Contract analysis

ARTICLE I — DEFINITIONS As used in this Agreement, the following terms shall have the meanings set forth below. Capitalized terms used but not defined in this Article I shall have the meanings ascribed to them elsewhere in this Agreement.

Section 1.1 "Affiliate" means, with respect to any Party, any entity that directly or indirectly controls, is controlled by, or is under common control with such Party. For purposes of this definition, "control" means the possession, directly or indirectly, of the power to direct or cause the direction of the management and policies of an entity, whether through the ownership of voting securities, by contract, or oth

Section 1.2 "Agreement" means this Master Clinical Trial Agreement, including all Exhibits, Schedules, and appendices attached hereto or incorporated herein by reference, as the same may be amended, modified, or supplemented from time to time in accordance with Section 15.6.

Section 1.3 "Applicable Law" means all applicable federal, state, and local laws, statutes, rules, regulations, ordinances, orders, decrees, guidelines, guidance documents, and directives, as the same may be in effect from time to time, including without limitation: (a) the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 301 et seq.; (b) regulations promulgated by the FDA at 21 C.F.R. Part 11 (Electronic Records; E

Section 1.4 "Briarcliff Policy" means Policy No. BM-CTL-2023-04182 issued by Briarcliff Mutual Insurance Company, 55 Constitution Plaza, Hartford, Connecticut 06103, providing clinical trial liability insurance coverage to Penterra, as more fully described in Article VIII and Exhibit E.

Section 1.5 "CLARION Trial" or "Study" means the Phase III, randomized, double-blind, placebo-controlled clinical trial of penterafenib (PPC-4871) versus placebo in subjects with advanced hepatocellular carcinoma who have received prior systemic therapy, conducted pursuant to the Protocol, as registered at ClinicalTrials.gov under identifier NCT05928174.

Section 1.6 "Closing Date" means the date on which all conditions precedent to the effectiveness of this Agreement have been satisfied or waived by the Party entitled to the benefit of such condition.

Section 1.7 "Confidential Information" means all information and data, whether oral, written, electronic, visual, or in any other form, that is disclosed by or on behalf of one Party (the "Disclosing Party") to the other Party (the "Receiving Party") in connection with this Agreement, including without limitation: (a) the Protocol and all Protocol-related information; (b) Investigational Product specifications, formu

Section 1.8 "CRO" means Meridian Contract Research Organization, Inc., a contract research organization separately engaged by Penterra pursuant to a Master Services Agreement dated January 15, 2023, to provide monitoring, data management, safety reporting, biostatistical analysis, and other clinical trial support services for the CLARION Trial.

Section 1.9 "EDC Platform" means the electronic data capture platform provided by Pinnacle Data Solutions, Inc. for the collection, management, and transfer of Study Data in connection with the CLARION Trial.

Section 1.10 "Effective Date" means the date on which all conditions precedent to this Agreement have been satisfied and this Agreement becomes operative, as set forth on the first page hereof.

Section 1.11 "First Patient In" or "FPI" means the date on which the first Subject is enrolled and randomized in the CLARION Trial at any Participating Site within the Veridian Network. The target date for First Patient In is August 14, 2023.

Section 1.12 "GCP" means Good Clinical Practice as defined by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ("ICH") Guideline E6(R2), as adopted by the FDA and as may be amended from time to time.

Section 1.13 "Global Principal Investigator" means Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, who has been designated by Penterra and Veridian to serve as the lead investigator for the CLARION Trial across all Participating Sites.

Section 1.14 "IND" means Investigational New Drug Application No. 157823, as filed by Penterra with the FDA for penterafenib (PPC-4871) and as amended from time to time.

Section 1.15 "Individual Site Agreement" means the joinder agreement to be executed by each Participating Site substantially in the form attached hereto as Exhibit C, pursuant to which each Participating Site agrees to be bound by the terms and conditions of this Agreement and the Protocol with respect to the conduct of the CLARION Trial at such Participating Site.

Section 1.16 "Investigational Product" means penterafenib (PPC-4871), a next-generation oral multi-kinase inhibitor, and matching placebo, as manufactured, labeled, and supplied by Penterra for use in the CLARION Trial in accordance with the Protocol.

