shall retain any recoveries (including
by settlement) of such action.
7.8 Patent Invalidity Claim.
(a) Each Party shall promptly notify the other in the event of any legal or administrative action
by any Third Party against a Licensed Patent Right or Joint Patent of which it becomes aware challenging the
validity or enforceability thereof, including any opposition, post-grant review, inter-partes review, nullity,
revocation, reexamination, third party observations, or compulsory license proceeding.
(b) Cara shall have the first right, but not the obligation, at its expense, to defend against any
such action relating to a Licensed Patent Right or Joint Patent in the United States. In such case, Cara shall keep
Vifor reasonably informed of the progress and results of such action and defense, including providing copies of all
substantive filings and orders in any such action. If Cara does not initiate a defense against any such action
involving a Licensed Patent Right or Joint Patent within [***] following such notice, then Vifor shall have the
right, but not the obligation, to defend such action at its expense, provided that Vifor shall keep Cara regularly
informed of all actions taken and results of such defense.
7.9 Patent Marking. Vifor shall ensure that all Licensed Products sold in the United States are
appropriately marked to indicate all relevant Patent Rights claiming the Licensed Product or its use, in accordance
with Applicable Law.
ARTICLE VIII
CONFIDENTIALITY AND PUBLICATION
8.1 Nondisclosure and Limited Use Obligations. Each of the Parties agree that during the Term, and
for a period of [***] thereafter, each Party and its Affiliates (and, with respect
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
33
to Vifor, its Sublicensees) shall (a) maintain in confidence the Confidential Information of the other Party, using
efforts to protect such information that are at least as strong as those that such Party uses to maintains its own
confidential information (but in no event less than reasonable efforts), (b) not disclose such Confidential
Information to any Third Party without the prior written consent of the other Party, or as otherwise expressly
permitted in this Agreement, and (c) not use such Confidential Information for any purpose except those permitted
by this Agreement.
8.2 Authorized Disclosure. Notwithstanding anything to the contrary in this Article 8, a Party may
disclose particular Confidential Information of the other Party to the extent such disclosure is reasonably
necessary in the following instances:
(a) Prosecuting, enforcing or defending applicable Patent Rights that are the subject of this
Agreement in accordance with Article 7 of this Agreement;
(b) making filings covering Licensed Products with Regulatory Authorities in accordance with
this Agreement;
(c) complying with Applicable Law (including securities laws and the requirements of the
securities exchange on which Cara’s stock is traded) or submitting information to tax or other Governmental
Authorities; provided that if a Party is required by Law to make any public disclosure of Confidential Information
of the other Party, to the extent it may legally do so, it will give reasonable advance notice to the other Party of
such disclosure and will use its reasonable efforts to secure confidential treatment of such Confidential
Information prior to its disclosure (whether through protective orders or otherwise);
(d) to its Affiliates, and to employees, accountants, and lawyers, on a need to know basis, each
of whom prior to disclosure must be subject to appropriate obligations of confidentiality and non-use equivalent in
scope to those set forth in this ARTICLE VIII and that are of reasonable duration in view of the circumstances of
the disclosure; or
(e) to the extent mutually agreed to in writing by the Parties.
8.3 Press Releases and Other Permitted Disclosures.
(a) Cara and Vifor each agree not to disclose any of the terms and conditions of this
Agreement to any Third Party, except as described below in this Section 8.3. The Parties will cooperate in the
release of a mutually agreed upon press release, within thirty (30) days following execution of the Agreement,
announcing the collaboration contemplated by this Agreement as soon as practicable after the Effective Date.
Subject to the other provisions of this Agreement, no other press release, public statement or public disclosure
concerning the existence or terms of this Agreement shall be made, either directly or indirectly, by either Party,
without first obtaining the written approval of the other Party, such approval not to be unreasonably withheld;
provided, however, the foregoing limitation does not apply to the extent a press release, public statement or public
disclosure contains information that was previously disclosed publicly.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
34
(b) Either Party may disclose the existence and terms of this Agreement in confidence to its
attorneys, professional accountants, auditors or other professional advisors, under an agreement with terms of
confidentiality and non-use no less rigorous than the terms contained in this Agreement (or pursuant to ethical
requirements of the professional that require the recipient to preserve the confidentiality of the disclosed
information).
(c) Notwithstanding the foregoing provisions of this ARTICLE VIII, a Party may disclose the
existence and terms of this Agreement (however, with it seeking to exclude, as far as legally possible, any and all
technical or financial information and terms contained within the Agreement, including applicable information in
Exhibits hereto, to the extent such information and terms may be redacted under a Confidential Treatment Request
or similar application under Applicable Law), or the Parties’ activities under this Agreement, where such
disclosure is required, as determined by the legal counsel of the disclosing Party, by Applicable Law, by
applicable stock exchange regulation or by order or other ruling of a competent court, although, to the extent
practicable, the other Party shall be given [***] advance notice of any such legally required disclosure to provide
comments to the disclosing Party, and the disclosing Party shall use its good faith diligent efforts to reasonably
consider such comments provided by such other Party on the proposed disclosure and seek to further redact the
information and terms contained within the Agreement in a consistent manner, to the extent such redactions are
permitted under Applicable Law. In case either Party is obliged to publish the Agreement as a “material
agreement” in accordance with the U.S. stock exchange regulations (“SEC Filing”), the Agreement shall be
redacted by the filing Party as far as legally possible, as determined reasonably by the filing Party’s legal counsel,
and the filing Party shall cooperate with the other Party reasonably in advance to such SEC Filing to enable the
other Party to review and comment on the scope of such redaction, all in accordance with the requirements found
in the immediately preceding sentence.
8.4 Data Security. During the Term of this Agreement, each Party will maintain (and, as applicable,
cause its Affiliates to maintain) reasonable environmental, safety and facility procedures, data security procedures
and other safeguards against the disclosure, destruction, loss, or alteration of the other Party’s Confidential
Information in the possession of such Party or its Affiliates, which efforts shall in any event be no less rigorous
than those maintained by such Party for its own Confidential Information of a similar nature.
