Clinical Trial Collaboration and Supply Agreement, dated as of November 1, 2018, by and between MSD International GmbH and RAPT Therapeutics, Inc
[***] = Certain confidential information contained in this document, marked by brackets, is filed with the Securities and Exchange Commission pursuant to Rule 406 of the Securities Act of 1933, as amended.
CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT
by and between
MSD International GmbH
FLX Bio, Inc.
Dated: November 1, 2018
TABLE OF CONTENTS
2. Scope of the Agreement
2.2. Manufacturing Delay
2.3. Compound Commitments
2.4. Delegation of Obligations
3. Conduct of the Study
3.3. Debarred Personnel; Exclusions Lists
3.4. Regulatory Matters
3.7. Sample Testing
3.8. Ownership and Use of Clinical Data
3.9. Ownership and Use of Monotherapy Data
3.10. Regulatory Submission
3.11. Joint Development Committee; Alliance Managers
3.12. Certain Memoranda and Reports
3.15. Subsequent Study
4. Protocol, Statistical Analysis Plan and Informed Consent; Certain Covenants
4.1. Protocol and Statistical Analysis Plan
4.2. Informed Consent
4.3. Transparency Reporting
5. Adverse Event Reporting
5.1. Pharmacovigilance Agreement
5.2. Transmission of SAEs
6. Term and Termination
6.2. Merck Termination for Safety
6.3. Termination for Material Breach
6.4. Termination for Patient Safety
6.5. Termination for Regulatory Action; Other Reasons
6.6. Termination related to Anti-Corruption Obligations
6.7. Return of Merck Compound
6.8. Termination related to Clinical Safety Data
6.10. No Prejudice
6.11. Confidential Information
7. Costs of Study
8. Supply and Use of the Compounds
8.1. Supply of the Compounds
8.2. Clinical Quality Agreement
8.3. Minimum Shelf Life Requirements
8.4. Provision of Compounds
8.5. Labeling and Packaging; Use, Handling and Storage
8.6. Product Specifications
8.7. Changes to Manufacturing
8.8. Product Testing; Noncompliance
8.10. Shortage; Allocation
8.11. Records; Audit Rights
8.13. Quality Control
8.14. Audits and Inspections
9.1. Confidential Information
9.3. Personal Identifiable Data
9.4. Publicity/Use of Names
10. Intellectual Property
10.1. Joint Ownership, Prosecution and Enforcement
10.2. Inventions Owned by FLX
10.3. Inventions Owned by Merck
10.4. Mutual Freedom to Operate for Combination Inventions
10.5. Ownership of Other Inventions
11. Reprints; Rights of Cross-Reference
12. Publications; Press Releases
12.1. Clinical Trial Registry
12.3. Press Releases
13. Representations and Warranties; Disclaimers
13.1. Due Authorization
14. Insurance; Indemnification; Limitation of Liability
14.3. LIMITATION OF LIABILITY
15. Use of Name
16. Force Majeure
17. Entire Agreement; Amendment; Waiver
18. Assignment and Affiliates
19. Invalid Provision
20. No Additional Obligations
21. Governing Law; Dispute Resolution
23. Relationship of the Parties
24. Counterparts and Due Execution
Appendix A Protocol
Appendix B Supply of Compound
Appendix C FLX Press Release
Schedule I Data Sharing and Sample Testing Schedule
CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT
This CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT (this Agreement), is entered into as of November 1, 2018 (the Effective Date), by and between MSD International GmbH, having a place of business at Weystrasse 20, 6000 Luzern 6, Switzerland (Merck), and FLX Bio, Inc., having a place of business at 561 Eccles Ave., South San Francisco, CA 94080 (FLX). Merck and FLX are each referred to herein individually as Party and collectively as Parties.
A. Merck holds intellectual property rights with respect to the Merck Compound (as defined below).
B. FLX is developing the FLX Compound (as defined below) for the treatment of certain tumor types.
C. Merck is developing the Merck Compound for the treatment of certain tumor types.
D. FLX desires to sponsor a clinical trial in which the FLX Compound and the Merck Compound would be dosed concurrently or in combination.
E. Merck and FLX, consistent with the terms of this Agreement, desire to collaborate as more fully described herein, including by providing the Merck Compound and the FLX Compound for the Study (as defined below) and subject to the Parties mutual agreement to proceed with the Study after review of the Clinical Safety Data (as defined below).
NOW, THEREFORE, in consideration of the premises and of the following mutual promises, covenants and conditions, the Parties, intending to be legally bound, mutually agree as follows:
For all purposes of this Agreement, the capitalized terms defined in this Article 1 and throughout this Agreement shall have the meanings herein specified.
1.1. Affiliate means, with respect to either Party, a firm, corporation, partnership, or other entity that, now or hereafter, directly or indirectly owns or controls said Party, or, now or hereafter, is owned or controlled by said Party, or is under common ownership or control with said Party. The word control as used in this definition means (a) the direct or indirect ownership of fifty percent (50%) or more of the outstanding voting securities of a legal entity, or (b) possession, directly or indirectly, of the power to direct the management or policies of a legal entity, whether through the ownership of voting securities, contract rights, voting rights, corporate governance or otherwise.
1.2. Agreement means this agreement, as amended by the Parties from time to time, and as set forth in the preamble.
1.3. Alliance Manager has the meaning set forth in Section 3.11.3.
1.4. Applicable Law means all federal, state, local, national and regional statutes, laws, rules, regulations and directives applicable to a particular activity hereunder, including performance of clinical trials, medical treatment and the processing and protection of personal and medical data, that may be in effect from time to time, including those promulgated by the United States Food and Drug Administration (FDA), national regulatory authorities, the European Medicines Agency (EMA) and any successor agency to the FDA or EMA or any agency or authority performing some or all of the functions of the FDA or EMA in any jurisdiction outside the United States or the European Union (each a Regulatory Authority and collectively, Regulatory Authorities), and including cGMP and GCP (each as defined below); all data protection requirements such as those specified in the EU General Data Protection Regulation and the regulations issued under the United States Health Insurance Portability and Accountability Act of 1996 (HIPAA); export control and economic sanctions regulations which prohibit the shipment of United States-origin products and technology to certain restricted countries, entities and individuals; anti-bribery and anti-corruption laws pertaining to interactions with government agents, officials and representatives; laws and regulations governing payments to healthcare providers; and any United States or other countrys or jurisdictions successor or replacement statutes, laws, rules, regulations and directives relating to the foregoing.
1.5. Business Day means any day other than a Saturday, Sunday, or a day on which commercial banks located in the country where the applicable obligations are to be performed are authorized or required by law to be closed.
1.6. cGMP means the current Good Manufacturing Practices officially published and interpreted by EMA, FDA and other applicable Regulatory Authorities that may be in effect from time to time and are applicable to the Manufacture of the Compounds.
1.7. Clinical Data means all data (including raw data) and results, [***], generated by or on behalf of either Party or at either Partys direction, or by or on behalf of the Parties together or at their direction, in the course of each such Partys performance of the Study; [***].
1.8. Clinical Quality Agreement has the meaning set forth in Section 8.2.
1.9. Clinical Safety Data means all safety-related data and results from the Monotherapy Arm [***] include safety reports containing information on adverse events, SAEs, and compilations and analyses to satisfy any FDA-reporting requirements, including summary tables of laboratory and radiographic data.
1.10. CMC means Chemistry Manufacturing and Controls as such term of art is used in the pharmaceutical industry.
1.11. Combination means the use or method of using the FLX Compound and the Merck Compound in concomitant or sequential administration.
1.12. Combination Data means all data (including raw data) and results solely related to the Combination and generated by or on behalf of either Party or at either Partys direction, or by or on behalf of the Parties together or at their direction, in the course of each such Partys performance of the Study; [***].
1.13. Comparative Data means all data (including raw data) and results generated by or on behalf of either Party or at either Partys direction, or by or on behalf of the Parties together or at their direction, in evaluating or comparing the Combination Data and the Monotherapy Data, [***].
1.14. Compounds means the FLX Compound and the Merck Compound. A Compound means either the FLX Compound or the Merck Compound, as applicable.
1.15. Confidential Information means any information, Know-How or other proprietary information or materials furnished to one Party (Receiving Party) by or on behalf of the other Party (Disclosing Party) in connection with this Agreement, except to the extent that such information or materials: (a) was already known to the Receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the Disclosing Party, as demonstrated by competent evidence; (b) was generally available to the public or otherwise part of the public domain at the time of its disclosure to the Receiving Party; (c) became generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the Receiving Party in breach of this Agreement; (d) was disclosed to the Receiving Party by a Third Party who had no obligation to the Disclosing Party not to disclose such information to others; or (e) was subsequently developed by the Receiving Party without use of the Disclosing Party Confidential Information, as demonstrated by competent evidence.
1.16. Continuing Party has the meaning set forth in Section 10.1.1(c).
1.17. Control or Controlled means, with respect to particular information or intellectual property, that the applicable Party owns or has a license to such information or intellectual property and has the ability to grant a right, license or sublicense to the other Party as provided for herein without violating the terms of any agreement or other arrangement with any Third Party.
1.18. CTA means an application to a Regulatory Authority for purposes of requesting the ability to start or continue a clinical trial.
1.19. Data Sharing and Sample Testing Schedule means the schedule attached hereto as Schedule I.
1.20. Defending Party has the meaning set forth in Section 14.2.3.
1.21. Delivery with respect to the Merck Compound has the meaning set forth in Section 8.4.1, and with respect to the FLX Compound, the meaning set forth in Section 8.4.2. Delivered has a correlative meaning.
1.22. [***] has the meaning set forth in Section [***].
1.23. Disclosing Party has the meaning set forth in the definition of Confidential Information.
1.24. Disposition Package has the meaning set forth in Section 8.8.1.
1.25. Effective Date has the meaning set forth in the preamble.
1.26. EMA has the meaning set forth in the definition of Applicable Law.
1.27. Enforcing Party has the meaning set forth in Section 10.1.2(e).
1.28. Exclusions List has the meaning set forth in the definition of Violation.
1.29. FDA has the meaning set forth in the definition of Applicable Law.
1.30. Filing Party has the meaning set forth in Section 10.1.1(c).
1.31. Final Study Report has the meaning set forth in Section 3.12.2.
1.32. FLX has the meaning set forth in the preamble.
1.33. FLX Background Patents has the meaning set forth in Section 10.4.1.
1.34. FLX Class Compound means any small or large molecule that binds to CCR4 or CCR4 ligands.
1.35. FLX Compound means the small molecule currently designated by FLX as FLX475, [***].
1.36. FLX Inventions has the meaning set forth in Section 10.2.
1.37. Force Majeure has the meaning set forth Article 16.
1.38. GAAP has the meaning set forth in Section 6.12.
1.39. GCP means the Good Clinical Practices officially published by EMA, FDA and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) that may be in effect from time to time and are applicable to the testing of the Compounds.
