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EXHIBIT I

FORM OF INVESTIGATOR UNDERTAKING

Attached to and forming part of the Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA") by and between Penterra Pharmaceuticals Corp. ("Sponsor") and Veridian Health Research Network, Inc. ("Site Network").

Protocol Reference: Protocol PPC-4871-III — CLARION (Clinical Assessment of Response with Longitudinal Investigation in ONcology)

Investigational Product: Penterafenib (PPC-4871)

IND Number: IND 157823

ClinicalTrials.gov Identifier: NCT05928174

PREAMBLE AND RECITALS

This Investigator Undertaking (this "Undertaking") is executed by the undersigned investigator (the "Investigator") in connection with Investigator's participation in the clinical trial conducted under Protocol PPC-4871-III, titled CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology (the "Study" or the "CLARION Trial"). The CLARION Trial is a Phase III, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of penterafenib (PPC-4871) in adult subjects with advanced hepatocellular carcinoma (HCC) who have received at least one line of prior systemic therapy.

WHEREAS, the Sponsor of the CLARION Trial is Penterra Pharmaceuticals Corp. ("Sponsor" or "Penterra"), a corporation organized and existing under the laws of the State of Delaware, with its principal offices located at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540;

WHEREAS, Veridian Health Research Network, Inc. ("Site Network" or "Veridian"), a 501(c)(3) nonprofit corporation organized and existing under the laws of the State of Delaware, with its principal offices located at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104, serves as the coordinating network for clinical trial sites participating in the CLARION Trial;

WHEREAS, the MCTA governs the conduct of the CLARION Trial across thirty-eight (38) participating Veridian Network member sites located in fourteen (14) states across the United States;

WHEREAS, the CLARION Trial is designed to enroll a total of approximately 1,200 subjects, randomized in a 2:1 ratio (800 subjects to the penterafenib treatment arm and 400 subjects to the matching placebo arm), in accordance with the statistical analysis plan set forth in the Protocol;

WHEREAS, the Investigator's execution of this Undertaking is a condition precedent to the Investigator's participation in the CLARION Trial and is required under Section 4.3(b) of the MCTA as a component of the site activation package;

WHEREAS, Investigator desires to participate in the CLARION Trial in the capacity and at the site identified herein, and acknowledges the importance of the obligations set forth in this Undertaking to the integrity of the Study and the safety and welfare of study subjects;

NOW, THEREFORE, in consideration of the foregoing recitals and the mutual covenants and agreements set forth herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Investigator agrees as follows:

Capitalized terms used but not otherwise defined in this Undertaking shall have the meanings ascribed to them in the MCTA, unless the context requires otherwise.

SECTION 1: IDENTIFICATION OF INVESTIGATOR

The Investigator provides the following information for purposes of identification and regulatory documentation:

Full Legal Name of Investigator: ________

Title / Academic Appointment: ________

Professional Degree(s): ________ (e.g., M.D., Ph.D., D.O., Pharm.D.)

Board Certification(s): ________

Name of Participating Site Institution: ________ (Must be a Veridian Health Research Network member institution in good standing)

Site Number Under the MCTA: ________

Address of Site Institution: ________

________________________________________

Role Designation (check one):

Principal Investigator

Sub-Investigator

Global or Co-Principal Investigator Designation (if applicable, check one):

Global Principal Investigator (e.g., Dr. Catherine Aldridge, M.D., Ph.D., Graystone University Medical Center, Site 001)

Co-Principal Investigator (e.g., Dr. Howard Matsuoka, M.D., Lakemont Medical Center, Site 002)

Not applicable

Medical License Number: ________

State(s) of Licensure: ________

DEA Registration Number (if applicable): ________

SECTION 2: PROTOCOL COMPLIANCE UNDERTAKINGS

2.1 Receipt and Review of Study Documents. Investigator hereby acknowledges receipt and thorough review of Protocol PPC-4871-III (CLARION), including all amendments thereto issued as of the date of this Undertaking, and the current version of the Investigator's Brochure for penterafenib (PPC-4871), including all supplements and updates provided by Sponsor. Investigator confirms that Investigator has had adequate opportunity to review these documents and to discuss any questions or concerns with the Sponsor's medical monitor prior to executing this Undertaking.

2.2 Conduct in Accordance with Protocol. Investigator undertakes to conduct the CLARION Trial strictly in accordance with the Protocol as approved by the applicable Institutional Review Board ("IRB") and accepted by the U.S. Food and Drug Administration ("FDA") under IND 157823. Without limiting the generality of the foregoing, Investigator shall adhere to (a) all subject inclusion and exclusion criteria as specified in Protocol Sections 5.1 and 5.2; (b) the dosing schedules, dose modification guidelines, and dose interruption criteria set forth in Protocol Section 6; (c) the visit windows and schedule of assessments set forth in Protocol Section 7 and the Schedule of Events (Protocol Appendix A); and (d) all procedures required for the determination and adjudication of study endpoints as specified in Protocol Sections 8 and 9.

2.3 Endpoint Assessments. The primary endpoint of the CLARION Trial is overall survival (OS). The key secondary endpoints include progression-free survival (PFS) as assessed by blinded independent central review (BICR) using RECIST v1.1, objective response rate (ORR), and duration of response (DOR). Investigator agrees to conduct all clinical assessments, imaging studies, laboratory evaluations, patient-reported outcome measurements, and other procedures required under the Protocol for the determination of the primary and secondary endpoints. Investigator further agrees to comply with the tumor assessment schedule and to ensure timely submission of imaging data to the independent radiology review center designated by Sponsor.

2.4 Protocol Deviations. Investigator shall not implement any deviation from or change to the Protocol unless such deviation is (a) necessary to eliminate an immediate hazard to the safety, rights, or well-being of study subjects, in which case the Investigator shall take appropriate action and promptly document the deviation and notify the Sponsor and the applicable IRB, or (b) specifically authorized in advance in writing by Sponsor. In the event of any protocol deviation, whether or not it falls within the categories described in clauses (a) or (b) above, Investigator shall promptly and accurately document the deviation, including the nature of the deviation, the reason therefor, the date(s) on which it occurred, the subject(s) affected, and any corrective or preventive actions taken. Investigator shall report all protocol deviations to Sponsor, Meridian Contract Research Organization, Inc. ("Meridian CRO"), and the applicable IRB in accordance with the timelines and procedures specified in the Protocol and the applicable IRB policies.

2.5 Qualified Personnel. Investigator shall ensure that all study procedures are performed by qualified personnel who have received appropriate training and who are operating under the Investigator's direct supervision or the supervision of a qualified designee. Investigator is responsible for ensuring that all members of the study team are adequately trained on the Protocol, applicable standard operating procedures, and Good Clinical Practice requirements prior to performing any study-related duties.

2.6 Delegation of Authority Log. Investigator shall prepare and maintain a delegation of authority log (the "Delegation Log") identifying all site personnel authorized to perform protocol-specified procedures at the site. The Delegation Log shall include the name, title, qualifications, and specific delegated tasks for each individual, along with the dates of delegation and the Investigator's signature acknowledging each delegation. The Delegation Log shall be updated promptly to reflect any additions, removals, or changes in delegated responsibilities and shall be available for review during monitoring visits, audits, and inspections.

SECTION 3: GOOD CLINICAL PRACTICE (GCP) COMPLIANCE

3.1 ICH E6(R2) Compliance. Investigator undertakes to conduct the CLARION Trial in full compliance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice, ICH E6(R2), as adopted by the FDA (82 Fed. Reg. 9691, Feb. 8, 2017), including all principles set forth therein regarding the protection of trial subjects, the scientific quality and integrity of clinical trial data, and the responsibilities of investigators.

3.2 U.S. Federal Regulations. Investigator shall comply with all applicable U.S. federal regulations governing the conduct of clinical investigations, including without limitation:

(a) Title 21, Code of Federal Regulations, Part 312 — Investigational New Drug Application, including the obligations of investigators set forth in 21 C.F.R. § 312.60 through § 312.70;

(b) Title 21, Code of Federal Regulations, Part 50 — Protection of Human Subjects, including the requirements for informed consent;

(c) Title 21, Code of Federal Regulations, Part 56 — Institutional Review Boards, including the requirements for IRB review and approval of research involving human subjects;

(d) Title 21, Code of Federal Regulations, Part 11 — Electronic Records; Electronic Signatures, including the requirements for the reliability, trustworthiness, and equivalence of electronic records and signatures maintained or submitted in connection with the Study; and

(e) All other applicable federal, state, and local laws and regulations governing the conduct of clinical research, the protection of human subjects, and the handling of investigational products.

3.3 Informed Consent. Investigator shall obtain written informed consent from each study subject (or the subject's legally authorized representative, where permitted under applicable law and the Protocol) prior to the performance of any study-related procedures, including screening assessments. Informed consent shall be obtained in accordance with the requirements of 21 C.F.R. Part 50, applicable state law, and the policies and procedures of the applicable IRB. Investigator shall ensure that the informed consent process provides each prospective subject with adequate time and opportunity to consider participation, addresses all questions raised by the subject, and is free from coercion or undue influence. The informed consent discussion and the subject's voluntary agreement to participate shall be documented in the subject's medical record and source documents.

3.4 Currency of Informed Consent Forms. Investigator shall ensure that the informed consent form used at the site is the version that has been reviewed and approved by the applicable IRB and that it remains current throughout the study period. In the event of any protocol amendment, new safety information, or other change that may affect the subject's willingness to continue participation, Investigator shall obtain re-consent from all actively enrolled subjects using an updated IRB-approved informed consent form, in accordance with applicable regulations and IRB policies.

3.5 GCP Training Certification. Investigator certifies that Investigator has completed a recognized program of training in Good Clinical Practice within the twenty-four (24) months preceding the date of site activation for the CLARION Trial at Investigator's site. Investigator agrees to maintain current GCP training certification throughout the duration of Investigator's participation in the Study, including by completing any refresher or recertification training required by Sponsor, the Site Network, or the applicable IRB. Documentation of GCP training shall be maintained in the Investigator's training file and in the site regulatory binder and shall be available for review upon request by Sponsor, Meridian CRO, or any regulatory authority.

SECTION 4: INSTITUTIONAL REVIEW BOARD (IRB) OBLIGATIONS

4.1 Prerequisite IRB Approval. Investigator shall not enroll any subjects in the CLARION Trial, nor initiate any study-related procedures (including screening activities), until the Protocol, the informed consent form, and all other required study documents (including, without limitation, subject recruitment materials, subject-facing questionnaires, and the HIPAA research authorization form) have been reviewed and approved by the applicable IRB. Investigator shall maintain evidence of initial IRB approval in the site regulatory binder and shall provide a copy of the IRB approval letter to Sponsor and Meridian CRO prior to site activation.

4.2 Pennsylvania Sites. For sites located in the Commonwealth of Pennsylvania, including Graystone University Medical Center (Site 001) and any other Veridian Network member institutions located within the Commonwealth, individual IRB approval is required from the Graystone University Institutional Review Board (IRB Registration Number: IRB00012847; OHRP Federal-Wide Assurance Number: FWA00009264). The Graystone University IRB shall serve as the IRB of record for all Pennsylvania sites unless an alternative arrangement is approved in writing by both Sponsor and the Site Network.

4.3 Non-Pennsylvania Sites. For participating sites located outside the Commonwealth of Pennsylvania, IRB approval may be obtained through reliance on the Veridian Central IRB (IRB Registration Number: IRB00018356) pursuant to an IRB Authorization Agreement executed between the site institution's IRB of record and the Veridian Central IRB, consistent with the requirements of the revised Common Rule (45 C.F.R. Part 46, as amended effective January 21, 2019) and the National Institutes of Health Single IRB Policy. Investigator shall cooperate with the Site Network and the site institution in establishing and maintaining any required IRB Authorization Agreement and shall ensure compliance with any institution-specific requirements that supplement the Veridian Central IRB's review.

