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....

Exhibit 10.21

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.

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, ▇▇▇ ▇▇▇ ▇▇▇▇▇▇, ▇▇▇ ▇▇▇▇▇ ▇▇▇▇▇▇▇▇, ▇▇ ▇▇▇▇▇ (“Cara”), and Vifor (International) Ltd., a corporation organized and existing under the laws of Switzerland and having an office located at ▇▇▇▇▇▇▇▇▇▇▇▇▇ ▇▇, ▇▇-▇▇▇▇ ▇▇. ▇▇▇▇▇▇, ▇▇▇▇▇▇▇▇▇▇▇ (“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 “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.

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

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

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,

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.

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).

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 [***].

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, ▇▇▇▇▇ 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.

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

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	Section
Additional I.V. Indications	2.10
Bankruptcy Code	2.8
Breach Notice	10.2(a)
Cara Indemnitees	9.5
Defaulting Party	10.2(a)
Dispute	11.1
Field Infringement	7.4(b)
Initiating Party	7.6(d)
Jointly-Owned Patent Rights	7.2
Knowledge	9.2
Losses	9.5
▇▇▇▇ Infringement	7.7
Non-Defaulting Party	10.2(a)
Patent Challenge	10.2(d)
Records	4.5
SEC Filing	8.3(c)
Supply Agreement	5.7
Supply Price	5.7
Taxes	6.10

Defined Term	Section
Third Party Claim	9.5
Vifor Indemnitees	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

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

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.

(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.

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

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

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

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

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.

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

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

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.

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

(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
[***]	[***]
[***]	[***]
[***]	[***]
[***]	[***]

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 = [***]