1.40. Government Official means: (a) any officer or employee of a government or any department, agency or instrument of a government; (b) any Person acting in an official capacity for or on behalf of a government or any department, agency, or instrument of a government; (c) any officer or employee of a company or business owned in whole or part by a government; (d) any officer or employee of a public international organization such as the World Bank or United Nations; (e) any officer or employee of a political party or any Person acting in an official capacity on behalf of a political party; and/or (f) any candidate for political office; who, when such Government Official is acting in an official capacity, or in an official decision-making role, has responsibility for performing regulatory inspections, government authorizations or licenses, or otherwise has the capacity to make decisions with the potential to affect the business of either of the Parties.
1.41. HIPAA has the meaning set forth in the definition of Applicable Law.
1.42. IND means any Investigational New Drug Application filed or to be filed with the FDA as described in Title 21 of the U.S. Code of Federal Regulations, Part 312, and the equivalent application in the jurisdictions outside the United States, including an Investigational Medicinal Product Dossier filed or to be filed with Regulatory Authorities in the European Union.
1.43. [***] has the meaning set forth in Section [***].
1.44. Inventions means all inventions and discoveries, whether or not patentable, that are made, conceived, or first actually reduced to practice by or on behalf of a Party, or by or on behalf of the Parties together, (a) in the design or performance of the Study or in the design or performance of any Subsequent Study performed pursuant to Section 3.15, (b) through use of unpublished Clinical Data, or (c) through use of Sample Testing Results that are shared between the Parties pursuant to the Data Sharing and Sample Testing Schedule.
1.45. Joint Development Committee or JDC has the meaning set forth in Section 3.11.1.
1.46. Joint Patent Application has the meaning set forth in Section 10.1.1(c).
1.47. Joint Patent means a Patent that issues from a Joint Patent Application.
1.48. Jointly Owned Invention has the meaning set forth in Section 10.1.1(a).
1.49. Know-How means any proprietary invention, innovation, improvement, development, discovery, computer program, device, trade secret, method, know-how, process, technique or the like, including manufacturing, use, process, structural, operational and other data and information, whether or not written or otherwise fixed in any form or medium, regardless of the media on which contained and whether or not patentable or copyrightable, that is not generally known or otherwise in the public domain.
1.50. Liability has the meaning set forth in Section 14.2.1.
1.51. Manufacture, Manufactured, or Manufacturing means all activities related to the manufacture of a Compound, including planning, purchasing, manufacture, processing, compounding, storage, filling, packaging, waste disposal, labeling, leafleting, testing, quality assurance, sample retention, stability testing, release, dispatch and supply, as applicable.
1.52. Manufacturers Release or Release has the meaning ascribed to such term in the Clinical Quality Agreement.
1.53. Manufacturing Site means the facilities where a Compound is Manufactured by or on behalf of a Party, as such Manufacturing Site may change from time to time in accordance with Section 8.7.
1.54. Merck has the meaning set forth in the preamble.
1.55. Merck Background Patents has the meaning set forth in Section 10.4.2.
1.56. Merck Compound means pembrolizumab, a humanized anti-human PD-1 monoclonal antibody, [***].
1.57. Merck Inventions has the meaning set forth in Section 10.3.
1.58. Monotherapy Arm means the arm(s) of the Study intended to evaluate the safety, pharmacokinetics, pharmacodynamics, and/or preliminary efficacy of the FLX Compound as a monotherapy in patients with advanced cancer. For clarity, references to the Monotherapy Arm in this Agreement refer solely to the specific arm(s) of the Study where the FLX Compound is dosed alone.
1.59. Monotherapy Data means all data (including raw data) and results generated by FLX in the course of FLXs performance of the Monotherapy Arm of the Study; [***].
1.60. NDA means a New Drug Application, Biologics License Application, Marketing Authorization Application, filing pursuant to Section 510(k) of the United States Federal Food, Drug and Cosmetic Act, or similar application or submission for a marketing authorization of a product filed with a Regulatory Authority to obtain marketing approval for a biological, pharmaceutical or diagnostic product in that country or in that group of countries.
1.61. Non-Enforcing Party has the meaning set forth in Section 10.1.2(e).
1.62. Non-Conformance means, with respect to a given unit of Compound, (a) an event that deviates from an approved cGMP requirement with respect to the applicable Compound, such as a procedure, Specification, or operating parameter, or that requires an investigation to assess impact to the quality of the applicable Compound or (b) that such Compound failed to meet the applicable representations and warranties set forth in Section 2.3. Classification of the Non-Conformance is detailed in the Clinical Quality Agreement.
1.63. Non-Filing Party has the meaning set forth in Section 10.1.1(c).
1.64. Other Party has the meaning set forth in Section 14.2.3.
1.65. Opting-out Party has the meaning set forth in Section 10.1.1(c).
1.66. Party has the meaning set forth in the preamble.
1.67. Patent means a patent, extension, registration, supplementary protection certificate or the like that issues from a given Patent Application.
1.68. Patent Application means a patent application (including any provisional, substitution, divisional, continuation, continuation in part, reissue, renewal, reexamination, extension, supplementary protection certificate and the like) in respect of a given invention.
1.69. PD-1 Antagonist means [***].
1.70. Person means any individual, sole proprietorship, partnership, corporation, business trust, joint stock company, trust, unincorporated organization, association, limited liability company, institution, public benefit corporation, joint venture, entity or governmental entity.
1.71. Pharmacovigilance Agreement has the meaning set forth in Section 5.1.
1.72. Project Manager has the meaning set forth in Section 3.11.1.
1.73. Protocol means the written documentation that describes the Study and sets forth specific activities to be performed as part of the conduct of the Study. The initial Protocol is set forth in Appendix A.
1.74. Receiving Party has the meaning set forth in the definition of Confidential Information.
1.75. Regulatory Approvals means, with respect to a Compound, any and all permissions (other than the Manufacturing approvals) required to be obtained from Regulatory Authorities and any other competent authority for the development, registration, importation, use (including use in clinical trials) and distribution of such Compound in the United States, Europe or other applicable jurisdictions for use in the Study.
1.76. Regulatory Authorities has the meaning set forth in the definition of Applicable Law.
1.77. Regulatory Documentation means, with respect to a Compound or Compounds, all submissions to Regulatory Authorities in connection with the development of such Compound(s), including all INDs and amendments thereto, NDAs and amendments thereto, drug master files, correspondence with regulatory agencies, periodic safety update reports, adverse event files, complaint files, inspection reports and manufacturing records, in each case together with all supporting documents (including documents that include Clinical Data).
1.78. Related Agreements means the Pharmacovigilance Agreement and the Clinical Quality Agreement.
1.79. Right of Reference means the right of reference defined in 21 CFR 314.3(b), including with regard to a Party, allowing the applicable Regulatory Authority in a country to have access to relevant information (by cross-reference, incorporation by reference or otherwise) contained in Regulatory Documentation (and any data contained therein) filed with such Regulatory Authority with respect to a Partys Compound, only to the extent necessary for the conduct of the Study in such country or as otherwise expressly permitted or required under this Agreement to enable a Party to exercise its rights or perform its obligations hereunder.
1.80. SAEs has the meaning set forth in Section 5.2.
1.81. Samples means biological specimens collected from subjects participating in the Study, including urine, blood and tissue samples.
1.82. Sample Testing means the analyses to be performed by each Party using the applicable Samples, as described in the Data Sharing and Sample Testing Schedule.
1.83. Sample Testing Results means those data and results arising from the Sample Testing performed by a Party.
1.84. Specifications means, with respect to a given Compound, the set of requirements for such Compound as set forth in the Clinical Quality Agreement.
1.85. Study means the Phase I/II clinical trial described in the Protocol to evaluate the safety, pharmacokinetics, pharmacodynamics, and/or preliminary efficacy of: (A) the FLX Compound as a monotherapy; and (B) the Combination in patients with advanced cancer.
1.86. Study Completion means database lock of the Study results.
1.87. Subcontractors has the meaning set forth in Section 2.4.
1.88. Subsequent Study has the meaning set forth in Section 3.15.1.
1.89. Term has the meaning set forth in Section 6.1.
1.90. Third Party means any Person or entity other than FLX, Merck or their respective Affiliates.
1.91. Third Party Infringement has the meaning set forth in Section 10.1.2(a).
1.92. Top-Line Data has the meaning set forth in Section 3.8.3.
1.93. Top-Line Results Memo has the meaning set forth in Section 3.12.1.
1.94. Toxicity & Safety Data means all clinical adverse event information and/or patient-related safety data [***].
1.95. Transparency Report has the meaning set forth in Section 4.3.3.
1.96. VAT has the meaning set forth in Section 8.16.1.
1.97. Violation means that a Party or any of its officers or directors or any other personnel (or other permitted agents of a Party performing activities hereunder) has been: (a) convicted of any of the felonies identified among the exclusion authorities listed on the U.S. Department of Health and Human Services, Office of Inspector General (OIG) website, including 42 U.S.C. 1320a-7(a) (http://oig.hhs.gov/exclusions/authorities.asp); (b) identified in the OIG List of Excluded Individuals/Entities (LEIE) database (http://exclusions.oig.hhs.gov/) or listed as having an active exclusion in the System for Award Management (http://www.sam.gov); or (c) listed by any US Federal agency as being suspended, proposed for debarment, debarred, excluded or otherwise ineligible to participate in Federal procurement or non-procurement programs, including under 21 U.S.C. 335a (http://www.fda.gov/ora/compliance_ref/debar/) (the lists in (a), (b) and (c) collectively, the Exclusions Lists).
Scope of the Agreement.
2.1.1. Each Party shall: (a) contribute to the Study such resources as are necessary to fulfill its obligations set forth in this Agreement; and (b) act in good faith in performing its obligations under this Agreement and each Related Agreement to which it is a Party.
2.1.2. Prior to dosing any patient in the Combination arm(s) of the Study (as currently set forth in Parts 1b and 2b of the Protocol) and in any event [***], FLX shall convene a meeting or teleconference, during regular business hours, to review the Clinical Safety Data. FLX shall provide Merck with reasonable advance notice of, and invite Merck to attend, such meeting or teleconference, as applicable. [***], Merck shall have the opportunity to review the Clinical Safety Data. FLX shall also provide Merck with a copy of the Clinical Safety Data for further review. Promptly following Mercks review of such Clinical Safety Data, but in no event later than [***] days after receipt of such Clinical Safety Data, the JDC shall meet and discuss whether to proceed with the Study. [***].
2.2. Manufacturing Delay. Each Party shall notify the other Party as promptly as possible in the event of any Manufacturing delay that is likely to adversely affect supply of its Compound as contemplated by this Agreement.