Section 1.17 "Investigator" means each qualified physician designated as a principal investigator or sub-investigator at a Participating Site, who has been delegated responsibility for the conduct of the CLARION Trial at such Site and who has executed a Form FDA 1572 (Statement of Investigator) and an Investigator Undertaking in the form of Exhibit I.

Section 1.18 "IRB" means an Institutional Review Board constituted and operating in accordance with 21 C.F.R. Part 56 and applicable OHRP requirements, including the Graystone University Institutional Review Board (IRB Registration: IRB00012847) and the Veridian Central IRB, or any other IRB with jurisdiction over a Participating Site as applicable.

Section 1.19 "Participating Site" or "Site" means each academic medical center or affiliated research institution within the Veridian Network that has executed an Individual Site Agreement in the form of Exhibit C and has been activated for participation in the CLARION Trial, as listed in Schedule 1.

Section 1.20 "Protocol" means Protocol PPC-4871-III (CLARION), including the protocol synopsis attached hereto as Exhibit A, as the same may be amended, modified, or supplemented from time to time with the written approval of Penterra and the applicable IRB.

Section 1.21 "SAE" means a serious adverse event, as defined in 21 C.F.R. § 312.32 and the ICH E6(R2) Guideline, including any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is a medically important event that may jeopardi

Section 1.22 "Site Network" means Veridian Health Research Network, Inc.

Section 1.23 "Site Personnel" means all investigators, sub-investigators, study coordinators, research nurses, clinical research associates, data entry personnel, laboratory personnel, pharmacists, and other staff at a Participating Site who are involved in the conduct of the CLARION Trial at such Site.

Section 1.24 "Sponsor" means Penterra Pharmaceuticals Corp.

Section 1.25 "Study Data" means all data, information, results, analyses, records, reports, case report forms, source documents, laboratory results, imaging data, pharmacokinetic data, pharmacodynamic data, biomarker data, safety data, efficacy data, and all other data and information generated, collected, compiled, or derived in connection with the conduct of the CLARION Trial at any Participating Site, whether in e

Section 1.26 "Subject" means a human research participant who has provided informed consent and has been enrolled in the CLARION Trial at a Participating Site in accordance with the Protocol and applicable regulatory requirements.

Section 1.27 "Subject Injury" means any bodily injury, illness, disease, or adverse health consequence sustained by a Subject as a direct result of the Subject's participation in the CLARION Trial, including but not limited to injuries resulting from the administration of the Investigational Product or the performance of Protocol-required procedures.

Section 1.28 "Veridian Network" means the collective group of thirty-eight (38) academic medical centers and affiliated research institutions located across fourteen (14) states that are operated by or affiliated with Veridian Health Research Network, Inc., as listed in Schedule 1.

ARTICLE II — SCOPE OF AGREEMENT

Section 2.1 — Purpose. Penterra hereby engages Veridian, and Veridian hereby agrees, to coordinate and facilitate the conduct of the CLARION Trial across the Veridian Network in accordance with the terms and conditions set forth in this Agreement. The CLARION Trial is a Phase III, randomized, double-blind, placebo-controlled study of penterafenib (PPC-4871) versus placebo in patients with advanced hepatocellular carc

Section 2.2 — Site Participation Structure. Each Participating Site within the Veridian Network that wishes to participate in the CLARION Trial shall execute an Individual Site Agreement substantially in the form attached hereto as Exhibit C. Each Individual Site Agreement shall incorporate the terms and conditions of this Agreement by reference and shall set forth any site-specific terms, including the identity of t

Section 2.3 — Role of Veridian Central Administration. Veridian shall serve as the coordinating entity for network-wide administrative, regulatory, and operational functions in connection with the CLARION Trial. In this capacity, Veridian shall be responsible for: (a) facilitating the execution of Individual Site Agreements with each Participating Site; (b) coordinating and facilitating IRB approvals across the Verid

Section 2.4 — Third-Party Service Providers. Penterra has separately engaged the following third-party service providers in connection with the conduct of the CLARION Trial, as more fully described in Exhibit K: (a) Meridian Contract Research Organization, Inc. ("CRO") — Penterra has engaged Meridian CRO pursuant to a Master Services Agreement dated January 15, 2023, to provide clinical trial monitoring services, dat