ARTICLE IX
REPRESENTATIONS AND WARRANTIES; INDEMNIFICATION
9.1 Representations and Warranties of the Parties. Vifor and Cara each represent, warrant and
covenant to each other Party that as of the Effective Date:
(a) it has the authority and right to enter into and perform this Agreement and grant the rights
embodied herein, and it is not aware of any legal impediment that could inhibit its ability to perform its
obligations under this Agreement;
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
35
(b) its execution, delivery and performance of this Agreement does not constitute a breach of
any order, judgment, agreement or instrument to which it is a party or is otherwise bound;
(c) such Party is a corporation duly organized, validly existing and in good standing under the
laws of the state or other jurisdiction of incorporation or formation and has full corporate power and authority to
enter into this Agreement and to carry out the provisions hereof except where failure to be in good standing would
not materially impact the Party’s ability to meet its obligations hereunder;
(d) as of the Effective Date, no consent of any Third Party is required for such Party to grant
the licenses and rights granted to the other Party under this Agreement or to perform its obligations hereunder;
(e) all of such Party’s personnel and employees and Third Parties, including agents and
consultants, hired by such Party and involved in the Development, manufacture or Commercialization of
Compounds or Licensed Products hereunder are, or when hired will be, under a written agreement whereby they
have presently assigned to such Party any right they may have in any Invention first invented, discovered, made,
conceived or reduced to practice in the conduct of activities pursuant to the Global Development Program or in
the Development, manufacture or Commercialization of any of such Compounds or Licensed Products, and all
intellectual property rights therein;
(f) it will not, after the Effective Date, enter into any written or oral contractual obligation with
any Third Party that would conflict with the obligations that arise on its part out of this Agreement; and
(g) no consent, approval, order or authorization of, or registration, qualification, designation,
declaration or filing with, any federal, state or local governmental authority is required on the part of such Party in
connection with the valid execution, delivery and performance of this Agreement.
(h) In performing under this Agreement, it and its Affiliates agree to comply with all applicable
anti-corruption laws, including the Foreign Corrupt Practices Act of 1977, as amended from time to time
(“FCPA”); the anti-corruption laws of the Territory; and all laws enacted to implement the Organization for
Economic Co-operation and Development Convention on Combating Bribery of Foreign Officials in International
Business Transactions;
(i) It is not aware of any government official or Other Covered Party having any financial
interest in the subject matter of this Agreement or in any way personally benefiting, directly or indirectly, from
this Agreement.
(j) No political contributions or charitable donations will be given, offered, promised or paid
by a Party (or its Affiliate) at the request of any Government Official or Other
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
36
Covered Party that is in any way related to this Agreement or any activity conducted pursuant to this Agreement
by such Party (or its Affiliate), without the other Party’s prior written approval.
(k) It has not been debarred by the FDA, is not the subject of a conviction described in Section
306 of the FD&C Act, and is not subject to any similar sanction of other Governmental Authorities outside the
Territory, and neither it nor any of its Affiliates has used, in any capacity, any person who either has been debarred
by the FDA, is the subject of a conviction described in Section 306 of the FD&C Act or is subject to any such
similar sanction. Neither Party will engage, in any capacity in connection with this Agreement or any ancillary
agreements, any person who either has been debarred by the FDA, is the subject of a conviction described in
Section 306 of the FD&C Act or is subject to any such similar sanction. Each Party will inform the other Party in
writing promptly if it or any person engaged by it or any of its Affiliates who is performing services under this
Agreement, or any ancillary agreements, is debarred or is the subject of a conviction described in Section 306 of
the FD&C Act, or if any action, suit, claim, investigation or legal or administrative proceeding is pending or, to
each Party’s knowledge, is threatened, relating to the debarment or conviction of a Party, any of its Affiliates or
any such person performing services hereunder or thereunder.
(l) It has been and will, for the Term, be in compliance with all applicable global trade laws
(including the Global Trade Control Laws), including those related to import controls, export controls or
economic sanctions, and it will cause each of its Affiliates to remain in compliance with the same during the
Term. Neither Party, nor any of its Affiliates or its or their respective directors, officers, employees, agents or
representatives is, or in the last five years was, a Restricted Party. Neither Licensee nor its Affiliates or
sublicensees will export, transfer, or sell the Licensed Product (i) to any country or territory that is subject to
comprehensive economic sanctions administered by OFAC, which currently includes Cuba, Iran, North Korea,
Sudan and Syria, as well the Crimea region of Ukraine, unless the sale of the product would be permissible if
Licensee, its Affiliates or sublicensees were subject to OFAC’s jurisdiction, (ii) to any Restricted Party unless the
sale of the product would be permissible if Licensee, its Affiliates or sublicensees was subject to OFAC’s
jurisdiction or (iii) in such a manner that would violate the Global Trade Control Laws.
(m) It will comply with all Applicable Law in performing its activities hereunder.
9.2 Representations and Warranties of Cara. Cara represents, warrants and covenants to Vifor, as
of the Effective Date, that:
(a) the existing Licensed Patents Rights and Product Trademarks have been duly filed in the
United States;
(b) all applicable filing, maintenance and other fees have been timely paid for all of the
Licensed Patent Rights and the Product Trademarks, including all issued patents or registered trademarks, and, to
Cara’s Knowledge, all of the Licensed Patent Rights and Product Trademarks that are issued patents or registered
trademarks are in full force and effect;
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
37
(c) (i) there is no pending or, to Cara’s Knowledge, threatened (in writing) re-examination,
opposition, interference, inter partes review or claim challenging the inventorship, ownership, validity,
enforceability or patentability of the Licensed Patent Rights owned by Cara or other litigation or proceeding
relating to any of the Licensed Patents Rights owned by Cara and (ii) to Cara’s Knowledge, there is no pending or
threatened (in writing) re-examination, opposition, interference, inter partes review or claim challenging the
inventorship, ownership, validity, enforceability or patentability of the Licensed Patent Rights in-licensed by Cara
or other litigation or proceeding relating to any of the Licensed Patent Rights in-licensed to Cara;
(d) to Cara’s Knowledge, the making, having made, selling, offering for sale, using or
importing of a Compound or Licensed Product (as currently existing) in the United States does not infringe any
valid Patent Right or other intellectual property rights of any Third Party in the United States;
(e) Cara has received no written notice of any claim that a patent or trade secret owned or
controlled by a Third Party is or would be infringed or misappropriated by the Development, manufacture, use,
sale, offer or sale, import or other Commercialization of the Licensed Compound or the Licensed Products in the
U.S.;
(f) to Cara’s Knowledge, all inventors of any Inventions that are claimed by the Licensed
Patent Rights have assigned their entire right, title and interest in and to such Inventions and the corresponding
Licensed Patent Rights to Cara (or to its licensor);
(g) Cara has not assigned, transferred, conveyed, granted rights to a Third Party or otherwise
encumbered its right, title and interest in Cara Product Technology in a manner inconsistent with the license rights
granted to Vifor under this Agreement;
(h) Cara is the legal and beneficial owner of the Licensed Patent Rights existing as of the
Effective Date, free and clear of all liens, charges and encumbrances (other than encumbrances that do not breach
the warranty in Section 9.2(g));
(i) to Cara’s Knowledge, the conception, development and reduction to practice of the
material Cara Product Technology has not constituted or involved the misappropriation of Know-How of any
Third Party or the infringement of the Patent Rights of any Third Party;
(j) Cara has not received any written notice of any unauthorized use, invalidity, infringement,
or misappropriation of any material Cara Product Technology by any person or entity, including any current or
former employee or consultant of Cara;
(k) Cara has no Knowledge of any information that it believes would render unenforceable or
unpatentable any claim in the Licensed Patent Rights existing as of the Effective Date.
