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CO-PRINCIPAL INVESTIGATOR AGREEMENT

Protocol PPC-4871-III

CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology

June 28, 2023

Between

PENTERRA PHARMACEUTICALS CORP. 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540

and

DR. HOWARD MATSUOKA, M.D. Associate Professor of Hepatology & Oncology Lakemont Medical Center 4400 North Michigan Drive Chicago, Illinois 60611

CONFIDENTIAL — This document and all attachments contain confidential and proprietary information of Penterra Pharmaceuticals Corp. and are subject to the confidentiality obligations set forth herein and in the Master Clinical Trial Agreement dated June 28, 2023. Unauthorized reproduction or distribution is strictly prohibited.

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RECITALS

This Co-Principal Investigator Agreement (this "Agreement") is entered into as of June 28, 2023 (the "Effective Date"), by and between:

PENTERRA PHARMACEUTICALS CORP., 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 (Nasdaq: PTRA) (hereinafter referred to as the "Sponsor" or "Penterra"); and

DR. HOWARD MATSUOKA, M.D., an individual residing and practicing in the State of Illinois, currently serving as Associate Professor of Hepatology & Oncology at Lakemont Medical Center, located at 4400 North Michigan Drive, Chicago, Illinois 60611 (hereinafter referred to as the "Co-Principal Investigator" or "Co-PI").

The Sponsor and the Co-PI are referred to individually as a "Party" and collectively as the "Parties."

WHEREAS, Penterra is the sponsor of a Phase III, randomized, double-blind, placebo-controlled clinical trial of its investigational compound penterafenib (PPC-4871), an oral multi-kinase inhibitor targeting VEGFR-1/2/3, PDGFR-α/β, FGFR1-4, and c-KIT, for the treatment of advanced hepatocellular carcinoma ("HCC") in the second-line setting after prior systemic therapy, designated as Protocol PPC-4871-III and entitled "CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology" (the "Study" or "Trial");

WHEREAS, Penterra holds Investigational New Drug Application No. 157823 ("IND 157823") for penterafenib (PPC-4871), filed with the United States Food and Drug Administration ("FDA") in October 2021, and the Phase II portion of the clinical development program was completed in January 2023, demonstrating a thirty-eight percent (38%) objective response rate in patients with advanced HCC, with a manageable safety profile and a median progression-free survival of 7.2 months, supporting advancement to Phase III evaluation;

WHEREAS, the Study is registered with the National Library of Medicine under ClinicalTrials.gov Identifier NCT05928174 and is subject to the registration and results-reporting requirements of the FDA Amendments Act of 2007 (FDAAA 801);

WHEREAS, Penterra and Veridian Health Research Network, Inc. ("Veridian"), a Delaware 501(c)(3) corporation headquartered at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104, have entered into a Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA") governing the conduct of the Study across thirty-eight (38) Veridian Network sites located in fourteen (14) states throughout the United States, with a total deal value of Eighty Million Dollars ($80,000,000);

WHEREAS, Lakemont Medical Center ("Lakemont" or the "Site") is a Veridian Network member institution that has executed an Individual Site Agreement (Joinder) as Site 002 under the MCTA, thereby agreeing to be bound by the terms and conditions of the MCTA as applicable to individual participating sites;

WHEREAS, Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, Philadelphia, Pennsylvania, serves as the Global Principal Investigator (the "Global PI") for the Study and is responsible for overall scientific leadership and multi-site coordination of the Trial;

WHEREAS, Penterra desires to appoint Dr. Howard Matsuoka as Co-Principal Investigator for the Study at Lakemont Medical Center, and Dr. Matsuoka desires to accept such appointment, subject to the terms and conditions set forth herein;

WHEREAS, Meridian Contract Research Organization, Inc. ("Meridian CRO"), headquartered at 9200 Corporate Boulevard, Raleigh, North Carolina 27615, serves as Penterra's contracted clinical research organization for monitoring, data management, safety reporting, pharmacovigilance, and biostatistics for the Study, pursuant to a separate Master Services Agreement dated January 15, 2023 between Penterra and Meridian CRO; and

WHEREAS, the Parties desire to set forth their respective rights, responsibilities, and obligations in connection with the conduct of the Study at the Site.

NOW, THEREFORE, in consideration of the mutual promises, covenants, representations, and warranties set forth herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:

ARTICLE 1 — DEFINITIONS

As used in this Agreement, the following terms shall have the meanings ascribed to them below. Capitalized terms used but not defined in this Agreement shall have the meanings ascribed to them in the MCTA.

1.1 "Agreement" means this Co-Principal Investigator Agreement, together with all exhibits, schedules, appendices, and attachments hereto, as may be amended from time to time in accordance with Article 15.2.

1.2 "Applicable Law" means all federal, state, and local statutes, regulations, rules, ordinances, guidances, and directives applicable to the conduct of the Study, including but not limited to: (a) Title 21 of the Code of Federal Regulations ("C.F.R."), Parts 11, 50, 54, 56, and 312; (b) the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ("ICH") E6(R2) Guideline for Good Clinical Practice; (c) the Health Insurance Portability and Accountability Act of 1996, as amended, and its implementing regulations at 45 C.F.R. Parts 160 and 164 ("HIPAA"); (d) the Federal Anti-Kickback Statute, 42 U.S.C. § 1320a-7b, and the regulations promulgated thereunder at 42 C.F.R. § 1001.952; (e) the Physician Payments Sunshine Act, Section 6002 of the Affordable Care Act, codified at 42 U.S.C. § 1320a-7h (Open Payments); (f) the FDA Amendments Act of 2007 (FDAAA 801), as applicable; and (g) any other applicable federal, state, or local laws, regulations, or guidelines governing the conduct of clinical research.

1.3 "Clinical Trial Data" means all data, information, and results generated in connection with the Study, including but not limited to completed case report forms (whether paper or electronic), source documents, electronic data captures, biomarker data, pharmacokinetic and pharmacodynamic data, safety data (including adverse event reports and serious adverse event reports), laboratory results, imaging data, patient-reported outcomes, and any analyses, compilations, or derivations thereof.

1.4 "Confidential Information" has the meaning set forth in Exhibit F of the MCTA, which is incorporated herein by reference. Without limiting the generality of such definition, Confidential Information includes the Protocol, the Investigator's Brochure, the financial terms of this Agreement and the MCTA, Investigational Product specifications, manufacturing processes, Clinical Trial Data, and any other proprietary information of Penterra disclosed to the Co-PI in connection with the Study. The confidentiality period applicable to all Confidential Information shall be ten (10) years from the date of disclosure.

1.5 "GCP" means Good Clinical Practice as set forth in the ICH E6(R2) Guideline, as may be updated, amended, or replaced from time to time.

1.6 "Global PI" means Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, Philadelphia, Pennsylvania, in her capacity as the Global Principal Investigator for the Study, or any successor appointed by Penterra.

1.7 "Investigational Product" means penterafenib (PPC-4871), the oral multi-kinase inhibitor that is the subject of the Study, in all dosage forms, formulations, and strengths supplied by Penterra for use in the Study, as well as any matching placebo supplied for the Study.

1.8 "IRB" means the Institutional Review Board providing ethical oversight for the conduct of the Study at the Site. For purposes of this Agreement, the IRB of record for Lakemont Medical Center is the Veridian Central IRB, which serves as the single IRB of record for all Veridian Network sites participating in the Study pursuant to the IRB Authorization Agreement described in the MCTA.

1.9 "MCTA" means the Master Clinical Trial Agreement dated June 28, 2023, between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc., as may be amended from time to time, governing the conduct of the Study across all Veridian Network sites.

1.10 "Protocol" means Protocol PPC-4871-III, entitled "CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology," as may be amended from time to time with the approval of Penterra and the IRB, including all protocol amendments, appendices, and associated guidance documents.

1.11 "SAE" means a Serious Adverse Event, as defined in ICH E6(R2) and 21 C.F.R. § 312.32, which includes any adverse event occurring at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or constitutes an important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the foregoing outcomes.

1.12 "Site" means Lakemont Medical Center, located at 4400 North Michigan Drive, Chicago, Illinois 60611, designated as Site 002 under the MCTA, including all clinical, laboratory, pharmacy, and administrative facilities at Lakemont that are used or will be used in connection with the conduct of the Study.

1.13 "Study" or "Trial" means the Phase III, randomized, double-blind, placebo-controlled clinical trial conducted under Protocol PPC-4871-III (CLARION), evaluating the efficacy and safety of penterafenib (PPC-4871) versus placebo in adult patients with advanced hepatocellular carcinoma in the second-line setting after prior systemic therapy.

1.14 "Sub-Investigator" means any physician or other qualified individual delegated study-related duties by the Co-PI at the Site, who is listed on the delegation log maintained by the Co-PI and, as applicable, on FDA Form 1572.

ARTICLE 2 — APPOINTMENT AND TERM

2.1 Appointment. Penterra hereby appoints Dr. Howard Matsuoka as Co-Principal Investigator for the Study at Lakemont Medical Center (Site 002). Dr. Matsuoka hereby accepts such appointment and agrees to serve as Co-PI for the Study at the Site, subject to the terms and conditions of this Agreement, the Protocol, the MCTA, the Lakemont Individual Site Agreement (Joinder), and all Applicable Law. The Co-PI shall have primary responsibility for the scientific and clinical conduct of the Study at the Site and shall serve as the principal point of contact between the Site and Penterra (and its designated agents, including Meridian CRO) with respect to all Study-related matters at Lakemont Medical Center.

2.2 Relationship to Global PI. The Co-PI shall conduct the Study at the Site under the overall scientific leadership and direction of the Global PI, Dr. Catherine Aldridge, M.D., Ph.D. The Co-PI shall coordinate with the Global PI on all matters of scientific design, protocol interpretation, multi-site consistency, and study governance. The Co-PI shall participate in Global PI-convened investigator meetings, scientific advisory calls, and governance committee meetings as reasonably requested by the Global PI or Penterra. The Co-PI acknowledges that the Global PI has primary responsibility for ensuring scientific consistency across all participating sites and agrees to adhere to scientific guidance issued by the Global PI in connection with the Study, provided that such guidance does not conflict with the Protocol, Applicable Law, or the Co-PI's independent medical judgment regarding the safety and well-being of individual Study subjects.

2.3 Term. This Agreement shall commence on the Effective Date and shall continue in full force and effect until the earliest to occur of: (a) the completion of all Study activities at the Site, including the completion of the eighteen (18)-month follow-up period for all subjects enrolled at the Site and the resolution of all outstanding data queries (the projected study completion date is August 2028, based on a sixty (60)-month total study duration from the anticipated first-patient-first-visit date of August 14, 2023); (b) the termination of the MCTA or the Lakemont Individual Site Agreement (Joinder) for any reason; or (c) the termination of this Agreement in accordance with Article 10 hereof. The period during which this Agreement remains in effect is referred to herein as the "Term."

2.4 Conditions to Commencement. Notwithstanding the appointment set forth in Section 2.1, the Co-PI's active participation in the Study (including the enrollment of any Study subjects at the Site) is expressly conditioned upon the satisfaction of all of the following conditions precedent:

(a) IRB Approval. Receipt of initial IRB approval from the Veridian Central IRB for the conduct of the Study at Lakemont Medical Center, including approval of the Protocol, informed consent form, and all recruitment materials;

(b) FDA Form 1572. Execution by the Co-PI of a completed FDA Form 1572 (Statement of Investigator) for the Study at the Site, in form and substance satisfactory to Penterra and in compliance with 21 C.F.R. § 312.53;

(c) Financial Disclosure Certification. Completion and delivery to Penterra of a Financial Disclosure Certification in accordance with Article 6 and 21 C.F.R. Part 54;

(d) Training. Completion by the Co-PI (and all Site personnel listed on the delegation log) of all required training, including (i) GCP training (ICH E6(R2)) current within the prior two (2) years, (ii) Protocol-specific training conducted by Penterra and/or Meridian CRO, (iii) HIPAA privacy and security training, (iv) EDC system training provided by Pinnacle Data Solutions, Inc., and (v) any other training required by the MCTA, the IRB, or Applicable Law; and

(e) Site Activation. Completion of all site activation activities as specified in the MCTA, including the pre-study site initiation visit conducted by Meridian CRO.

The Co-PI shall not enroll any Study subjects or perform any Study procedures (other than preliminary administrative and training activities) until all conditions set forth in this Section 2.4 have been satisfied and Penterra (or its designated agent, Meridian CRO) has issued a written site activation notice for Lakemont Medical Center.