2.3. Compound Commitments.
2.3.1. FLX agrees to Manufacture and supply the FLX Compound for purposes of the Study in accordance with Article 8, and FLX hereby represents and warrants to Merck that, at the time of Delivery of the FLX Compound, such FLX Compound shall have been Manufactured and supplied in compliance with: (a) the Specifications for the FLX Compound; (b) the Clinical Quality Agreement; and (c) all Applicable Law, including cGMP and health, safety and environmental protections.
2.3.2. Merck agrees to Manufacture and supply the Merck Compound for purposes of the Study in accordance with Article 8, and Merck hereby represents and warrants to FLX that, at the time of Delivery of the Merck Compound, such Merck Compound shall have been Manufactured and supplied in compliance with: (a) the Specifications for the Merck Compound; (b) the Clinical Quality Agreement; and (c) all Applicable Law, including cGMP and health, safety and environmental protections.
2.3.3. Without limiting the foregoing, each Party is responsible for obtaining all regulatory approvals (including facility licenses) that are required to Manufacture its Compound in accordance with Applicable Law (provided that, for clarity, FLX shall be responsible for obtaining Regulatory Approvals for the Study as set forth in Section 3.4).
2.4. Delegation of Obligations. Each Party shall have the right to delegate any portion of its obligations hereunder as follows: (a) to such Partys Affiliates; (b) to Third Parties that are
set forth in the Protocol as performing Study activities or as conducting Sample Testing for such Party; (c) to Third Parties to the extent related to the Manufacture of such Partys Compound; and/or (d) to Third Parties upon the other Partys prior written consent, [***]. Any and all Third Parties to whom a Party delegates any of its obligations hereunder are referred to as Subcontractors. Notwithstanding any delegation of its obligations hereunder, each Party shall remain solely and fully liable for the performance of its Affiliates and Subcontractors to which such Party delegates the performance of its obligations under this Agreement. Each Party shall ensure that each of its Affiliates and Subcontractors performs such Partys obligations pursuant to the terms of this Agreement, including the Appendices and Schedules attached hereto, and Related Agreements. Each Party shall use reasonable efforts to obtain and maintain copies of documents relating to the obligations performed by such Affiliates and Subcontractors that are required to be provided to the other Party under this Agreement.
2.5. Compounds. [***], this Agreement does not create any obligation on the part of Merck to provide the Merck Compound for any activities other than the Study, nor does it create any obligation on the part of FLX to provide the FLX Compound for any activities other than the Study.
Conduct of the Study.
3.1. Sponsor. FLX shall be the sponsor of the Study under its existing IND for the FLX Compound with a Right of Reference to the IND of the Merck Compound, as necessary, as further described in Section 3.4; provided, however, that in no event shall FLX file an additional IND for the Study unless required by Regulatory Authorities to do so. If a Regulatory Authority requests an additional IND for the Study the Parties shall meet and mutually agree on an approach to address such requirement.
3.2. Performance. FLX shall ensure that the Study is performed in accordance with this Agreement, the Protocol and all Applicable Law, including GCP.
3.3. Debarred Personnel; Exclusions Lists. [***].
3.4. Regulatory Matters. FLX shall: (a) obtain, prior to initiating the Study, all Regulatory Approvals from all Regulatory Authorities, ethics committees and/or institutional review boards with jurisdiction over the Study; and (b) follow all directions from any such Regulatory Authorities, ethics committees and/or institutional review boards. [***]. If a Right of Reference is necessary, each Party shall provide to the other a cross-reference letter or similar communication to the applicable Regulatory Authority if needed to effectuate the Right of Reference (including a Right of Reference to the Monotherapy Data solely to the extent necessary or useful in connection with regulatory approval of a Compound in the Combination). Notwithstanding anything to the contrary in this Agreement, neither Party shall have any right to [***] with respect to such other Partys Compound. Merck shall authorize the FDA and other applicable Regulatory Authorities to cross-reference the appropriate Merck Compound INDs and CTAs to provide data access to FLX sufficient to support conduct of the Study. If Mercks CTA is not available in a given country, Merck will [***] with the Regulatory Authority for such country, referencing FLXs CTA as appropriate (however, FLX shall [***].
3.5. Documentation. FLX shall maintain reports related to the Study and all related documentation in good scientific manner and in compliance with Applicable Law. FLX shall provide to Merck all Study information and documentation ([***]) requested by Merck to enable Merck to (a) comply with any of its legal, regulatory and/or contractual obligations, or any request by any Regulatory Authority, related to the Merck Compound and (b) determine whether the Study has been performed in accordance with this Agreement. If requested by Merck for purposes of complying with Applicable Law, any submissions or responses to Regulatory Authorities, [***] FLX shall work in good faith with Merck to provide required access to [***] information and documentation, including [***], or otherwise make available under Applicable Law or to the Regulatory Authority directly for such purposes.
3.6. Copies. FLX shall provide to Merck copies of all Clinical Data [***], in electronic form or other mutually agreeable alternate form and on the timelines specified in the Data Sharing and Sample Testing Schedule (if applicable) or upon mutually agreeable timelines; provided, however, that a complete copy of the Clinical Data [***], shall be provided to Merck no later than [***] days following Study Completion. FLX shall ensure that all patient authorizations and consents required under HIPAA, the EU General Data Protection Regulation or any other similar Applicable Law in connection with the Study permit such sharing of Clinical Data [***] with Merck. The Parties shall comply with any Applicable Law relating to processing of personal data in connection with the Clinical Data [***].
3.7. Sample Testing.
3.7.1. FLX shall provide Samples to Merck as specified in the Protocol or as agreed to by the Joint Development Committee. Each Party shall (a) use the Samples only for the Sample Testing and (b) conduct the Sample Testing solely in accordance with the Data Sharing and Sample Testing Schedule and the Protocol.
3.7.2. [***], in electronic form or other mutually agreeable alternate form, on the timelines specified in the Data Sharing and Sample Testing Schedule or as otherwise mutually agreed.
3.7.3. [***]. Solely to the extent specified on the Data Sharing and Sample Testing Schedule as being shared, [***] the Sample Testing Results for the Sample Testing conducted [***], in electronic form or other mutually agreeable alternate form, on the timelines specified in the Data Sharing and Sample Testing Schedule or as otherwise mutually agreed.
3.7.4. Except to the extent otherwise agreed in a writing signed by authorized representatives of each Party, each Party may use and disclose the Sample Testing Results [***] in accordance with the Data Sharing and Sample Testing Schedule solely for the purposes of: [***]
3.8. Ownership and Use of Clinical Data.
3.8.1. [***]. FLX shall maintain the Clinical Data in its internal database; provided, however, that at all times during the Term, FLX shall [***] all Clinical Data [***].
3.8.2. Notwithstanding the foregoing, before publication of the Clinical Data in accordance with Article 12, neither Party may disclose the Clinical Data publicly or to a Third Party without the consent of the other Party and each Partys use of such unpublished Clinical Data is restricted to: [***]; provided, however, that the foregoing shall not limit or restrict either Partys ability to [***].
3.9. Ownership and Use of Monotherapy Data. All Monotherapy Data shall be owned by FLX. [***].
3.9.1. Before publication by FLX of the Monotherapy Data, [***] (a) [***]; provided, however, that the foregoing shall not limit or restrict [***] ability to [***]. For clarity, after publication by FLX of Monotherapy Data, the above restrictions shall continue to apply to any such Monotherapy Data that has not been publicly disclosed.
3.10. Regulatory Submission. It is understood and acknowledged by the Parties that positive Clinical Data could be used to obtain label changes for the Compounds, and each Party may propose a Subsequent Study (as defined below) in connection therewith in accordance with Section 3.15.
3.11. Joint Development Committee; Alliance Managers.
3.11.1. The Parties shall form a joint development committee (the Joint Development Committee or JDC) made up of an equal number of representatives of Merck and FLX, which shall have responsibility for coordinating all regulatory and other activities under, and pursuant to, this Agreement. The JDC will review and finalize the Protocol in accordance with Section 4.1 and review and discuss the Clinical Safety Data in accordance with Section 2.1.2. Each Party shall designate a project manager (the Project Manager) who shall be responsible for implementing and coordinating activities and facilitating the exchange of information between the Parties with respect to the Study and shall be a member of the JDC. Other JDC members will be agreed by both Parties. Each Party may replace its Project Manager and other JDC members upon notice to the other Party.
3.11.2. The JDC shall meet as soon as practicable after the Effective Date and then no less than [***], and more often as reasonably considered necessary at the request of either Party, to provide an update on the progress of the Study. The JDC may meet in person or by means of teleconference, Internet conference, videoconference or other similar communications equipment. Prior to any such meeting, FLXs Project Manager shall provide an update in writing to Mercks Project Manager, which update shall contain information about the overall progress of the Study, recruitment status, interim analysis (if results available), final analysis and other information relevant to the conduct of the Study.
3.11.3. In addition to a Project Manager, each Party shall designate an alliance manager (the Alliance Manager), who shall endeavor to ensure clear and responsive communication between the Parties and the effective exchange of information and shall serve as the primary point of contact for any issues arising under this Agreement. The Alliance Managers shall have the right to attend all JDC meetings and may bring to the attention of the JDC any
matters or issues either of them reasonably believes should be discussed and shall have such other responsibilities as the Parties may mutually agree in writing. Each Party may replace its Alliance Manager upon notice to the other Party. In the event that an issue arises and the Alliance Managers cannot or do not, after good faith efforts, reach agreement on such issue, or if there is a decision to be made by the JDC on which the members of the JDC cannot unanimously agree, the issue shall be elevated to the [***] for Merck and the Chief Executive Officer for FLX. In the event such escalation does not result in resolution or consensus: [***] unless mutually agreed otherwise by the Parties in writing through the JDC.
3.12. Certain Memoranda and Reports. Without limiting any other provision of this Agreement requiring FLX to provide to Merck documentation related to the Study, FLX shall provide to Merck drafts and final versions of: (a) a memorandum having top-line results from the completed Study (the Top-Line Results Memo); and (b) final Study report (Final Study Report) for the Study as described below.
3.12.1. Top-Line Results Memo. Promptly following Study Completion, FLX shall provide to Merck an electronic draft of the Top-Line Results Memo, and Merck shall have [***] days after receipt of such draft to provide comments thereon. FLX shall consider in good faith any comments provided by Merck on the Top-Line Results Memo and shall not include any statements therein relating to the Merck Compound that have not been approved by Merck. FLX shall deliver to Merck a final version of the Top-Line Results Memo promptly following finalization thereof.