(l) the research, Development and manufacture of the Licensed Product conducted by Cara or
its Affiliates has been conducted in material compliance with Applicable
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
38
Law, and to Cara’s Knowledge, the research, Development and manufacture of the Licensed Product conducted by
Cara’s Third Party contractors has been conducted in material compliance with Applicable Law.
As used herein, “Knowledge” means that, based on the actual knowledge of the executive officers
(including General Counsel and the Head of IP) of Cara, such officers are not aware of facts that make the
statement, by which the term Knowledge is qualified, materially untrue.
9.3 Representations and Warranties of Vifor. Vifor represents, warrants and covenants to Cara that:
(a) as of the Effective Date, it and its Affiliates do not have any ongoing program to identify,
research or Develop any drug products that may be competitive with Licensed Product.
9.4 No Other Warranties. EXCEPT AS EXPRESSLY SET FORTH IN SECTIONS 9.1 – 9.3,
NEITHER OF THE PARTIES MAKES ANY REPRESENTATIONS OR EXTENDS ANY WARRANTIES OF
ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING AND PARTICULARLY THAT THE
INTELLECTUAL PROPERTY LICENSED HEREUNDER IS NON-INFRINGING OR THAT PRODUCT(S)
WILL BE SUCCESSFULLY DEVELOPED HEREUNDER, AND FURTHER, THE PARTIES HEREBY
DISCLAIM ALL OTHER WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTIES OF
TITLE, NON-INFRINGEMENT, MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE.
9.5 Indemnification by Vifor. Vifor shall indemnify, hold harmless and defend Cara, its Affiliates
and all of their respective officers, directors, employees, agents, licensors and shareholders (collectively, the
“Cara Indemnitees”) from and against any and all losses, damages, liabilities, judgments, fines, amounts paid in
settlement, expenses and costs of defense (including reasonable attorneys’ fees) (“Losses”) resulting from any
allegation, demand, claim, suit, action or proceeding brought or initiated by a Third Party (each a “Third Party
Claim”) against any Cara Indemnitee to the extent arising out of (a) a Default by Vifor or its Affiliates; (b) the
gross negligence or willful misconduct of, or violation of Applicable Law by, Vifor or its Affiliate or Sublicensee;
or (c) the marketing, promotion, offer for sale, sale or use or other Commercialization of any Compound or
Licensed Product by, on behalf of or under authority of, Vifor or its Affiliate, Sublicensee, Third Party distributor,
or end user; provided that the foregoing defense, hold harmless and indemnity obligations shall not apply to the
extent such Third Party Claim is caused by the gross negligence, willful misconduct or violation of Applicable
Law by Cara or is due to any action, omission or activity covered by Section 9.6(a) or (b) below, or by an action
or omission of Cara for which Cara has an indemnity obligation under the terms of the Supply Agreement with
respect to defective Licensed Product supplied by Cara. Further, Vifor shall indemnify, hold harmless and defend
the Cara Indemnitees from and against any and all Losses resulting from any allegation, demand, claim, suit,
action or proceeding brought or initiated by VFMCRP (or its Affiliate) against any Cara Indemnitee to the extent
arising out of (a) an action or omission by
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
39
Vifor under this Agreement (including failure to pay VFMCRP for its share of Net Profits) that is alleged or
asserted to be contrary to the rights of VFMCRP under the VFMCRP Agreement; provided that the foregoing
defense, hold harmless and indemnity obligations shall not apply to the extent such Third Party Claim is caused
by the gross negligence, willful misconduct or violation of Applicable Law by Cara.
9.6 Indemnification by Cara. Cara shall indemnify, hold harmless and defend Vifor and its Affiliates
and all of their respective officers, directors, employees, agents, licensors and shareholders (collectively, the
“Vifor Indemnitees”) from and against any and all Losses resulting from any Third Party Claim against any Vifor
Indemnitee to the extent arising out of (a) a Default by Cara or its Affiliates; (b) the gross negligence or willful
misconduct of, or violation of Applicable Law by, Cara or its Affiliates; or (c) the Development, offer for sale,
sale or use or other Commercialization of any Compound or Licensed Product by, or on behalf of or under the
authority of Cara or its Affiliate or Third Party licensee (for clarity, other than Vifor, VFMCRP, or either of its
Affiliates or Sublicensees), or the manufacture of any Compound or Licensed Product by, on behalf of or under
authority of, Cara or its Affiliate (for clarity, other than Vifor or its Affiliate or Sublicensee); provided that the
foregoing defense, hold harmless and indemnity obligations shall not apply to the extent such Third Party Claim is
caused by the gross negligence, willful misconduct or violation of Law by a Vifor Indemnitee or is due to
exclusively or solely any action, omission or activity covered by Section 9.5(a) or (b) above.
9.7 Indemnification Procedure.
(a) To be eligible for the Cara Indemnitees to be indemnified hereunder, Cara shall provide
Vifor with prompt notice of the Third Party Claim giving rise to the indemnification obligation under Section 9.5
(provided that any delay in giving such notice shall not exempt Vifor from its indemnity, hold harmless and
defense obligations if such delay does not cause any material prejudice to Vifor) and the exclusive (provided that
Vifor timely undertakes and continues to fully defend against the Third Party Claim) ability to defend or settle any
such claim; provided however that Vifor shall not enter into any settlement for damages, or that imposes upon any
Cara Indemnitee any obligation or liability, without Cara’s prior written consent, such consent not to be
unreasonably withheld, delayed or conditioned. Cara shall have the right to participate, at its own expense and
with counsel of its choice, in the defense of any claim or suit that has been assumed by Vifor, provided that Vifor
shall in any event control the defense of the claim or suit.
(b) To be eligible for the Vifor Indemnitees to be indemnified hereunder, Vifor shall provide
Cara with prompt notice of the Third Party Claim giving rise to the indemnification obligation under Section 9.6
(provided that any delay in giving such notice shall not exempt Cara from its indemnity, hold harmless and
defense obligations if such delay does not cause any material prejudice to Cara) and the exclusive (provided that
Cara timely undertakes and continues to fully defend against the Third Party Claim) ability to defend or settle any
such claim; provided however that Cara shall not enter into any settlement for damages, or that imposes upon any
Vifor Indemnitee any obligation or liability, without Vifor’s prior written consent, such consent not to be
unreasonably withheld, delayed or conditioned. Vifor shall have the right to participate, at its
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
40
own expense and with counsel of its choice, in the defense of any claim or suit that has been assumed by Cara,
provided that Cara shall in any event control the defense of the claim or suit.