4.4 Submissions to IRB. Investigator shall submit all protocol amendments, revisions to the informed consent form, IND safety reports and investigator notifications received from Sponsor, annual or continuing review applications, and any other documents required by the applicable IRB, in a timely manner and in accordance with the applicable IRB's submission requirements and timelines. Investigator shall not implement any protocol amendment (other than one necessary to eliminate an immediate hazard to subjects) until the amendment has been approved by the applicable IRB.

4.5 Reporting to IRB. Investigator shall promptly report to the applicable IRB any of the following:

(a) Unanticipated problems involving risks to subjects or others, as defined under 21 C.F.R. § 56.108(b)(1) and the applicable IRB's policies;

(b) Protocol deviations, including those that may have affected the safety, rights, or welfare of subjects or the integrity of the study data;

(c) New information that may affect the benefit-risk assessment of the Study, including but not limited to new safety data, findings from other clinical trials of penterafenib, or changes to the Investigator's Brochure; and

(d) Any other events or information required to be reported under the applicable IRB's policies or applicable regulations.

Such reports shall be made within the timeframes specified by the applicable IRB and, in any event, within any timeframes required by applicable federal regulations.

4.6 Documentation of IRB Activities. Investigator shall maintain complete and organized documentation of all IRB approvals, correspondence with the IRB, continuing review submissions and approvals, and any modifications or conditions imposed by the IRB, in the site regulatory binder. This documentation shall be readily accessible for review during monitoring visits, audits, and regulatory inspections.

SECTION 5: SAFETY REPORTING OBLIGATIONS

5.1 Reporting of Serious Adverse Events. Investigator shall report all serious adverse events ("SAEs"), as defined in the Protocol and ICH E6(R2), to Sponsor (Penterra Pharmaceuticals Corp.) and to Meridian Contract Research Organization, Inc. (the contracted CRO for the CLARION Trial pursuant to the Master Services Agreement dated January 15, 2023, between Sponsor and Meridian CRO) within twenty-four (24) hours of the Investigator becoming aware of the event. The initial SAE report shall include, at a minimum, the subject identification number, a description of the event, the date of onset, the severity and seriousness criteria met, the Investigator's assessment of causality, and the current status of the subject. Follow-up reports providing additional information shall be submitted as information becomes available, and no later than five (5) calendar days following the initial report.

5.2 Safety Reporting Forms and Procedures. All SAE reports shall be submitted using the safety reporting forms, electronic reporting portals, and procedures set forth in Exhibit J to the MCTA (Safety Reporting Procedures). Investigator shall ensure that all members of the site study team who may become aware of SAEs are trained on these reporting procedures and understand the applicable timelines and requirements.

5.3 Sponsor's IND Safety Reporting Obligations. Investigator acknowledges that Sponsor is responsible for the evaluation and reporting of IND safety reports to the FDA in accordance with 21 C.F.R. § 312.32. Without limiting the foregoing, Sponsor is responsible for submitting (a) seven (7)-calendar-day reports to the FDA for any fatal or life-threatening unexpected suspected adverse reaction, and (b) fifteen (15)-calendar-day reports for all other reportable safety information, including unexpected serious suspected adverse reactions that are not fatal or life-threatening. Investigator acknowledges that the timely and complete reporting of SAEs by the Investigator is essential to Sponsor's ability to fulfill these regulatory obligations.

5.4 Cooperation with Safety Inquiries. Investigator shall cooperate fully and promptly with Sponsor, Meridian CRO, and the FDA in any safety-related inquiries, including the provision of complete follow-up information on reported SAEs, the completion of MedWatch forms or other regulatory safety reports as requested, and participation in safety review committee meetings or teleconferences as reasonably requested by Sponsor.

5.5 Reporting to IRB. Investigator shall promptly report to the applicable IRB any safety information that may affect the welfare of study subjects, including but not limited to site-specific SAEs, IND safety reports received from Sponsor, and any new safety information that may alter the benefit-risk assessment of the Study, in accordance with the applicable IRB's reporting requirements and the timelines specified in Section 4.5 of this Undertaking.

SECTION 6: DATA COLLECTION, RECORDING, AND SOURCE DOCUMENTS

6.1 Electronic Data Capture. Investigator shall ensure the accurate, complete, legible, and timely recording of all study data in the electronic data capture ("EDC") system provided by Pinnacle Data Solutions, Inc. ("Pinnacle"), in compliance with the requirements of 21 C.F.R. Part 11 and the data management plan for the CLARION Trial. Investigator shall ensure that all data entries are made by authorized personnel whose identities and access credentials have been established in the EDC system, and that all entries and modifications are tracked by the EDC system's audit trail. Investigator shall ensure that data queries issued through the EDC system are resolved accurately and within the timelines established in the data management plan.

6.2 Source Documents. Investigator shall create and maintain adequate and accurate source documents supporting all data entered into the EDC system. Source documents include, but are not limited to, hospital records, clinic charts, laboratory reports, imaging reports, subject diaries, pharmacy dispensing records, and any other original documents, data, or records from which study data are derived. Source documents shall be legible, contemporaneous, original, accurate, and complete, and shall be maintained in an organized and secure manner at the site.

6.3 Central Laboratory. All laboratory analyses required under the Protocol, including hematology, chemistry, biomarker, and pharmacokinetic assessments, shall be performed by Northbridge Bioanalytical Laboratories, Inc. ("Northbridge"), designated as the central laboratory for the CLARION Trial, unless otherwise specified in the Protocol for local laboratory assessments (e.g., certain safety labs requiring rapid turnaround). Investigator shall ensure the timely collection, processing, labeling, and shipment of all biological specimens in accordance with the laboratory manual provided by Northbridge and the specimen handling instructions set forth in the Protocol.

6.4 Access to Records. Investigator shall permit authorized representatives of Sponsor, Meridian CRO, the applicable IRB, the FDA, and any other applicable regulatory authority to access, review, and copy source documents, study records, and all other documents related to the conduct of the CLARION Trial, for the purposes of monitoring, auditing, and regulatory inspection. Investigator shall ensure that appropriate arrangements are in place at the site institution to facilitate such access, including compliance with any institutional policies governing access to medical records.

6.5 Record Retention. Investigator shall retain all source documents, study records, and regulatory documents related to the CLARION Trial for a minimum period of fifteen (15) years following study completion (defined as the date of Sponsor's final clinical study report for the CLARION Trial), or for such longer period as may be required by applicable federal, state, or local law, or by the applicable IRB, whichever is longer. Investigator shall notify Sponsor in writing at least sixty (60) days prior to any proposed relocation or transfer of study records and shall not transfer such records without Sponsor's prior written approval.

6.6 Prohibition on Destruction of Records. Investigator shall not destroy, discard, or otherwise dispose of any study records, source documents, or regulatory files related to the CLARION Trial without the prior written consent of Sponsor. In the event that Investigator is unable to continue to maintain custody of study records (e.g., due to retirement, relocation, or closure of the site institution), Investigator shall notify Sponsor promptly and shall cooperate with Sponsor to arrange for the transfer of such records to Sponsor or to a mutually agreed-upon custodian.

SECTION 7: DATA OWNERSHIP

7.1 Sponsor Ownership. Investigator acknowledges and agrees that Sponsor (Penterra Pharmaceuticals Corp.) retains exclusive ownership of all clinical trial data generated under Protocol PPC-4871-III (the CLARION Trial), including but not limited to all case report form data, electronic data captured in the EDC system, compiled datasets, statistical analyses, interim and final results, safety data, and any other data or information derived from the Study, as set forth in Section 10 of the MCTA and Exhibit G thereto (Intellectual Property and Publication Rights). This ownership vests in Sponsor upon the creation or generation of such data and does not require any further act or instrument.

7.2 Restrictions on Use. Investigator shall not use clinical trial data generated under the CLARION Trial for any purpose other than the conduct of the Study in accordance with the Protocol, or as expressly permitted under the MCTA (including the publication rights set forth in Section 12 of this Undertaking and Exhibit G to the MCTA), without the prior written consent of Sponsor. Without limiting the foregoing, Investigator shall not use clinical trial data for the purpose of supporting any regulatory submission, patent application, grant application, or commercial endeavor on behalf of any party other than Sponsor.

7.3 Custody of Source Documents. Notwithstanding Sponsor's ownership of clinical trial data as described in Section 7.1, the site institution and Investigator shall retain physical and administrative custody of source documents created and maintained at the site in accordance with Section 6 of this Undertaking. For the avoidance of doubt, all case report form data, electronic data captured in the EDC system, and compiled datasets derived therefrom are and shall remain the exclusive property of Sponsor.

SECTION 8: CONFIDENTIALITY OBLIGATIONS

8.1 Definition of Confidential Information. Investigator acknowledges that all information received from or on behalf of Sponsor in connection with the CLARION Trial constitutes confidential and proprietary information of Sponsor ("Confidential Information"). Confidential Information includes, but is not limited to, the Protocol, the Investigator's Brochure, study data and results (whether interim or final), investigational product specifications, formulation and manufacturing information, pharmacokinetic and pharmacodynamic data, regulatory strategies and submissions, financial terms and payment schedules, business plans, trade secrets, and all other non-public information disclosed by Sponsor or generated in connection with the Study, regardless of the form or medium in which such information is communicated or recorded.

8.2 Confidentiality Term. The obligations of confidentiality set forth in this Section 8 shall continue for a period of ten (10) years from the date of disclosure of the applicable Confidential Information, as set forth in Exhibit F to the MCTA (Confidentiality Agreement), unless a longer period is required by applicable law or regulation.

8.3 Restrictions on Disclosure. Investigator shall not disclose Confidential Information to any third party, except as expressly permitted under the MCTA and this Undertaking, including:

(a) Submissions to the applicable IRB that are necessary for the IRB's review, approval, and oversight of the Study;

(b) Disclosures required by applicable law, regulation, or order of a court or regulatory authority of competent jurisdiction, provided that Investigator shall provide Sponsor with prompt written notice of any such required disclosure (to the extent legally permitted) and shall cooperate with Sponsor in seeking a protective order or other appropriate remedy to limit the scope of the disclosure;

(d) Disclosures to members of the site study team who have a need to know such information for the conduct of the Study and who are bound by written confidentiality obligations no less restrictive than those set forth in this Undertaking.

8.4 Site Personnel Obligations. Investigator shall ensure that all site personnel, including study coordinators, research nurses, pharmacists, laboratory technicians, and any other individuals at the site who have access to Confidential Information, are bound by written confidentiality obligations no less restrictive than those imposed on Investigator under this Undertaking. Investigator shall be responsible for any breach of confidentiality by such personnel.

8.5 Return or Destruction of Materials. Upon the completion or termination of Investigator's participation in the CLARION Trial, all Confidential Information and materials containing or embodying Confidential Information (other than source documents that Investigator is required to retain under Section 6.5 of this Undertaking) shall be returned to Sponsor or destroyed at Sponsor's election, within thirty (30) days of Sponsor's written request. Investigator shall certify in writing to Sponsor that all such materials have been returned or destroyed, as applicable.

SECTION 9: FINANCIAL DISCLOSURE AND CONFLICT OF INTEREST

9.1 Financial Disclosure Certification. Investigator shall complete and submit to Sponsor the Financial Disclosure Certification form required under 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators) prior to Investigator's participation in any study-related activities under the CLARION Trial. The Financial Disclosure Certification shall be in the form specified by Sponsor and shall contain all information required under 21 C.F.R. § 54.4.

9.2 Disclosure of Financial Interests. Investigator certifies that Investigator has disclosed (or, prior to site activation, will disclose) all financial interests, arrangements, and relationships with Sponsor that are required to be reported under 21 C.F.R. Part 54, including but not limited to:

(a) Any equity interests in Penterra Pharmaceuticals Corp. (Nasdaq ticker symbol: PTRA), including stock, stock options, warrants, or other ownership interests, exceeding Fifty Thousand Dollars ($50,000) in aggregate value at the time of disclosure;

(b) Significant payments of other sorts, as that term is defined in 21 C.F.R. § 54.2(f), received from Sponsor during the course of the Study or within one (1) year prior to the beginning of the Study;

(c) Any proprietary interest in penterafenib (PPC-4871) or related technology, including any patent, trademark, copyright, or licensing agreement;

(d) Any significant equity interest in Sponsor, as that term is defined in 21 C.F.R. § 54.2(b); and

(e) Any other financial interest, arrangement, or relationship that could be affected by the outcome of the Study and that is required to be disclosed under applicable federal or state regulations or institutional policies.