ARTICLE 3 — CO-PRINCIPAL INVESTIGATOR RESPONSIBILITIES

3.1 General Duties. The Co-PI shall conduct the Study at Lakemont Medical Center in strict accordance with the Protocol (PPC-4871-III), GCP (ICH E6(R2)), and all Applicable Law. The Co-PI shall exercise the degree of care, skill, and diligence expected of a reasonably qualified physician-investigator conducting a Phase III clinical trial in oncology. The Co-PI shall devote sufficient time, attention, and resources to the Study to fulfill all obligations set forth in this Agreement and shall not undertake any commitments that would materially interfere with the proper conduct of the Study at the Site.

3.2 Study Oversight at Site. The Co-PI shall supervise all Sub-Investigators, clinical research coordinators, study nurses, pharmacists, and other study staff at the Site who are involved in the conduct of the Study. The Co-PI shall maintain adequate resources and qualified personnel at all times throughout the Term to conduct the Study in accordance with the Protocol and enrollment timelines. The Co-PI shall be personally responsible for the acts and omissions of all Site personnel performing Study-related duties under his supervision, to the extent such acts and omissions relate to the conduct of the Study. The Co-PI shall ensure that all study functions delegated to Sub-Investigators or other Site personnel are delegated only to individuals who are appropriately qualified by education, training, and experience to perform such functions.

3.3 Subject Enrollment. The Study is designed to enroll a total of one thousand two hundred (1,200) subjects, randomized in a two-to-one (2:1) ratio of penterafenib to placebo (i.e., eight hundred (800) subjects in the treatment arm and four hundred (400) subjects in the placebo arm), across all thirty-eight (38) Veridian Network sites over a forty-two (42)-month enrollment period. The target date for first patient in (FPI) is August 14, 2023. The Co-PI shall use diligent and commercially reasonable efforts to meet the enrollment allocation assigned to Lakemont Medical Center (Site 002) as set forth in Schedule 1 of the MCTA, while ensuring that all enrollment decisions are based on appropriate medical judgment and the eligibility criteria specified in the Protocol. The Co-PI acknowledges that enrollment targets are subject to adjustment by Penterra in consultation with the Global PI based on competitive enrollment across all sites.

3.4 Informed Consent. The Co-PI shall ensure that all subjects (or their legally authorized representatives) provide valid informed consent in compliance with 21 C.F.R. Part 50, ICH E6(R2), applicable state law, and the requirements of the Veridian Central IRB before any study-specific procedures are performed. The informed consent process shall include a thorough discussion of the nature of the Study, the risks and benefits of participation, the randomization and blinding procedures, alternative treatments, and the subject's right to withdraw from the Study at any time without prejudice to future medical care. The Co-PI shall ensure that the informed consent discussion is conducted by an appropriately qualified member of the study team and that adequate time is provided for the subject to consider participation. All informed consent forms shall be the IRB-approved versions, and documentation of the informed consent process shall be maintained in the subject's source documents.

3.5 Protocol Compliance. The Co-PI shall conduct the Study in strict compliance with the Protocol, including all Protocol amendments approved by the IRB and implemented at the Site. Any deviations from the Protocol, whether intentional or unintentional, must be documented and reported in accordance with the procedures specified in the MCTA and IRB policies. Medically necessary protocol deviations undertaken to protect the immediate safety, well-being, or rights of a Study subject shall be reported promptly to Penterra, Meridian CRO, and the Veridian Central IRB, and shall be documented in the case report form and the subject's source documents. The Co-PI acknowledges that non-authorized protocol deviations—i.e., deviations that are not medically necessary and are not authorized in advance by Penterra—may give rise to liability allocation consequences under the indemnification provisions of the MCTA (Article 12 hereof) and may, in cases of repeated or material non-compliance, constitute grounds for termination of this Agreement under Article 10.2(a).

3.6 Investigational Product Accountability. The Co-PI shall account for all Investigational Product (penterafenib and matching placebo) received at the Site, dispensed to Study subjects, returned by Study subjects, and destroyed or returned to Penterra (or its designee), in accordance with the Protocol, 21 C.F.R. § 312.62, and the Investigational Product management procedures specified in the MCTA. The Co-PI shall maintain accurate and current drug accountability records at the Site and shall ensure that the Investigational Product is stored under the conditions specified in the Protocol and the Investigator's Brochure. The Co-PI shall ensure that the Investigational Product is administered only to enrolled Study subjects and only in accordance with the Protocol. The Co-PI shall cooperate fully with Meridian CRO monitors during drug accountability reconciliation visits.

3.7 Source Documents and Records. The Co-PI shall maintain complete, accurate, and contemporaneous source documents and study records at the Site for each Study subject, in accordance with GCP, 21 C.F.R. Part 312, and the MCTA. Source documents include, but are not limited to, hospital records, clinical charts, laboratory reports, imaging reports, pharmacy dispensing records, subject diaries, electronic health records, and any other original documents or certified copies used to verify data entered in the case report forms. The Co-PI shall retain all source documents and study records for a minimum of fifteen (15) years following the completion or termination of the Study at the Site, or for such longer period as may be required by Applicable Law, the MCTA, or written direction from Penterra. The Co-PI shall not destroy or dispose of any study records without the prior written consent of Penterra.

3.8 Data Entry and Integrity. The Co-PI shall ensure timely and accurate data entry into the electronic data capture ("EDC") system provided by Pinnacle Data Solutions, Inc. in accordance with the data management plan specified in the MCTA. All electronic records and electronic signatures associated with the Study shall comply with 21 C.F.R. Part 11 regarding electronic records and electronic signatures, including requirements for audit trails, system validations, and access controls. The Co-PI shall ensure that data queries issued by Meridian CRO or Pinnacle Data Solutions are resolved within the timeframes specified in the MCTA (generally within five (5) business days of receipt). The Co-PI shall not alter, falsify, or fabricate any Clinical Trial Data and shall report any suspected data integrity concerns to Penterra and the IRB.

3.9 Laboratory Coordination. The Co-PI shall coordinate the collection, processing, labeling, storage, and shipment of biological specimens (including blood samples, tumor tissue samples, and other biospecimens) to Northbridge Bioanalytical Laboratories, Inc. (the central laboratory for the Study), located at 2900 Commerce Way, Baltimore, Maryland 21224, for pharmacokinetic/pharmacodynamic ("PK/PD"), biomarker, and safety laboratory analyses as specified in the Protocol. The Co-PI shall ensure that all specimen handling procedures comply with the laboratory manual provided by Northbridge Bioanalytical Laboratories and the Protocol, including temperature requirements, shipping timelines, and chain-of-custody documentation. The Co-PI shall also ensure that local laboratory assessments performed at Lakemont Medical Center (if any) are conducted at laboratories that are certified under the Clinical Laboratory Improvement Amendments ("CLIA") and meet the standards specified in the Protocol.

3.10 Staff Delegation and Training. The Co-PI shall maintain a current delegation log (Form FDA 1572 supplement) identifying all individuals at the Site who are authorized to perform study functions, specifying the particular functions delegated to each individual. The delegation log shall be updated promptly to reflect additions or removals of study personnel. The Co-PI shall ensure that all Site personnel complete all required training—including GCP training, Protocol-specific training, EDC training, HIPAA training, and any other training mandated by the MCTA, the IRB, or Applicable Law—prior to performing any study duties. Documentation of all training shall be maintained at the Site and made available for inspection by Penterra, Meridian CRO, the IRB, or regulatory authorities upon request.

3.11 Cooperation with Monitors. The Co-PI shall provide full cooperation to Meridian CRO clinical research associates ("monitors") and Penterra personnel during site monitoring visits, remote monitoring activities, audits, and inspections. The Co-PI shall make available all source documents, study records, Investigational Product accountability records, and other study materials for review during monitoring visits. The Co-PI shall ensure that study staff are available during monitoring visits to address data queries and facilitate source data verification. Monitoring visits shall be scheduled at mutually convenient times, but the Co-PI shall make reasonable accommodations to facilitate the monitoring schedule established by Meridian CRO. The Co-PI shall also cooperate with any audits conducted by Penterra's quality assurance department or any regulatory inspections conducted by the FDA or other regulatory authorities.

ARTICLE 4 — SAFETY REPORTING OBLIGATIONS

4.1 SAE Reporting. The Co-PI shall report all Serious Adverse Events occurring in Study subjects at the Site to Penterra and Meridian CRO within twenty-four (24) hours of becoming aware of the event, using the SAE reporting procedures and forms set forth in Exhibit J of the MCTA. Initial SAE reports shall contain all available information at the time of reporting, including the subject identification number, a description of the event, the date of onset, the severity and seriousness criteria, the relationship to the Investigational Product (in the Co-PI's assessment), the outcome, and any relevant medical history or concomitant medications. The Co-PI shall provide follow-up reports within the timeframes specified in Exhibit J as additional information becomes available, until the event is resolved, stabilized, or the subject is lost to follow-up.

4.2 IND Safety Reports. The Co-PI acknowledges that Penterra, as the holder of IND 157823, bears primary responsibility for the preparation and filing of IND safety reports with the FDA, including seven (7)-calendar-day telephone or facsimile reports for fatal or life-threatening unexpected suspected adverse reactions and fifteen (15)-calendar-day written reports for all other reportable safety events, in accordance with 21 C.F.R. § 312.32. The Co-PI shall cooperate fully and promptly with Penterra and Meridian CRO in providing all clinical information, source documentation, and medical assessments necessary for the preparation and filing of such IND safety reports. The Co-PI shall promptly review and respond to requests for additional information from Penterra's pharmacovigilance team or Meridian CRO's safety reporting group.

4.3 IRB Reporting. The Co-PI shall report all adverse events, serious adverse events, protocol deviations, unanticipated problems involving risks to subjects or others, and any other reportable events to the Veridian Central IRB, as required by IRB policies, 21 C.F.R. Part 56, and Applicable Law. The Co-PI shall comply with the Veridian Central IRB's specific reporting timelines and procedures, as communicated to the Site in the IRB's standard operating procedures and approval correspondence. The Co-PI acknowledges that the Veridian Central IRB may require expedited reporting (within specified timeframes) for certain categories of events and shall ensure that such reporting is completed in a timely manner.

4.4 Subject Safety. The Co-PI shall at all times prioritize the safety, well-being, and rights of all Study subjects enrolled at the Site. The Co-PI shall exercise independent medical judgment on all treatment decisions affecting Study subjects, including decisions regarding dose modifications, treatment interruptions, treatment discontinuations, and management of adverse events, and shall not permit the Study protocol, Penterra's instructions, or any other consideration to override the Co-PI's clinical judgment regarding the best interests of individual subjects. The Co-PI shall ensure that appropriate medical care is available to Study subjects for adverse events related to the Study, including referral to appropriate specialists as needed, and shall provide or arrange for the provision of medical care for the duration of the subject's participation in the Study and for a reasonable period thereafter, as clinically appropriate.

ARTICLE 5 — REGULATORY OBLIGATIONS

5.1 FDA Form 1572. The Co-PI shall execute and maintain a current FDA Form 1572 (Statement of Investigator) for the duration of the Study, in accordance with 21 C.F.R. § 312.53. The initial Form 1572 shall be completed and submitted to Penterra prior to commencement of Study activities at the Site, as a condition to site activation under Section 2.4. The Co-PI shall promptly update Form 1572 to reflect any changes in Sub-Investigators, study facilities, the IRB of record, or any other information required to be reported on the form, and shall submit updated forms to Penterra within ten (10) business days of any such change. The Co-PI acknowledges that by signing Form 1572, the Co-PI commits to conducting the Study in accordance with the Protocol, to personally conducting or supervising the investigation, and to reporting adverse experiences in accordance with 21 C.F.R. § 312.64.

5.2 IRB Compliance. The Co-PI shall obtain and maintain IRB approval from the Veridian Central IRB for the Study and all Protocol amendments throughout the duration of the Study at the Site. The Co-PI shall submit continuing review applications to the Veridian Central IRB in accordance with the IRB's policies and timelines, and in no event less frequently than annually. The Co-PI shall also submit to the IRB all Protocol amendments, revised informed consent forms, recruitment materials, and other study documents requiring IRB review and approval before implementation at the Site (except for amendments necessary to eliminate an apparent immediate hazard to subjects, which may be implemented prior to IRB approval and reported promptly thereafter). The IRB reliance structure for the Study is governed by an IRB Authorization Agreement executed between Lakemont Medical Center's local IRB and the Veridian Central IRB, as contemplated by the MCTA and in accordance with the requirements of 45 C.F.R. Part 46 and the Common Rule.