9.8 Insurance. Each Party will, at its own expense, obtain and maintain insurance with respect to the
Development and Commercialization of the Compound and the Licensed Products under this Agreement in such
amount and subject to such deductibles and other limitations as biopharmaceutical companies in the Territory
customarily maintain with respect to the research, development, and commercialization of similar products. Each
Party will provide a copy of such insurance policy to the other Party upon request.
9.9 No Consequential or Punitive Damages. EXCEPT AS OTHERWISE PROVIDED HEREIN
AND EXCEPT FOR DAMAGES RESULTING FROM (a) A BREACH OF THE CONFIDENTIALITY
OBLIGATIONS OF ARTICLE VIII, OR (b) A PARTY’S WILLFUL MISCONDUCT OR GROSS
NEGLIGENCE, NEITHER PARTY HERETO WILL BE LIABLE TO THE OTHER PARTY FOR ANY
INDIRECT, INCIDENTAL, CONSEQUENTIAL, SPECIAL, EXEMPLARY OR PUNITIVE DAMAGES,
INCLUDING LOST PROFITS, ARISING FROM OR RELATING TO THIS AGREEMENT, REGARDLESS OF
ANY NOTICE OF SUCH DAMAGES. FOR CLARITY, THIS SECTION 9.9 SHALL NOT LIMIT EITHER
PARTY’S RIGHTS OR OBLIGATIONS UNDER SECTIONS 9.5 OR 9.6.
ARTICLE X
TERM AND TERMINATION
10.1 Term and Expiration. This Agreement shall be effective as of the Effective Date and shall
continue in effect until expiration upon the cessation of commercial sale of Licensed Product in the U.S. by Vifor
and its Affiliates and Sublicensees, or until earlier termination of the Agreement pursuant to Section 10.2 (such
period of effectiveness, the “Term”).
10.2 Termination.
(a) Termination of Agreement for Cause. Except as otherwise provided in Section 10.4, if at
any time during the Term a Party (the “Non-Defaulting Party”) believes that the other Party (the “Defaulting
Party”) has committed a Default, then the Non-Defaulting Party may provide written notice (a “Breach Notice”)
to the Defaulting Party, which Breach Notice shall identify in detail the Default, the intent to terminate the
Agreement if the Default is not cured, and the actions or conduct that it considers would be a cure of such Default.
If such a Breach Notice has been provided, and such Default is not cured by the date [***] after such Breach
Notice was provided, then the Non-Defaulting Party may terminate the Agreement on written notice of
termination to Defaulting Party.
(b) Termination for Bankruptcy. Either Party shall have the right to terminate this
Agreement in the event of the commencement of any proceeding in or for
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
41
bankruptcy, insolvency, dissolution or winding up by or against the other Party (other than pursuant to a corporate
restructuring) that is not dismissed or otherwise disposed of within [***] thereafter, subject to a Party’s rights and
licenses that are retained under Section 2.7.
(c) Termination by Consent. The Parties may terminate this Agreement by mutual written
consent.
(d) Termination for Patent Challenge. Except to the extent the following is unenforceable
under the laws of a particular jurisdiction, Cara may terminate this Agreement on written notice if Vifor or its
Affiliates or Sublicensees, individually or in association with any other person or entity, commences a legal action
challenging the validity or enforceability of any of the Licensed Patent Rights (a “Patent Challenge”); provided,
however, that Cara may not terminate this Agreement pursuant to this Section 10.2(d) as a result of any Patent
Challenge brought in response to an action brought against Vifor or its Affiliates or Sublicensees by Cara for
infringement of any Licensed Patent in the United States.
(e) Termination by Vifor for Convenience. Upon the earlier of (i) the acceptance for filing of
an NDA covering Licensed Product filed with the FDA (after completion of the phase 3 program), or (ii) the third
anniversary of the Effective Date, Vifor may terminate this Agreement in its entirety, by providing written notice
to Cara thereof, which termination will be effective 12 months following the date of such notice; provided,
however, that such 12 month notice period may be shortened by mutual agreement of the Parties.
10.3 Effect of Termination. If this Agreement terminates early in its entirety pursuant to a termination
under Section 10.2 (that is, prior to expiration under Section 10.1), then:
(a) Cara shall, within [***] after the effective date of such termination, return or cause to be
returned to Vifor copies of all Vifor’s Confidential Information (other than Vifor Product Technology); for clarity,
Cara may retain (i) all copies of Joint Know-How, (ii) one copy of such returned Vifor Confidential Information
solely for legal archive purposes, and (iii) copies of all Vifor Product Technology (for use in exercising the license
rights granted to Cara under the Agreement that survive termination of this Agreement;
(b) Vifor’s licenses pursuant to Sections 2.1 and 2.3 shall terminate as of the effective date of
termination. For clarity, notwithstanding the foregoing provision, any termination of this Agreement shall not
have any effect on the VFMCRP Agreement;
(c) within [***] after the effective date of termination Vifor shall return or cause to be returned
to Cara, all copies of all Cara’s Confidential Information and all Licensed Know-How; except that Vifor may
retain (i) all copies of Joint Know-How, and (ii) one copy of the Cara Confidential Information solely for legal
archive purposes;
(d) all of Vifor’s rights to use Cara Confidential Information and Cara Know-How, including
with respect to Compounds and Licensed Products, shall terminate and revert exclusively to Cara, and Vifor
covenants that, for [***] after the date of such termination, Vifor
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
42
and its Affiliates and Sublicensees shall not market, promote, use, offer for sale or sell Compound or Licensed
Product (except as may otherwise be permitted in Section 10.3(f) with respect to remaining inventory);
(e) immediately and automatically upon termination, Vifor will be deemed to grant to Cara,
effective solely upon, and exercisable from and after, such termination: (A) the exclusive, worldwide license,
with full rights to grant sublicenses through multiple tiers, under Vifor’s and its Affiliates’ interest in all
applicable Joint Patents as specified by Cara, such license solely to research, Develop, make, have made, use,
offer for sale, sell, export and import all Compounds and Licensed Products, in the Field throughout the world;
and (B) a worldwide, fully sublicenseable (through multiple tiers), non-exclusive license, under all applicable
Vifor Product Technology, including all regulatory documentation and applications relating to Compound or
Licensed Product, such license to research, Develop, make, have made, use, offer for sale, sell, export and import
Compound and Licensed Products existing for all purposes in the United States.