9.3 Ongoing Disclosure Obligation. Investigator shall promptly notify Sponsor in writing of any change in Investigator's financial interests, or any new financial arrangement or relationship with Sponsor or any entity with a financial interest in the outcome of the CLARION Trial, that arises during the course of the Study or within one (1) year after the completion of Investigator's participation in the Study. Such notification shall be provided within thirty (30) days of the occurrence of the relevant change or event.

9.4 Consequences of Non-Disclosure. Investigator acknowledges that failure to disclose a financial interest as required under 21 C.F.R. Part 54 or this Undertaking may result in (a) Investigator's disqualification from the CLARION Trial, (b) regulatory consequences under 21 C.F.R. Part 54, including the potential inability of Sponsor to rely on data generated by the Investigator in support of marketing applications, and (c) potential debarment or disqualification proceedings under applicable FDA regulations.

9.5 Fair Market Value Compensation. Investigator certifies that all compensation received by Investigator for participation in the CLARION Trial, including investigator fees, per-subject payments, and any other remuneration, is consistent with fair market value for the services rendered, taking into account the nature, scope, and complexity of the study procedures. Investigator further certifies that such compensation was determined independently of the volume or value of any referrals or business otherwise generated between Investigator and Sponsor, as required by the Federal Anti-Kickback Statute, 42 U.S.C. § 1320a-7b, and its implementing regulations, the Stark Law (42 U.S.C. § 1395nn), and all other applicable federal and state laws governing physician compensation arrangements.

SECTION 10: ANTI-KICKBACK AND SUNSHINE ACT COMPLIANCE

10.1 Anti-Kickback Representations. Investigator represents and warrants that Investigator's participation in the CLARION Trial is not conditioned upon, and Investigator has not received any promise, offer, or provision of, any payment, benefit, remuneration, or thing of value beyond fair market value compensation for legitimate services actually rendered in connection with the Study. Investigator further represents that Investigator's participation in the CLARION Trial was not solicited through, and does not involve, any arrangement that constitutes or could constitute a violation of the Federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b) or any comparable state law.

10.2 Physician Payments Sunshine Act. Investigator acknowledges that Sponsor is required to report payments and transfers of value made to physicians and teaching hospitals under Section 1128G of the Social Security Act (42 U.S.C. § 1320a-7h), commonly known as the Physician Payments Sunshine Act, and the implementing regulations of the Centers for Medicare & Medicaid Services ("CMS") establishing the Open Payments program (42 C.F.R. Part 403, Subpart I). Investigator agrees to cooperate with Sponsor in fulfilling Sponsor's reporting obligations under the Open Payments program and acknowledges that certain payments and transfers of value made to Investigator in connection with the CLARION Trial may be subject to public disclosure through the Open Payments database.

10.3 Information for Open Payments Reporting. Investigator shall promptly provide to Sponsor any information reasonably requested by Sponsor for purposes of Open Payments reporting, including but not limited to verification of reportable amounts, identification of payment categories, confirmation of Investigator's National Provider Identifier (NPI) and state licensure information, and any other data elements required for accurate and complete reporting. Investigator shall review and respond to any dispute or attestation requests received from Sponsor or through the CMS Open Payments system within the applicable timelines.

SECTION 11: HIPAA AND SUBJECT PRIVACY

11.1 HIPAA Compliance. Investigator shall comply with the Health Insurance Portability and Accountability Act of 1996 ("HIPAA"), as amended by the Health Information Technology for Economic and Clinical Health Act ("HITECH Act"), and the implementing regulations of the U.S. Department of Health and Human Services at 45 C.F.R. Parts 160 and 164, in connection with the collection, use, storage, and disclosure of protected health information ("PHI") of study subjects in the CLARION Trial. Investigator shall ensure that all PHI collected or accessed in connection with the Study is handled in accordance with the HIPAA Privacy Rule (45 C.F.R. Part 164, Subpart E) and the HIPAA Security Rule (45 C.F.R. Part 164, Subpart C).

11.2 HIPAA Research Authorization. Investigator shall obtain a valid HIPAA research authorization from each study subject (or the subject's personal representative, as defined under HIPAA) prior to accessing, using, or disclosing the subject's PHI for purposes of the CLARION Trial, unless a waiver or alteration of the authorization requirement has been approved by the applicable IRB or Privacy Board in accordance with 45 C.F.R. § 164.512(i). The HIPAA research authorization shall meet all requirements set forth in 45 C.F.R. § 164.508 and shall be maintained as part of the subject's study file.

11.3 Minimum Necessary Standard. Investigator shall limit the use and disclosure of PHI to the minimum necessary to accomplish the purposes of the Study, consistent with the minimum necessary standard set forth in 45 C.F.R. § 164.502(b) and § 164.514(d). Investigator shall de-identify study data to the extent practicable and consistent with the Protocol and applicable regulatory requirements.

11.4 Safeguards. Investigator shall implement and maintain appropriate administrative, technical, and physical safeguards to protect the confidentiality, integrity, and security of subject PHI, in accordance with the HIPAA Security Rule and consistent with the site institution's HIPAA policies and procedures. Such safeguards shall include, without limitation, access controls for electronic systems containing PHI, encryption of PHI transmitted electronically, secure storage of paper records containing PHI, and workforce training on privacy and security obligations.

SECTION 12: PUBLICATION RIGHTS

12.1 Right to Publish. Investigator may publish or present the results of the CLARION Trial in peer-reviewed journals, at scientific or medical conferences, or through other professional or academic channels, subject to the terms and conditions set forth in Exhibit G to the MCTA (Intellectual Property and Publication Rights) and this Section 12. Nothing in this Undertaking shall be construed as obligating Investigator to publish the results of the Study.

12.2 Pre-Publication Review. Prior to the submission of any manuscript, abstract, poster, oral presentation, or other publication or public presentation containing data or results from the CLARION Trial for publication or presentation, Investigator shall provide Sponsor with a complete copy of the proposed manuscript, abstract, or other materials at least sixty (60) days in advance of the intended date of submission or presentation (the "Review Period"). Sponsor shall review the proposed publication for the purpose of identifying (a) Confidential Information of Sponsor, (b) patentable subject matter, and (c) any factual inaccuracies. Sponsor shall communicate any comments, objections, or requests for modifications to Investigator within the Review Period.

12.3 Delay for Patent Filing. In the event that Sponsor identifies patentable subject matter in a proposed publication, Sponsor may request a delay of up to an additional ninety (90) days beyond the initial sixty (60)-day Review Period (for a total delay of up to one hundred fifty (150) days from the date of Sponsor's receipt of the proposed publication) to allow for the preparation and filing of patent applications on such patentable subject matter. Investigator shall not submit or present the proposed publication during any such delay period unless Sponsor provides written consent. Sponsor shall use commercially reasonable efforts to complete any patent filings within the delay period.

12.4 Exclusion of Confidential Information. Investigator shall not include any Confidential Information of Sponsor (as defined in Section 8.1) in any publication or public presentation without Sponsor's prior written consent. In the event that Sponsor identifies Confidential Information in a proposed publication during the Review Period, Investigator shall remove or redact such Confidential Information prior to submission or presentation.

12.5 Multi-Center Publication Priority. Investigator acknowledges that the CLARION Trial is a multi-center clinical study and agrees that, consistent with good scientific practice and the principles of the International Committee of Medical Journal Editors (ICMJE), multi-center trial results should generally be published first as a multi-center report reflecting the aggregate results of all participating sites. Individual site results or sub-analyses may be published only after the primary multi-center publication has been submitted for publication or with Sponsor's prior written consent. Investigator shall cooperate with the CLARION Trial publication committee and Sponsor in the preparation and review of the primary multi-center publication.

SECTION 13: INVESTIGATIONAL PRODUCT ACCOUNTABILITY

13.1 Receipt, Storage, Dispensing, and Accounting. Investigator shall ensure the proper receipt, storage, dispensing, and accounting of the investigational product (penterafenib/PPC-4871 and matching placebo) in accordance with the Protocol, the Investigator's Brochure, the Pharmacy Manual provided by Sponsor, and all applicable federal and state regulations governing the handling of investigational drugs. Investigator shall designate a qualified pharmacist or other authorized individual at the site to be responsible for the receipt, storage, dispensing, and inventory of the investigational product, and shall ensure that such individual is identified on the Delegation Log.

13.2 Exclusive Use. The investigational product supplied by Sponsor shall be used solely for the conduct of the CLARION Trial in accordance with the Protocol and shall not be supplied, administered, dispensed, or otherwise made available to any person who is not a duly enrolled subject in the Study. Investigator shall not use the investigational product for any purpose other than the conduct of the CLARION Trial.

13.3 Drug Accountability Records. Investigator shall maintain accurate and contemporaneous drug accountability records documenting the receipt, inventory, dispensing (including subject identification, date, dose, and lot number), return, and disposition of all investigational product at the site. Investigator shall reconcile drug accountability records at each monitoring visit and shall return or dispose of all unused, expired, or damaged investigational product in accordance with Sponsor's written instructions and applicable regulations. Investigator shall not dispose of any investigational product without prior authorization from Sponsor.

13.4 Storage Conditions. Investigator shall store the investigational product under the conditions specified in the Protocol and the Investigator's Brochure, including the required temperature range, protection from light, and any other storage requirements. Investigator shall ensure that temperature monitoring equipment is in place and functioning at all times, and shall maintain records of temperature monitoring throughout the study period. Investigator shall immediately report any storage deviation (including temperature excursions, equipment failures, or environmental events affecting storage conditions) to Sponsor and Meridian CRO. Investigator shall quarantine any investigational product affected by a storage deviation and shall not dispense such product until Sponsor has evaluated the deviation and provided written authorization to release or destroy the affected product.

SECTION 14: MONITORING, AUDITING, AND INSPECTIONS

14.1 Monitoring Visits. Investigator shall cooperate with and permit site monitoring visits by Meridian CRO, the contracted clinical research organization retained by Sponsor pursuant to the Master Services Agreement dated January 15, 2023, between Sponsor and Meridian CRO, and/or by Sponsor's other authorized representatives. Investigator shall ensure the availability of study records, source documents, investigational product accountability records, regulatory files, and site personnel during scheduled monitoring visits, and shall provide adequate workspace for monitors at the site. Investigator shall review and respond to monitoring visit reports and action items in a timely manner.

14.2 Quality Assurance Audits. Investigator shall cooperate with quality assurance audits of the site conducted by Sponsor or its designee, including internal audits, for-cause audits, and audits conducted as part of Sponsor's overall quality management system for the CLARION Trial. Investigator shall provide auditors with full access to study records, source documents, regulatory files, and site facilities, and shall cooperate in the implementation of any corrective and preventive actions identified as a result of audit findings.

14.3 Regulatory Inspections. In the event of an inspection of the site by the FDA or any other domestic or international regulatory authority in connection with the CLARION Trial, Investigator shall (a) promptly notify Sponsor (and Meridian CRO) of the inspection, including the identity of the inspecting authority, the date(s) of the inspection, and the scope of the inspection, to the extent known; (b) cooperate fully with the inspection, including providing the inspecting authority with access to all study records, source documents, investigational product, and site facilities as required; and (c) promptly provide Sponsor with copies of any correspondence, written observations (including FDA Form 483 observations), Establishment Inspection Reports, Warning Letters, findings, or reports received from the inspecting authority in connection with the CLARION Trial or related to Investigator's conduct of clinical research.

14.4 Copies of Regulatory Correspondence. Investigator shall promptly provide Sponsor with copies of any correspondence, communications, findings, reports, or other documents received from any regulatory authority in connection with the CLARION Trial, including but not limited to requests for information, compliance actions, enforcement actions, or other regulatory inquiries. Such copies shall be provided within five (5) business days of Investigator's receipt thereof.