5.3 GCP Compliance. The Co-PI shall conduct the Study in accordance with the principles of GCP as set forth in ICH E6(R2), as updated from time to time. The Co-PI shall ensure that all study activities at the Site, including but not limited to subject enrollment, informed consent, study procedures, data collection, adverse event reporting, and record retention, comply with GCP requirements. The Co-PI shall maintain current GCP certification and shall ensure that all Sub-Investigators and study staff are similarly trained and certified.

5.4 Regulatory Inspections. The Co-PI shall notify Penterra promptly, and in no event later than forty-eight (48) hours, upon receiving notice of any FDA inspection, audit, or regulatory inquiry related to the Study, the Site, or the Co-PI's clinical research activities generally. The Co-PI shall cooperate fully with such inspections and audits, including providing access to study records, source documents, and study facilities. The Co-PI shall provide Penterra with copies of all inspection-related correspondence, including FDA Form 483 observations, establishment inspection reports, warning letters, untitled letters, and any other regulatory communications, promptly upon receipt. The Co-PI shall consult with Penterra prior to submitting any written responses to FDA inspection observations and shall provide Penterra with an opportunity to review and comment on such responses.

5.5 Anti-Kickback and Sunshine Act Compliance. The Co-PI represents and covenants that all compensation received under this Agreement constitutes fair market value for services actually rendered by the Co-PI in connection with the Study, and that such compensation has been determined without regard to the volume or value of any referrals of patients, prescriptions, or other business between the Parties or between the Co-PI and Penterra. The Co-PI further represents that the compensation structure set forth herein and in the MCTA is consistent with the personal services and management contracts safe harbor under the Federal Anti-Kickback Statute, 42 U.S.C. § 1320a-7b, as set forth in the regulations at 42 C.F.R. § 1001.952(d). The Co-PI acknowledges that payments made under this Agreement are subject to reporting by Penterra under the Physician Payments Sunshine Act (Open Payments), codified at 42 U.S.C. § 1320a-7h, and the Co-PI shall cooperate with Penterra's reporting obligations thereunder, including providing timely confirmation of payment amounts and other information required for accurate reporting to the Centers for Medicare & Medicaid Services.

ARTICLE 6 — FINANCIAL DISCLOSURE

6.1 Initial Certification. Prior to the enrollment of the first Study subject at the Site, the Co-PI shall execute and deliver to Penterra a Financial Disclosure Certification in the form set forth in the MCTA (which incorporates the template certification form required by 21 C.F.R. Part 54), a copy of which is attached hereto as Exhibit B. Such certification shall disclose the presence or absence of any financial interests in Penterra or penterafenib (PPC-4871) that could be affected by the outcome of the Study, or certify that no such financial interests exist, as applicable. Failure to deliver a complete and accurate Financial Disclosure Certification shall preclude the enrollment of any Study subjects at the Site.

6.2 Covered Financial Interests. The Co-PI shall disclose any of the following financial interests, as defined in 21 C.F.R. Part 54:

(a) Any financial interest in Penterra Pharmaceuticals Corp., including any equity interest (stock, stock options, warrants, or other ownership interests), regardless of amount;

(b) Any proprietary interest in penterafenib (PPC-4871), including patent rights, trademarks, copyrights, or licensing rights;

(c) Any significant payments of other sorts from Penterra, as defined in 21 C.F.R. § 54.2(f), meaning payments made by the Sponsor to the Co-PI or to the Co-PI's institution to support activities of the Co-PI that have a monetary value of $25,000 or more, exclusive of the costs of conducting the Study, for the period covering the Study and for one (1) year following completion; and

(d) Any significant equity interest in Penterra, as defined in 21 C.F.R. § 54.2(e), meaning any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices, or any equity interest in a publicly traded company that exceeds $50,000 in value.

6.3 Ongoing Obligation. The Co-PI shall promptly notify Penterra, in writing, of any changes in the Co-PI's financial interests, as described in Section 6.2, that occur during the course of the Study and for a period of one (1) year following the completion of the Study at the Site. The Co-PI shall update the Financial Disclosure Certification annually, or more frequently if a change in financial interests occurs, and shall provide such updated certifications to Penterra within thirty (30) days of any change.

6.4 Sub-Investigator Disclosures. The Co-PI shall ensure that all Sub-Investigators and any other individuals who are directly involved in the treatment or evaluation of Study subjects at the Site complete Financial Disclosure Certifications in accordance with 21 C.F.R. Part 54 and deliver such certifications to Penterra prior to such individuals' involvement in the Study. The Co-PI shall monitor Sub-Investigators' compliance with the ongoing disclosure obligations described in this Article 6.

ARTICLE 7 — COMPENSATION

7.1 Per-Patient Fees. The Co-PI's compensation for services rendered in connection with the Study is incorporated within the per-patient site fees established in the MCTA and the Lakemont Individual Site Agreement (Joinder), which provide for a total per-subject payment of Fifty-Two Thousand Dollars ($52,000) for each subject enrolled, randomized, and completing Study activities at the Site. The allocation of the per-patient site fee between institutional overhead costs (including facilities, administrative support, pharmacy services, and nursing support) and Co-PI/investigator compensation shall be determined by Lakemont Medical Center's internal policies and procedures governing the distribution of clinical trial revenues, provided that the portion allocated to the Co-PI as personal compensation shall reflect fair market value for the Co-PI's professional services and shall be consistent with the requirements of Article 5.5 and Article 7.6 hereof.

7.2 Payment Structure. Per-patient payments under the MCTA are milestone-based, payable to Lakemont Medical Center in four (4) equal installments of Thirteen Thousand Dollars ($13,000) per subject, triggered upon the achievement of the following Study milestones:

(a) Installment 1 (25%): Thirteen Thousand Dollars ($13,000), payable upon randomization of the subject into the Study;

(b) Installment 2 (25%): Thirteen Thousand Dollars ($13,000), payable upon completion of the Week 12 efficacy and safety assessment;

(c) Installment 3 (25%): Thirteen Thousand Dollars ($13,000), payable upon completion of the Week 24 efficacy and safety assessment; and

(d) Installment 4 (25%): Thirteen Thousand Dollars ($13,000), payable upon completion of the subject's final study visit (end-of-treatment visit or end-of-study visit, as applicable).

All milestone payments flow from Penterra through the MCTA payment mechanism to Lakemont Medical Center, and from Lakemont Medical Center to the Co-PI in accordance with the Site's standard disbursement policies and procedures. Penterra shall have no obligation to make payments directly to the Co-PI. The Co-PI acknowledges that the timing and amount of compensation received by the Co-PI is subject to Lakemont's internal disbursement processes and policies.

7.3 Start-Up Fees. Site start-up fees in the amount of Seventy-Five Thousand Dollars ($75,000) per site are payable to Lakemont Medical Center under the MCTA, with fifty percent (50%) ($37,500) payable upon site activation and fifty percent (50%) ($37,500) payable upon enrollment of the first subject at the Site. Start-up fees are institutional fees intended to compensate Lakemont for the costs of site preparation, regulatory submissions, staff hiring and training, equipment procurement, and other start-up activities. Start-up fees are not direct Co-PI compensation and shall not be allocated to the Co-PI as personal compensation unless otherwise determined by Lakemont's internal policies.

7.4 Investigator Grants. The Co-PI may be eligible for investigator grants from the One Million Five Hundred Thousand Dollar ($1,500,000) total allocation established under the MCTA for academic publication support across all Veridian Network sites. Investigator grants are intended to support the preparation, submission, and publication of Study-related manuscripts in peer-reviewed scientific journals and shall be disbursed upon acceptance of manuscripts for publication. The terms and conditions governing investigator grants, including application procedures, review criteria, and maximum grant amounts, are set forth in Exhibit G of the MCTA. Investigator grants are subject to all publication review and delay provisions set forth in Article 9 hereof.

7.5 No Other Compensation. The Co-PI shall not receive any compensation, fees, honoraria, consulting payments, grants, or other payments of any kind from Penterra in connection with the Study, other than as expressly provided in this Agreement and through the MCTA/Site Agreement payment structure described herein. The Co-PI shall not directly or indirectly solicit or accept any additional compensation from Penterra related to the Study without the prior written approval of Penterra's General Counsel and the Co-PI's compliance with all Applicable Law.

7.6 Fair Market Value Representation. Both Parties represent and warrant that the compensation structure set forth in this Agreement and in the MCTA reflects the fair market value of the services to be provided by the Co-PI in connection with the Study, as determined by an independent fair market value assessment conducted by Penterra in accordance with industry standards. The compensation has been determined without regard to the volume or value of any referrals or other business between the Parties, and is consistent with the personal services and management contracts safe harbor under the Anti-Kickback Statute, 42 U.S.C. § 1320a-7b(b)(3)(B), and the implementing regulations at 42 C.F.R. § 1001.952(d).

7.7 Payment Terms. All payments under the MCTA are due and payable Net Forty-Five (45) days from Penterra's receipt of a proper invoice from Lakemont Medical Center (or Veridian on behalf of Lakemont). The Co-PI acknowledges that payment to the Co-PI is subject to Lakemont's internal disbursement processes and that Penterra shall not be responsible for any delay in payment to the Co-PI caused by Lakemont's internal procedures. In the event that a payment dispute arises between Penterra and Lakemont or Veridian under the MCTA, such dispute shall be resolved in accordance with the dispute resolution procedures set forth in the MCTA, and the Co-PI agrees to cooperate with Penterra and Lakemont as reasonably necessary to resolve such disputes.

ARTICLE 8 — INTELLECTUAL PROPERTY AND DATA OWNERSHIP

8.1 Clinical Trial Data Ownership. All Clinical Trial Data generated in connection with the Study at the Site shall be the exclusive property of Penterra, consistent with the terms and conditions of the MCTA and the IP Side Letter executed concurrently by Penterra and Veridian on June 28, 2023. The Co-PI hereby irrevocably assigns, transfers, and conveys to Penterra all right, title, and interest in and to the Clinical Trial Data, including all rights to use, analyze, compile, publish, disclose, submit to regulatory authorities, and otherwise exploit such data in connection with the development, regulatory approval, and commercialization of penterafenib (PPC-4871) and for any other lawful purpose. This assignment includes all rights in any analyses, compilations, derivations, reports, or other works based on or incorporating Clinical Trial Data. The Co-PI shall execute and deliver to Penterra any additional documents or instruments reasonably requested by Penterra to evidence or perfect such assignment.

8.2 Pre-Existing IP. Each Party retains all right, title, and interest in and to its respective pre-existing intellectual property, including patents, patent applications, copyrights, trade secrets, know-how, and other proprietary rights that exist as of the Effective Date or that are developed independently of the Study. Nothing in this Agreement shall be construed as transferring or assigning any pre-existing intellectual property of either Party to the other Party.

8.3 Inventions. Any inventions, discoveries, improvements, or innovations (whether or not patentable) conceived, developed, or reduced to practice by the Co-PI, either alone or jointly with others, during the course of and arising from the Study shall be governed by the IP Side Letter executed between Penterra and Veridian on June 28, 2023, which is incorporated herein by reference. Joint inventions—i.e., inventions conceived or developed jointly by personnel of Penterra and the Co-PI (or the Site)—shall be allocated in accordance with the terms of such IP Side Letter, including provisions governing ownership, licensing, prosecution, and enforcement of any resulting intellectual property rights. The Co-PI shall promptly disclose to Penterra any inventions arising from the Study and shall cooperate with Penterra in the preparation and prosecution of any patent applications as may be reasonably requested.

8.4 No Implied License. Nothing in this Agreement shall be construed to grant the Co-PI any license, right, or interest (express or implied) to use Penterra's proprietary information, trade secrets, patents, patent applications, know-how, or other intellectual property, including without limitation the composition, formulation, manufacturing processes, or methods of use of penterafenib (PPC-4871), except as strictly necessary for the Co-PI to conduct the Study at the Site in accordance with the Protocol. Any use of Penterra's intellectual property by the Co-PI beyond the scope of the Study is expressly prohibited without Penterra's prior written consent.