3.12.2. Final Study Report. FLX shall provide Merck with an electronic draft of the final Study report promptly following Study Completion, and Merck shall have [***] days after receipt of such draft to provide comments thereon. FLX shall consider in good faith any comments provided by Merck on the draft final Study report and shall not include any statements therein relating to the Merck Compound that have not been approved by Merck. FLX shall deliver to Merck a final version of the final Study report promptly following finalization thereof (the Final Study Report).
3.13. Relationship. Except as expressly set forth in this Agreement, nothing in this Agreement shall: [***]; or (b) create an exclusive relationship between the Parties with respect to any Compound. Each Party acknowledges and agrees that nothing in this Agreement shall be construed as a representation or inference that the other Party will not develop for itself, or enter into business relationships with other Third Parties regarding, any products, programs, studies (including combination studies), technologies or processes that are similar to or that may compete with the Combination or any other product, program, technology or process, including [***] are not used or disclosed in connection therewith in violation of this Agreement.
3.14. Licensing. Nothing in this Agreement shall prohibit or restrict a Party from licensing, assigning or otherwise transferring to an Affiliate or Third Party such Partys Compound or any Inventions, Confidential Information or Sample Testing Results owned solely by such Party. A Party may license, assign or transfer to an Affiliate or Third Party such Partys interest in the Clinical Data, Confidential Information owned jointly by the Parties and/or Jointly Owned Inventions, and in connection therewith share the shared Sample Testing Results owned by the other Party, solely to the extent such licensee, assignee or transferee agrees in writing to be bound by the terms of this Agreement with respect to such Clinical Data, Monotherapy Data, Confidential Information, Jointly Owned Inventions, and shared Sample Testing Results. For purposes of clarity, any assignment or transfer of this Agreement must comply with Article 18 of this Agreement.
3.15. Subsequent Study.
4. Protocol, Statistical Analysis Plan and Informed Consent; Certain Covenants.
4.1. Protocol and Statistical Analysis Plan. An initial Protocol and a draft statistical analysis plan for the Study have been agreed to by the Parties as of the Effective Date and are attached hereto as Appendix A. Through the JDC, FLX shall (a) provide any proposed revisions to the then current Protocol or statistical analysis plan to Merck for Mercks review and comment, (b) consider in good faith any changes requested by Merck, and (c) incorporate any changes requested by Merck with respect to Merck Compound. FLX shall then submit the proposed revised Protocol or statistical analysis plan, as applicable, to the JDC for approval. To the extent the JDC cannot agree unanimously regarding the Protocol or statistical analysis plan for final approval: (i) [***] shall have final decision-making authority with respect to matters related to [***] (including with respect to [***]); (ii) [***] shall have final decision-making authority with respect to matters related to [***] (including with respect to [***]); and (iii) all other matters on which the JDC cannot agree shall be resolved in accordance with Section 3.11.3. Once the final Protocol or statistical analysis plan has been approved in accordance with this Section 4.1, Mercks prior written consent shall be required for: (i) any [***] changes to such approved final Protocol or statistical analysis plan (other than [***] changes relating [***]); or (ii) any changes to such approved final Protocol or statistical analysis plan [***] relating to [***]. Any such proposed changes will be sent in writing to Mercks Project Manager and Mercks Alliance Manager.
4.1.1. Notwithstanding anything to the contrary contained herein, [***], in its sole discretion, shall have the sole right to determine [***] and shall have the final decision on all matters relating to [***] (including [***]) and any information regarding [***].
4.1.2. Notwithstanding anything to the contrary contained herein, [***], in its sole discretion, shall have the sole right to determine [***] and shall have the final decision on all matters relating to [***] (including [***]), [***], and any information regarding [***].
4.2. Informed Consent. FLX shall prepare the patient informed consent form for the Study (which shall include provisions regarding the use of Samples in Sample Testing) in consultation with Merck (it being understood and agreed that the portion of the informed consent form relating to the Sample Testing of the Merck Compound shall be provided to FLX by Merck). Any proposed changes to such form that relate to the Merck Compound, including Sample Testing of the Merck Compound, shall be subject to Mercks prior written consent. Any such proposed changes will be sent in writing to Mercks Project Manager and Mercks Alliance Manager. [***].
4.3. Transparency Reporting.
4.3.1. With respect to any annual reporting period in which FLX is not an entity that is required to make a Transparency Report under Applicable Law, FLX will: (a) notify Merck, in writing, within [***] days after the commencement of such reporting period that FLX is not so required; and (b) during such reporting period FLX will track and provide to Merck data regarding indirect payments or other transfers of value by FLX to such health care professionals to the extent such payments or other transfers of value were required, instructed, directed or otherwise caused by Merck pursuant to this Agreement in the format requested by Merck and provided on a basis to be agreed upon by both Parties. FLX represents and warrants that any data provided by FLX to Merck pursuant to Section 4.3.1(b) above will be complete and accurate to the best of FLXs knowledge.
4.3.2. With respect to any annual reporting period in which FLX is required to make a Transparency Report under Applicable Law, FLX will provide to Merck, in writing, FLXs point of contact for purposes of receiving information from Merck pursuant to this Section 4.3, along with such contacts full name, email address, and telephone number. FLX may update such contact from time to time by notifying Merck in writing pursuant to Article 22 (Notices). Where applicable, Merck will provide to such FLX contact all information regarding the value of the Merck Compound provided for use in the Study required for such reporting. In the event that the value of the Merck Compound provided pursuant to this Section 4.3.2 changes, Merck shall notify FLX of such revised value and the effective date thereof.
4.3.3. For purposes of this Section 4.3, Transparency Report means a transparency report in connection with reporting payments and other transfers of value made to health care professionals, including, without limitation, investigators, steering committee members, data monitoring committee members, and consultants in connection with the Study in accordance with reporting requirements under Applicable Law, including, without limitation, the Physician Payment Sunshine Act and state gift laws, and the European Federation of Pharmaceutical Industries and Associations Disclosure Code, or a Partys applicable policies.
5. Adverse Event Reporting.
5.1. Pharmacovigilance Agreement. FLX will be solely responsible for compliance with all Applicable Laws pertaining to safety reporting for the Study and related activities. The Parties (or their respective Affiliates) will execute a pharmacovigilance agreement (the Pharmacovigilance Agreement) prior to the initiation of clinical activities under the Study, but in any event within [***] days after the Effective Date, to ensure the exchange of relevant safety data within appropriate timeframes and in an appropriate format to enable the Parties to fulfill local and international regulatory reporting obligations and to facilitate appropriate safety reviews. In the event of any inconsistency between the terms of this Agreement and the Pharmacovigilance Agreement, [***]. The Pharmacovigilance Agreement will include safety data exchange procedures governing the coordination of collection, investigation, reporting, and exchange of information concerning any adverse experiences, pregnancy reports, and any other safety information arising from or related to the use of the Merck Compound [***] in the Study, consistent with Applicable Law. Such guidelines and procedures shall be in accordance with, and enable the Parties and their Affiliates to fulfill, local and international regulatory reporting obligations to Regulatory Authorities.
5.2. Transmission of SAEs. FLX will transmit to Merck all serious adverse events (SAEs) [***]:
5.2.1. For drug-related fatal and life-threatening SAEs, FLX will send a processed case (on a CIOMS-1 form in English) within [***] by FLX of such SAEs.
5.2.2. For all other SAEs, including non-drug-related fatal and life-threatening SAEs, FLX will send a processed case (on a CIOMS-1 form in English) within [***] by FLX of such SAEs.
6. Term and Termination.
6.1. Term. The term of this Agreement shall commence on the Effective Date and shall continue in full force and effect until delivery of the Final Study Report, unless terminated earlier by either Party pursuant to this Article 6 (the Term).
6.2. Merck Termination for Safety. In the event that Merck in good faith believes that the Merck Compound is being used in the Study in an unsafe manner and notifies FLX in writing of the grounds for such belief, and FLX fails to promptly incorporate changes into the Protocol requested by Merck to address such issue or to otherwise address such issue reasonably and in good faith, Merck may terminate this Agreement and the supply of the Merck Compound immediately upon written notice to FLX.
6.3. Termination for Material Breach. Either Party may terminate this Agreement if the other Party commits a material breach of this Agreement, and such material breach continues for [***] after receipt of written notice thereof from the non-breaching Party; provided that if such material breach cannot reasonably be cured within [***], the breaching Party shall be given a reasonable period of time to cure such breach; provided further, that if such material breach is incapable of cure, then the notifying Party may terminate this Agreement effective after the expiration of such [***] period.
6.4. Termination for Patient Safety. If either Party determines in good faith, based on a review of the [***] or other information, that the Study may [***] affect patient safety, such Party shall promptly notify the other Party of such determination. The Party receiving such notice may propose modifications to the Study to address the safety issue identified by the other Party and, if the notifying Party agrees, shall act to implement immediately such modifications; provided, however, that if the notifying Party, in its sole discretion, believes that there is imminent danger to patients, such Party need not wait for the other Party to propose modifications and may instead terminate this Agreement immediately upon written notice to such other Party. Furthermore, if the notifying Party, in its sole discretion, believes that any modifications proposed by the other Party will not resolve the patient safety issue, such Party may terminate this Agreement effective upon written notice to such other Party.
6.5. Termination for Regulatory Action; Other Reasons. Either Party may terminate this Agreement immediately upon written notice to the other Party in the event that any Regulatory
Authority takes any action, or raises any objection, that prevents the terminating Party from supplying its Compound for purposes of the Study. Additionally, either Party shall have the right to terminate this Agreement immediately upon written notice to the other Party in the event that it determines in its sole discretion to withdraw any applicable regulatory approval for its Compound or to discontinue development of its Compound, for medical, scientific or legal reasons.
6.6. Termination related to Anti-Corruption Obligations. Either Party shall have the right to terminate this Agreement immediately upon written notice to the other Party, if such other Party fails to perform any of its obligations under Section 13.4 or breaches any representation or warranty contained in Section 13.4. Except as set forth in Section [***], the non-terminating Party shall have no claim against the terminating Party for compensation for any loss of whatever nature by virtue of the termination of this Agreement in accordance with this Section 6.6.
6.7. Return of Merck Compound. In the event that this Agreement is terminated, or in the event FLX remains in possession (including through any Affiliate or Subcontractor) of Merck Compound at the time this Agreement expires, FLX shall, at Mercks sole discretion, promptly either return or destroy all unused Merck Compound pursuant to Mercks instructions; [***]. If Merck requests that FLX destroy the unused Merck Compound, FLX shall provide written certification of such destruction.
6.8. Termination related to Clinical Safety Data. In the event that either Party or both Parties make a No-Go Decision, this Agreement shall terminate immediately upon the date of such No-Go Decision. [***].
6.9. Survival. The provisions [***].
6.10. No Prejudice. Termination of this Agreement shall be without prejudice to any claim or right of action of either Party against the other Party for any prior breach of this Agreement.