SECTION 15: INSURANCE

15.1 Sponsor's Clinical Trial Liability Insurance. Investigator acknowledges that Sponsor maintains clinical trial liability insurance in connection with the CLARION Trial through Briarcliff Mutual Insurance Company (Policy Number: BM-CTL-2023-04182), with limits of liability of Twenty-Five Million Dollars ($25,000,000) per occurrence and Seventy-Five Million Dollars ($75,000,000) in the aggregate, including a subject-injury sublimit of Ten Million Dollars ($10,000,000) per occurrence and Fifty Million Dollars ($50,000,000) in the aggregate, as more fully described in Exhibit E to the MCTA (Insurance). Investigator acknowledges receipt of a summary of coverage and agrees to review the applicable policy provisions.

15.2 Site Institution Insurance. Investigator acknowledges that the participating site institution at which Investigator conducts the CLARION Trial is required to obtain and maintain, throughout the term of the Study, general liability insurance and professional liability (medical malpractice) insurance with combined limits of at least Five Million Dollars ($5,000,000) per occurrence and Ten Million Dollars ($10,000,000) in the aggregate, as set forth in Section 12.2 of the MCTA. Investigator shall cooperate with the site institution in ensuring that such coverage is obtained and maintained and that evidence of coverage is provided to Sponsor upon request.

15.3 Incident Reporting. Investigator agrees to cooperate in the timely reporting of any incidents, events, or circumstances that may give rise to a claim under any applicable insurance policy, including any subject injuries, adverse events, property damage, or third-party claims. Investigator shall notify Sponsor of any such incidents within the timeframes specified in Exhibit E to the MCTA and shall provide such information and documentation as may be reasonably requested by Sponsor or its insurers.

SECTION 16: INDEMNIFICATION ACKNOWLEDGMENT

16.1 Acknowledgment of Indemnification Provisions. Investigator acknowledges and has reviewed the indemnification provisions set forth in Section 11 of the MCTA and Exhibit D thereto (Indemnification). Investigator understands the scope and limitations of the indemnification obligations of Sponsor and the reciprocal obligations of the Site Network and Investigator as described in the MCTA.

16.2 Scope of Sponsor Indemnification. Sponsor provides indemnification to Investigator and the site institution, subject to the terms and conditions of the MCTA and Exhibit D, against third-party claims, demands, actions, suits, judgments, losses, damages, liabilities, costs, and expenses (including reasonable attorneys' fees and costs of defense) arising out of or resulting from:

(a) Subject injury caused by the investigational product (penterafenib/PPC-4871 or matching placebo) when administered in accordance with the Protocol;

(b) Defects in the investigational product, including defects in design, manufacture, formulation, labeling, or packaging;

(d) The negligence or willful misconduct of Sponsor or its employees, agents, or contractors (other than Investigator or site personnel).

16.3 Exclusions from Indemnification. Investigator acknowledges that Sponsor's indemnification obligations do not extend to losses, liabilities, claims, or damages arising from or attributable to:

(a) The negligence or willful misconduct of Investigator, the site institution, or any member of the site study team;

(b) Protocol deviations not authorized by Sponsor or not undertaken to protect the safety of subjects;

(d) The use of the investigational product in a manner not consistent with the Protocol or the Investigator's Brochure.

16.4 Medical Care for Study-Related Injuries. Sponsor will cover the reasonable costs of medical care for study-related injuries sustained by subjects in the CLARION Trial that are not covered by the subject's own insurance, health plan, or other third-party coverage, subject to the terms and conditions of the MCTA, including a per-subject cap of Five Hundred Thousand Dollars ($500,000) and an aggregate cap of Fifteen Million Dollars ($15,000,000) for all subjects across all sites. The determination of whether an injury is study-related shall be made by Sponsor in consultation with the Investigator, and any disputes shall be resolved in accordance with the dispute resolution procedures set forth in the MCTA.

16.5 Notice of Claims. Investigator shall provide written notice to Sponsor of any claim, demand, action, or suit that may be subject to indemnification under the MCTA within thirty (30) calendar days of Investigator's becoming aware of such claim. Written notice shall be provided to Sponsor at the address set forth in Section 20.6 of this Undertaking. Failure by Investigator to provide timely notice shall not relieve Sponsor of its indemnification obligation under the MCTA, except to the extent that Sponsor demonstrates that it has been materially prejudiced by such failure.

SECTION 17: TERM AND TERMINATION

17.1 Effective Date and Term. This Undertaking shall be effective as of the date of Investigator's signature below and shall continue in full force and effect until the earliest of: (a) the completion of all study-related obligations of Investigator under the Protocol, including all follow-up visits, data queries, record retention obligations, and final regulatory submissions; (b) the termination of the Individual Site Agreement for the site at which Investigator conducts the CLARION Trial, whether by expiration of the term, mutual agreement, or otherwise; or (c) the withdrawal or removal of Investigator from the Study, whether voluntary or involuntary.

17.2 Wind-Down Obligations. In the event of termination of this Undertaking for any reason, Investigator shall cooperate with Sponsor, Meridian CRO, and the Site Network during the one-hundred-twenty (120)-day wind-down period specified in Section 14.3 of the MCTA, to ensure the safety and welfare of all subjects enrolled at Investigator's site. During the wind-down period, Investigator shall (a) facilitate the transition of subjects in active treatment to an alternative qualified investigator within the Veridian Network, or (b) permit subjects to complete their current treatment cycle if clinically appropriate and agreed upon by Sponsor, Investigator, and the applicable IRB. Investigator shall continue to report all adverse events and SAEs during the wind-down period and shall complete all outstanding data entries and queries in the EDC system.

17.3 Surviving Obligations. The following obligations shall survive the expiration or termination of this Undertaking and shall continue in full force and effect for the periods specified therein or, if no specific period is stated, indefinitely: (a) confidentiality obligations under Section 8, subject to the ten (10)-year confidentiality term set forth in Section 8.2; (b) data ownership provisions under Section 7; (c) financial disclosure obligations under Section 9, including the obligation to report changes in financial interests for one (1) year following the completion of Investigator's participation; (d) publication rights and restrictions under Section 12; and (e) record retention obligations under Section 6.5.

SECTION 18: REPRESENTATIONS AND WARRANTIES

18.1 Valid Medical License. Investigator represents and warrants that Investigator holds a current, valid, and unrestricted license to practice medicine in the state or states where the participating site institution is located, and that such license has not been suspended, revoked, restricted, or made subject to any disciplinary action that would impair Investigator's ability to conduct the CLARION Trial.

18.2 No Debarment. Investigator represents and warrants that Investigator has not been debarred, and is not subject to a pending debarment proceeding, under Section 306(a) or (b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 335a), and that Investigator is not subject to any FDA clinical investigator disqualification under 21 C.F.R. § 312.70 or any restriction on Investigator's eligibility to receive investigational products.

18.3 No Exclusion from Federal Healthcare Programs. Investigator represents and warrants that Investigator has not been excluded from participation in any federal healthcare program, including Medicare and Medicaid, and that Investigator's name does not appear on the U.S. Department of Health and Human Services Office of Inspector General (HHS/OIG) List of Excluded Individuals/Entities (LEIE) or the General Services Administration (GSA) System for Award Management (SAM) Excluded Parties List.

18.4 Qualifications and Experience. Investigator represents and warrants that Investigator has the professional qualifications, scientific training, clinical experience, and expertise necessary to conduct the CLARION Trial in accordance with the Protocol, ICH E6(R2), and all applicable regulatory requirements. Investigator's qualifications are evidenced by the curriculum vitae on file with Sponsor and the applicable IRB.

18.5 Adequate Resources. Investigator represents and warrants that the participating site institution has adequate resources, facilities, equipment, and qualified staff to conduct the CLARION Trial as described in the Protocol, including the capability to enroll and follow subjects, perform required study assessments, store investigational product under specified conditions, and maintain study records in compliance with applicable requirements.

18.6 Notification of Changes. Investigator shall promptly notify Sponsor in writing if any of the representations and warranties set forth in Sections 18.1 through 18.5 ceases to be true or accurate at any time during the course of the Study. Such notification shall be provided within ten (10) business days of the occurrence of the relevant event or circumstance.

SECTION 19: GOVERNING LAW

19.1 Governing Law. This Undertaking shall be governed by and construed in accordance with the laws of the State of New York, without regard to any conflict-of-laws rules or principles that would result in the application of the laws of any other jurisdiction. The choice of New York law is consistent with the governing law provision set forth in Section 17.1 of the MCTA.

19.2 Dispute Resolution. Any dispute, controversy, or claim arising out of or relating to this Undertaking, or the breach, termination, or validity thereof, shall be resolved in accordance with the dispute resolution procedures set forth in Section 17.2 of the MCTA, which provide for (a) an initial period of thirty (30) days for good-faith negotiation between the designated representatives of the parties; (b) if negotiation is unsuccessful, mediation under the American Arbitration Association ("AAA") Commercial Mediation Rules for a period of sixty (60) days; and (c) if mediation is unsuccessful, final and binding arbitration in New York, New York, under the AAA Commercial Arbitration Rules, before a panel of three (3) arbitrators selected in accordance with the AAA rules. Judgment on the arbitration award may be entered in any court of competent jurisdiction.

19.3 Injunctive Relief. Notwithstanding anything to the contrary in this Section 19, nothing herein shall limit the right of any party to seek temporary, preliminary, or permanent injunctive relief, specific performance, or other equitable remedies from the state and federal courts located in New York County, New York, to prevent irreparable harm pending the resolution of any dispute through the procedures described in Section 19.2.

SECTION 20: MISCELLANEOUS

20.1 Entire Agreement. This Undertaking, together with the MCTA and all Exhibits and Schedules thereto (including, without limitation, Exhibit D — Indemnification, Exhibit E — Insurance, Exhibit F — Confidentiality Agreement, Exhibit G — Intellectual Property and Publication Rights, and Exhibit J — Safety Reporting Procedures), and the Individual Site Agreement for Investigator's site, constitutes the entire agreement between the parties with respect to the subject matter hereof and supersedes all prior or contemporaneous oral or written agreements, understandings, representations, and warranties relating thereto.

20.2 Amendments. No amendment, modification, or supplement to this Undertaking shall be effective or binding upon any party unless such amendment is set forth in a writing duly executed by Investigator, Sponsor, and the Site Network (or their respective authorized representatives).

20.3 Counterparts. This Undertaking may be executed in one or more counterparts, including by facsimile or electronic signature (in compliance with the Electronic Signatures in Global and National Commerce Act, 15 U.S.C. § 7001 et seq.), each of which shall be deemed an original and all of which together shall constitute one and the same instrument.

20.4 Severability. If any provision of this Undertaking is held to be invalid, illegal, or unenforceable by a court or arbitral tribunal of competent jurisdiction, the validity, legality, and enforceability of the remaining provisions shall not in any way be affected or impaired thereby, and such invalid, illegal, or unenforceable provision shall be modified to the minimum extent necessary to make it valid, legal, and enforceable while preserving the intent of the parties.

20.5 Assignment. Investigator may not assign, delegate, or transfer this Undertaking or any of Investigator's rights, duties, or obligations hereunder without the prior written consent of Sponsor. Any purported assignment in violation of this Section shall be null and void. Sponsor may assign its rights and obligations under this Undertaking to a successor in interest, affiliate, or acquirer of substantially all of Sponsor's assets or the penterafenib program, upon written notice to Investigator.