ARTICLE 9 — PUBLICATION RIGHTS

9.1 Right to Publish. The Co-PI retains the right to publish or present the results of the Study in peer-reviewed scientific journals, at scientific conferences, and in other academic and professional settings, subject to the review and delay provisions set forth in this Article 9 and in Exhibit G of the MCTA. Both Parties acknowledge the importance of publication of clinical trial results to the advancement of medical science and to the academic mission of the Co-PI and Lakemont Medical Center.

9.2 Sponsor Review Period. Prior to the submission of any manuscript, abstract, poster, oral presentation, or any other written or oral communication intended for publication or public disclosure that contains or discusses Clinical Trial Data, Study results, or Confidential Information, the Co-PI shall provide Penterra with a complete copy of such proposed publication or presentation at least sixty (60) days in advance of the intended submission date. During this sixty (60)-day review period, Penterra shall review the proposed publication for (a) the presence of Confidential Information that should be removed, (b) patentable subject matter that may require protection through patent filing, and (c) accuracy and consistency with the overall Study data. Penterra shall provide written comments to the Co-PI within the sixty (60)-day review period. If Penterra does not provide comments within the sixty (60)-day period, the Co-PI may proceed with submission, subject to Section 9.3 below.

9.3 Patent Delay. If Penterra identifies patentable subject matter in a proposed publication during the review period described in Section 9.2, Penterra may request, by written notice to the Co-PI, a delay of up to an additional ninety (90) days beyond the initial sixty (60)-day review period to allow Penterra to prepare and file patent applications protecting such subject matter. The total maximum delay from the date of submission of the proposed publication to Penterra to the date on which the Co-PI is free to submit the publication shall not exceed one hundred fifty (150) days. During any patent delay period, Penterra shall use diligent efforts to complete the necessary patent filings as promptly as practicable.

9.4 Removal of Confidential Information. The Co-PI shall remove from any proposed publication or presentation any Confidential Information identified by Penterra during the review period described in Section 9.2. The Co-PI shall make such modifications as are reasonably necessary to protect Penterra's Confidential Information while preserving the scientific integrity and academic merit of the publication. Any disputes regarding the scope of modifications shall be resolved by good-faith discussion between the Co-PI and Penterra's medical affairs department.

9.5 Multi-Center Publication Policy. The Co-PI acknowledges and agrees that results of multi-center analyses should, when feasible, be published first in aggregate multi-center form (reflecting data from all participating sites) rather than as single-site publications, consistent with the guidelines of the International Committee of Medical Journal Editors ("ICMJE") and the scientific coordination of the Global PI. Single-site publications by the Co-PI may be permitted following the initial publication of multi-center results, subject to the review and delay provisions of this Article 9 and the multi-center publication policy established by the Global PI and Penterra, as set forth in Exhibit G of the MCTA.

9.6 Academic Freedom. Subject to the foregoing review and delay provisions, Penterra acknowledges and respects the Co-PI's academic freedom and right to publish the results of the Study. Penterra shall not unreasonably withhold its consent to publication of Study results following completion of the review process described in this Article 9. The Co-PI's right to publish shall include the right to present accurate and balanced scientific findings, including negative or inconclusive results, and Penterra shall not suppress or unduly influence the content of such publications.

ARTICLE 10 — TERM AND TERMINATION

10.1 Term. The Term of this Agreement shall be as set forth in Section 2.3 of this Agreement.

10.2 Termination by Penterra. Penterra may terminate this Agreement under any of the following circumstances:

(a) For Cause. Upon written notice to the Co-PI if the Co-PI materially breaches any provision of this Agreement, the Protocol, or Applicable Law, and fails to cure such breach within thirty (30) calendar days of receipt of written notice from Penterra specifying the nature of the breach in reasonable detail. Notwithstanding the foregoing, in the event that the Co-PI's breach involves fraud, scientific misconduct, falsification of data, or conduct that poses an immediate risk to subject safety, Penterra may terminate this Agreement immediately upon written notice without opportunity to cure;

(b) Termination of MCTA or Site Agreement. Immediately upon written notice to the Co-PI, if the MCTA or the Lakemont Individual Site Agreement (Joinder) is terminated for any reason;

(c) Study discontinuation. Upon written notice to the Co-PI, if the Study is discontinued by Penterra for any reason, including but not limited to a clinical hold imposed by the FDA under 21 C.F.R. § 312.42, a recommendation of the Data Safety Monitoring Board, a strategic business decision by Penterra, or a determination by Penterra that the Study is no longer scientifically viable; and

(d) Without Cause. Without cause, upon sixty (60) days' prior written notice to the Co-PI.

10.3 Termination by Co-PI. The Co-PI may terminate this Agreement upon sixty (60) days' prior written notice to Penterra. In the event of termination by the Co-PI, the Co-PI shall comply with all wind-down obligations set forth in Section 10.5 and shall cooperate with Penterra and Lakemont Medical Center to ensure an orderly transition of Study responsibilities at the Site, including the identification and qualification of a replacement investigator if Penterra elects to continue the Study at the Site.

10.4 Termination by Lakemont/Veridian. If the Lakemont Individual Site Agreement (Joinder) or the MCTA is terminated by Lakemont Medical Center, Veridian, or Penterra, this Agreement shall automatically terminate upon the effective date of such termination, subject to the wind-down provisions set forth in Section 10.5 and the survival provisions set forth in Section 10.6.

10.5 Wind-Down Obligations. Upon termination of this Agreement for any reason, the Co-PI shall:

(a) Ensure the safety and continuity of care for all Study subjects enrolled at the Site during the one hundred twenty (120)-day wind-down period specified in the MCTA, including the provision of all necessary medical treatment and monitoring for the duration of the wind-down period;

(b) Facilitate the transfer of enrolled subjects to alternative participating sites, in coordination with Penterra and the Global PI, or permit subjects who are in active treatment to complete their current treatment cycle at the Site if clinically appropriate and agreed upon by Penterra;

(c) Return all unused Investigational Product, including all supplies of penterafenib and matching placebo, and all study materials (including the Investigator's Brochure, Protocol, laboratory kits, and EDC equipment) to Penterra or its designee, in accordance with the return procedures specified in the MCTA;

(d) Complete all outstanding case report forms, resolve all pending data queries, and ensure that all Clinical Trial Data is entered into the EDC system accurately and completely;

(e) Archive and secure all source documents, regulatory files, correspondence, and other study records in accordance with the document retention requirements set forth in Section 3.7 (minimum fifteen (15) years following completion or termination of the Study), and inform Penterra of the location and custodian of such archived records; and

(f) Cooperate with Penterra and Meridian CRO in the conduct of a close-out monitoring visit at the Site.

10.6 Survival. The following provisions of this Agreement shall survive the expiration or termination of this Agreement for any reason: Article 6 (Financial Disclosure, including the ongoing disclosure obligations for one (1) year post-Study); Article 8 (Intellectual Property and Data Ownership); Article 9 (Publication Rights, with respect to the review and delay provisions applicable to any publications submitted after termination); Article 11 (Confidentiality, for the full ten (10)-year confidentiality period); Article 12 (Indemnification); Article 14 (Governing Law and Dispute Resolution); and any other provisions of this Agreement that, by their nature, are intended to survive termination.

ARTICLE 11 — CONFIDENTIALITY

11.1 Obligations. The Co-PI shall hold all Confidential Information received from Penterra or generated in connection with the Study in strict confidence for a period of ten (10) years from the date of disclosure or generation of such information, consistent with the confidentiality provisions set forth in Exhibit F of the MCTA. The Co-PI shall not disclose, publish, or disseminate Confidential Information to any third party, except as expressly permitted by this Agreement, and shall use Confidential Information solely for the purpose of conducting the Study at the Site in accordance with the Protocol. The Co-PI shall protect Confidential Information using the same degree of care that the Co-PI uses to protect his own confidential and proprietary information, but in no event less than a reasonable degree of care.

11.2 Scope. Confidential Information includes, without limitation: (a) the Protocol (PPC-4871-III / CLARION) and all Protocol amendments; (b) the Investigator's Brochure for penterafenib; (c) Investigational Product specifications, formulation information, and analytical data; (d) all Clinical Trial Data generated at the Site or provided by Penterra; (e) the financial terms of this Agreement, the MCTA, and the Lakemont Individual Site Agreement; (f) Penterra's business plans, strategies, and regulatory plans for penterafenib; (g) any proprietary information, trade secrets, or know-how of Penterra disclosed to the Co-PI in connection with the Study; and (h) the existence and terms of this Agreement (except as required to be disclosed under Applicable Law or institutional policy).

11.3 Permitted Disclosures. Notwithstanding the foregoing, the Co-PI may disclose Confidential Information under the following circumstances:

(a) To the Veridian Central IRB, to the extent required for IRB review, approval, and ongoing oversight of the Study;

(b) To regulatory authorities, including the FDA, to the extent required by Applicable Law or in response to a valid subpoena, court order, or regulatory request (provided that the Co-PI shall provide Penterra with prompt written notice of any such disclosure requirement, to the extent legally permissible, and shall cooperate with Penterra in seeking any available protective order or other appropriate remedy);

(c) To the Co-PI's legal counsel, to the extent reasonably necessary for the Co-PI to obtain legal advice regarding the Co-PI's rights and obligations under this Agreement, provided that such counsel is bound by an obligation of confidentiality no less restrictive than those set forth herein;

(d) To Sub-Investigators, clinical research coordinators, study nurses, pharmacists, and other Site personnel at Lakemont Medical Center who have a documented need to know the Confidential Information in order to perform their assigned study duties, provided that such individuals are bound by written confidentiality obligations no less restrictive than those set forth in this Article 11; and

(e) To institutional officials at Lakemont Medical Center, to the extent required by Lakemont's internal policies governing clinical research, provided that such officials are subject to confidentiality obligations at least as protective as those set forth herein.

11.4 Exclusions. Information shall not constitute Confidential Information, and the obligations of this Article 11 shall not apply, to the extent that such information:

(a) Is or becomes publicly available through no act or omission of the Co-PI or any person to whom the Co-PI has disclosed such information;

(b) Was lawfully known to the Co-PI, without obligation of confidentiality, prior to disclosure by Penterra, as evidenced by written records predating such disclosure;

(c) Is lawfully disclosed to the Co-PI by a third party who is not subject to any obligation of confidentiality to Penterra with respect to such information; or

(d) Is independently developed by the Co-PI without reference to or use of any Confidential Information of Penterra, as evidenced by written records.

The burden of establishing that any of the foregoing exclusions applies shall rest with the Co-PI.

ARTICLE 12 — INDEMNIFICATION

12.1 Sponsor Indemnification of Co-PI. Subject to the terms and conditions set forth in this Article 12 and in Exhibit D of the MCTA, Penterra shall defend, indemnify, and hold harmless the Co-PI, and the Co-PI's heirs, executors, administrators, successors, and assigns, from and against any and all third-party claims, demands, actions, suits, proceedings, losses, damages, liabilities, judgments, settlements, penalties, fines, costs, and expenses (including reasonable attorneys' fees and costs of litigation) (collectively, "Losses") arising from or related to:

(a) Subject injury or death caused by the Investigational Product (penterafenib, PPC-4871) when such Investigational Product is administered to Study subjects in accordance with the Protocol and this Agreement;

(b) Any defect in the design, manufacture, labeling, packaging, storage, or distribution of the Investigational Product, including any failure of the Investigational Product to conform to applicable cGMP requirements or the specifications set forth in the Investigator's Brochure;

(c) Penterra's material breach of the MCTA, this Agreement, or any representation or warranty made by Penterra herein; and

(d) The negligence, gross negligence, or willful misconduct of Penterra or its employees, agents, or contractors (excluding the Co-PI and Site personnel) in connection with the Study.

Penterra's indemnification obligations for product-defect claims arising under subsection (b) above shall be uncapped. For claims arising under subsection (a) above relating to subject medical care costs (including costs of diagnosis, treatment, hospitalization, and rehabilitation for Study-related injuries), Penterra's indemnification obligation shall be subject to a per-subject cap of Five Hundred Thousand Dollars ($500,000) and an aggregate cap across all sites participating in the Study of Fifteen Million Dollars ($15,000,000).