Section 2.5 — Protocol Compliance. All Study activities conducted at each Participating Site shall be performed in strict accordance with the Protocol (as set forth in Exhibit A), GCP (ICH E6(R2)), and all Applicable Law. No deviation from the Protocol shall be made without the prior written approval of Penterra, except where such deviation is necessary to protect the immediate safety, rights, or welfare of a Subject

ARTICLE III — IRB AND REGULATORY APPROVALS

Section 3.1 — IRB Approval Required Prior to Enrollment. No Subject may be enrolled or randomized at any Participating Site until such Participating Site has obtained written approval from the applicable IRB for the Protocol, the informed consent form, and all other study documents requiring IRB approval in accordance with 21 C.F.R. Part 56 and applicable institutional policies. The lead sites shall obtain IRB approv

Section 3.2 — IND Maintenance. Penterra, as the holder of IND 157823 for penterafenib (PPC-4871), shall be solely responsible for all aspects of IND maintenance, including the submission of IND amendments, annual reports, safety reports, and other required submissions to the FDA in accordance with 21 C.F.R. Part 312. Each Participating Site and each Investigator shall provide Penterra with all information, data, repo

Section 3.3 — Regulatory Inspections. Each Participating Site shall permit and facilitate inspections by the FDA and other applicable regulatory authorities, as well as monitoring and audit visits by Penterra, Meridian CRO, and their authorized representatives, in connection with the CLARION Trial. Each Participating Site shall promptly notify Penterra, and Veridian shall promptly notify Penterra, of any inquiry, ins

Section 3.4 — Safety Reporting. Detailed safety reporting procedures for the CLARION Trial are set forth in Exhibit J. Without limiting the provisions of Exhibit J, the Parties agree to the following: (a) SAE Reporting by Sites: Each Participating Site and each Investigator shall report all SAEs to Penterra and to Meridian CRO within twenty-four (24) hours of becoming aware of the SAE. SAE reports shall be submitted

Section 4.1 — Total Compensation. The total compensation to be paid by Penterra to Veridian and the Participating Sites under this Agreement for the conduct of the CLARION Trial across all Veridian Network sites over the projected life of the Study shall not exceed Eighty Million Dollars ($80,000,000) (the "Total Deal Value"), subject to the component breakdown and payment schedule set forth in this Article IV and in

Section 4.2 — Component Breakdown. The Total Deal Value of Eighty Million Dollars ($80,000,000) is comprised of the following components: (a) Per-Patient Site Fees (Screen-to-Completion): Fifty-Two Thousand Dollars ($52,000) per Subject for each of the twelve hundred (1,200) planned Subjects from screening through study completion, for an aggregate amount of Sixty-Two Million Four Hundred Thousand Dollars ($62,400,00

Section 4.3 — Payment Milestones and Schedule. Payments under this Agreement shall be made in accordance with the following milestone-based payment schedule: (a) Start-Up Fees: Start-up fees of Seventy-Five Thousand Dollars ($75,000) per Participating Site shall be paid in two equal installments: (i) Fifty percent (50%) of the start-up fee (Thirty-Seven Thousand Five Hundred Dollars ($37,500)) shall be payable upon s

Section 4.4 — Payment Terms. All payments under this Agreement shall be due and payable within forty-five (45) calendar days from the date of receipt by Penterra of a proper invoice (the "Payment Period"). Invoices shall be submitted by Veridian on behalf of the Participating Sites to Penterra's clinical contracts department, attention: Samantha Novak, Director, Clinical Contracts, at 200 Biopharma Boulevard, Suite 1

Section 4.5 — Invoice Disputes. In the event that Penterra disputes any amount set forth in an invoice submitted by Veridian, Penterra shall provide Veridian with written notice of such dispute within fifteen (15) business days of receipt of the invoice. Such notice shall specify in reasonable detail the nature and basis of the dispute and the amount in dispute. The Parties shall endeavor in good faith to resolve any

Section 4.6 — Fair Market Value; Regulatory Compliance. The Parties acknowledge and agree that all payments to be made under this Agreement represent fair market value for the services to be rendered and the obligations to be performed by Veridian, the Participating Sites, and the Investigators hereunder. All payments under this Agreement have been structured in compliance with the applicable safe harbor requirements