(f) Cara shall have the option, exercisable within [***] following such termination, to purchase
and obtain Vifor’s and Vifor’s Affiliate’s or Sublicensee’s existing inventory of Licensed Products (or a portion of
any such inventory) at the supply price paid for such Licensed Products by, and/or any costs for manufacturing,
formulating, tableting and packaging the Licensed Products incurred by, Vifor, its Affiliates or their permitted
Sublicensees (such supply price or costs, the “Product Price” for the applicable Licensed Product), provided that
if Cara desires to exercise such option, Vifor shall provide to Cara, within [***] of request, a listing of the
expiration dates for each lot in such inventory (with each lot identified by lot number), and for any such inventory
purchased by Cara hereunder, Vifor shall provide to Cara a typical product warranty as to remaining shelf life,
storage in accordance with cGMP, and compliance with specifications and Applicable Law. Cara may exercise
such option by written notice to Vifor during such [***] period. In addition, if this Agreement is terminated by
Cara pursuant to Section 10.2(a), then the purchase price for any Licensed Product purchased by Cara by exercise
of this option shall be [***] of the Product Price for the applicable Licensed Product purchased hereunder by
Cara. If Cara does not exercise such option, Vifor, its Affiliates or their respective permitted sublicensees will be
permitted to sell, subject to the payment to Cara in full of applicable royalties and any other amounts due under
this Agreement, any Licensed Products in inventory (including completion for sale of any work in progress) as of
the date of termination, such sales solely during the [***] period following such termination, and provided that
Vifor covenants and warrants that any such sale of Licensed Product after such termination shall comply with all
Applicable Laws.
(g) Automatically and immediately upon termination of this Agreement in its entirety Vifor
shall assign and transfer and hereby assigns and transfers to Cara all right, title and interest in any and all
regulatory applications (such as INDs and NDAs) and Regulatory Approval applications and Regulatory
Approvals in the United States covering Licensed Product. Vifor and Vifor’s Affiliates each shall sign all
documents and instruments and take all such actions as reasonable needed to effect and perfect such assignments
and transfers.
(h) If Vifor terminates this Agreement solely with respect to a particular country or countries in
the United States, rather than in its entirety, pursuant to Section 10.2(e), then such
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
43
countries are automatically excluded from the United States, and all rights hereunder as to Compound and
Licensed Product in such countries revert automatically and exclusively to Cara, and the definition of the United
States for the purposes of this Agreement will automatically be amended to remove such terminated country or
countries.
10.4 Termination of Vifor Marketing. If Vifor has committed a Default of its obligations under
Section 5.1, 5.2 or 5.3, then instead of proceeding under Section 10.2(a) for a remedy for such marketing Default,
Cara must proceed under this Section 10.4. In such case, Cara may provide Vifor written notice of such marketing
Default, specifying in reasonable detail the basis for Cara’s assertion that a marketing Default has occurred.
Within [***] of any such Cara notice, the Senior Executives of the Parties shall meet in person and shall discuss
reasonably and in good faith the Default issue and shall seek in good faith to agree on a resolution that either
concludes that no such Default has occurred or that resolves the Default by Vifor committing particular resources
and efforts to comply with its applicable obligations under Sections 5.1, 5.2 and/or 5.3 that were breached. If the
Parties do not agree in writing on such resolution within [***] after such Cara notice, then Cara may terminate
Vifor’s rights hereunder to market and promote the Licensed Products in the U.S. by providing written notice
under the process set forth below, provided Vifor has committed a Default of its obligations under Sections 5.1,
5.2 and/or 5.3. In addition, if the Parties agree to a resolution of the Default issue hereunder that commits Vifor to
devote particular resources and efforts to comply with its applicable obligations under Sections 5.1, 5.2 and/or 5.3,
and Vifor thereafter fails materially to comply with the terms of the resolution, then Cara may terminate Vifor’s
rights hereunder to market and promote the Licensed Products in the U.S. according to the process set forth below.
Cara shall exercise its termination rights under this Section 10.4 by giving written notice to Vifor (a “Termination
of Marketing Notice”). Upon providing such Termination of Marketing Notice, the following shall apply:
(a) Vifor shall continue its Commercialization efforts in the U.S. as instructed by Cara, with
such efforts being “ramped down” in accordance with the marketing ramp-down plan provided by Cara within
[***] thereafter;
(b) Cara shall use reasonable efforts to develop its own marketing and sales capabilities, and/or
to engage a contract sales force, to market Licensed Product in the U.S., as soon as reasonably practicable after
the notice is give, taking into account commercial practicalities and maintaining sales efforts in the U.S., and to
undertake sales and marketing of Licensed Product in the U.S. after such capabilities and/or sales force are
available, consistent with Cara’s marketing ramp-down plan;
(c) Cara shall compensate Vifor reasonably for the sales and marketing costs incurred by Vifor
under subsection (a) above;
(d) Section 6.4 shall be deemed automatically amended so that the Marketing/Distribution Fees
shall be paid by Vifor to Cara, to compensate Cara for the Commercialization efforts of Cara under this Section
10.4;
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
44
(e) Vifor shall continue to book sales and effect the distribution of Licensed Products to
customers in the U.S., and Cara shall pay Vifor a commercial reasonable distribution fee for such distribution
activities.
Notwithstanding the foregoing, if Cara has served a Termination of Marketing Notice, thereafter, at Cara’s
request, the Parties will meet and discuss in good faith the possibility of Vifor undertaking again the
Commercialization of Licensed Product in the U.S., under the terms of Article 5, and if the Parties agree on such
undertaking, the details of such undertaking shall be in a written amendment to this Agreement setting forth such
details and the transition back to Vifor of all such marketing, promotion and sales activities from Cara.
10.5 Effect of Expiration or Termination; Survival.
(a) Expiration or termination of the Agreement shall not relieve the Parties of any obligation
accruing prior to such expiration or termination. Any expiration or termination of this Agreement shall be without
prejudice to the rights of either Party against the other Party accrued or accruing under this Agreement prior to
expiration or termination, including the obligation to pay royalties for Licensed Product(s) sold prior to such
expiration or termination. Termination of this Agreement shall be in addition to, and shall not prejudice, the
Parties’ remedies at law or in equity, including the Parties’ ability to receive legal damages or equitable relief with
respect to any breach of this Agreement, regardless of whether or not such breach was the reason for the
termination.
(b) The following Articles and Sections: Articles I, VI (until completion of all payments owed
to Cara), VIII, X, XI and XII, and Sections 2.5, 7.1, 7.2, 9.4, 9.5, 9.6, 9.7 and 9.9, shall survive the expiration or
termination of the Agreement.