20.6 Notices. All notices, requests, demands, consents, approvals, and other communications required or permitted under this Undertaking shall be in writing and shall be deemed duly given when (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent by nationally recognized overnight courier service, or (d) sent by email with confirmation of receipt, to the parties at the following addresses (or such other addresses as a party may designate in writing from time to time):

To Sponsor:

Penterra Pharmaceuticals Corp. 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540

Attention: Nathaniel Briggs, Esq., Vice President & General Counsel

Email: n.briggs@penterra.com

With a copy (which shall not constitute notice) to:

Rebecc

EXHIBIT I
FORM OF INVESTIGATOR UNDERTAKING
Attached to and forming part of the Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA") by and between Penterra Pharmaceuticals Corp. ("Sponsor") and Veridian Health Research Network, Inc. ("Site Network").
Protocol Reference: Protocol PPC-4871-III — CLARION (Clinical Assessment of Response with Longitudinal Investigation in ONcology)
Investigational Product: Penterafenib (PPC-4871)
IND Number: IND 157823
ClinicalTrials.gov Identifier: NCT05928174
PREAMBLE AND RECITALS
This Investigator Undertaking (this "Undertaking") is executed by the undersigned investigator (the "Investigator") in connection with Investigator's participation in the clinical trial conducted under Protocol PPC-4871-III, titled CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology (the "Study" or the "CLARION Trial"). The CLARION Trial is a Phase III, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of penterafenib (PPC-4871) in adult subjects with advanced hepatocellular carcinoma (HCC) who have received at least one line of prior systemic therapy.
WHEREAS, the Sponsor of the CLARION Trial is Penterra Pharmaceuticals Corp. ("Sponsor" or "Penterra"), a corporation organized and existing under the laws of the State of Delaware, with its principal offices located at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540;
WHEREAS, Veridian Health Research Network, Inc. ("Site Network" or "Veridian"), a 501(c)(3) nonprofit corporation organized and existing under the laws of the State of Delaware, with its principal offices located at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104, serves as the coordinating network for clinical trial sites participating in the CLARION Trial;
WHEREAS, the MCTA governs the conduct of the CLARION Trial across thirty-eight (38) participating Veridian Network member sites located in fourteen (14) states across the United States;
WHEREAS, the CLARION Trial is designed to enroll a total of approximately 1,200 subjects, randomized in a 2:1 ratio (800 subjects to the penterafenib treatment arm and 400 subjects to the matching placebo arm), in accordance with the statistical analysis plan set forth in the Protocol;
WHEREAS, the Investigator's execution of this Undertaking is a condition precedent to the Investigator's participation in the CLARION Trial and is required under Section 4.3(b) of the MCTA as a component of the site activation package;
WHEREAS, Investigator desires to participate in the CLARION Trial in the capacity and at the site identified herein, and acknowledges the importance of the obligations set forth in this Undertaking to the integrity of the Study and the safety and welfare of study subjects;
NOW, THEREFORE, in consideration of the foregoing recitals and the mutual covenants and agreements set forth herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Investigator agrees as follows:
Capitalized terms used but not otherwise defined in this Undertaking shall have the meanings ascribed to them in the MCTA, unless the context requires otherwise.
SECTION 1: IDENTIFICATION OF INVESTIGATOR
The Investigator provides the following information for purposes of identification and regulatory documentation:
Full Legal Name of Investigator: ________
Title / Academic Appointment: ________
Professional Degree(s): ________ (e.g., M.D., Ph.D., D.O., Pharm.D.)
Board Certification(s): ________
Name of Participating Site Institution: ________ (Must be a Veridian Health Research Network member institution in good standing)
Site Number Under the MCTA: ________
Address of Site Institution: ________
________________________________________
________________________________________
Role Designation (check one):
Principal Investigator
Sub-Investigator
Global or Co-Principal Investigator Designation (if applicable, check one):
Global Principal Investigator (e.g., Dr. Catherine Aldridge, M.D., Ph.D., Graystone University Medical Center, Site 001)
Co-Principal Investigator (e.g., Dr. Howard Matsuoka, M.D., Lakemont Medical Center, Site 002)
Not applicable
Medical License Number: ________
State(s) of Licensure: ________
DEA Registration Number (if applicable): ________
SECTION 2: PROTOCOL COMPLIANCE UNDERTAKINGS
2.1 Receipt and Review of Study Documents. Investigator hereby acknowledges receipt and thorough review of Protocol PPC-4871-III (CLARION), including all amendments thereto issued as of the date of this Undertaking, and the current version of the Investigator's Brochure for penterafenib (PPC-4871), including all supplements and updates provided by Sponsor. Investigator confirms that Investigator has had adequate opportunity to review these documents and to discuss any questions or concerns with the Sponsor's medical monitor prior to executing this Undertaking.
2.2 Conduct in Accordance with Protocol. Investigator undertakes to conduct the CLARION Trial strictly in accordance with the Protocol as approved by the applicable Institutional Review Board ("IRB") and accepted by the U.S. Food and Drug Administration ("FDA") under IND 157823. Without limiting the generality of the foregoing, Investigator shall adhere to (a) all subject inclusion and exclusion criteria as specified in Protocol Sections 5.1 and 5.2; (b) the dosing schedules, dose modification guidelines, and dose interruption criteria set forth in Protocol Section 6; (c) the visit windows and schedule of assessments set forth in Protocol Section 7 and the Schedule of Events (Protocol Appendix A); and (d) all procedures required for the determination and adjudication of study endpoints as specified in Protocol Sections 8 and 9.
2.3 Endpoint Assessments. The primary endpoint of the CLARION Trial is overall survival (OS). The key secondary endpoints include progression-free survival (PFS) as assessed by blinded independent central review (BICR) using RECIST v1.1, objective response rate (ORR), and duration of response (DOR). Investigator agrees to conduct all clinical assessments, imaging studies, laboratory evaluations, patient-reported outcome measurements, and other procedures required under the Protocol for the determination of the primary and secondary endpoints. Investigator further agrees to comply with the tumor assessment schedule and to ensure timely submission of imaging data to the independent radiology review center designated by Sponsor.
2.4 Protocol Deviations. Investigator shall not implement any deviation from or change to the Protocol unless such deviation is (a) necessary to eliminate an immediate hazard to the safety, rights, or well-being of study subjects, in which case the Investigator shall take appropriate action and promptly document the deviation and notify the Sponsor and the applicable IRB, or (b) specifically authorized in advance in writing by Sponsor. In the event of any protocol deviation, whether or not it falls within the categories described in clauses (a) or (b) above, Investigator shall promptly and accurately document the deviation, including the nature of the deviation, the reason therefor, the date(s) on which it occurred, the subject(s) affected, and any corrective or preventive actions taken. Investigator shall report all protocol deviations to Sponsor, Meridian Contract Research Organization, Inc. ("Meridian CRO"), and the applicable IRB in accordance with the timelines and procedures specified in the Protocol and the applicable IRB policies.
2.5 Qualified Personnel. Investigator shall ensure that all study procedures are performed by qualified personnel who have received appropriate training and who are operating under the Investigator's direct supervision or the supervision of a qualified designee. Investigator is responsible for ensuring that all members of the study team are adequately trained on the Protocol, applicable standard operating procedures, and Good Clinical Practice requirements prior to performing any study-related duties.
2.6 Delegation of Authority Log. Investigator shall prepare and maintain a delegation of authority log (the "Delegation Log") identifying all site personnel authorized to perform protocol-specified procedures at the site. The Delegation Log shall include the name, title, qualifications, and specific delegated tasks for each individual, along with the dates of delegation and the Investigator's signature acknowledging each delegation. The Delegation Log shall be updated promptly to reflect any additions, removals, or changes in delegated responsibilities and shall be available for review during monitoring visits, audits, and inspections.
SECTION 3: GOOD CLINICAL PRACTICE (GCP) COMPLIANCE
3.1 ICH E6(R2) Compliance. Investigator undertakes to conduct the CLARION Trial in full compliance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice, ICH E6(R2), as adopted by the FDA (82 Fed. Reg. 9691, Feb. 8, 2017), including all principles set forth therein regarding the protection of trial subjects, the scientific quality and integrity of clinical trial data, and the responsibilities of investigators.
3.2 U.S. Federal Regulations. Investigator shall comply with all applicable U.S. federal regulations governing the conduct of clinical investigations, including without limitation:
(a) Title 21, Code of Federal Regulations, Part 312 — Investigational New Drug Application, including the obligations of investigators set forth in 21 C.F.R. § 312.60 through § 312.70;
(b) Title 21, Code of Federal Regulations, Part 50 — Protection of Human Subjects, including the requirements for informed consent;
(c) Title 21, Code of Federal Regulations, Part 56 — Institutional Review Boards, including the requirements for IRB review and approval of research involving human subjects;
(d) Title 21, Code of Federal Regulations, Part 11 — Electronic Records; Electronic Signatures, including the requirements for the reliability, trustworthiness, and equivalence of electronic records and signatures maintained or submitted in connection with the Study; and
(e) All other applicable federal, state, and local laws and regulations governing the conduct of clinical research, the protection of human subjects, and the handling of investigational products.
3.3 Informed Consent. Investigator shall obtain written informed consent from each study subject (or the subject's legally authorized representative, where permitted under applicable law and the Protocol) prior to the performance of any study-related procedures, including screening assessments. Informed consent shall be obtained in accordance with the requirements of 21 C.F.R. Part 50, applicable state law, and the policies and procedures of the applicable IRB. Investigator shall ensure that the informed consent process provides each prospective subject with adequate time and opportunity to consider participation, addresses all questions raised by the subject, and is free from coercion or undue influence. The informed consent discussion and the subject's voluntary agreement to participate shall be documented in the subject's medical record and source documents.
3.4 Currency of Informed Consent Forms. Investigator shall ensure that the informed consent form used at the site is the version that has been reviewed and approved by the applicable IRB and that it remains current throughout the study period. In the event of any protocol amendment, new safety information, or other change that may affect the subject's willingness to continue participation, Investigator shall obtain re-consent from all actively enrolled subjects using an updated IRB-approved informed consent form, in accordance with applicable regulations and IRB policies.
3.5 GCP Training Certification. Investigator certifies that Investigator has completed a recognized program of training in Good Clinical Practice within the twenty-four (24) months preceding the date of site activation for the CLARION Trial at Investigator's site. Investigator agrees to maintain current GCP training certification throughout the duration of Investigator's participation in the Study, including by completing any refresher or recertification training required by Sponsor, the Site Network, or the applicable IRB. Documentation of GCP training shall be maintained in the Investigator's training file and in the site regulatory binder and shall be available for review upon request by Sponsor, Meridian CRO, or any regulatory authority.
SECTION 4: INSTITUTIONAL REVIEW BOARD (IRB) OBLIGATIONS
4.1 Prerequisite IRB Approval. Investigator shall not enroll any subjects in the CLARION Trial, nor initiate any study-related procedures (including screening activities), until the Protocol, the informed consent form, and all other required study documents (including, without limitation, subject recruitment materials, subject-facing questionnaires, and the HIPAA research authorization form) have been reviewed and approved by the applicable IRB. Investigator shall maintain evidence of initial IRB approval in the site regulatory binder and shall provide a copy of the IRB approval letter to Sponsor and Meridian CRO prior to site activation.
4.2 Pennsylvania Sites. For sites located in the Commonwealth of Pennsylvania, including Graystone University Medical Center (Site 001) and any other Veridian Network member institutions located within the Commonwealth, individual IRB approval is required from the Graystone University Institutional Review Board (IRB Registration Number: IRB00012847; OHRP Federal-Wide Assurance Number: FWA00009264). The Graystone University IRB shall serve as the IRB of record for all Pennsylvania sites unless an alternative arrangement is approved in writing by both Sponsor and the Site Network.
4.3 Non-Pennsylvania Sites. For participating sites located outside the Commonwealth of Pennsylvania, IRB approval may be obtained through reliance on the Veridian Central IRB (IRB Registration Number: IRB00018356) pursuant to an IRB Authorization Agreement executed between the site institution's IRB of record and the Veridian Central IRB, consistent with the requirements of the revised Common Rule (45 C.F.R. Part 46, as amended effective January 21, 2019) and the National Institutes of Health Single IRB Policy. Investigator shall cooperate with the Site Network and the site institution in establishing and maintaining any required IRB Authorization Agreement and shall ensure compliance with any institution-specific requirements that supplement the Veridian Central IRB's review.