12.2 Carve-Outs from Sponsor Indemnification. Penterra's indemnification obligations under Section 12.1 shall not extend to Losses to the extent such Losses arise from or are attributable to:

(a) The negligence, gross negligence, or willful misconduct of the Co-PI, Sub-Investigators, or any other

CO-PRINCIPAL INVESTIGATOR AGREEMENT
Protocol PPC-4871-III
CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology
June 28, 2023
Between
PENTERRA PHARMACEUTICALS CORP. 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540
and
DR. HOWARD MATSUOKA, M.D. Associate Professor of Hepatology & Oncology Lakemont Medical Center 4400 North Michigan Drive Chicago, Illinois 60611
CONFIDENTIAL — This document and all attachments contain confidential and proprietary information of Penterra Pharmaceuticals Corp. and are subject to the confidentiality obligations set forth herein and in the Master Clinical Trial Agreement dated June 28, 2023. Unauthorized reproduction or distribution is strictly prohibited.
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RECITALS
This Co-Principal Investigator Agreement (this "Agreement") is entered into as of June 28, 2023 (the "Effective Date"), by and between:
PENTERRA PHARMACEUTICALS CORP., 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 (Nasdaq: PTRA) (hereinafter referred to as the "Sponsor" or "Penterra"); and
DR. HOWARD MATSUOKA, M.D., an individual residing and practicing in the State of Illinois, currently serving as Associate Professor of Hepatology & Oncology at Lakemont Medical Center, located at 4400 North Michigan Drive, Chicago, Illinois 60611 (hereinafter referred to as the "Co-Principal Investigator" or "Co-PI").
The Sponsor and the Co-PI are referred to individually as a "Party" and collectively as the "Parties."
WHEREAS, Penterra is the sponsor of a Phase III, randomized, double-blind, placebo-controlled clinical trial of its investigational compound penterafenib (PPC-4871), an oral multi-kinase inhibitor targeting VEGFR-1/2/3, PDGFR-α/β, FGFR1-4, and c-KIT, for the treatment of advanced hepatocellular carcinoma ("HCC") in the second-line setting after prior systemic therapy, designated as Protocol PPC-4871-III and entitled "CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology" (the "Study" or "Trial");
WHEREAS, Penterra holds Investigational New Drug Application No. 157823 ("IND 157823") for penterafenib (PPC-4871), filed with the United States Food and Drug Administration ("FDA") in October 2021, and the Phase II portion of the clinical development program was completed in January 2023, demonstrating a thirty-eight percent (38%) objective response rate in patients with advanced HCC, with a manageable safety profile and a median progression-free survival of 7.2 months, supporting advancement to Phase III evaluation;
WHEREAS, the Study is registered with the National Library of Medicine under ClinicalTrials.gov Identifier NCT05928174 and is subject to the registration and results-reporting requirements of the FDA Amendments Act of 2007 (FDAAA 801);
WHEREAS, Penterra and Veridian Health Research Network, Inc. ("Veridian"), a Delaware 501(c)(3) corporation headquartered at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104, have entered into a Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA") governing the conduct of the Study across thirty-eight (38) Veridian Network sites located in fourteen (14) states throughout the United States, with a total deal value of Eighty Million Dollars ($80,000,000);
WHEREAS, Lakemont Medical Center ("Lakemont" or the "Site") is a Veridian Network member institution that has executed an Individual Site Agreement (Joinder) as Site 002 under the MCTA, thereby agreeing to be bound by the terms and conditions of the MCTA as applicable to individual participating sites;
WHEREAS, Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, Philadelphia, Pennsylvania, serves as the Global Principal Investigator (the "Global PI") for the Study and is responsible for overall scientific leadership and multi-site coordination of the Trial;
WHEREAS, Penterra desires to appoint Dr. Howard Matsuoka as Co-Principal Investigator for the Study at Lakemont Medical Center, and Dr. Matsuoka desires to accept such appointment, subject to the terms and conditions set forth herein;
WHEREAS, Meridian Contract Research Organization, Inc. ("Meridian CRO"), headquartered at 9200 Corporate Boulevard, Raleigh, North Carolina 27615, serves as Penterra's contracted clinical research organization for monitoring, data management, safety reporting, pharmacovigilance, and biostatistics for the Study, pursuant to a separate Master Services Agreement dated January 15, 2023 between Penterra and Meridian CRO; and
WHEREAS, the Parties desire to set forth their respective rights, responsibilities, and obligations in connection with the conduct of the Study at the Site.
NOW, THEREFORE, in consideration of the mutual promises, covenants, representations, and warranties set forth herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:
ARTICLE 1 — DEFINITIONS
As used in this Agreement, the following terms shall have the meanings ascribed to them below. Capitalized terms used but not defined in this Agreement shall have the meanings ascribed to them in the MCTA.
1.1 "Agreement" means this Co-Principal Investigator Agreement, together with all exhibits, schedules, appendices, and attachments hereto, as may be amended from time to time in accordance with Article 15.2.
1.2 "Applicable Law" means all federal, state, and local statutes, regulations, rules, ordinances, guidances, and directives applicable to the conduct of the Study, including but not limited to: (a) Title 21 of the Code of Federal Regulations ("C.F.R."), Parts 11, 50, 54, 56, and 312; (b) the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use ("ICH") E6(R2) Guideline for Good Clinical Practice; (c) the Health Insurance Portability and Accountability Act of 1996, as amended, and its implementing regulations at 45 C.F.R. Parts 160 and 164 ("HIPAA"); (d) the Federal Anti-Kickback Statute, 42 U.S.C. § 1320a-7b, and the regulations promulgated thereunder at 42 C.F.R. § 1001.952; (e) the Physician Payments Sunshine Act, Section 6002 of the Affordable Care Act, codified at 42 U.S.C. § 1320a-7h (Open Payments); (f) the FDA Amendments Act of 2007 (FDAAA 801), as applicable; and (g) any other applicable federal, state, or local laws, regulations, or guidelines governing the conduct of clinical research.
1.3 "Clinical Trial Data" means all data, information, and results generated in connection with the Study, including but not limited to completed case report forms (whether paper or electronic), source documents, electronic data captures, biomarker data, pharmacokinetic and pharmacodynamic data, safety data (including adverse event reports and serious adverse event reports), laboratory results, imaging data, patient-reported outcomes, and any analyses, compilations, or derivations thereof.
1.4 "Confidential Information" has the meaning set forth in Exhibit F of the MCTA, which is incorporated herein by reference. Without limiting the generality of such definition, Confidential Information includes the Protocol, the Investigator's Brochure, the financial terms of this Agreement and the MCTA, Investigational Product specifications, manufacturing processes, Clinical Trial Data, and any other proprietary information of Penterra disclosed to the Co-PI in connection with the Study. The confidentiality period applicable to all Confidential Information shall be ten (10) years from the date of disclosure.
1.5 "GCP" means Good Clinical Practice as set forth in the ICH E6(R2) Guideline, as may be updated, amended, or replaced from time to time.
1.6 "Global PI" means Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, Philadelphia, Pennsylvania, in her capacity as the Global Principal Investigator for the Study, or any successor appointed by Penterra.
1.7 "Investigational Product" means penterafenib (PPC-4871), the oral multi-kinase inhibitor that is the subject of the Study, in all dosage forms, formulations, and strengths supplied by Penterra for use in the Study, as well as any matching placebo supplied for the Study.
1.8 "IRB" means the Institutional Review Board providing ethical oversight for the conduct of the Study at the Site. For purposes of this Agreement, the IRB of record for Lakemont Medical Center is the Veridian Central IRB, which serves as the single IRB of record for all Veridian Network sites participating in the Study pursuant to the IRB Authorization Agreement described in the MCTA.
1.9 "MCTA" means the Master Clinical Trial Agreement dated June 28, 2023, between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc., as may be amended from time to time, governing the conduct of the Study across all Veridian Network sites.
1.10 "Protocol" means Protocol PPC-4871-III, entitled "CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology," as may be amended from time to time with the approval of Penterra and the IRB, including all protocol amendments, appendices, and associated guidance documents.
1.11 "SAE" means a Serious Adverse Event, as defined in ICH E6(R2) and 21 C.F.R. § 312.32, which includes any adverse event occurring at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or constitutes an important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent one of the foregoing outcomes.
1.12 "Site" means Lakemont Medical Center, located at 4400 North Michigan Drive, Chicago, Illinois 60611, designated as Site 002 under the MCTA, including all clinical, laboratory, pharmacy, and administrative facilities at Lakemont that are used or will be used in connection with the conduct of the Study.
1.13 "Study" or "Trial" means the Phase III, randomized, double-blind, placebo-controlled clinical trial conducted under Protocol PPC-4871-III (CLARION), evaluating the efficacy and safety of penterafenib (PPC-4871) versus placebo in adult patients with advanced hepatocellular carcinoma in the second-line setting after prior systemic therapy.
1.14 "Sub-Investigator" means any physician or other qualified individual delegated study-related duties by the Co-PI at the Site, who is listed on the delegation log maintained by the Co-PI and, as applicable, on FDA Form 1572.
ARTICLE 2 — APPOINTMENT AND TERM
2.1 Appointment. Penterra hereby appoints Dr. Howard Matsuoka as Co-Principal Investigator for the Study at Lakemont Medical Center (Site 002). Dr. Matsuoka hereby accepts such appointment and agrees to serve as Co-PI for the Study at the Site, subject to the terms and conditions of this Agreement, the Protocol, the MCTA, the Lakemont Individual Site Agreement (Joinder), and all Applicable Law. The Co-PI shall have primary responsibility for the scientific and clinical conduct of the Study at the Site and shall serve as the principal point of contact between the Site and Penterra (and its designated agents, including Meridian CRO) with respect to all Study-related matters at Lakemont Medical Center.
2.2 Relationship to Global PI. The Co-PI shall conduct the Study at the Site under the overall scientific leadership and direction of the Global PI, Dr. Catherine Aldridge, M.D., Ph.D. The Co-PI shall coordinate with the Global PI on all matters of scientific design, protocol interpretation, multi-site consistency, and study governance. The Co-PI shall participate in Global PI-convened investigator meetings, scientific advisory calls, and governance committee meetings as reasonably requested by the Global PI or Penterra. The Co-PI acknowledges that the Global PI has primary responsibility for ensuring scientific consistency across all participating sites and agrees to adhere to scientific guidance issued by the Global PI in connection with the Study, provided that such guidance does not conflict with the Protocol, Applicable Law, or the Co-PI's independent medical judgment regarding the safety and well-being of individual Study subjects.
2.3 Term. This Agreement shall commence on the Effective Date and shall continue in full force and effect until the earliest to occur of: (a) the completion of all Study activities at the Site, including the completion of the eighteen (18)-month follow-up period for all subjects enrolled at the Site and the resolution of all outstanding data queries (the projected study completion date is August 2028, based on a sixty (60)-month total study duration from the anticipated first-patient-first-visit date of August 14, 2023); (b) the termination of the MCTA or the Lakemont Individual Site Agreement (Joinder) for any reason; or (c) the termination of this Agreement in accordance with Article 10 hereof. The period during which this Agreement remains in effect is referred to herein as the "Term."
2.4 Conditions to Commencement. Notwithstanding the appointment set forth in Section 2.1, the Co-PI's active participation in the Study (including the enrollment of any Study subjects at the Site) is expressly conditioned upon the satisfaction of all of the following conditions precedent:
(a) IRB Approval. Receipt of initial IRB approval from the Veridian Central IRB for the conduct of the Study at Lakemont Medical Center, including approval of the Protocol, informed consent form, and all recruitment materials;
(b) FDA Form 1572. Execution by the Co-PI of a completed FDA Form 1572 (Statement of Investigator) for the Study at the Site, in form and substance satisfactory to Penterra and in compliance with 21 C.F.R. § 312.53;
(c) Financial Disclosure Certification. Completion and delivery to Penterra of a Financial Disclosure Certification in accordance with Article 6 and 21 C.F.R. Part 54;
(d) Training. Completion by the Co-PI (and all Site personnel listed on the delegation log) of all required training, including (i) GCP training (ICH E6(R2)) current within the prior two (2) years, (ii) Protocol-specific training conducted by Penterra and/or Meridian CRO, (iii) HIPAA privacy and security training, (iv) EDC system training provided by Pinnacle Data Solutions, Inc., and (v) any other training required by the MCTA, the IRB, or Applicable Law; and
(e) Site Activation. Completion of all site activation activities as specified in the MCTA, including the pre-study site initiation visit conducted by Meridian CRO.
The Co-PI shall not enroll any Study subjects or perform any Study procedures (other than preliminary administrative and training activities) until all conditions set forth in this Section 2.4 have been satisfied and Penterra (or its designated agent, Meridian CRO) has issued a written site activation notice for Lakemont Medical Center.
ARTICLE 3 — CO-PRINCIPAL INVESTIGATOR RESPONSIBILITIES