ARTICLE XI
DISPUTE RESOLUTION
11.1 Seeking Consensus. If any dispute or issue between the Parties arises out of, in connection with or
related to this Agreement, including disputes over the interpretation, performance, enforcement or breach of this
Agreement, including any disagreements at the JCC level described in Section 3.2(c), (any such dispute or issue, a
“Dispute”), then upon the written request of either Party, the matter shall be referred to the Senior Executives,
who shall meet in a good faith effort to resolve the Dispute. Any final decision mutually agreed to by the Senior
Executives shall be conclusive and binding on the Parties. If the Senior Executives are not able to agree on the
resolution of any such Dispute within [***] (or such other period of time as mutually agreed by the Senior
Executives) after such Dispute was first referred to them, then such Dispute shall be resolved (if at all) pursuant to
the provisions of Section 11.2 or 11.4, as applicable.
11.2 Courts. If the Parties do not fully settle or otherwise resolve a Dispute pursuant to Section 11.1,
and a Party wishes to pursue the further resolution of such Dispute, then, except for Disputes arising under Section
3.2(b) (which shall be resolved under Section 11.4 below), each
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
45
such Dispute shall be finally and exclusively resolved by litigation in the courts in the State of New York. Each
Party hereby consents to the jurisdiction and proper venue of the courts in the State of New York for any such
action or claim initiated by a Party in accordance with this Article XI.
11.3 Preliminary Relief. Notwithstanding Section 11.1, a Party may seek and apply for preliminary
and/or permanent injunctive relief through the equitable powers of courts in the State of New York at any time to
prevent ongoing or threatened harm due to an applicable breach of this Agreement or other good cause.
11.4 Baseball Arbitration as to Particular Disputes. If a Dispute arises under Section 3.2(b), and
such Dispute is not resolved by the Senior Executives under Section 11.1, within [***] of the Dispute being
referred to them, then either Party may have such Dispute resolved by “baseball arbitration” in accordance with
the following provisions, by sending written notice of such arbitration:
(a) Promptly following receipt of any notice requiring Dispute resolution pursuant to this
Section 11.4, the Parties shall meet and discuss in good faith and agree on an expert panel of three individuals to
resolve the issue, which expert panel shall be neutral and independent of both Parties and all of their respective
Affiliates, shall have significant experience and expertise in the negotiating and operating under license
agreements in the pharmaceutical industry, and in preparing or operating under commercialization plans, and shall
have some experience in mediating or arbitrating issues relating to such agreements. If the Parties cannot agree
on such expert panel within [***] of request by a Party for arbitration, then each Party shall select [***] expert for
such panel and the [***] selected by the Parties shall select [***] for the panel, provided that [***] experts must
meet the foregoing criteria.
(b) Within [***] after the panel of arbitrators are selected (or appointed, as the case may be),
each Party will deliver to both the expert panel and the other Party a detailed written proposal setting forth its
proposed detailed Commercial Plan (or amendment or modification to, as applicable) to resolve the matter at issue
in the Dispute (the “Proposed Terms” of the Party) and a memorandum (the “Support Memorandum”) in support
thereof, not exceeding ten (10) pages in length. The Parties will also provide the expert panel a copy of this
Agreement, as may be amended at such time.
(c) Within [***] after receipt of the other Party’s Proposed Terms and Support Memorandum,
each Party may submit to the expert panel (with a copy to the other Party) a response to the other Party’s Support
Memorandum, such response not exceeding five (5) pages in length. Neither Party may have any other
communications (either written or oral) with the expert panel other than for the sole purpose of engaging the
expert panel or as expressly permitted in this Section 11.4; provided that the expert panel may convene a hearing
if the expert panel so chooses to ask questions of the Parties and hear oral argument and discussion regarding each
Party’s Proposed Terms.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
46
(d) Within [***] after the expert panel’s receipt of both Party’s Proposed Terms, the expert
panel will select one of the two Proposed Terms (without modification) provided by the Parties that the expert
panel believes is most consistent with the intention underlying and agreed principles set forth in this Agreement.
The decision of the expert panel shall be final, binding, and unappealable. The expert panel must select as the
only method to resolve the Dispute at issue one of the two sets of Proposed Terms, and may not combine elements
of both Proposed Terms or award any other relief or take any other action.
ARTICLE XII
MISCELLANEOUS
12.1 Governing Law. This Agreement shall be governed by and construed in accordance with the laws
of New York and applicable federal laws of the U.S., other than any principle of conflict or choice of laws that
would cause the application of the laws of any other jurisdiction.
12.2 Waiver. Waiver by a Party of a breach hereunder by the other Party shall not be construed as a
waiver of any succeeding breach of the same or any other provision. No delay or omission by a Party to exercise
or avail itself of any right, power or privilege that it has or may have hereunder shall operate as a waiver of any
right, power or privilege by such Party. No waiver shall be effective unless made in writing with specific
reference to the relevant provision(s) of this Agreement and signed by a duly authorized representative of the
Party granting the waiver.
12.3 Notices. Unless otherwise provided for in this Agreement, all notices, instructions and other
communications hereunder or in connection herewith shall be in writing, shall be sent to the address specified in
this Section 12.3 and shall be: (a) delivered personally; (b) transmitted by facsimile; (c) sent by registered or
certified mail, return receipt requested, postage prepaid; or (d) sent via a reputable international overnight delivery
service. Any such notice, instruction or communication shall be deemed to have been delivered (i) upon receipt if
delivered by hand or when transmitted with electronic confirmation of receipt, if transmitted by facsimile (if such
transmission is on a Business Day; otherwise, on the next Business Day following such transmission), provided
that an original document is sent via an internationally recognized overnight delivery service (receipt requested),
(ii) three (3) Business Days after it is sent by registered or certified mail, return receipt requested, postage prepaid,
or (iii) one (1) Business Day after it is sent via a reputable international overnight delivery service.
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
47
If to Cara, to:
with a copies to:
and:
If to Vifor, to:
with a copy to:
Cara Therapeutics, Inc.
4 Stamford Plaza
107 Elm Street, 9th Floor
Stamford, CT 06902
Attention: Chief Executive Officer
Facsimile:+1 (203) 406-3770
Cara Therapeutics, Inc.
4 Stamford Plaza
107 Elm Street, 9th Floor
Stamford, CT 06902
Attention: Office of the General Counsel
Facsimile: +1 (203) 406-3770
Cooley LLP
3175 Hanover St.
Palo Alto, CA 94306
USA
Attn: Babak Yaghmaie, Esq.
Vifor (International) Ltd
Rechenstrasse 37
9014 St. Gallen
Switzerland
Attn: CEO
Fax: +41 58 851 8001
Vifor Pharma Management Ltd
Flughofstrasse 61
8152 Glattbrugg
Switzerland
Attn: Group General Counsel
Fax: +41 58 851 89 07
or to such other address as the Party to whom notice is to be given may have furnished to the other Party in
writing in accordance herewith.