4.4 Submissions to IRB. Investigator shall submit all protocol amendments, revisions to the informed consent form, IND safety reports and investigator notifications received from Sponsor, annual or continuing review applications, and any other documents required by the applicable IRB, in a timely manner and in accordance with the applicable IRB's submission requirements and timelines. Investigator shall not implement any protocol amendment (other than one necessary to eliminate an immediate hazard to subjects) until the amendment has been approved by the applicable IRB.
4.5 Reporting to IRB. Investigator shall promptly report to the applicable IRB any of the following:
(a) Unanticipated problems involving risks to subjects or others, as defined under 21 C.F.R. § 56.108(b)(1) and the applicable IRB's policies;
(b) Protocol deviations, including those that may have affected the safety, rights, or welfare of subjects or the integrity of the study data;
(c) New information that may affect the benefit-risk assessment of the Study, including but not limited to new safety data, findings from other clinical trials of penterafenib, or changes to the Investigator's Brochure; and
(d) Any other events or information required to be reported under the applicable IRB's policies or applicable regulations.
Such reports shall be made within the timeframes specified by the applicable IRB and, in any event, within any timeframes required by applicable federal regulations.
4.6 Documentation of IRB Activities. Investigator shall maintain complete and organized documentation of all IRB approvals, correspondence with the IRB, continuing review submissions and approvals, and any modifications or conditions imposed by the IRB, in the site regulatory binder. This documentation shall be readily accessible for review during monitoring visits, audits, and regulatory inspections.
SECTION 5: SAFETY REPORTING OBLIGATIONS
5.1 Reporting of Serious Adverse Events. Investigator shall report all serious adverse events ("SAEs"), as defined in the Protocol and ICH E6(R2), to Sponsor (Penterra Pharmaceuticals Corp.) and to Meridian Contract Research Organization, Inc. (the contracted CRO for the CLARION Trial pursuant to the Master Services Agreement dated January 15, 2023, between Sponsor and Meridian CRO) within twenty-four (24) hours of the Investigator becoming aware of the event. The initial SAE report shall include, at a minimum, the subject identification number, a description of the event, the date of onset, the severity and seriousness criteria met, the Investigator's assessment of causality, and the current status of the subject. Follow-up reports providing additional information shall be submitted as information becomes available, and no later than five (5) calendar days following the initial report.
5.2 Safety Reporting Forms and Procedures. All SAE reports shall be submitted using the safety reporting forms, electronic reporting portals, and procedures set forth in Exhibit J to the MCTA (Safety Reporting Procedures). Investigator shall ensure that all members of the site study team who may become aware of SAEs are trained on these reporting procedures and understand the applicable timelines and requirements.
5.3 Sponsor's IND Safety Reporting Obligations. Investigator acknowledges that Sponsor is responsible for the evaluation and reporting of IND safety reports to the FDA in accordance with 21 C.F.R. § 312.32. Without limiting the foregoing, Sponsor is responsible for submitting (a) seven (7)-calendar-day reports to the FDA for any fatal or life-threatening unexpected suspected adverse reaction, and (b) fifteen (15)-calendar-day reports for all other reportable safety information, including unexpected serious suspected adverse reactions that are not fatal or life-threatening. Investigator acknowledges that the timely and complete reporting of SAEs by the Investigator is essential to Sponsor's ability to fulfill these regulatory obligations.
5.4 Cooperation with Safety Inquiries. Investigator shall cooperate fully and promptly with Sponsor, Meridian CRO, and the FDA in any safety-related inquiries, including the provision of complete follow-up information on reported SAEs, the completion of MedWatch forms or other regulatory safety reports as requested, and participation in safety review committee meetings or teleconferences as reasonably requested by Sponsor.
5.5 Reporting to IRB. Investigator shall promptly report to the applicable IRB any safety information that may affect the welfare of study subjects, including but not limited to site-specific SAEs, IND safety reports received from Sponsor, and any new safety information that may alter the benefit-risk assessment of the Study, in accordance with the applicable IRB's reporting requirements and the timelines specified in Section 4.5 of this Undertaking.
SECTION 6: DATA COLLECTION, RECORDING, AND SOURCE DOCUMENTS
6.1 Electronic Data Capture. Investigator shall ensure the accurate, complete, legible, and timely recording of all study data in the electronic data capture ("EDC") system provided by Pinnacle Data Solutions, Inc. ("Pinnacle"), in compliance with the requirements of 21 C.F.R. Part 11 and the data management plan for the CLARION Trial. Investigator shall ensure that all data entries are made by authorized personnel whose identities and access credentials have been established in the EDC system, and that all entries and modifications are tracked by the EDC system's audit trail. Investigator shall ensure that data queries issued through the EDC system are resolved accurately and within the timelines established in the data management plan.
6.2 Source Documents. Investigator shall create and maintain adequate and accurate source documents supporting all data entered into the EDC system. Source documents include, but are not limited to, hospital records, clinic charts, laboratory reports, imaging reports, subject diaries, pharmacy dispensing records, and any other original documents, data, or records from which study data are derived. Source documents shall be legible, contemporaneous, original, accurate, and complete, and shall be maintained in an organized and secure manner at the site.
6.3 Central Laboratory. All laboratory analyses required under the Protocol, including hematology, chemistry, biomarker, and pharmacokinetic assessments, shall be performed by Northbridge Bioanalytical Laboratories, Inc. ("Northbridge"), designated as the central laboratory for the CLARION Trial, unless otherwise specified in the Protocol for local laboratory assessments (e.g., certain safety labs requiring rapid turnaround). Investigator shall ensure the timely collection, processing, labeling, and shipment of all biological specimens in accordance with the laboratory manual provided by Northbridge and the specimen handling instructions set forth in the Protocol.
6.4 Access to Records. Investigator shall permit authorized representatives of Sponsor, Meridian CRO, the applicable IRB, the FDA, and any other applicable regulatory authority to access, review, and copy source documents, study records, and all other documents related to the conduct of the CLARION Trial, for the purposes of monitoring, auditing, and regulatory inspection. Investigator shall ensure that appropriate arrangements are in place at the site institution to facilitate such access, including compliance with any institutional policies governing access to medical records.
6.5 Record Retention. Investigator shall retain all source documents, study records, and regulatory documents related to the CLARION Trial for a minimum period of fifteen (15) years following study completion (defined as the date of Sponsor's final clinical study report for the CLARION Trial), or for such longer period as may be required by applicable federal, state, or local law, or by the applicable IRB, whichever is longer. Investigator shall notify Sponsor in writing at least sixty (60) days prior to any proposed relocation or transfer of study records and shall not transfer such records without Sponsor's prior written approval.
6.6 Prohibition on Destruction of Records. Investigator shall not destroy, discard, or otherwise dispose of any study records, source documents, or regulatory files related to the CLARION Trial without the prior written consent of Sponsor. In the event that Investigator is unable to continue to maintain custody of study records (e.g., due to retirement, relocation, or closure of the site institution), Investigator shall notify Sponsor promptly and shall cooperate with Sponsor to arrange for the transfer of such records to Sponsor or to a mutually agreed-upon custodian.
SECTION 7: DATA OWNERSHIP
7.1 Sponsor Ownership. Investigator acknowledges and agrees that Sponsor (Penterra Pharmaceuticals Corp.) retains exclusive ownership of all clinical trial data generated under Protocol PPC-4871-III (the CLARION Trial), including but not limited to all case report form data, electronic data captured in the EDC system, compiled datasets, statistical analyses, interim and final results, safety data, and any other data or information derived from the Study, as set forth in Section 10 of the MCTA and Exhibit G thereto (Intellectual Property and Publication Rights). This ownership vests in Sponsor upon the creation or generation of such data and does not require any further act or instrument.
7.2 Restrictions on Use. Investigator shall not use clinical trial data generated under the CLARION Trial for any purpose other than the conduct of the Study in accordance with the Protocol, or as expressly permitted under the MCTA (including the publication rights set forth in Section 12 of this Undertaking and Exhibit G to the MCTA), without the prior written consent of Sponsor. Without limiting the foregoing, Investigator shall not use clinical trial data for the purpose of supporting any regulatory submission, patent application, grant application, or commercial endeavor on behalf of any party other than Sponsor.
7.3 Custody of Source Documents. Notwithstanding Sponsor's ownership of clinical trial data as described in Section 7.1, the site institution and Investigator shall retain physical and administrative custody of source documents created and maintained at the site in accordance with Section 6 of this Undertaking. For the avoidance of doubt, all case report form data, electronic data captured in the EDC system, and compiled datasets derived therefrom are and shall remain the exclusive property of Sponsor.
SECTION 8: CONFIDENTIALITY OBLIGATIONS
8.1 Definition of Confidential Information. Investigator acknowledges that all information received from or on behalf of Sponsor in connection with the CLARION Trial constitutes confidential and proprietary information of Sponsor ("Confidential Information"). Confidential Information includes, but is not limited to, the Protocol, the Investigator's Brochure, study data and results (whether interim or final), investigational product specifications, formulation and manufacturing information, pharmacokinetic and pharmacodynamic data, regulatory strategies and submissions, financial terms and payment schedules, business plans, trade secrets, and all other non-public information disclosed by Sponsor or generated in connection with the Study, regardless of the form or medium in which such information is communicated or recorded.
8.2 Confidentiality Term. The obligations of confidentiality set forth in this Section 8 shall continue for a period of ten (10) years from the date of disclosure of the applicable Confidential Information, as set forth in Exhibit F to the MCTA (Confidentiality Agreement), unless a longer period is required by applicable law or regulation.
8.3 Restrictions on Disclosure. Investigator shall not disclose Confidential Information to any third party, except as expressly permitted under the MCTA and this Undertaking, including:
(a) Submissions to the applicable IRB that are necessary for the IRB's review, approval, and oversight of the Study;
(b) Disclosures required by applicable law, regulation, or order of a court or regulatory authority of competent jurisdiction, provided that Investigator shall provide Sponsor with prompt written notice of any such required disclosure (to the extent legally permitted) and shall cooperate with Sponsor in seeking a protective order or other appropriate remedy to limit the scope of the disclosure;
(c) Disclosures to Investigator's legal counsel who are under a professional obligation of confidentiality; and
(d) Disclosures to members of the site study team who have a need to know such information for the conduct of the Study and who are bound by written confidentiality obligations no less restrictive than those set forth in this Undertaking.
8.4 Site Personnel Obligations. Investigator shall ensure that all site personnel, including study coordinators, research nurses, pharmacists, laboratory technicians, and any other individuals at the site who have access to Confidential Information, are bound by written confidentiality obligations no less restrictive than those imposed on Investigator under this Undertaking. Investigator shall be responsible for any breach of confidentiality by such personnel.
8.5 Return or Destruction of Materials. Upon the completion or termination of Investigator's participation in the CLARION Trial, all Confidential Information and materials containing or embodying Confidential Information (other than source documents that Investigator is required to retain under Section 6.5 of this Undertaking) shall be returned to Sponsor or destroyed at Sponsor's election, within thirty (30) days of Sponsor's written request. Investigator shall certify in writing to Sponsor that all such materials have been returned or destroyed, as applicable.
SECTION 9: FINANCIAL DISCLOSURE AND CONFLICT OF INTEREST
9.1 Financial Disclosure Certification. Investigator shall complete and submit to Sponsor the Financial Disclosure Certification form required under 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators) prior to Investigator's participation in any study-related activities under the CLARION Trial. The Financial Disclosure Certification shall be in the form specified by Sponsor and shall contain all information required under 21 C.F.R. § 54.4.
9.2 Disclosure of Financial Interests. Investigator certifies that Investigator has disclosed (or, prior to site activation, will disclose) all financial interests, arrangements, and relationships with Sponsor that are required to be reported under 21 C.F.R. Part 54, including but not limited to:
(a) Any equity interests in Penterra Pharmaceuticals Corp. (Nasdaq ticker symbol: PTRA), including stock, stock options, warrants, or other ownership interests, exceeding Fifty Thousand Dollars ($50,000) in aggregate value at the time of disclosure;