3.1 General Duties. The Co-PI shall conduct the Study at Lakemont Medical Center in strict accordance with the Protocol (PPC-4871-III), GCP (ICH E6(R2)), and all Applicable Law. The Co-PI shall exercise the degree of care, skill, and diligence expected of a reasonably qualified physician-investigator conducting a Phase III clinical trial in oncology. The Co-PI shall devote sufficient time, attention, and resources to the Study to fulfill all obligations set forth in this Agreement and shall not undertake any commitments that would materially interfere with the proper conduct of the Study at the Site.
3.2 Study Oversight at Site. The Co-PI shall supervise all Sub-Investigators, clinical research coordinators, study nurses, pharmacists, and other study staff at the Site who are involved in the conduct of the Study. The Co-PI shall maintain adequate resources and qualified personnel at all times throughout the Term to conduct the Study in accordance with the Protocol and enrollment timelines. The Co-PI shall be personally responsible for the acts and omissions of all Site personnel performing Study-related duties under his supervision, to the extent such acts and omissions relate to the conduct of the Study. The Co-PI shall ensure that all study functions delegated to Sub-Investigators or other Site personnel are delegated only to individuals who are appropriately qualified by education, training, and experience to perform such functions.
3.3 Subject Enrollment. The Study is designed to enroll a total of one thousand two hundred (1,200) subjects, randomized in a two-to-one (2:1) ratio of penterafenib to placebo (i.e., eight hundred (800) subjects in the treatment arm and four hundred (400) subjects in the placebo arm), across all thirty-eight (38) Veridian Network sites over a forty-two (42)-month enrollment period. The target date for first patient in (FPI) is August 14, 2023. The Co-PI shall use diligent and commercially reasonable efforts to meet the enrollment allocation assigned to Lakemont Medical Center (Site 002) as set forth in Schedule 1 of the MCTA, while ensuring that all enrollment decisions are based on appropriate medical judgment and the eligibility criteria specified in the Protocol. The Co-PI acknowledges that enrollment targets are subject to adjustment by Penterra in consultation with the Global PI based on competitive enrollment across all sites.
3.4 Informed Consent. The Co-PI shall ensure that all subjects (or their legally authorized representatives) provide valid informed consent in compliance with 21 C.F.R. Part 50, ICH E6(R2), applicable state law, and the requirements of the Veridian Central IRB before any study-specific procedures are performed. The informed consent process shall include a thorough discussion of the nature of the Study, the risks and benefits of participation, the randomization and blinding procedures, alternative treatments, and the subject's right to withdraw from the Study at any time without prejudice to future medical care. The Co-PI shall ensure that the informed consent discussion is conducted by an appropriately qualified member of the study team and that adequate time is provided for the subject to consider participation. All informed consent forms shall be the IRB-approved versions, and documentation of the informed consent process shall be maintained in the subject's source documents.
3.5 Protocol Compliance. The Co-PI shall conduct the Study in strict compliance with the Protocol, including all Protocol amendments approved by the IRB and implemented at the Site. Any deviations from the Protocol, whether intentional or unintentional, must be documented and reported in accordance with the procedures specified in the MCTA and IRB policies. Medically necessary protocol deviations undertaken to protect the immediate safety, well-being, or rights of a Study subject shall be reported promptly to Penterra, Meridian CRO, and the Veridian Central IRB, and shall be documented in the case report form and the subject's source documents. The Co-PI acknowledges that non-authorized protocol deviations—i.e., deviations that are not medically necessary and are not authorized in advance by Penterra—may give rise to liability allocation consequences under the indemnification provisions of the MCTA (Article 12 hereof) and may, in cases of repeated or material non-compliance, constitute grounds for termination of this Agreement under Article 10.2(a).
3.6 Investigational Product Accountability. The Co-PI shall account for all Investigational Product (penterafenib and matching placebo) received at the Site, dispensed to Study subjects, returned by Study subjects, and destroyed or returned to Penterra (or its designee), in accordance with the Protocol, 21 C.F.R. § 312.62, and the Investigational Product management procedures specified in the MCTA. The Co-PI shall maintain accurate and current drug accountability records at the Site and shall ensure that the Investigational Product is stored under the conditions specified in the Protocol and the Investigator's Brochure. The Co-PI shall ensure that the Investigational Product is administered only to enrolled Study subjects and only in accordance with the Protocol. The Co-PI shall cooperate fully with Meridian CRO monitors during drug accountability reconciliation visits.
3.7 Source Documents and Records. The Co-PI shall maintain complete, accurate, and contemporaneous source documents and study records at the Site for each Study subject, in accordance with GCP, 21 C.F.R. Part 312, and the MCTA. Source documents include, but are not limited to, hospital records, clinical charts, laboratory reports, imaging reports, pharmacy dispensing records, subject diaries, electronic health records, and any other original documents or certified copies used to verify data entered in the case report forms. The Co-PI shall retain all source documents and study records for a minimum of fifteen (15) years following the completion or termination of the Study at the Site, or for such longer period as may be required by Applicable Law, the MCTA, or written direction from Penterra. The Co-PI shall not destroy or dispose of any study records without the prior written consent of Penterra.
3.8 Data Entry and Integrity. The Co-PI shall ensure timely and accurate data entry into the electronic data capture ("EDC") system provided by Pinnacle Data Solutions, Inc. in accordance with the data management plan specified in the MCTA. All electronic records and electronic signatures associated with the Study shall comply with 21 C.F.R. Part 11 regarding electronic records and electronic signatures, including requirements for audit trails, system validations, and access controls. The Co-PI shall ensure that data queries issued by Meridian CRO or Pinnacle Data Solutions are resolved within the timeframes specified in the MCTA (generally within five (5) business days of receipt). The Co-PI shall not alter, falsify, or fabricate any Clinical Trial Data and shall report any suspected data integrity concerns to Penterra and the IRB.
3.9 Laboratory Coordination. The Co-PI shall coordinate the collection, processing, labeling, storage, and shipment of biological specimens (including blood samples, tumor tissue samples, and other biospecimens) to Northbridge Bioanalytical Laboratories, Inc. (the central laboratory for the Study), located at 2900 Commerce Way, Baltimore, Maryland 21224, for pharmacokinetic/pharmacodynamic ("PK/PD"), biomarker, and safety laboratory analyses as specified in the Protocol. The Co-PI shall ensure that all specimen handling procedures comply with the laboratory manual provided by Northbridge Bioanalytical Laboratories and the Protocol, including temperature requirements, shipping timelines, and chain-of-custody documentation. The Co-PI shall also ensure that local laboratory assessments performed at Lakemont Medical Center (if any) are conducted at laboratories that are certified under the Clinical Laboratory Improvement Amendments ("CLIA") and meet the standards specified in the Protocol.
3.10 Staff Delegation and Training. The Co-PI shall maintain a current delegation log (Form FDA 1572 supplement) identifying all individuals at the Site who are authorized to perform study functions, specifying the particular functions delegated to each individual. The delegation log shall be updated promptly to reflect additions or removals of study personnel. The Co-PI shall ensure that all Site personnel complete all required training—including GCP training, Protocol-specific training, EDC training, HIPAA training, and any other training mandated by the MCTA, the IRB, or Applicable Law—prior to performing any study duties. Documentation of all training shall be maintained at the Site and made available for inspection by Penterra, Meridian CRO, the IRB, or regulatory authorities upon request.
3.11 Cooperation with Monitors. The Co-PI shall provide full cooperation to Meridian CRO clinical research associates ("monitors") and Penterra personnel during site monitoring visits, remote monitoring activities, audits, and inspections. The Co-PI shall make available all source documents, study records, Investigational Product accountability records, and other study materials for review during monitoring visits. The Co-PI shall ensure that study staff are available during monitoring visits to address data queries and facilitate source data verification. Monitoring visits shall be scheduled at mutually convenient times, but the Co-PI shall make reasonable accommodations to facilitate the monitoring schedule established by Meridian CRO. The Co-PI shall also cooperate with any audits conducted by Penterra's quality assurance department or any regulatory inspections conducted by the FDA or other regulatory authorities.
ARTICLE 4 — SAFETY REPORTING OBLIGATIONS
4.1 SAE Reporting. The Co-PI shall report all Serious Adverse Events occurring in Study subjects at the Site to Penterra and Meridian CRO within twenty-four (24) hours of becoming aware of the event, using the SAE reporting procedures and forms set forth in Exhibit J of the MCTA. Initial SAE reports shall contain all available information at the time of reporting, including the subject identification number, a description of the event, the date of onset, the severity and seriousness criteria, the relationship to the Investigational Product (in the Co-PI's assessment), the outcome, and any relevant medical history or concomitant medications. The Co-PI shall provide follow-up reports within the timeframes specified in Exhibit J as additional information becomes available, until the event is resolved, stabilized, or the subject is lost to follow-up.
4.2 IND Safety Reports. The Co-PI acknowledges that Penterra, as the holder of IND 157823, bears primary responsibility for the preparation and filing of IND safety reports with the FDA, including seven (7)-calendar-day telephone or facsimile reports for fatal or life-threatening unexpected suspected adverse reactions and fifteen (15)-calendar-day written reports for all other reportable safety events, in accordance with 21 C.F.R. § 312.32. The Co-PI shall cooperate fully and promptly with Penterra and Meridian CRO in providing all clinical information, source documentation, and medical assessments necessary for the preparation and filing of such IND safety reports. The Co-PI shall promptly review and respond to requests for additional information from Penterra's pharmacovigilance team or Meridian CRO's safety reporting group.
4.3 IRB Reporting. The Co-PI shall report all adverse events, serious adverse events, protocol deviations, unanticipated problems involving risks to subjects or others, and any other reportable events to the Veridian Central IRB, as required by IRB policies, 21 C.F.R. Part 56, and Applicable Law. The Co-PI shall comply with the Veridian Central IRB's specific reporting timelines and procedures, as communicated to the Site in the IRB's standard operating procedures and approval correspondence. The Co-PI acknowledges that the Veridian Central IRB may require expedited reporting (within specified timeframes) for certain categories of events and shall ensure that such reporting is completed in a timely manner.
4.4 Subject Safety. The Co-PI shall at all times prioritize the safety, well-being, and rights of all Study subjects enrolled at the Site. The Co-PI shall exercise independent medical judgment on all treatment decisions affecting Study subjects, including decisions regarding dose modifications, treatment interruptions, treatment discontinuations, and management of adverse events, and shall not permit the Study protocol, Penterra's instructions, or any other consideration to override the Co-PI's clinical judgment regarding the best interests of individual subjects. The Co-PI shall ensure that appropriate medical care is available to Study subjects for adverse events related to the Study, including referral to appropriate specialists as needed, and shall provide or arrange for the provision of medical care for the duration of the subject's participation in the Study and for a reasonable period thereafter, as clinically appropriate.
ARTICLE 5 — REGULATORY OBLIGATIONS
5.1 FDA Form 1572. The Co-PI shall execute and maintain a current FDA Form 1572 (Statement of Investigator) for the duration of the Study, in accordance with 21 C.F.R. § 312.53. The initial Form 1572 shall be completed and submitted to Penterra prior to commencement of Study activities at the Site, as a condition to site activation under Section 2.4. The Co-PI shall promptly update Form 1572 to reflect any changes in Sub-Investigators, study facilities, the IRB of record, or any other information required to be reported on the form, and shall submit updated forms to Penterra within ten (10) business days of any such change. The Co-PI acknowledges that by signing Form 1572, the Co-PI commits to conducting the Study in accordance with the Protocol, to personally conducting or supervising the investigation, and to reporting adverse experiences in accordance with 21 C.F.R. § 312.64.
5.2 IRB Compliance. The Co-PI shall obtain and maintain IRB approval from the Veridian Central IRB for the Study and all Protocol amendments throughout the duration of the Study at the Site. The Co-PI shall submit continuing review applications to the Veridian Central IRB in accordance with the IRB's policies and timelines, and in no event less frequently than annually. The Co-PI shall also submit to the IRB all Protocol amendments, revised informed consent forms, recruitment materials, and other study documents requiring IRB review and approval before implementation at the Site (except for amendments necessary to eliminate an apparent immediate hazard to subjects, which may be implemented prior to IRB approval and reported promptly thereafter). The IRB reliance structure for the Study is governed by an IRB Authorization Agreement executed between Lakemont Medical Center's local IRB and the Veridian Central IRB, as contemplated by the MCTA and in accordance with the requirements of 45 C.F.R. Part 46 and the Common Rule.