6.11. Confidential Information. Upon termination of this Agreement, each Receiving Party and its Affiliates shall promptly return to the Disclosing Party or destroy any Confidential Information of the Disclosing Party ([***]) furnished to the Receiving Party by the Disclosing Party; provided, however that the Receiving Party may retain one copy of such Confidential Information in its confidential files, solely for purposes of exercising the Receiving Partys rights hereunder, satisfying its obligations hereunder or complying with any legal proceeding or requirement with respect thereto, and provided further that the Receiving Party shall not be required to erase electronic files created in the ordinary course of business during automatic system back-up procedures pursuant to its electronic record retention and destruction practices that apply to its own general electronic files and information so long as such electronic files are (a) maintained only on centralized storage servers (and not on personal computers or devices), (b) not accessible by any of its personnel (other than its information technology specialists), and (c) are not otherwise accessed subsequently except with the written consent of the Disclosing Party or as required by law or legal process. Such retained copies of Confidential Information shall remain subject to the confidentiality and non-use obligations herein.
6.12. [***]. In the event of termination [***] pursuant to Section [***] above, [***] shall be entitled to [***] and [***] for the Study. [***].
7. Costs of Study.
The Parties agree that: (a) Merck shall provide the Merck Compound for use in the Study, [***].
8. Supply and Use of the Compounds.
8.1. Supply of the Compounds. Subject to the terms and conditions of this Agreement, each of FLX and Merck will use commercially reasonable efforts to supply, or cause to be supplied, the quantities of its respective Compound as are set forth in Appendix B, on the timelines set forth in Appendix B, in each case for use in the Study. If the Protocol is changed in accordance with Article 4 in such a manner that may affect the quantities of Compound to be provided or the timing for providing such quantities, the Parties shall amend Appendix B to reflect any changes required to be consistent with the Protocol. Each Party shall also provide to the other Party a contact person for the supply of its Compound under this Agreement. Notwithstanding the foregoing, or anything to the contrary herein, in the event that a Party is: (a) not supplying its Compound in accordance with the terms of this Agreement, then the other Party shall have no obligation to supply its Compound; or (b) allocating under Section 8.10, then the other Party may allocate proportionally.
8.2. Clinical Quality Agreement. [***], the Parties (or their respective Affiliates) shall enter into a quality agreement that shall address and govern issues related to the quality of clinical drug supply to be supplied by the Parties for use in the Study (the Clinical Quality Agreement). In the event of any inconsistency between the terms of this Agreement and the Clinical Quality Agreement, [***]. The Clinical Quality Agreement shall, among other things: (a) detail classification of any Compound found to have a Non-Conformance; (b) include criteria for Manufacturers Release and related certificates and documentation; (c) include criteria and timeframes for acceptance of Merck Compound; (d) include procedures for the resolution of disputes regarding any Compounds found to have a Non-Conformance; and (e) include provisions governing the recall of Compounds.
8.3. Minimum Shelf Life Requirements. Each Party shall use commercially reasonable efforts to supply its Compound hereunder with an adequate remaining shelf life at the time of Delivery to meet the Study requirements.
8.4. Provision of Compounds.
8.4.1. Merck will deliver the Merck Compound [***] to FLXs, or its designees, location as specified by FLX (Delivery with respect to such Merck Compound). Title and risk of loss for the Merck Compound shall transfer from Merck to FLX at Delivery. All costs associated with the subsequent transportation, warehousing and distribution of Merck Compound shall be borne by FLX. FLX will, or will cause its designee to: (a) take delivery of the Merck Compound supplied hereunder; (b) perform the acceptance (including testing) procedures allocated to it under the Clinical Quality Agreement; (c) subsequently label and pack the Merck Compound (in accordance with Section 8.5); and promptly ship the Merck Compound to the Study
sites for use in the Study, in compliance with cGMP, GCP and other Applicable Law and the Clinical Quality Agreement; and (d) provide, from time to time at the reasonable request of Merck, the following information [***]: any applicable chain of custody forms, in-transport temperature recorder(s), records and receipt verification documentation, such other transport or storage documentation as may be reasonably requested by Merck, and usage and inventory reconciliation documentation related to the Merck Compound.
8.4.2. FLX is solely responsible, at its own cost, for supplying (including all Manufacturing, acceptance and release testing) the FLX Compound for the Study, and the subsequent handling, storage, transportation, warehousing and distribution of the FLX Compound supplied hereunder. FLX shall ensure that all such activities are conducted in compliance with cGMP, GCP and other Applicable Law and the Clinical Quality Agreement. For purposes of this Agreement, the Delivery of a given quantity of the FLX Compound shall be deemed to occur when such quantity is packaged for shipment to a Study site.
8.5. Labeling and Packaging; Use, Handling and Storage.
8.5.1. The Parties obligations with respect to the labeling and packaging of the Compounds are as set forth in the Clinical Quality Agreement. Notwithstanding the foregoing or anything to the contrary contained herein, Merck shall provide the Merck Compound to FLX in the form of [***], and FLX shall be responsible for labeling, packaging and leafleting such Merck Compound in accordance with the terms and conditions of the Clinical Quality Agreement and otherwise in accordance with all Applicable Law, including cGMP, GCP, and health, safety and environmental protections.
8.5.2. FLX shall: (a) use the Merck Compound solely for purposes of performing the Study; (b) not use the Merck Compound in any manner that is inconsistent with this Agreement or for any commercial purpose; and (c) label, use, store, transport, handle and dispose of the Merck Compound in compliance with Applicable Law and the Clinical Quality Agreement, as well as all instructions of Merck. FLX shall not reverse engineer, reverse compile, disassemble or otherwise attempt to derive the composition or underlying information, structure or ideas of the Merck Compound, and in particular shall not analyze the Merck Compound by physical, chemical or biochemical means except as necessary to perform its obligations under the Clinical Quality Agreement.
8.6. Product Specifications. A certificate of analysis shall accompany each shipment of the Merck Compound to FLX. Upon written request of Merck, FLX shall provide Merck with a certificate of analysis for [***] shipment of FLX Compound used in the Study.
8.7. Changes to Manufacturing. Each Party may make changes from time to time to its Compound or the Manufacturing Site, provided that such changes shall be in accordance with the Clinical Quality Agreement.
8.8. Product Testing; Noncompliance.
8.8.1. After Manufacturers Release. After Manufacturers Release of the Merck Compound and concurrently with Delivery of the Compound to FLX, Merck shall provide FLX with such certificates and documentation as are described in the Clinical Quality Agreement
(Disposition Package). FLX shall, within the time defined in the Clinical Quality Agreement, perform, with respect to the Merck Compound, the acceptance (including testing) procedures allocated to it under the Clinical Quality Agreement. FLX shall be solely responsible for taking all steps necessary to determine that Merck Compound or FLX Compound, as applicable, is suitable for release before making such Merck Compound or FLX Compound, as applicable, available for human use, and Merck shall provide cooperation or assistance as reasonably requested by FLX in connection with such determination with respect to the Merck Compound. FLX shall be responsible for storage and maintenance of the Merck Compound until it is tested and/or released, which storage and maintenance shall be in compliance with (a) the Specifications for the Merck Compound, the Clinical Quality Agreement and Applicable Law and (b) any specific storage and maintenance requirements as may be provided by Merck from time to time. FLX shall be responsible for any failure of the Merck Compound to meet the Specifications to the extent caused by shipping, storage or handling conditions after Delivery to FLX hereunder.
(a) In the event that either Party becomes aware that any Compound may have a Non-Conformance, despite testing and quality assurance activities (including any activities conducted by the Parties under Section 8.8.1), such Party shall immediately notify the other Party in accordance with the procedures of the Clinical Quality Agreement. The Parties shall investigate any Non-Conformance in accordance with Section 8.9 (Investigations) and any discrepancy between them shall be resolved in accordance with Section 8.8.3.
(b) In the event that any proposed or actual shipment of the Merck Compound (or portion thereof) shall be agreed to have a Non-Conformance at the time of Delivery to FLX, then unless otherwise agreed to by the Parties, Merck shall replace such Merck Compound as is found to have a Non-Conformance (with respect to Merck Compound that has not yet been administered in the course of performing the Study). Unless otherwise agreed to by the Parties in writing, [***] with respect to any Merck Compound that is found to have a Non-Conformance at the time of Delivery shall be [***]; provided that, for clarity, [***]. In the event Merck Compound is lost or damaged [***], Merck shall provide additional Merck Compound (if available for the Study) to FLX; provided that [***] such replaced Merck Compound; and provided further that [***]. Except as set forth in the foregoing sentence, Merck shall have no obligation to provide replacement Merck Compound for any Merck Compound supplied hereunder other than such Merck Compound as has been agreed or determined to have a Non-Conformance at the time of Delivery to FLX.
(c) FLX shall be responsible for, and Merck shall have no obligation or liability with respect to, any FLX Compound supplied hereunder that is found to have a Non-Conformance. FLX shall replace any FLX Compound as is found to have a Non-Conformance (with respect to FLX Compound that has not yet been administered in the course of performing the Study). Unless otherwise agreed to by the Parties in writing, [***] with respect to any FLX Compound that is found to have a Non-Conformance at the time of Delivery shall be [***]; provided that, for clarity, [***].
8.8.3. Resolution of Discrepancies. Disagreements regarding any determination of Non-Conformance by FLX shall be resolved in accordance with the provisions of the Clinical Quality Agreement.
8.9. Investigations. The process for investigations of any Non-Conformance shall be handled in accordance with the Clinical Quality Agreement.
8.10. Shortage; Allocation. In the event that a Partys Compound is in short supply such that a Party reasonably believes in good faith that it will not be able to fulfill its supply obligations hereunder with respect to its Compound, such Party will provide prompt written notice to the other Party thereof (including the shipments of Compound hereunder expected to be impacted and the quantity of its Compound that such Party reasonably determines it will be able to supply) and the Parties will promptly discuss such situation (including how the quantity of Compound that such Party is able to supply hereunder will be allocated within the Study). In such event, the Party experiencing such shortage shall (i) use its commercially reasonable efforts to remedy the situation giving rise to such shortage and to take action to minimize the impact of the shortage on the Study, and (ii) [***].
8.11. Records; Audit Rights. FLX shall keep complete and accurate records pertaining to its use and disposition of Merck Compound (including its storage, shipping (cold chain) and chain of custody activities) and, upon request of Merck, [***], shall make such records available during regular business hours to review by Merck for the purpose of conducting investigations for the determination of Merck Compound safety and/or efficacy and FLXs compliance with this Agreement with respect to the Merck Compound.
8.12. Quality. Quality matters related to the Manufacture of the Compounds shall be governed by the terms of the Clinical Quality Agreement in addition to the relevant quality provisions of this Agreement.