12.4 Entire Agreement; Amendment. This Agreement (including its Exhibits and Schedules) contains
the complete understanding of the Parties with respect to the subject matter of this Agreement and supersedes all
prior understandings and writings relating to such subject
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
48
matter. No amendment, change or addition to this Agreement will be effective or binding on either Party unless
reduced to writing and duly executed on behalf of both Parties.
12.5 Headings. Headings in this Agreement are for convenience of reference only and shall not be
considered in construing this Agreement.
12.6 Severability. If any provision or portion thereof in this Agreement is for any reason held to be
invalid, illegal or unenforceable, the same shall not affect any other portion of this Agreement, as it is the intent of
the Parties that this Agreement shall be construed in such fashion as to maintain its existence, validity and
enforceability to the greatest extent possible. In any such event, this Agreement shall be construed as if such
clause of portion thereof had never been contained in this Agreement, and there shall be deemed substituted
therefor such provision as will most nearly carry out the intent of the Parties as expressed in this Agreement to the
fullest extent permitted by Applicable Law.
12.7 Assignment. Neither this Agreement nor any right or obligation hereunder may be assigned or
otherwise transferred by any Party without the consent of the other Party, which consent shall not be unreasonably
withheld; provided, however, that (a) a Party may, without such consent, assign this Agreement, in whole or in
part to any of its respective Affiliates; provided that the assigning Party shall remain jointly and severally liable
with such Affiliate in respect of all obligations so assigned, and (b) a Party may assign this Agreement, without
such consent, to its successor in interest in connection with the merger, acquisition, sale of all or substantially all
of the assets of or similar transaction of such Party. In addition, if a Party is acquired by or mergers with a Third
Party, any Patent Rights or other intellectual property rights owned or controlled by such Third Party, as of just
prior to the closing of such transaction, shall be excluded from all rights licensed by such Party to the other Party
under this Agreement. Without limiting the generality of the foregoing, Vifor may assign this Agreement to
VFMCRP, subject to complying with the above provisions, and upon any such assignment, all references herein to
“Vifor” shall mean and refer solely to VFMCRP.
12.8 Counterparts. This Agreement may be executed in any number of counterparts, each of which
shall be deemed an original but all of which together shall constitute one and the same instrument.
12.9 Force Majeure. No Party shall be liable for failure of or delay in performing obligations (other
than payment obligations) set forth in this Agreement, and no Party shall be deemed in breach of its obligations, if
such failure or delay is due to Acts of God, a public or natural disaster, explosion, fire, flood, tornado,
thunderstorm, hurricane, earthquake, war, terrorism, riot, embargo, loss or shortage of power, labor stoppage,
substance or material shortage, events caused by reason of laws of any Governmental Authority, events caused by
acts or omissions of a Third Party, or any other cause reasonably beyond the control of such Party, if the Party
affected gives prompt notice of any such cause to the other Party. The Party giving such notice shall thereupon be
excused from such of its obligations hereunder as it is thereby disabled from performing for so long as it is so
disabled; provided, however, that such affected Party commences and continues to use its Commercially
Reasonable Efforts to cure or avoid the effects
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
49
of such cause. If any such delay resulting from such a force majeure exceeds [***] (from the date the applicable
obligation was required to be performed), then the Party not affected by the force majeure will have the right to
terminate this Agreement on written notice to the other Party, with the consequences set out in Section 10.3.
12.10 Third Party Beneficiaries. None of the provisions of this Agreement shall be for the benefit of or
enforceable by any Third Party, other than an Cara Indemnitee under Section 9.5 or Vifor Indemnitee under
Section 9.6. No such Third Party shall obtain any right under any provision of this Agreement or shall by reason
of any such provision make any claim in respect of any debt, liability or obligation (or otherwise) against either
Party.
12.11 Relationship of the Parties. Each Party shall bear its own costs incurred in the performance of its
obligations hereunder without charge or expense to the other, except as expressly provided in this Agreement.
Neither Party shall have any responsibility for the hiring, termination or compensation of the other Party’s
employees or for any employee compensation or benefits of the other Party’s employees. No employee or
representative of a Party shall have any authority to bind or obligate the other Party for any sum or in any manner
whatsoever, or to create or impose any contractual or other liability on the other Party without said other Party’s
approval. For all purposes, and notwithstanding any other provision of this Agreement to the contrary, the legal
relationship under this Agreement of each Party to the other Party shall be that of independent contractor.
Nothing in this Agreement shall be construed to establish a relationship of partners or joint ventures between the
Parties, or to grant a Party the right to bind the other Party to any obligations to any Third Party.
12.12 Performance by Affiliates. To the extent that this Agreement imposes obligations on Affiliates of
a Party or permits a Party to exercise its rights or perform its obligations through its Affiliates, such Party agrees
to cause its Affiliates to perform such obligations and shall guarantee performance of this Agreement by its
Affiliates. If any disagreement arises out of the performance of this Agreement by an Affiliate of a Party, or the
alleged failure of an Affiliate to comply with the conditions and obligations of this Agreement, the Party seeking
to resolve such dispute shall have the right do so directly with the other Party, without any obligation to first
pursue an action against, or recovery from, the Affiliate which is alleged to have caused a breach of this
Agreement.
12.13 Construction. Each Party acknowledges that it has been advised by counsel during the course of
negotiation of this Agreement, and, therefore, that this Agreement shall be interpreted without regard to any
presumption or rule requiring construction against the Party causing this Agreement to be drafted. Any reference
in this Agreement to an ARTICLE, Section, subsection, paragraph, clause, Schedule or Exhibit shall be deemed to
be a reference to any article, section, subsection, paragraph, clause, schedule or exhibit, of or to, as the case may
be, this Agreement. Except where the context otherwise requires, (a) wherever used, the use of any gender will be
applicable to all genders; (b) the word “or” is used in the inclusive sense (and/or); (c) any definition of or
reference to any agreement, instrument or other document refers to such agreement, instrument other document as
from time to time amended, supplemented or otherwise modified (subject to any restriction on such amendments,
supplements or modifications set forth herein or
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
50
therein); (d) any reference to any Law refers to such Law as from time to time enacted, repealed or amended; (e)
the words “herein”, “hereof” and hereunder”, and words of similar import, refer to this Agreement in its entirety
and not to any particular provision hereof; and (f) the words “include”, “includes” and “including” shall not limit
the scope of the matter coming before such words and shall be deemed to be followed by the phrase “but not
limited to”, “without limitation” or words of similar import.
[Signature page follows]
51
CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY [***], HAS BEEN OMITTED
BECAUSE CARA THERAPEUTICS, INC. HAS DETERMINED THE INFORMATION (I) IS NOT MATERIAL AND (II) WOULD
LIKELY CAUSE COMPETITIVE HARM TO CARA THERAPEUTICS, INC. IF PUBLICLY DISCLOSED.