5.3 GCP Compliance. The Co-PI shall conduct the Study in accordance with the principles of GCP as set forth in ICH E6(R2), as updated from time to time. The Co-PI shall ensure that all study activities at the Site, including but not limited to subject enrollment, informed consent, study procedures, data collection, adverse event reporting, and record retention, comply with GCP requirements. The Co-PI shall maintain current GCP certification and shall ensure that all Sub-Investigators and study staff are similarly trained and certified.
5.4 Regulatory Inspections. The Co-PI shall notify Penterra promptly, and in no event later than forty-eight (48) hours, upon receiving notice of any FDA inspection, audit, or regulatory inquiry related to the Study, the Site, or the Co-PI's clinical research activities generally. The Co-PI shall cooperate fully with such inspections and audits, including providing access to study records, source documents, and study facilities. The Co-PI shall provide Penterra with copies of all inspection-related correspondence, including FDA Form 483 observations, establishment inspection reports, warning letters, untitled letters, and any other regulatory communications, promptly upon receipt. The Co-PI shall consult with Penterra prior to submitting any written responses to FDA inspection observations and shall provide Penterra with an opportunity to review and comment on such responses.
5.5 Anti-Kickback and Sunshine Act Compliance. The Co-PI represents and covenants that all compensation received under this Agreement constitutes fair market value for services actually rendered by the Co-PI in connection with the Study, and that such compensation has been determined without regard to the volume or value of any referrals of patients, prescriptions, or other business between the Parties or between the Co-PI and Penterra. The Co-PI further represents that the compensation structure set forth herein and in the MCTA is consistent with the personal services and management contracts safe harbor under the Federal Anti-Kickback Statute, 42 U.S.C. § 1320a-7b, as set forth in the regulations at 42 C.F.R. § 1001.952(d). The Co-PI acknowledges that payments made under this Agreement are subject to reporting by Penterra under the Physician Payments Sunshine Act (Open Payments), codified at 42 U.S.C. § 1320a-7h, and the Co-PI shall cooperate with Penterra's reporting obligations thereunder, including providing timely confirmation of payment amounts and other information required for accurate reporting to the Centers for Medicare & Medicaid Services.
ARTICLE 6 — FINANCIAL DISCLOSURE
6.1 Initial Certification. Prior to the enrollment of the first Study subject at the Site, the Co-PI shall execute and deliver to Penterra a Financial Disclosure Certification in the form set forth in the MCTA (which incorporates the template certification form required by 21 C.F.R. Part 54), a copy of which is attached hereto as Exhibit B. Such certification shall disclose the presence or absence of any financial interests in Penterra or penterafenib (PPC-4871) that could be affected by the outcome of the Study, or certify that no such financial interests exist, as applicable. Failure to deliver a complete and accurate Financial Disclosure Certification shall preclude the enrollment of any Study subjects at the Site.
6.2 Covered Financial Interests. The Co-PI shall disclose any of the following financial interests, as defined in 21 C.F.R. Part 54:
(a) Any financial interest in Penterra Pharmaceuticals Corp., including any equity interest (stock, stock options, warrants, or other ownership interests), regardless of amount;
(b) Any proprietary interest in penterafenib (PPC-4871), including patent rights, trademarks, copyrights, or licensing rights;
(c) Any significant payments of other sorts from Penterra, as defined in 21 C.F.R. § 54.2(f), meaning payments made by the Sponsor to the Co-PI or to the Co-PI's institution to support activities of the Co-PI that have a monetary value of $25,000 or more, exclusive of the costs of conducting the Study, for the period covering the Study and for one (1) year following completion; and
(d) Any significant equity interest in Penterra, as defined in 21 C.F.R. § 54.2(e), meaning any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices, or any equity interest in a publicly traded company that exceeds $50,000 in value.
6.3 Ongoing Obligation. The Co-PI shall promptly notify Penterra, in writing, of any changes in the Co-PI's financial interests, as described in Section 6.2, that occur during the course of the Study and for a period of one (1) year following the completion of the Study at the Site. The Co-PI shall update the Financial Disclosure Certification annually, or more frequently if a change in financial interests occurs, and shall provide such updated certifications to Penterra within thirty (30) days of any change.
6.4 Sub-Investigator Disclosures. The Co-PI shall ensure that all Sub-Investigators and any other individuals who are directly involved in the treatment or evaluation of Study subjects at the Site complete Financial Disclosure Certifications in accordance with 21 C.F.R. Part 54 and deliver such certifications to Penterra prior to such individuals' involvement in the Study. The Co-PI shall monitor Sub-Investigators' compliance with the ongoing disclosure obligations described in this Article 6.
ARTICLE 7 — COMPENSATION
7.1 Per-Patient Fees. The Co-PI's compensation for services rendered in connection with the Study is incorporated within the per-patient site fees established in the MCTA and the Lakemont Individual Site Agreement (Joinder), which provide for a total per-subject payment of Fifty-Two Thousand Dollars ($52,000) for each subject enrolled, randomized, and completing Study activities at the Site. The allocation of the per-patient site fee between institutional overhead costs (including facilities, administrative support, pharmacy services, and nursing support) and Co-PI/investigator compensation shall be determined by Lakemont Medical Center's internal policies and procedures governing the distribution of clinical trial revenues, provided that the portion allocated to the Co-PI as personal compensation shall reflect fair market value for the Co-PI's professional services and shall be consistent with the requirements of Article 5.5 and Article 7.6 hereof.
7.2 Payment Structure. Per-patient payments under the MCTA are milestone-based, payable to Lakemont Medical Center in four (4) equal installments of Thirteen Thousand Dollars ($13,000) per subject, triggered upon the achievement of the following Study milestones:
(a) Installment 1 (25%): Thirteen Thousand Dollars ($13,000), payable upon randomization of the subject into the Study;
(b) Installment 2 (25%): Thirteen Thousand Dollars ($13,000), payable upon completion of the Week 12 efficacy and safety assessment;
(c) Installment 3 (25%): Thirteen Thousand Dollars ($13,000), payable upon completion of the Week 24 efficacy and safety assessment; and
(d) Installment 4 (25%): Thirteen Thousand Dollars ($13,000), payable upon completion of the subject's final study visit (end-of-treatment visit or end-of-study visit, as applicable).
All milestone payments flow from Penterra through the MCTA payment mechanism to Lakemont Medical Center, and from Lakemont Medical Center to the Co-PI in accordance with the Site's standard disbursement policies and procedures. Penterra shall have no obligation to make payments directly to the Co-PI. The Co-PI acknowledges that the timing and amount of compensation received by the Co-PI is subject to Lakemont's internal disbursement processes and policies.
7.3 Start-Up Fees. Site start-up fees in the amount of Seventy-Five Thousand Dollars ($75,000) per site are payable to Lakemont Medical Center under the MCTA, with fifty percent (50%) ($37,500) payable upon site activation and fifty percent (50%) ($37,500) payable upon enrollment of the first subject at the Site. Start-up fees are institutional fees intended to compensate Lakemont for the costs of site preparation, regulatory submissions, staff hiring and training, equipment procurement, and other start-up activities. Start-up fees are not direct Co-PI compensation and shall not be allocated to the Co-PI as personal compensation unless otherwise determined by Lakemont's internal policies.
7.4 Investigator Grants. The Co-PI may be eligible for investigator grants from the One Million Five Hundred Thousand Dollar ($1,500,000) total allocation established under the MCTA for academic publication support across all Veridian Network sites. Investigator grants are intended to support the preparation, submission, and publication of Study-related manuscripts in peer-reviewed scientific journals and shall be disbursed upon acceptance of manuscripts for publication. The terms and conditions governing investigator grants, including application procedures, review criteria, and maximum grant amounts, are set forth in Exhibit G of the MCTA. Investigator grants are subject to all publication review and delay provisions set forth in Article 9 hereof.
7.5 No Other Compensation. The Co-PI shall not receive any compensation, fees, honoraria, consulting payments, grants, or other payments of any kind from Penterra in connection with the Study, other than as expressly provided in this Agreement and through the MCTA/Site Agreement payment structure described herein. The Co-PI shall not directly or indirectly solicit or accept any additional compensation from Penterra related to the Study without the prior written approval of Penterra's General Counsel and the Co-PI's compliance with all Applicable Law.
7.6 Fair Market Value Representation. Both Parties represent and warrant that the compensation structure set forth in this Agreement and in the MCTA reflects the fair market value of the services to be provided by the Co-PI in connection with the Study, as determined by an independent fair market value assessment conducted by Penterra in accordance with industry standards. The compensation has been determined without regard to the volume or value of any referrals or other business between the Parties, and is consistent with the personal services and management contracts safe harbor under the Anti-Kickback Statute, 42 U.S.C. § 1320a-7b(b)(3)(B), and the implementing regulations at 42 C.F.R. § 1001.952(d).
7.7 Payment Terms. All payments under the MCTA are due and payable Net Forty-Five (45) days from Penterra's receipt of a proper invoice from Lakemont Medical Center (or Veridian on behalf of Lakemont). The Co-PI acknowledges that payment to the Co-PI is subject to Lakemont's internal disbursement processes and that Penterra shall not be responsible for any delay in payment to the Co-PI caused by Lakemont's internal procedures. In the event that a payment dispute arises between Penterra and Lakemont or Veridian under the MCTA, such dispute shall be resolved in accordance with the dispute resolution procedures set forth in the MCTA, and the Co-PI agrees to cooperate with Penterra and Lakemont as reasonably necessary to resolve such disputes.
ARTICLE 8 — INTELLECTUAL PROPERTY AND DATA OWNERSHIP
8.1 Clinical Trial Data Ownership. All Clinical Trial Data generated in connection with the Study at the Site shall be the exclusive property of Penterra, consistent with the terms and conditions of the MCTA and the IP Side Letter executed concurrently by Penterra and Veridian on June 28, 2023. The Co-PI hereby irrevocably assigns, transfers, and conveys to Penterra all right, title, and interest in and to the Clinical Trial Data, including all rights to use, analyze, compile, publish, disclose, submit to regulatory authorities, and otherwise exploit such data in connection with the development, regulatory approval, and commercialization of penterafenib (PPC-4871) and for any other lawful purpose. This assignment includes all rights in any analyses, compilations, derivations, reports, or other works based on or incorporating Clinical Trial Data. The Co-PI shall execute and deliver to Penterra any additional documents or instruments reasonably requested by Penterra to evidence or perfect such assignment.
8.2 Pre-Existing IP. Each Party retains all right, title, and interest in and to its respective pre-existing intellectual property, including patents, patent applications, copyrights, trade secrets, know-how, and other proprietary rights that exist as of the Effective Date or that are developed independently of the Study. Nothing in this Agreement shall be construed as transferring or assigning any pre-existing intellectual property of either Party to the other Party.
8.3 Inventions. Any inventions, discoveries, improvements, or innovations (whether or not patentable) conceived, developed, or reduced to practice by the Co-PI, either alone or jointly with others, during the course of and arising from the Study shall be governed by the IP Side Letter executed between Penterra and Veridian on June 28, 2023, which is incorporated herein by reference. Joint inventions—i.e., inventions conceived or developed jointly by personnel of Penterra and the Co-PI (or the Site)—shall be allocated in accordance with the terms of such IP Side Letter, including provisions governing ownership, licensing, prosecution, and enforcement of any resulting intellectual property rights. The Co-PI shall promptly disclose to Penterra any inventions arising from the Study and shall cooperate with Penterra in the preparation and prosecution of any patent applications as may be reasonably requested.
8.4 No Implied License. Nothing in this Agreement shall be construed to grant the Co-PI any license, right, or interest (express or implied) to use Penterra's proprietary information, trade secrets, patents, patent applications, know-how, or other intellectual property, including without limitation the composition, formulation, manufacturing processes, or methods of use of penterafenib (PPC-4871), except as strictly necessary for the Co-PI to conduct the Study at the Site in accordance with the Protocol. Any use of Penterra's intellectual property by the Co-PI beyond the scope of the Study is expressly prohibited without Penterra's prior written consent.
ARTICLE 9 — PUBLICATION RIGHTS
9.1 Right to Publish. The Co-PI retains the right to publish or present the results of the Study in peer-reviewed scientific journals, at scientific conferences, and in other academic and professional settings, subject to the review and delay provisions set forth in this Article 9 and in Exhibit G of the MCTA. Both Parties acknowledge the importance of publication of clinical trial results to the advancement of medical science and to the academic mission of the Co-PI and Lakemont Medical Center.