8.13. Quality Control. Each Party shall implement and perform operating procedures and controls for sampling, stability and other testing of its Compound, and for validation, documentation and release of its Compound and such other quality assurance and quality control procedures as are required by the Specifications, cGMPs and the Clinical Quality Agreement.
8.14. Audits and Inspections. The Parties audit and inspection rights related to this Agreement shall be governed by the terms of the Clinical Quality Agreement.
8.15. Recalls. Recalls of the Compounds shall be governed by the terms of the Clinical Quality Agreement.
8.16.1. It is understood and agreed between the Parties that any payments made and any other consideration given under this Agreement are each exclusive of any value added or similar tax (VAT), which shall be added thereon as applicable and at the relevant rate. Subject to Section 8.16.1, where VAT is properly charged by the supplying Party and added to a payment made or other consideration provided (as applicable) under this Agreement, the Party making the payment or providing the other consideration (as applicable) will pay the amount of VAT properly
chargeable only on receipt of a valid tax invoice from the supplying Party issued in accordance with the laws and regulations of the country in which the VAT is chargeable. Each Party agrees that it shall provide to the other Party any information and copies of any documents within its Control to the extent reasonably requested by the other Party for the purposes of (i) determining the amount of VAT chargeable on any supply made under this Agreement, (ii) establishing the place of supply for VAT purposes, or (iii) complying with its VAT reporting or accounting obligations.
8.16.2. Where one Party or its Affiliate (the First Party) is treated as making supply of goods or services in a particular jurisdiction (for VAT purposes) [***], and the other Party or its Affiliate (the Second Party) is treated as receiving such supply in the same jurisdiction, thus resulting in an amount of VAT being properly chargeable on such supply, the Second Party shall only be obliged to pay to the First Party the amount of VAT properly chargeable on such supply (and no other amount). The Second Party shall pay such VAT to the First Party on receipt of a valid VAT invoice from the First Party (issued in accordance with the laws and regulations of the jurisdiction in which the VAT is properly chargeable). Each Party agrees to (i) use its reasonable efforts to determine and agree the value of the supply that has been made and, as a result, the corresponding amount of VAT that is properly chargeable and (ii) provide to the other Party any information or copies of documents in its Control as are reasonably necessary to evidence that such supply will take, or has taken, place in the same jurisdiction (for VAT purposes).
9.1. Confidential Information. Subject to Section 13.4.8, FLX and Merck agree to hold in confidence any Confidential Information provided by or on behalf of the other Party, and neither Party shall use Confidential Information of the other Party except to fulfill such Partys obligations under this Agreement or exercising its rights. Without limiting the foregoing, the Receiving Party may not, without the prior written permission of the Disclosing Party, disclose any Confidential Information of the Disclosing Party to any Third Party except to the extent disclosure (i) is required by Applicable Law; (ii) is pursuant to the terms of this Agreement; or (iii) is necessary for the conduct of the Study, and in each case ((i) through (iii)) provided that the Receiving Party shall provide reasonable advance notice to the Disclosing Party before making such disclosure. For the avoidance of doubt, FLX may, without Mercks consent, disclose Confidential Information to clinical trial sites and clinical trial investigators performing the Study, the data safety monitoring and advisory board relating to the Study, and Regulatory Authorities working with FLX on the Study, in each case to the extent necessary for the performance of the Study and provided that such Persons (other than governmental entities) are bound by an obligation of confidentiality at least as stringent as the obligations contained herein.
9.2. Inventions. Notwithstanding the foregoing: (i) Inventions that constitute Confidential Information and are jointly owned by the Parties, shall constitute the Confidential Information of both Parties and each Party shall have the right to use and disclose such Confidential Information consistent with Articles 10, 11 and 12; and (ii) Inventions that constitute Confidential Information and are solely owned by one Party shall constitute the Confidential Information of that Party and each Party shall have the right to use and disclose such Confidential Information consistent with Articles 10, 11 and 12.
9.3. Personal Identifiable Data. All Confidential Information containing personal identifiable data shall be handled in accordance with all Applicable Laws relating to data protection and privacy.
9.4. Publicity/Use of Names. No disclosure of the existence, or the terms, of this Agreement may be made by either Party, and no Party shall use the name, trademark, trade name or logo of the other Party, its Affiliates or their respective employee(s) in any publicity, promotion, news release or disclosure relating to this Agreement or its subject matter, without the prior express written permission of that other Party, except as may be required by Applicable Law.
10.1. Joint Ownership, Prosecution and Enforcement.
10.1.1. Joint Ownership and Prosecution.
(d) Except as expressly provided in Section 10.1.1(c) and in furtherance and not in limitation of Section 9.1, each Party agrees to make no Patent Application based on the other Partys Confidential Information, and to give no assistance to any Third Party for such application, without the other Partys prior written authorization.
10.1.2. Patent Enforcement
(a) Each Party shall promptly notify the other in writing of any actual or threatened infringement or misappropriation by a Third Party of any Joint Patent or Jointly Owned Invention of which such Party becomes aware (Third Party Infringement).
(b) [***] shall have the first right to initiate legal action to [***]. In the event that [***] fails to initiate or defend such action by the earlier of (i) [***] after first being notified or made aware of such Third Party Infringement and (ii) [***] before the expiration for initiating or defending such action, [***] shall have the right to initiate or defend such action at its sole expense.
(c) [***] shall have the first right to initiate legal action to enforce all Joint Patents and Jointly Owned Inventions against Third Party Infringement, where such Third Party Infringement [***] or to defend any declaratory judgment action relating thereto, at its sole expense. In the event that [***] fails to initiate or defend such action by the earlier of (i) [***] after first being notified or made aware of such Third Party Infringement and (ii) [***] before the expiration for initiating or defending such action, [***] shall have the right to do so at its sole expense.
(d) The Parties shall cooperate in good faith to jointly control legal action to enforce all [***] against any Third Party Infringement where such Third Party Infringement [***] or to defend any declaratory judgment action relating thereto, and [***]. Notwithstanding the foregoing, either Party shall have the right to opt-out of controlling such legal action by providing written notice to the other Party by the earliest of (1) [***] after first being noticed of such Third Party Infringement, (2) [***] before the expiration date for filing such action, (3) [***] before the expiration date for filing an answer to a complaint in a declaratory judgment action, and (4) [***] after receipt of an application to the FDA under Section 351(k) of the U.S. Public Health Services Act (42 U.S.C. 262(k)), or to a similar agency under any similar provisions in another country, seeking approval of a biosimilar or interchangeable biological product of the Merck Compound, whichever comes first.
(e) If one Party (the Enforcing Party) brings any prosecution or enforcement action or proceeding against a Third Party with respect to any [***], the second Party (the Non-Enforcing Party) agrees to be joined as a party plaintiff where necessary and to give the Enforcing Party reasonable assistance and authority to file and prosecute the suit, at the Enforcing Partys cost and expense. The costs and expenses of the Enforcing Party under this Section 10.1.2 shall be borne by such Enforcing Party, and any damages or other monetary awards recovered shall be shared as follows: [***]. A settlement or consent judgment or other voluntary final disposition of a suit under this Section 10.1.2 may not be entered into without the consent of the Party not bringing the suit.
10.2. Inventions Owned by FLX. [***]. FLX shall (a) be entitled to file and prosecute in its own name Patent Applications in respect of FLX Inventions and (b) own Patents that issue from any such Patent Applications in respect of FLX Inventions. For the avoidance of doubt, any Invention [***].
10.3. Inventions Owned by Merck. [***]. Merck shall (a) be entitled to file and prosecute in its own name Patent Applications in respect of Merck Inventions and (b) own Patents that issue from any such Patent Applications in respect of Merck Inventions. For the avoidance of doubt, any Invention [***].
10.4. Mutual Freedom to Operate for Combination Inventions.
10.4.1. FLX License to Merck. FLX hereby grants to Merck a non-exclusive, worldwide, royalty-free, fully paid-up, transferable and sublicensable license to any patent Controlled by FLX that (a) [***] (the FLX Background Patents) solely for the purposes of: [***].
10.4.2. Merck License to FLX. Merck hereby grants to FLX a non-exclusive, worldwide, royalty-free, fully paid-up, transferable and sublicensable license to any patent Controlled by Merck that (a) [***] (the Merck Background Patents) solely for the purposes of: [***].
10.4.3. No Other Rights. For clarity, the terms of this Section 10.4 do not provide Merck or FLX with any rights, title or interest or any license to the other Partys intellectual property rights which [***].
10.4.4. Termination. Any and all licenses granted under this Section 10.4 shall terminate upon the expiration or earlier termination of this Agreement and shall not survive such expiration or termination; provided, however [***].
10.5. Ownership of Other Inventions. Ownership of all Inventions other than Jointly Owned Inventions, Merck Inventions and FLX Inventions shall be based on inventorship as determined under United States patent law.
Reprints; Rights of Cross-Reference.
Consistent with applicable copyright and other laws, each Party may use, refer to, and disseminate reprints of scientific, medical and other published articles and materials from journals, conferences and/or symposia relating to the Study that disclose the name of a Party, provided, however, that such use does not constitute an endorsement of any commercial product or service by the other Party.
Publications; Press Releases.
12.1. Clinical Trial Registry. FLX shall register the Study with the Clinical Trials Registry located at www.clinicaltrials.gov and is committed to timely publication of the results following Study Completion, after taking appropriate action to secure intellectual property rights (if any) arising from the Study. The publication of the results of the Study will be in accordance with the Protocol.
12.2. Publication. Each Party shall use reasonable efforts to publish or present scientific papers dealing with the Study in accordance with accepted scientific practice. The Parties agree that prior to submission of the results of the Study for publication or presentation or any other dissemination of such results including oral dissemination, the publishing Party shall invite the other to comment on the content of the material to be published, presented, or otherwise disseminated according to the following procedure:
12.2.1. [***], the publishing Party shall provide to the other Party the full details of the proposed publication, presentation, or dissemination in an electronic version (cd-rom or email attachment). Upon written request from the other Party, the publishing Party agrees not to submit data for publication/presentation/dissemination for an additional [***] in order to allow for actions to be taken to preserve rights for patent protection.
12.2.2. The publishing Party shall give reasonable consideration to any request by the other Party made within the periods mentioned in Section 12.2.1 to modify the publication and the Parties shall work in good faith and in a timely manner to resolve any issue regarding the content for publication.
12.2.3. The publishing Party shall remove all Confidential Information of the other Party before finalizing the publication.
12.3. Press Releases. Promptly following the Effective Date, FLX may issue the press release attached hereto as Appendix C. Unless otherwise required by Applicable Law, neither Party shall make any public announcement concerning this Agreement without the prior written consent of the other Party. To the extent a Party desires to make such public announcement, such Party shall provide the other Party with a draft thereof at least [***] prior to the date on which such Party would like to make the public announcement.
Representations and Warranties; Disclaimers.