(b) Significant payments of other sorts, as that term is defined in 21 C.F.R. § 54.2(f), received from Sponsor during the course of the Study or within one (1) year prior to the beginning of the Study;
(c) Any proprietary interest in penterafenib (PPC-4871) or related technology, including any patent, trademark, copyright, or licensing agreement;
(d) Any significant equity interest in Sponsor, as that term is defined in 21 C.F.R. § 54.2(b); and
(e) Any other financial interest, arrangement, or relationship that could be affected by the outcome of the Study and that is required to be disclosed under applicable federal or state regulations or institutional policies.
9.3 Ongoing Disclosure Obligation. Investigator shall promptly notify Sponsor in writing of any change in Investigator's financial interests, or any new financial arrangement or relationship with Sponsor or any entity with a financial interest in the outcome of the CLARION Trial, that arises during the course of the Study or within one (1) year after the completion of Investigator's participation in the Study. Such notification shall be provided within thirty (30) days of the occurrence of the relevant change or event.
9.4 Consequences of Non-Disclosure. Investigator acknowledges that failure to disclose a financial interest as required under 21 C.F.R. Part 54 or this Undertaking may result in (a) Investigator's disqualification from the CLARION Trial, (b) regulatory consequences under 21 C.F.R. Part 54, including the potential inability of Sponsor to rely on data generated by the Investigator in support of marketing applications, and (c) potential debarment or disqualification proceedings under applicable FDA regulations.
9.5 Fair Market Value Compensation. Investigator certifies that all compensation received by Investigator for participation in the CLARION Trial, including investigator fees, per-subject payments, and any other remuneration, is consistent with fair market value for the services rendered, taking into account the nature, scope, and complexity of the study procedures. Investigator further certifies that such compensation was determined independently of the volume or value of any referrals or business otherwise generated between Investigator and Sponsor, as required by the Federal Anti-Kickback Statute, 42 U.S.C. § 1320a-7b, and its implementing regulations, the Stark Law (42 U.S.C. § 1395nn), and all other applicable federal and state laws governing physician compensation arrangements.
SECTION 10: ANTI-KICKBACK AND SUNSHINE ACT COMPLIANCE
10.1 Anti-Kickback Representations. Investigator represents and warrants that Investigator's participation in the CLARION Trial is not conditioned upon, and Investigator has not received any promise, offer, or provision of, any payment, benefit, remuneration, or thing of value beyond fair market value compensation for legitimate services actually rendered in connection with the Study. Investigator further represents that Investigator's participation in the CLARION Trial was not solicited through, and does not involve, any arrangement that constitutes or could constitute a violation of the Federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b) or any comparable state law.
10.2 Physician Payments Sunshine Act. Investigator acknowledges that Sponsor is required to report payments and transfers of value made to physicians and teaching hospitals under Section 1128G of the Social Security Act (42 U.S.C. § 1320a-7h), commonly known as the Physician Payments Sunshine Act, and the implementing regulations of the Centers for Medicare & Medicaid Services ("CMS") establishing the Open Payments program (42 C.F.R. Part 403, Subpart I). Investigator agrees to cooperate with Sponsor in fulfilling Sponsor's reporting obligations under the Open Payments program and acknowledges that certain payments and transfers of value made to Investigator in connection with the CLARION Trial may be subject to public disclosure through the Open Payments database.
10.3 Information for Open Payments Reporting. Investigator shall promptly provide to Sponsor any information reasonably requested by Sponsor for purposes of Open Payments reporting, including but not limited to verification of reportable amounts, identification of payment categories, confirmation of Investigator's National Provider Identifier (NPI) and state licensure information, and any other data elements required for accurate and complete reporting. Investigator shall review and respond to any dispute or attestation requests received from Sponsor or through the CMS Open Payments system within the applicable timelines.
SECTION 11: HIPAA AND SUBJECT PRIVACY
11.1 HIPAA Compliance. Investigator shall comply with the Health Insurance Portability and Accountability Act of 1996 ("HIPAA"), as amended by the Health Information Technology for Economic and Clinical Health Act ("HITECH Act"), and the implementing regulations of the U.S. Department of Health and Human Services at 45 C.F.R. Parts 160 and 164, in connection with the collection, use, storage, and disclosure of protected health information ("PHI") of study subjects in the CLARION Trial. Investigator shall ensure that all PHI collected or accessed in connection with the Study is handled in accordance with the HIPAA Privacy Rule (45 C.F.R. Part 164, Subpart E) and the HIPAA Security Rule (45 C.F.R. Part 164, Subpart C).
11.2 HIPAA Research Authorization. Investigator shall obtain a valid HIPAA research authorization from each study subject (or the subject's personal representative, as defined under HIPAA) prior to accessing, using, or disclosing the subject's PHI for purposes of the CLARION Trial, unless a waiver or alteration of the authorization requirement has been approved by the applicable IRB or Privacy Board in accordance with 45 C.F.R. § 164.512(i). The HIPAA research authorization shall meet all requirements set forth in 45 C.F.R. § 164.508 and shall be maintained as part of the subject's study file.
11.3 Minimum Necessary Standard. Investigator shall limit the use and disclosure of PHI to the minimum necessary to accomplish the purposes of the Study, consistent with the minimum necessary standard set forth in 45 C.F.R. § 164.502(b) and § 164.514(d). Investigator shall de-identify study data to the extent practicable and consistent with the Protocol and applicable regulatory requirements.
11.4 Safeguards. Investigator shall implement and maintain appropriate administrative, technical, and physical safeguards to protect the confidentiality, integrity, and security of subject PHI, in accordance with the HIPAA Security Rule and consistent with the site institution's HIPAA policies and procedures. Such safeguards shall include, without limitation, access controls for electronic systems containing PHI, encryption of PHI transmitted electronically, secure storage of paper records containing PHI, and workforce training on privacy and security obligations.
SECTION 12: PUBLICATION RIGHTS
12.1 Right to Publish. Investigator may publish or present the results of the CLARION Trial in peer-reviewed journals, at scientific or medical conferences, or through other professional or academic channels, subject to the terms and conditions set forth in Exhibit G to the MCTA (Intellectual Property and Publication Rights) and this Section 12. Nothing in this Undertaking shall be construed as obligating Investigator to publish the results of the Study.
12.2 Pre-Publication Review. Prior to the submission of any manuscript, abstract, poster, oral presentation, or other publication or public presentation containing data or results from the CLARION Trial for publication or presentation, Investigator shall provide Sponsor with a complete copy of the proposed manuscript, abstract, or other materials at least sixty (60) days in advance of the intended date of submission or presentation (the "Review Period"). Sponsor shall review the proposed publication for the purpose of identifying (a) Confidential Information of Sponsor, (b) patentable subject matter, and (c) any factual inaccuracies. Sponsor shall communicate any comments, objections, or requests for modifications to Investigator within the Review Period.
12.3 Delay for Patent Filing. In the event that Sponsor identifies patentable subject matter in a proposed publication, Sponsor may request a delay of up to an additional ninety (90) days beyond the initial sixty (60)-day Review Period (for a total delay of up to one hundred fifty (150) days from the date of Sponsor's receipt of the proposed publication) to allow for the preparation and filing of patent applications on such patentable subject matter. Investigator shall not submit or present the proposed publication during any such delay period unless Sponsor provides written consent. Sponsor shall use commercially reasonable efforts to complete any patent filings within the delay period.
12.4 Exclusion of Confidential Information. Investigator shall not include any Confidential Information of Sponsor (as defined in Section 8.1) in any publication or public presentation without Sponsor's prior written consent. In the event that Sponsor identifies Confidential Information in a proposed publication during the Review Period, Investigator shall remove or redact such Confidential Information prior to submission or presentation.
12.5 Multi-Center Publication Priority. Investigator acknowledges that the CLARION Trial is a multi-center clinical study and agrees that, consistent with good scientific practice and the principles of the International Committee of Medical Journal Editors (ICMJE), multi-center trial results should generally be published first as a multi-center report reflecting the aggregate results of all participating sites. Individual site results or sub-analyses may be published only after the primary multi-center publication has been submitted for publication or with Sponsor's prior written consent. Investigator shall cooperate with the CLARION Trial publication committee and Sponsor in the preparation and review of the primary multi-center publication.
SECTION 13: INVESTIGATIONAL PRODUCT ACCOUNTABILITY
13.1 Receipt, Storage, Dispensing, and Accounting. Investigator shall ensure the proper receipt, storage, dispensing, and accounting of the investigational product (penterafenib/PPC-4871 and matching placebo) in accordance with the Protocol, the Investigator's Brochure, the Pharmacy Manual provided by Sponsor, and all applicable federal and state regulations governing the handling of investigational drugs. Investigator shall designate a qualified pharmacist or other authorized individual at the site to be responsible for the receipt, storage, dispensing, and inventory of the investigational product, and shall ensure that such individual is identified on the Delegation Log.
13.2 Exclusive Use. The investigational product supplied by Sponsor shall be used solely for the conduct of the CLARION Trial in accordance with the Protocol and shall not be supplied, administered, dispensed, or otherwise made available to any person who is not a duly enrolled subject in the Study. Investigator shall not use the investigational product for any purpose other than the conduct of the CLARION Trial.
13.3 Drug Accountability Records. Investigator shall maintain accurate and contemporaneous drug accountability records documenting the receipt, inventory, dispensing (including subject identification, date, dose, and lot number), return, and disposition of all investigational product at the site. Investigator shall reconcile drug accountability records at each monitoring visit and shall return or dispose of all unused, expired, or damaged investigational product in accordance with Sponsor's written instructions and applicable regulations. Investigator shall not dispose of any investigational product without prior authorization from Sponsor.
13.4 Storage Conditions. Investigator shall store the investigational product under the conditions specified in the Protocol and the Investigator's Brochure, including the required temperature range, protection from light, and any other storage requirements. Investigator shall ensure that temperature monitoring equipment is in place and functioning at all times, and shall maintain records of temperature monitoring throughout the study period. Investigator shall immediately report any storage deviation (including temperature excursions, equipment failures, or environmental events affecting storage conditions) to Sponsor and Meridian CRO. Investigator shall quarantine any investigational product affected by a storage deviation and shall not dispense such product until Sponsor has evaluated the deviation and provided written authorization to release or destroy the affected product.
SECTION 14: MONITORING, AUDITING, AND INSPECTIONS
14.1 Monitoring Visits. Investigator shall cooperate with and permit site monitoring visits by Meridian CRO, the contracted clinical research organization retained by Sponsor pursuant to the Master Services Agreement dated January 15, 2023, between Sponsor and Meridian CRO, and/or by Sponsor's other authorized representatives. Investigator shall ensure the availability of study records, source documents, investigational product accountability records, regulatory files, and site personnel during scheduled monitoring visits, and shall provide adequate workspace for monitors at the site. Investigator shall review and respond to monitoring visit reports and action items in a timely manner.
14.2 Quality Assurance Audits. Investigator shall cooperate with quality assurance audits of the site conducted by Sponsor or its designee, including internal audits, for-cause audits, and audits conducted as part of Sponsor's overall quality management system for the CLARION Trial. Investigator shall provide auditors with full access to study records, source documents, regulatory files, and site facilities, and shall cooperate in the implementation of any corrective and preventive actions identified as a result of audit findings.
14.3 Regulatory Inspections. In the event of an inspection of the site by the FDA or any other domestic or international regulatory authority in connection with the CLARION Trial, Investigator shall (a) promptly notify Sponsor (and Meridian CRO) of the inspection, including the identity of the inspecting authority, the date(s) of the inspection, and the scope of the inspection, to the extent known; (b) cooperate fully with the inspection, including providing the inspecting authority with access to all study records, source documents, investigational product, and site facilities as required; and (c) promptly provide Sponsor with copies of any correspondence, written observations (including FDA Form 483 observations), Establishment Inspection Reports, Warning Letters, findings, or reports received from the inspecting authority in connection with the CLARION Trial or related to Investigator's conduct of clinical research.