9.2 Sponsor Review Period. Prior to the submission of any manuscript, abstract, poster, oral presentation, or any other written or oral communication intended for publication or public disclosure that contains or discusses Clinical Trial Data, Study results, or Confidential Information, the Co-PI shall provide Penterra with a complete copy of such proposed publication or presentation at least sixty (60) days in advance of the intended submission date. During this sixty (60)-day review period, Penterra shall review the proposed publication for (a) the presence of Confidential Information that should be removed, (b) patentable subject matter that may require protection through patent filing, and (c) accuracy and consistency with the overall Study data. Penterra shall provide written comments to the Co-PI within the sixty (60)-day review period. If Penterra does not provide comments within the sixty (60)-day period, the Co-PI may proceed with submission, subject to Section 9.3 below.
9.3 Patent Delay. If Penterra identifies patentable subject matter in a proposed publication during the review period described in Section 9.2, Penterra may request, by written notice to the Co-PI, a delay of up to an additional ninety (90) days beyond the initial sixty (60)-day review period to allow Penterra to prepare and file patent applications protecting such subject matter. The total maximum delay from the date of submission of the proposed publication to Penterra to the date on which the Co-PI is free to submit the publication shall not exceed one hundred fifty (150) days. During any patent delay period, Penterra shall use diligent efforts to complete the necessary patent filings as promptly as practicable.
9.4 Removal of Confidential Information. The Co-PI shall remove from any proposed publication or presentation any Confidential Information identified by Penterra during the review period described in Section 9.2. The Co-PI shall make such modifications as are reasonably necessary to protect Penterra's Confidential Information while preserving the scientific integrity and academic merit of the publication. Any disputes regarding the scope of modifications shall be resolved by good-faith discussion between the Co-PI and Penterra's medical affairs department.
9.5 Multi-Center Publication Policy. The Co-PI acknowledges and agrees that results of multi-center analyses should, when feasible, be published first in aggregate multi-center form (reflecting data from all participating sites) rather than as single-site publications, consistent with the guidelines of the International Committee of Medical Journal Editors ("ICMJE") and the scientific coordination of the Global PI. Single-site publications by the Co-PI may be permitted following the initial publication of multi-center results, subject to the review and delay provisions of this Article 9 and the multi-center publication policy established by the Global PI and Penterra, as set forth in Exhibit G of the MCTA.
9.6 Academic Freedom. Subject to the foregoing review and delay provisions, Penterra acknowledges and respects the Co-PI's academic freedom and right to publish the results of the Study. Penterra shall not unreasonably withhold its consent to publication of Study results following completion of the review process described in this Article 9. The Co-PI's right to publish shall include the right to present accurate and balanced scientific findings, including negative or inconclusive results, and Penterra shall not suppress or unduly influence the content of such publications.
ARTICLE 10 — TERM AND TERMINATION
10.1 Term. The Term of this Agreement shall be as set forth in Section 2.3 of this Agreement.
10.2 Termination by Penterra. Penterra may terminate this Agreement under any of the following circumstances:
(a) For Cause. Upon written notice to the Co-PI if the Co-PI materially breaches any provision of this Agreement, the Protocol, or Applicable Law, and fails to cure such breach within thirty (30) calendar days of receipt of written notice from Penterra specifying the nature of the breach in reasonable detail. Notwithstanding the foregoing, in the event that the Co-PI's breach involves fraud, scientific misconduct, falsification of data, or conduct that poses an immediate risk to subject safety, Penterra may terminate this Agreement immediately upon written notice without opportunity to cure;
(b) Termination of MCTA or Site Agreement. Immediately upon written notice to the Co-PI, if the MCTA or the Lakemont Individual Site Agreement (Joinder) is terminated for any reason;
(c) Study discontinuation. Upon written notice to the Co-PI, if the Study is discontinued by Penterra for any reason, including but not limited to a clinical hold imposed by the FDA under 21 C.F.R. § 312.42, a recommendation of the Data Safety Monitoring Board, a strategic business decision by Penterra, or a determination by Penterra that the Study is no longer scientifically viable; and
(d) Without Cause. Without cause, upon sixty (60) days' prior written notice to the Co-PI.
10.3 Termination by Co-PI. The Co-PI may terminate this Agreement upon sixty (60) days' prior written notice to Penterra. In the event of termination by the Co-PI, the Co-PI shall comply with all wind-down obligations set forth in Section 10.5 and shall cooperate with Penterra and Lakemont Medical Center to ensure an orderly transition of Study responsibilities at the Site, including the identification and qualification of a replacement investigator if Penterra elects to continue the Study at the Site.
10.4 Termination by Lakemont/Veridian. If the Lakemont Individual Site Agreement (Joinder) or the MCTA is terminated by Lakemont Medical Center, Veridian, or Penterra, this Agreement shall automatically terminate upon the effective date of such termination, subject to the wind-down provisions set forth in Section 10.5 and the survival provisions set forth in Section 10.6.
10.5 Wind-Down Obligations. Upon termination of this Agreement for any reason, the Co-PI shall:
(a) Ensure the safety and continuity of care for all Study subjects enrolled at the Site during the one hundred twenty (120)-day wind-down period specified in the MCTA, including the provision of all necessary medical treatment and monitoring for the duration of the wind-down period;
(b) Facilitate the transfer of enrolled subjects to alternative participating sites, in coordination with Penterra and the Global PI, or permit subjects who are in active treatment to complete their current treatment cycle at the Site if clinically appropriate and agreed upon by Penterra;
(c) Return all unused Investigational Product, including all supplies of penterafenib and matching placebo, and all study materials (including the Investigator's Brochure, Protocol, laboratory kits, and EDC equipment) to Penterra or its designee, in accordance with the return procedures specified in the MCTA;
(d) Complete all outstanding case report forms, resolve all pending data queries, and ensure that all Clinical Trial Data is entered into the EDC system accurately and completely;
(e) Archive and secure all source documents, regulatory files, correspondence, and other study records in accordance with the document retention requirements set forth in Section 3.7 (minimum fifteen (15) years following completion or termination of the Study), and inform Penterra of the location and custodian of such archived records; and
(f) Cooperate with Penterra and Meridian CRO in the conduct of a close-out monitoring visit at the Site.
10.6 Survival. The following provisions of this Agreement shall survive the expiration or termination of this Agreement for any reason: Article 6 (Financial Disclosure, including the ongoing disclosure obligations for one (1) year post-Study); Article 8 (Intellectual Property and Data Ownership); Article 9 (Publication Rights, with respect to the review and delay provisions applicable to any publications submitted after termination); Article 11 (Confidentiality, for the full ten (10)-year confidentiality period); Article 12 (Indemnification); Article 14 (Governing Law and Dispute Resolution); and any other provisions of this Agreement that, by their nature, are intended to survive termination.
ARTICLE 11 — CONFIDENTIALITY
11.1 Obligations. The Co-PI shall hold all Confidential Information received from Penterra or generated in connection with the Study in strict confidence for a period of ten (10) years from the date of disclosure or generation of such information, consistent with the confidentiality provisions set forth in Exhibit F of the MCTA. The Co-PI shall not disclose, publish, or disseminate Confidential Information to any third party, except as expressly permitted by this Agreement, and shall use Confidential Information solely for the purpose of conducting the Study at the Site in accordance with the Protocol. The Co-PI shall protect Confidential Information using the same degree of care that the Co-PI uses to protect his own confidential and proprietary information, but in no event less than a reasonable degree of care.
11.2 Scope. Confidential Information includes, without limitation: (a) the Protocol (PPC-4871-III / CLARION) and all Protocol amendments; (b) the Investigator's Brochure for penterafenib; (c) Investigational Product specifications, formulation information, and analytical data; (d) all Clinical Trial Data generated at the Site or provided by Penterra; (e) the financial terms of this Agreement, the MCTA, and the Lakemont Individual Site Agreement; (f) Penterra's business plans, strategies, and regulatory plans for penterafenib; (g) any proprietary information, trade secrets, or know-how of Penterra disclosed to the Co-PI in connection with the Study; and (h) the existence and terms of this Agreement (except as required to be disclosed under Applicable Law or institutional policy).
11.3 Permitted Disclosures. Notwithstanding the foregoing, the Co-PI may disclose Confidential Information under the following circumstances:
(a) To the Veridian Central IRB, to the extent required for IRB review, approval, and ongoing oversight of the Study;
(b) To regulatory authorities, including the FDA, to the extent required by Applicable Law or in response to a valid subpoena, court order, or regulatory request (provided that the Co-PI shall provide Penterra with prompt written notice of any such disclosure requirement, to the extent legally permissible, and shall cooperate with Penterra in seeking any available protective order or other appropriate remedy);
(c) To the Co-PI's legal counsel, to the extent reasonably necessary for the Co-PI to obtain legal advice regarding the Co-PI's rights and obligations under this Agreement, provided that such counsel is bound by an obligation of confidentiality no less restrictive than those set forth herein;
(d) To Sub-Investigators, clinical research coordinators, study nurses, pharmacists, and other Site personnel at Lakemont Medical Center who have a documented need to know the Confidential Information in order to perform their assigned study duties, provided that such individuals are bound by written confidentiality obligations no less restrictive than those set forth in this Article 11; and
(e) To institutional officials at Lakemont Medical Center, to the extent required by Lakemont's internal policies governing clinical research, provided that such officials are subject to confidentiality obligations at least as protective as those set forth herein.
11.4 Exclusions. Information shall not constitute Confidential Information, and the obligations of this Article 11 shall not apply, to the extent that such information:
(a) Is or becomes publicly available through no act or omission of the Co-PI or any person to whom the Co-PI has disclosed such information;
(b) Was lawfully known to the Co-PI, without obligation of confidentiality, prior to disclosure by Penterra, as evidenced by written records predating such disclosure;
(c) Is lawfully disclosed to the Co-PI by a third party who is not subject to any obligation of confidentiality to Penterra with respect to such information; or
(d) Is independently developed by the Co-PI without reference to or use of any Confidential Information of Penterra, as evidenced by written records.
The burden of establishing that any of the foregoing exclusions applies shall rest with the Co-PI.
ARTICLE 12 — INDEMNIFICATION
12.1 Sponsor Indemnification of Co-PI. Subject to the terms and conditions set forth in this Article 12 and in Exhibit D of the MCTA, Penterra shall defend, indemnify, and hold harmless the Co-PI, and the Co-PI's heirs, executors, administrators, successors, and assigns, from and against any and all third-party claims, demands, actions, suits, proceedings, losses, damages, liabilities, judgments, settlements, penalties, fines, costs, and expenses (including reasonable attorneys' fees and costs of litigation) (collectively, "Losses") arising from or related to:
(a) Subject injury or death caused by the Investigational Product (penterafenib, PPC-4871) when such Investigational Product is administered to Study subjects in accordance with the Protocol and this Agreement;
(b) Any defect in the design, manufacture, labeling, packaging, storage, or distribution of the Investigational Product, including any failure of the Investigational Product to conform to applicable cGMP requirements or the specifications set forth in the Investigator's Brochure;
(c) Penterra's material breach of the MCTA, this Agreement, or any representation or warranty made by Penterra herein; and
(d) The negligence, gross negligence, or willful misconduct of Penterra or its employees, agents, or contractors (excluding the Co-PI and Site personnel) in connection with the Study.
Penterra's indemnification obligations for product-defect claims arising under subsection (b) above shall be uncapped. For claims arising under subsection (a) above relating to subject medical care costs (including costs of diagnosis, treatment, hospitalization, and rehabilitation for Study-related injuries), Penterra's indemnification obligation shall be subject to a per-subject cap of Five Hundred Thousand Dollars ($500,000) and an aggregate cap across all sites participating in the Study of Fifteen Million Dollars ($15,000,000).
12.2 Carve-Outs from Sponsor Indemnification. Penterra's indemnification obligations under Section 12.1 shall not extend to Losses to the extent such Losses arise from or are attributable to:
(a) The negligence, gross negligence, or willful misconduct of the Co-PI, Sub-Investigators, or any other

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