Section 4.7 — Taxes. Each Party shall be responsible for the payment of any and all taxes, assessments, duties, or other governmental charges imposed on such Party in connection with this Agreement or the payments made hereunder. Veridian, as a tax-exempt organization recognized under Section 501(c)(3) of the Internal Revenue Code (Employer Identification Number: 23-4178205), shall provide Penterra with evidence of i

ARTICLE V — OBLIGATIONS OF THE SPONSOR

Section 5.1 — Supply of Investigational Product. Penterra shall supply penterafenib (PPC-4871) and matching placebo to each Participating Site in quantities sufficient for the conduct of the CLARION Trial at no cost to the Participating Sites or to the Subjects. Penterra shall be solely responsible for the manufacturing, quality control, labeling, packaging, and shipping of the Investigational Product in accordance w

Section 5.2 — Protocol and Study Documents. Penterra shall provide Veridian and each Participating Site with: (a) Protocol PPC-4871-III (CLARION), including any amendments thereto; (b) the current Investigator's Brochure for penterafenib (PPC-4871), including any updates thereto; (c) electronic case report forms ("eCRFs") via the Pinnacle EDC Platform; (d) a template informed consent form for adaptation by each Parti

Section 5.3 — Monitoring. Penterra, through Meridian CRO, shall conduct site monitoring visits at each Participating Site in accordance with GCP and the monitoring plan developed for the CLARION Trial. Site monitoring visits shall include, without limitation: (a) source document verification; (b) verification of informed consent documentation; (c) drug accountability reconciliation; (d) review of regulatory files; (e

Section 5.4 — Regulatory Submissions. Penterra shall be responsible for all regulatory submissions to the FDA in connection with the CLARION Trial, including without limitation IND amendments, protocol amendments, IND safety reports (as described in Section 3.4), IND annual reports, and all other submissions required under 21 C.F.R. Part 312. Penterra shall provide copies of relevant regulatory correspondence to Veri

Section 5.5 — Insurance. Penterra shall obtain and maintain clinical trial liability insurance coverage throughout the term of this Agreement and for a period of [2] years following Study completion, as more fully described in Article VIII. Penterra shall comply with the insurance requirements set forth in Article VIII and Exhibit E, including the obligation to name Veridian and each Participating Site as additional

Section 5.6 — Training. Penterra and Meridian CRO shall provide comprehensive training to Investigators and Site Personnel in connection with the CLARION Trial, including: (a) an investigator meeting to be held prior to First Patient In, at which the Protocol, study procedures, safety reporting requirements, EDC Platform operation, and regulatory requirements shall be reviewed; (b) site initiation visits at each Part

ARTICLE VI — OBLIGATIONS OF VERIDIAN AND PARTICIPATING SITES

Section 6.1 — Conduct of the Study. Each Participating Site shall conduct the CLARION Trial in accordance with the Protocol, GCP (ICH E6(R2)), IRB requirements, and all Applicable Law. Each Participating Site shall enroll Subjects in accordance with the inclusion and exclusion criteria set forth in the Protocol and shall not enroll any Subject who does not meet such criteria. Each Participating Site shall ensure that

Section 6.2 — Investigator Qualifications. Each principal investigator at a Participating Site shall: (a) execute a completed Form FDA 1572 (Statement of Investigator) in accordance with 21 C.F.R. § 312.53; (b) execute an Investigator Undertaking in the form attached hereto as Exhibit I; and (c) complete and submit a financial disclosure certification in accordance with 21 C.F.R. Part 54 and the Financial Disclosure

Section 6.3 — Records and Source Documentation. Each Participating Site shall prepare, maintain, and retain complete and accurate source documents and study records for each Subject enrolled at such Site, in accordance with GCP, 21 C.F.R. § 312.62, and applicable institutional policies. Source documents shall include, without limitation, medical records, hospital charts, laboratory reports, imaging reports, pharmacy

Section 6.4 — Access and Monitoring. Each Participating Site shall provide Penterra, Meridian CRO, and their authorized representatives with reasonable access to study records, source documents, and facilities at such Participating Site for the purposes of: (a) monitoring visits conducted in accordance with the monitoring plan; (b) audits conducted by or on behalf of Penterra; (c) inspections by the FDA or other appl