IN WITNESS WHEREOF, the Parties have executed this Agreement as of the Effective Date.
Cara Therapeutics, Inc.
Vifor (International) Ltd.
BY: /s/ Derek Chalmers
NAME: Derek Chalmers
TITLE: CEO
BY: /s/ Stefan Schulze
NAME: Stefan Schulze
TITLE: CEO
Vifor (International) Ltd.
BY: /s/ Dr. Christoph Springer
NAME: Dr. Christoph Springer
TITLE: Chief Strategy Officer
Approved and agreed with respect to Sections 2.2, 5.2 and 6.5 by Vifor Fresenius Medical Care Renal Pharma
Ltd:
BY: /s/ Alfredo Merino
Alfredo Merino
CEO
BY: /s/ Marcus Kracht
Marcus Kracht
CFO
Approved by Legal: /s/ Dr. Oliver P. Kronenberg
Dr. Oliver P. Kronenberg
15-Oct-20
[Signature Page to License Agreement]
EXHIBIT 1.17
[***]
[***]
EXHIBIT 1.30
Excluded Clinics and Programs
[***]
KORSUVA
EXHIBIT 1.52
Trademark
EXHIBIT 2.4(a)
Vifor Affiliates – Permitted Sublicensees
[***]
EXHIBIT 23.1
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We consent to the incorporation by reference in the following Registration Statements:
(1) Registration Statement (Form S-3ASR No. 333-233666) of Cara Therapeutics, Inc.
(2) Registration Statement (Form S-3 No. 333-230333) of Cara Therapeutics, Inc.
(3) Registration Statement (Form S-8 No. 333-236728) of Cara Therapeutics, Inc., pertaining to the 2014 Equity
Incentive Plan of Cara Therapeutics, Inc.
(4) Registration Statement (Form S-8 No. 333-234800) of Cara Therapeutics, Inc., pertaining to the Cara
Therapeutics, Inc. 2019 Inducement Plan
(5) Registration Statement (Form S-8 No. 333-230335) of Cara Therapeutics, Inc., pertaining to the 2014 Equity
Incentive Plan of Cara Therapeutics, Inc.
(6) Registration Statement (Form S-8 No. 333-223726) of Cara Therapeutics, Inc., pertaining to the 2014 Equity
Incentive Plan of Cara Therapeutics, Inc.
(7) Registration Statement (Form S-8 No. 333-216606) of Cara Therapeutics, Inc., pertaining to the 2014 Equity
Incentive Plan of Cara Therapeutics, Inc.
(8) Registration Statement (Form S-8 No. 333-210096) of Cara Therapeutics, Inc., pertaining to the 2014 Equity
Incentive Plan of Cara Therapeutics, Inc.
(9) Registration Statement (Form S-8 No. 333-203057) of Cara Therapeutics, Inc., pertaining to the 2014 Equity
Incentive Plan of Cara Therapeutics, Inc., and
(10) Registration Statement (Form S-8 No. 333-193905) pertaining to the 2004 Stock Incentive Plan, as amended,
and 2014 Equity Incentive Plan;
of our reports dated February 25, 2021, with respect to the financial statements of Cara Therapeutics, Inc. and the
effectiveness of internal control over financial reporting of Cara Therapeutics, Inc. included in this Annual Report
(Form 10-K) of Cara Therapeutics, Inc., for the year ended December 31, 2020.
/s/ Ernst & Young LLP
Stamford, Connecticut
February 25, 2021
EXHIBIT 31.1
Certification of Chief Executive Officer Pursuant to
Rule 13a-14(a) under the Securities Exchange Act
of 1934, as Adopted Pursuant to
Section 302 of the Sarbanes-Oxley Act of 2002
I, Derek Chalmers, certify that:
1. I have reviewed this Annual Report on Form 10-K of Cara Therapeutics, Inc.;
2. 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;
3. 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;
4. The registrant's other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as
defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules
13a-15(f) and 15d-15(f)) for the registrant and have:
(a) 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;
(b) 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;
(c) 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
(d) 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 that has materially affected, or is reasonably likely to materially affect, the registrant's
internal control over financial reporting; and
5. The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial
reporting, to the registrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent
functions):
(a) 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
(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's
internal control over financial reporting.
Date: February 25, 2021
By:/s/ Derek Chalmers
DEREK CHALMERS, Ph.D., D.Sc.
CHIEF EXECUTIVE OFFICER
EXHIBIT 31.2
Certification of Chief Financial Officer Pursuant to
Rule 13a-14(a) under the Securities Exchange Act
of 1934, as Adopted Pursuant to
Section 302 of the Sarbanes-Oxley Act of 2002
I, Thomas Reilly, certify that:
1. I have reviewed this Annual Report on Form 10-K of Cara Therapeutics, Inc.;
2. 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;
3. 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;
4. The registrant's other certifying officer and I are responsible for establishing and maintaining disclosure controls and procedures (as
defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules
13a-15(f) and 15d-15(f)) for the registrant and have:
(a) 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;
(b) 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;
(c) 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
(d) 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 that has materially affected, or is reasonably likely to materially affect, the registrant's
internal control over financial reporting; and
5. The registrant's other certifying officer and I have disclosed, based on our most recent evaluation of internal control over financial
reporting, to the registrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent
functions):
(a) 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
(b) Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's
internal control over financial reporting.
Date: February 25, 2021
By:
/s/ Thomas Reilly
THOMAS REILLY
CHIEF FINANCIAL OFFICER
CERTIFICATIONS OF
CHIEF EXECUTIVE OFFICER AND CHIEF FINANCIAL OFFICER
OF CARA THERAPEUTICS, INC.
PURSUANT TO 18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO SECTION 906 OF THE
SARBANES-OXLEY ACT OF 2002
EXHIBIT 32.1
In connection with the Annual Report on Form 10-K of Cara Therapeutics, Inc. (the "Company") for the year ended December 31,
2020, as filed with the Securities and Exchange Commission on the date hereof (the "Report"), Derek Chalmers, Ph.D., D.Sc., as Chief
Executive Officer of the Company, and Thomas Reilly, as Chief Financial Officer of the Company, each hereby certifies, pursuant to 18
U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002, that, to the best of his knowledge, based
upon a review of the Report:
(1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended;
and
(2) The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations
of the Company.
/s/ DEREK CHALMERS
Name: Derek Chalmers, Ph.D., D.Sc.
Title: Chief Executive Officer
Date: February 25, 2021
/s/ THOMAS REILLY
Name: Thomas Reilly
Title: Chief Financial Officer
Date: February 25, 2021