13.1. Due Authorization. Each of FLX and Merck represents and warrants to the other that: (a) it has the corporate power and authority and the legal right to enter into this Agreement and perform its obligations hereunder; (b) it has taken all necessary corporate action on its part required to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder; and (c) this Agreement has been duly executed and delivered on behalf of such Party and constitutes a legal, valid and binding obligation of such Party that is enforceable against it in accordance with its terms.
13.2.1. FLX Compound. FLX hereby represents and warrants to Merck that: (a) FLX has the full right, power and authority to grant all of the licenses granted to Merck under this Agreement; and (b) FLX Controls the FLX Compound.
13.2.2. Merck Compound. Merck hereby represents and warrants to FLX that: (a) Merck has the full right, power and authority to grant all of the licenses granted to FLX under this Agreement; and (b) Merck Controls the Merck Compound.
13.3. Results. FLX does not undertake that the Study shall lead to any particular result, nor is the success of the Study guaranteed. Neither Party shall be liable for any use that the other Party may make of the Clinical Data, or Sample Testing Results that are shared between the Parties in accordance with the Data Sharing and Sample Testing Schedule, nor for advice or information given in connection therewith.
13.4.1. In performing their respective obligations hereunder, the Parties acknowledge that the corporate policies of FLX and Merck and their respective Affiliates require that each Partys business be conducted within the letter and spirit of the law. By signing this Agreement, each Party agrees to conduct the business contemplated herein in a manner that is consistent with all Applicable Law, including the Stark Act, Anti-Kickback Statute, Sunshine Act, and the U.S. Foreign Corrupt Practices Act, good business ethics, and its ethics and other corporate policies and agrees to abide by the spirit of the other Partys guidelines, which may be provided by such other Party from time to time.
13.4.2. Specifically, each Party represents and warrants that it has not, and covenants that it, its Affiliates, and its and its Affiliates directors, employees, officers, and anyone acting on its behalf, will not, in connection with the performance of this Agreement, directly or indirectly, make, promise, authorize, ratify or offer to make, or take any action in furtherance of, any payment or transfer of anything of value for the purpose of influencing, inducing or rewarding any act, omission or decision to secure an improper advantage; or improperly assisting it in obtaining or retaining business for it or the other Party, or in any way with the purpose or effect of public or commercial bribery.
13.4.3. Neither Party shall contact, or otherwise knowingly meet with, any Government Official for the purpose of discussing activities arising out of or in connection with this Agreement, without the prior written approval of the other Party, except where such meeting is consistent with the purpose and terms of this Agreement and in compliance with Applicable Law.
13.4.4. Each Party represents and warrants that it (a) is not excluded, debarred, suspended, proposed for suspension or debarment, in Violation or otherwise ineligible for government programs; and (b) has not employed or subcontracted with any Person for the performance of the Study who is excluded, debarred, suspended, proposed for suspension or debarment, or is in Violation or otherwise ineligible for government programs.
13.4.5. Each Party represents and warrants that, except as disclosed to the other in writing prior to the Effective Date, such Party: (a) does not have any interest that directly or indirectly conflicts with its proper and ethical performance of this Agreement; (b) shall maintain arms length relations with all Third Parties with which it deals for or on behalf of the other in performance of this Agreement; and (c) has provided complete and accurate information and documentation to the other Party, the other Partys Affiliates and its and their personnel in the course of any due diligence conducted by the other Party for this Agreement, including disclosure of any officers, employees, owners or Persons directly or indirectly retained by such Party in relation to the performance of this Agreement who are Government Officials or relatives of Government Officials. Each Party shall make all further disclosures to the other Party as are necessary to ensure the information provided remains complete and accurate throughout the Term. Subject to the foregoing, each Party agrees that it shall not hire or retain any Government Official to assist in its performance of this Agreement, with the sole exception of conduct of or participation in clinical trials under this Agreement, provided that such hiring or retention shall be subject to the completion by the hiring or retaining Party of a satisfactory anti-corruption and bribery (e.g., FCPA) due diligence review of such Government Official. Each Party further covenants that any future information and documentation submitted to the other Party as part of further due diligence or a certification shall be complete and accurate.
13.4.6. Each Party shall have the right during the Term, and for a period of [***], to conduct an investigation and audit of the other Partys activities, books and records, to the extent they relate to that other Partys performance under this Agreement, to verify compliance with the terms of this Section 13.4. Such other Party shall cooperate fully with such investigation or audit, the scope, method, nature and duration of which shall be at the sole reasonable discretion of the Party requesting such audit. [***]. The auditing Party shall provide the other Party with [***] advance notice prior to such audit.
13.4.7. Each Party shall use commercially reasonable efforts to ensure that all transactions under the Agreement are properly and accurately recorded in all material respects on its books and records and that each document upon which entries in such books and records are based is complete and accurate in all material respects. Each Party further represents, warrants and covenants that all books, records, invoices and other documents relating to payments and
expenses under this Agreement are and shall be complete and accurate and reflect in reasonable detail the character and amount of transactions and expenditures. Each Party shall maintain a system of internal accounting controls reasonably designed to ensure that no off-the-books or similar funds or accounts will be maintained or used in connection with this Agreement.
13.4.8. Each Party agrees that in the event that the other Party believes in good faith that there has been a possible violation of any provision of Section 13.4, such other Party may make full disclosure of such belief and related information needed to support such belief at any time and for any reason to any competent government bodies and agencies, and to anyone else such Party determines in good faith has a legitimate need to know.
13.4.9. Each Party shall comply with its own ethical business practices policy and any corporate integrity agreement (if applicable) to which it is subject, and shall conduct its Study-related activities in accordance with Applicable Law. Each Party shall ensure that all of its employees involved in performing its obligations under this Agreement are made specifically aware of the compliance requirements under this Section 13.4. In addition, each Party shall ensure that all such employees participate in and complete mandatory compliance training to be conducted by each Party, including specific training on anti-bribery and corruption, prior to his/her performance of any obligations or activities under this Agreement. Each Party shall certify its continuing compliance with the requirements under this Section 13.4 on a periodic basis during the Term in such form as may be reasonably specified by the other Party.
13.4.10. Each Party shall have the right to terminate this Agreement immediately upon violation of this Section 13.4 in accordance with Section 6.6.
13.5. DISCLAIMER. EXCEPT AS EXPRESSLY PROVIDED HEREIN, MERCK MAKES NO WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, WITH RESPECT TO THE MERCK COMPOUND, AND FLX MAKES NO WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, WITH RESPECT TO THE FLX COMPOUND.
Insurance; Indemnification; Limitation of Liability.
14.1. Insurance. Each Party warrants that it maintains a policy or program of insurance or self-insurance at levels sufficient to support the indemnification obligations assumed herein. Upon request, a Party shall provide evidence of such insurance.
14.2.1. Indemnification by FLX. FLX agrees to defend, indemnify and hold harmless Merck, its Affiliates, and its and their employees, directors, subcontractors and agents from and against any loss, damage, reasonable costs and expenses (including reasonable attorneys fees and expenses) incurred in connection with any claim, proceeding, or investigation by a Third Party arising out of this Agreement or the Study (a Liability), [***] the extent that such Liability was directly caused by [***].
14.2.2. Indemnification by Merck. Merck agrees to defend, indemnify and hold harmless FLX, its Affiliates, and its and their employees, directors, Subcontractors and agents from and against any Liability to the extent such Liability was directly caused by [***].
14.2.3. Procedure. The obligations of Merck and FLX under this Section 14.2 are conditioned upon the delivery of written notice to Merck or FLX, as the case might be, of any potential Liability within a reasonable time after a Party becomes aware of such potential Liability. The indemnifying Party will have the right to assume the defense of any suit or claim related to the Liability (using counsel reasonably satisfactory to the indemnified Party) if it has assumed responsibility for the suit or claim in writing; provided that the indemnified Party may assume the responsibility for such defense to the extent the indemnifying Party does not do so in a timely manner). The indemnified Party may participate in (but not control) the defense thereof at its sole cost and expense. The Party controlling such defense (the Defending Party) shall keep the other Party (the Other Party) advised of the status of such action, suit, proceeding or claim and the defense thereof and shall consider recommendations made by the Other Party with respect thereto. The Defending Party shall not agree to any settlement of such action, suit, proceeding or claim without the prior written consent of the Other Party, which shall not be unreasonably withheld. The Defending Party, but solely to the extent the Defending Party is also the indemnifying Party, shall not agree to any settlement of such action, suit, proceeding or claim or consent to any judgment in respect thereof that does not include a complete and unconditional release of the Other Party from all liability with respect thereto or that imposes any liability or obligation on the Other Party without the prior written consent of the Other Party.
14.2.4. Study Subjects. FLX shall not offer compensation on behalf of Merck to any Study subject or bind Merck to any indemnification obligations in favor of any Study subject. Merck shall not offer compensation on behalf of FLX to any Study subject or bind FLX to any indemnification obligations in favor of any Study subject.
14.3. LIMITATION OF LIABILITY. IN NO EVENT SHALL EITHER PARTY (OR ANY OF ITS AFFILIATES OR SUBCONTRACTORS) BE LIABLE TO THE OTHER PARTY UNDER ANY THEORY FOR, NOR SHALL ANY INDEMNIFIED PARTY HAVE THE RIGHT TO RECOVER, ANY SPECIAL, INDIRECT, INCIDENTAL, CONSEQUENTIAL OR OTHER SIMILAR DAMAGES OR ANY PUNITIVE DAMAGES OR ANY LOST PROFIT, LOST SALE OR LOST OPPORTUNITY DAMAGES (WHETHER SUCH CLAIMED DAMAGES ARE DIRECT OR INDIRECT), WHETHER ARISING DIRECTLY OR INDIRECTLY OUT OF (A) THE MANUFACTURE OR USE OF ANY COMPOUND SUPPLIED HEREUNDER OR (B) ANY BREACH OF OR FAILURE TO PERFORM ANY OF THE PROVISIONS OF THIS AGREEMENT OR ANY REPRESENTATION, WARRANTY OR COVENANT CONTAINED IN OR MADE PURSUANT TO THIS AGREEMENT, EXCEPT THAT SUCH LIMITATION SHALL NOT APPLY TO DAMAGES PAID OR PAYABLE TO A THIRD PARTY BY AN INDEMNIFIED PARTY FOR WHICH THE INDEMNIFIED PARTY IS ENTITLED TO INDEMNIFICATION HEREUNDER OR WITH RESPECT TO DAMAGES ARISING OUT OF OR RELATED TO A PARTYS BREACH OF ITS OBLIGATIONS UNDER THIS AGREEMENT WITH RESPECT TO USE, DISCLOSURE, LICENSE, ASSIGNMENT OR OTHER TRANSFER OF [***].
Use of Name.