14.4 Copies of Regulatory Correspondence. Investigator shall promptly provide Sponsor with copies of any correspondence, communications, findings, reports, or other documents received from any regulatory authority in connection with the CLARION Trial, including but not limited to requests for information, compliance actions, enforcement actions, or other regulatory inquiries. Such copies shall be provided within five (5) business days of Investigator's receipt thereof.
SECTION 15: INSURANCE
15.1 Sponsor's Clinical Trial Liability Insurance. Investigator acknowledges that Sponsor maintains clinical trial liability insurance in connection with the CLARION Trial through Briarcliff Mutual Insurance Company (Policy Number: BM-CTL-2023-04182), with limits of liability of Twenty-Five Million Dollars ($25,000,000) per occurrence and Seventy-Five Million Dollars ($75,000,000) in the aggregate, including a subject-injury sublimit of Ten Million Dollars ($10,000,000) per occurrence and Fifty Million Dollars ($50,000,000) in the aggregate, as more fully described in Exhibit E to the MCTA (Insurance). Investigator acknowledges receipt of a summary of coverage and agrees to review the applicable policy provisions.
15.2 Site Institution Insurance. Investigator acknowledges that the participating site institution at which Investigator conducts the CLARION Trial is required to obtain and maintain, throughout the term of the Study, general liability insurance and professional liability (medical malpractice) insurance with combined limits of at least Five Million Dollars ($5,000,000) per occurrence and Ten Million Dollars ($10,000,000) in the aggregate, as set forth in Section 12.2 of the MCTA. Investigator shall cooperate with the site institution in ensuring that such coverage is obtained and maintained and that evidence of coverage is provided to Sponsor upon request.
15.3 Incident Reporting. Investigator agrees to cooperate in the timely reporting of any incidents, events, or circumstances that may give rise to a claim under any applicable insurance policy, including any subject injuries, adverse events, property damage, or third-party claims. Investigator shall notify Sponsor of any such incidents within the timeframes specified in Exhibit E to the MCTA and shall provide such information and documentation as may be reasonably requested by Sponsor or its insurers.
SECTION 16: INDEMNIFICATION ACKNOWLEDGMENT
16.1 Acknowledgment of Indemnification Provisions. Investigator acknowledges and has reviewed the indemnification provisions set forth in Section 11 of the MCTA and Exhibit D thereto (Indemnification). Investigator understands the scope and limitations of the indemnification obligations of Sponsor and the reciprocal obligations of the Site Network and Investigator as described in the MCTA.
16.2 Scope of Sponsor Indemnification. Sponsor provides indemnification to Investigator and the site institution, subject to the terms and conditions of the MCTA and Exhibit D, against third-party claims, demands, actions, suits, judgments, losses, damages, liabilities, costs, and expenses (including reasonable attorneys' fees and costs of defense) arising out of or resulting from:
(a) Subject injury caused by the investigational product (penterafenib/PPC-4871 or matching placebo) when administered in accordance with the Protocol;
(b) Defects in the investigational product, including defects in design, manufacture, formulation, labeling, or packaging;
(c) Sponsor's material breach of the MCTA or this Undertaking; and
(d) The negligence or willful misconduct of Sponsor or its employees, agents, or contractors (other than Investigator or site personnel).
16.3 Exclusions from Indemnification. Investigator acknowledges that Sponsor's indemnification obligations do not extend to losses, liabilities, claims, or damages arising from or attributable to:
(a) The negligence or willful misconduct of Investigator, the site institution, or any member of the site study team;
(b) Protocol deviations not authorized by Sponsor or not undertaken to protect the safety of subjects;
(c) Investigator's breach of the MCTA, this Undertaking, or applicable law or regulation; or
(d) The use of the investigational product in a manner not consistent with the Protocol or the Investigator's Brochure.
16.4 Medical Care for Study-Related Injuries. Sponsor will cover the reasonable costs of medical care for study-related injuries sustained by subjects in the CLARION Trial that are not covered by the subject's own insurance, health plan, or other third-party coverage, subject to the terms and conditions of the MCTA, including a per-subject cap of Five Hundred Thousand Dollars ($500,000) and an aggregate cap of Fifteen Million Dollars ($15,000,000) for all subjects across all sites. The determination of whether an injury is study-related shall be made by Sponsor in consultation with the Investigator, and any disputes shall be resolved in accordance with the dispute resolution procedures set forth in the MCTA.
16.5 Notice of Claims. Investigator shall provide written notice to Sponsor of any claim, demand, action, or suit that may be subject to indemnification under the MCTA within thirty (30) calendar days of Investigator's becoming aware of such claim. Written notice shall be provided to Sponsor at the address set forth in Section 20.6 of this Undertaking. Failure by Investigator to provide timely notice shall not relieve Sponsor of its indemnification obligation under the MCTA, except to the extent that Sponsor demonstrates that it has been materially prejudiced by such failure.
SECTION 17: TERM AND TERMINATION
17.1 Effective Date and Term. This Undertaking shall be effective as of the date of Investigator's signature below and shall continue in full force and effect until the earliest of: (a) the completion of all study-related obligations of Investigator under the Protocol, including all follow-up visits, data queries, record retention obligations, and final regulatory submissions; (b) the termination of the Individual Site Agreement for the site at which Investigator conducts the CLARION Trial, whether by expiration of the term, mutual agreement, or otherwise; or (c) the withdrawal or removal of Investigator from the Study, whether voluntary or involuntary.
17.2 Wind-Down Obligations. In the event of termination of this Undertaking for any reason, Investigator shall cooperate with Sponsor, Meridian CRO, and the Site Network during the one-hundred-twenty (120)-day wind-down period specified in Section 14.3 of the MCTA, to ensure the safety and welfare of all subjects enrolled at Investigator's site. During the wind-down period, Investigator shall (a) facilitate the transition of subjects in active treatment to an alternative qualified investigator within the Veridian Network, or (b) permit subjects to complete their current treatment cycle if clinically appropriate and agreed upon by Sponsor, Investigator, and the applicable IRB. Investigator shall continue to report all adverse events and SAEs during the wind-down period and shall complete all outstanding data entries and queries in the EDC system.
17.3 Surviving Obligations. The following obligations shall survive the expiration or termination of this Undertaking and shall continue in full force and effect for the periods specified therein or, if no specific period is stated, indefinitely: (a) confidentiality obligations under Section 8, subject to the ten (10)-year confidentiality term set forth in Section 8.2; (b) data ownership provisions under Section 7; (c) financial disclosure obligations under Section 9, including the obligation to report changes in financial interests for one (1) year following the completion of Investigator's participation; (d) publication rights and restrictions under Section 12; and (e) record retention obligations under Section 6.5.
SECTION 18: REPRESENTATIONS AND WARRANTIES
18.1 Valid Medical License. Investigator represents and warrants that Investigator holds a current, valid, and unrestricted license to practice medicine in the state or states where the participating site institution is located, and that such license has not been suspended, revoked, restricted, or made subject to any disciplinary action that would impair Investigator's ability to conduct the CLARION Trial.
18.2 No Debarment. Investigator represents and warrants that Investigator has not been debarred, and is not subject to a pending debarment proceeding, under Section 306(a) or (b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. § 335a), and that Investigator is not subject to any FDA clinical investigator disqualification under 21 C.F.R. § 312.70 or any restriction on Investigator's eligibility to receive investigational products.
18.3 No Exclusion from Federal Healthcare Programs. Investigator represents and warrants that Investigator has not been excluded from participation in any federal healthcare program, including Medicare and Medicaid, and that Investigator's name does not appear on the U.S. Department of Health and Human Services Office of Inspector General (HHS/OIG) List of Excluded Individuals/Entities (LEIE) or the General Services Administration (GSA) System for Award Management (SAM) Excluded Parties List.
18.4 Qualifications and Experience. Investigator represents and warrants that Investigator has the professional qualifications, scientific training, clinical experience, and expertise necessary to conduct the CLARION Trial in accordance with the Protocol, ICH E6(R2), and all applicable regulatory requirements. Investigator's qualifications are evidenced by the curriculum vitae on file with Sponsor and the applicable IRB.
18.5 Adequate Resources. Investigator represents and warrants that the participating site institution has adequate resources, facilities, equipment, and qualified staff to conduct the CLARION Trial as described in the Protocol, including the capability to enroll and follow subjects, perform required study assessments, store investigational product under specified conditions, and maintain study records in compliance with applicable requirements.
18.6 Notification of Changes. Investigator shall promptly notify Sponsor in writing if any of the representations and warranties set forth in Sections 18.1 through 18.5 ceases to be true or accurate at any time during the course of the Study. Such notification shall be provided within ten (10) business days of the occurrence of the relevant event or circumstance.
SECTION 19: GOVERNING LAW
19.1 Governing Law. This Undertaking shall be governed by and construed in accordance with the laws of the State of New York, without regard to any conflict-of-laws rules or principles that would result in the application of the laws of any other jurisdiction. The choice of New York law is consistent with the governing law provision set forth in Section 17.1 of the MCTA.
19.2 Dispute Resolution. Any dispute, controversy, or claim arising out of or relating to this Undertaking, or the breach, termination, or validity thereof, shall be resolved in accordance with the dispute resolution procedures set forth in Section 17.2 of the MCTA, which provide for (a) an initial period of thirty (30) days for good-faith negotiation between the designated representatives of the parties; (b) if negotiation is unsuccessful, mediation under the American Arbitration Association ("AAA") Commercial Mediation Rules for a period of sixty (60) days; and (c) if mediation is unsuccessful, final and binding arbitration in New York, New York, under the AAA Commercial Arbitration Rules, before a panel of three (3) arbitrators selected in accordance with the AAA rules. Judgment on the arbitration award may be entered in any court of competent jurisdiction.
19.3 Injunctive Relief. Notwithstanding anything to the contrary in this Section 19, nothing herein shall limit the right of any party to seek temporary, preliminary, or permanent injunctive relief, specific performance, or other equitable remedies from the state and federal courts located in New York County, New York, to prevent irreparable harm pending the resolution of any dispute through the procedures described in Section 19.2.
SECTION 20: MISCELLANEOUS
20.1 Entire Agreement. This Undertaking, together with the MCTA and all Exhibits and Schedules thereto (including, without limitation, Exhibit D — Indemnification, Exhibit E — Insurance, Exhibit F — Confidentiality Agreement, Exhibit G — Intellectual Property and Publication Rights, and Exhibit J — Safety Reporting Procedures), and the Individual Site Agreement for Investigator's site, constitutes the entire agreement between the parties with respect to the subject matter hereof and supersedes all prior or contemporaneous oral or written agreements, understandings, representations, and warranties relating thereto.
20.2 Amendments. No amendment, modification, or supplement to this Undertaking shall be effective or binding upon any party unless such amendment is set forth in a writing duly executed by Investigator, Sponsor, and the Site Network (or their respective authorized representatives).
20.3 Counterparts. This Undertaking may be executed in one or more counterparts, including by facsimile or electronic signature (in compliance with the Electronic Signatures in Global and National Commerce Act, 15 U.S.C. § 7001 et seq.), each of which shall be deemed an original and all of which together shall constitute one and the same instrument.
20.4 Severability. If any provision of this Undertaking is held to be invalid, illegal, or unenforceable by a court or arbitral tribunal of competent jurisdiction, the validity, legality, and enforceability of the remaining provisions shall not in any way be affected or impaired thereby, and such invalid, illegal, or unenforceable provision shall be modified to the minimum extent necessary to make it valid, legal, and enforceable while preserving the intent of the parties.
20.5 Assignment. Investigator may not assign, delegate, or transfer this Undertaking or any of Investigator's rights, duties, or obligations hereunder without the prior written consent of Sponsor. Any purported assignment in violation of this Section shall be null and void. Sponsor may assign its rights and obligations under this Undertaking to a successor in interest, affiliate, or acquirer of substantially all of Sponsor's assets or the penterafenib program, upon written notice to Investigator.
20.6 Notices. All notices, requests, demands, consents, approvals, and other communications required or permitted under this Undertaking shall be in writing and shall be deemed duly given when (a) delivered personally, (b) sent by registered or certified mail, return receipt requested, postage prepaid, (c) sent by nationally recognized overnight courier service, or (d) sent by email with confirmation of receipt, to the parties at the following addresses (or such other addresses as a party may designate in writing from time to time):
To Sponsor:
Penterra Pharmaceuticals Corp. 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540
Attention: Nathaniel Briggs, Esq., Vice President & General Counsel
Email: n.briggs@penterra.com
With a copy (which shall not constitute notice) to:
Rebecc