Except as otherwise provided herein, neither Party shall have any right, express or implied, to use in any manner the name or other designation of the other Party or any other trade name, trademark or logo of the other Party for any purpose in connection with the performance of this Agreement without the other Partys prior written consent.
If, in the performance of this Agreement, one of the Parties is prevented, hindered or delayed by reason of any cause beyond such Partys reasonable control (e.g., war, riots, fire, strike, acts of terror, governmental laws), such Party shall be excused from performance to the extent that it is necessarily prevented, hindered or delayed (Force Majeure). The non-performing Party shall notify the other Party of such Force Majeure within [***] days after such occurrence by giving written notice to the other Party stating the nature of the event, its anticipated duration, and any action being taken to avoid or minimize its effect. The suspension of performance will be of no greater scope and no longer duration than is necessary and the non-performing Party shall use commercially reasonable efforts to remedy its inability to perform.
Entire Agreement; Amendment; Waiver.
This Agreement, together with the Appendices and Schedules hereto and the Related Agreements, constitutes the sole, full and complete agreement by and between the Parties with respect to the subject matter of this Agreement, and all prior agreements, understandings, promises and representations, whether written or oral, with respect thereto are superseded by this Agreement. In the event of a conflict between a Related Agreement and this Agreement, the terms of this Agreement shall control. No amendments, changes, additions, deletions or modifications to or of this Agreement shall be valid unless reduced to writing and signed by the Parties hereto. Any term or condition of this Agreement may be waived at any time by the Party that is entitled to the benefit thereof, but no such waiver shall be effective unless set forth in a written instrument duly executed by or on behalf of the Party waiving such term or condition. The waiver by either Party of any right hereunder or of the failure to perform or of a breach by the other Party shall not be deemed a waiver of any other right hereunder or of any other breach or failure by said other Party whether of a similar nature or otherwise.
Assignment and Affiliates.
Neither Party shall assign or transfer this Agreement without the prior written consent of the other Party; provided, however, that either Party may assign all or any part of this Agreement to: (i) one or more of its Affiliates; [***] without the other Partys consent, and any and all rights and obligations of either Party may be exercised or performed by its Affiliates, provided that any such Affiliate [***] agrees agree to be bound by this Agreement, and provided further that [***]. Any assignment not in conformance with this Article 18 shall be null and void.
If any provision of this Agreement is held to be illegal, invalid or unenforceable, the remaining provisions shall remain in full force and effect and will not be affected by the illegal, invalid or unenforceable provision. In lieu of the illegal, invalid or unenforceable provision, the Parties shall negotiate in good faith to agree upon a reasonable provision that is legal, valid and enforceable to carry out as nearly as practicable the original intention of the entire Agreement.
No Additional Obligations.
FLX and Merck have no obligation to renew this Agreement or apply this Agreement to any clinical trial other than the Study. Nothing in this Agreement obligates the Parties to enter into any other agreement (other than the Related Agreements) at this time or in the future.
Governing Law; Dispute Resolution.
21.1. The Parties shall attempt in good faith to settle all disputes arising out of or in connection with this Agreement in an amicable manner. Any claim, dispute or controversy arising out of or relating to this Agreement, including the breach, termination or validity hereof or thereof, shall be governed by and construed in accordance with the substantive laws of the State of New York, without giving effect to its choice of law principles.
21.2. Nothing contained in this Agreement shall deny either Partys right to seek injunctive or other equitable relief from a court of competent jurisdiction in the context of a bona fide emergency or prospective irreparable harm, and such an action may be filed or maintained notwithstanding any ongoing discussions between the Parties.
All notices or other communications that are required or permitted hereunder shall be in writing and delivered personally, sent by facsimile (and promptly confirmed by personal delivery or overnight courier), or sent by internationally-recognized overnight courier addressed as follows:
If to FLX, to:
FLX Bio, Inc.
561 Eccles Ave.
South San Francisco, CA 94080
Attention: Chief Operating Officer
With copy (which shall not constitute notice) to:
Cooley Godward Kronish LLP
3175 Hanover St.
Palo Alto, CA 94034-1130
If to Merck, to:
MSD International GmbH
6000 Luzern 6
Facsimile: +41 ###-###-####
With copies (which shall not constitute notice) to:
Relationship of the Parties.
The relationship between the Parties is and shall be that of independent contractors, and does not and shall not constitute a partnership, joint venture, agency or fiduciary relationship. Neither Party shall have the authority to make any statements, representations or commitments of any kind, or take any actions, that are binding on the other Party, except with the prior written consent of the other Party to do so. All Persons employed by a Party will be the employees of such Party and not of the other Party and all costs and obligations incurred by reason of any such employment shall be for the account and expense of such Party.
Counterparts and Due Execution.
This Agreement and any amendment may be executed in any number of counterparts (including by way of facsimile or electronic transmission), each of which shall be deemed an original, but all of which together shall constitute one and the same instrument, notwithstanding any electronic transmission, storage and printing of copies of this Agreement from computers or printers. When executed by the Parties, this Agreement shall constitute an original instrument, notwithstanding any electronic transmission, storage and printing of copies of this Agreement from computers or printers. For clarity, facsimile signatures and signatures transmitted via PDF shall be treated as original signatures.
Except where the context otherwise requires, wherever used, the singular will include the plural, the plural the singular, the use of any gender will be applicable to all genders, and the word or is used in the inclusive sense (and/or). Whenever this Agreement refers to a number of days, unless otherwise specified, such number refers to calendar days. The captions of this Agreement are for convenience of reference only and in no way define, describe, extend or limit the scope or intent of this Agreement or the intent of any provision contained in this Agreement. The term including as used herein shall be deemed to be followed by the phrase without limitation or like expression. The term will as used herein means shall. The terms hereof, hereto, herein and hereunder and words of similar import when used in this Agreement refer to this Agreement as a whole and no to any particular provision of this Agreement. References to Article, Section, Appendix or Schedule are references to the numbered sections of this Agreement and the appendices attached to this Agreement, unless expressly stated otherwise. Except where the context otherwise requires, references to this Agreement shall include the appendices attached to this Agreement. The language of this Agreement shall be deemed to be the language mutually chosen by the Parties and no rule of strict construction will be applied against either Party hereto.
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IN WITNESS WHEREOF, the respective representatives of the Parties have executed this Agreement as of the Effective Date.
|FLX Bio, Inc.|
|By:||/s/ Brian R. Wong|
|Brian R. Wong|
|Chief Executive Officer|
|MSD International GmbH|
|By:||/s/ Franz Escherich|
SUPPLY OF COMPOUND
Schedule of Deliveries for FLX475
|Quantity of Tablets|
Schedule of Deliveries for Pembrolizumab1,2
Pembrolizumab delivery dates and quantities are estimated. Dates and quantities may change based on Study requirements and agreement between the Parties. Total estimated quantities may [***].
FLX PRESS RELEASE
FLX BIO ANNOUNCES CLINICAL TRIAL COLLABORATION AGREEMENT WITH MERCK FOR ONGOING PHASE 1/2 STUDY OF FLX475
Trial will evaluate FLX Bios CCR4 inhibitor, FLX475, in combination with Mercks KEYTRUDA® (pembrolizumab), an anti-PD-1 therapy, in multiple types of cancer
SOUTH SAN FRANCISCO, Calif. November XX, 2018 FLX Bio, Inc., a clinical-stage, biopharmaceutical company focused on the development of oral small-molecule drugs that target drivers of cancer and other immune-related disorders, today announced that it has established a clinical trial collaboration agreement with Merck (known as MSD outside the U.S. and Canada) to conduct a Phase 1/2 study evaluating the safety and efficacy of the combination of KEYTRUDA® (pembrolizumab), Mercks anti-PD-1 therapy , and FLX Bios investigational oral small molecule CCR4 inhibitor, FLX475, in patients with multiple types of cancer.
The open-label, dose-escalation and cohort expansion Phase 1/2 study is enrolling patients with multiple types of cancer at leading cancer centers across the United States, Australia and Asia. In addition to evaluating the safety and tolerability of FLX475 as a monotherapy and in combination with pembrolizumab, the study will evaluate changes in the tumor microenvironment and the antitumor activity of both monotherapy and combination therapy. For more information please visit clinicaltrials.gov identifier NCT03674567.
We are extremely pleased to collaborate with Merck, an established leader in the field of cancer immunotherapy, said Brian Wong, M.D., Ph.D., CEO of FLX Bio. KEYTRUDA is an anti-PD1 immunotherapy that has demonstrated efficacy in a range of cancers. FLX475 targets a novel mechanism to selectively inhibit the recruitment of regulatory T cells (Treg) into the tumor, where Treg potentially suppress the anti-tumor immune response; thus FLX475 has the potential to deepen and broaden the efficacy of KEYTRUDA when combined. We are excited to collaborate with the Merck team to evaluate the efficacy of a combination of FLX475 and KEYTRUDA which we believe could substantially improve patient outcomes.
Keytruda® is a registered trademark of Merck Sharp & Dohme Corp, a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
FLX475 is a best-in-class oral, small molecule antagonist of CCR4 which selectively blocks suppressive regulatory T cells in tumor tissue and promotes a durable anti-tumor immune response. FLX Bio has completed a study of FLX475 in healthy volunteers, demonstrating that the compound is safe with excellent pharmacokinetic and pharmacodynamic properties. In preclinical studies, FLX475 inhibited tumor growth and increased tumor regression as a single agent. In addition, FLX475 enhanced the anti-tumor effects of various checkpoint inhibitors as well as immune agonist antibodies. FLX475 also has the potential to enhance cell-based immunotherapies such as CAR-T and cancer vaccines. In contrast to depleting antibody approaches, FLX475 selectively blocks the recruitment of regulatory T cells to the tumor site and does not deplete cells beneficial to an anti-tumor response or regulatory T cells in healthy tissue.
About FLX Bio
FLX Bio, Inc. is a privately-held biopharmaceutical company focused on the discovery, development and commercialization of best-in-class, oral small molecule therapeutics for the treatment of cancers and other immune disorders. Our lead compounds inhibit the CCR4 pathway which plays a key role in both suppressing the immune response to cancer and in the initiation, progression and persistence of allergic inflammation. We leverage big data and proprietary informatics together with our advanced drug discovery capabilities and deep biology expertise, to develop therapeutics that address key pressure points in pathways that propagate an abnormal immune response.
Located in South San Francisco, Calif., and funded by leading investors, including The Column Group (TCG), Kleiner Perkins (KP), Topspin Partners, GV (formerly Google Ventures) and Celgene Corporation, FLX Bio has assembled a leadership team and advisory group with a proven track record of success and team of scientists with substantial knowledge and expertise in drug discovery and translational areas essential to execute on this approach. For more information, please visit www.flxbio.com.
For FLX Bio, Inc.