INDIVIDUAL SITE AGREEMENT (JOINDER)
Joinder to Master Clinical Trial Agreement for Protocol PPC-4871-III (CLARION)
Site 005 — Weston Memorial Health System
PARTIES:
Penterra Pharmaceuticals Corp. ("Sponsor") a Delaware corporation 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540
Veridian Health Research Network, Inc. ("Network") a Delaware 501(c)(3) corporation 750 Research Parkway, 8th Floor Philadelphia, Pennsylvania 19104
Weston Memorial Health System ("Site" or "Site Institution") a Georgia nonprofit corporation 1420 Peachtree Medical Drive NE Atlanta, Georgia 30309 A Veridian Network Member Institution
Date of Execution: June 28, 2023
This Individual Site Agreement is entered into with reference to that certain Master Clinical Trial Agreement dated June 28, 2023, between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. (the "MCTA").
CONFIDENTIAL — This document contains confidential and proprietary information of Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. Unauthorized disclosure, reproduction, or distribution is strictly prohibited.
INDIVIDUAL SITE AGREEMENT (JOINDER) Site 005 — Weston Memorial Health System
This Individual Site Agreement (this "Agreement" or "ISA") is entered into as of June 28, 2023 (the "Effective Date"), by and among:
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 (the "Sponsor");
Veridian Health Research Network, Inc., a nonprofit corporation organized and existing under the laws of the State of Delaware and recognized as tax-exempt under Section 501(c)(3) of the Internal Revenue Code, with its principal offices located at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104 (the "Network"); and
Weston Memorial Health System, a nonprofit corporation organized and existing under the laws of the State of Georgia, with its principal offices located at 1420 Peachtree Medical Drive NE, Atlanta, Georgia 30309, a member institution of the Veridian Health Research Network (the "Site" or "Site Institution," and, together with the Sponsor and the Network, each a "Party" and collectively the "Parties").
RECITALS
WHEREAS (A), the Sponsor and the Network entered into that certain Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA") governing the conduct of a Phase III, randomized, double-blind, placebo-controlled clinical trial of penterafenib (PPC-4871), an oral multi-kinase inhibitor, in subjects with advanced hepatocellular carcinoma (HCC), under Protocol PPC-4871-III, titled "CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology" (the "Study");
WHEREAS (B), the investigational product to be studied under the Protocol is penterafenib (PPC-4871), which is the subject of Investigational New Drug Application No. IND 157823 filed with the United States Food and Drug Administration ("FDA"), and is registered on ClinicalTrials.gov under Identifier NCT05928174;
WHEREAS (C), the MCTA contemplates that each participating site within the Veridian Health Research Network shall execute an Individual Site Agreement in the form of Exhibit C to the MCTA, thereby joining as a participating site institution and agreeing to be bound by the terms and conditions of the MCTA as supplemented by such Individual Site Agreement;
WHEREAS (D), Weston Memorial Health System is a member institution of the Veridian Health Research Network and has been designated as Site 005 for purposes of the Study, possessing the clinical research infrastructure, facilities, and qualified personnel necessary to support the conduct of the Study in accordance with the Protocol;
WHEREAS (E), the Site desires to participate in the Study and to be bound by the terms and conditions of the MCTA as supplemented by this Individual Site Agreement, and the Sponsor and the Network desire to have the Site participate in the Study on the terms and conditions set forth herein and in the MCTA; and
WHEREAS (F), the Veridian Central Institutional Review Board ("Veridian Central IRB") will serve as the Institutional Review Board of record for this Site in connection with the Study, consistent with the requirements of the 2018 revised Common Rule and the applicable policies of the Network.
NOW, THEREFORE, in consideration of the mutual covenants and agreements set forth herein and in the MCTA, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as follows:
ARTICLE 1 — DEFINITIONS AND INCORPORATION BY REFERENCE
Section 1.1 — Defined Terms
All capitalized terms used but not otherwise defined in this Agreement shall have the meanings ascribed to them in the MCTA. In addition, the following definitions shall apply to this Agreement:
(a) "MCTA" means that certain Master Clinical Trial Agreement dated June 28, 2023, between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc., including all Exhibits and Schedules thereto, as the same may be amended from time to time in accordance with its terms.
(b) "Protocol" means Protocol PPC-4871-III (CLARION), as amended from time to time in accordance with the MCTA and applicable regulatory requirements.
(c) "Investigational Product" means penterafenib (PPC-4871), including all dosage forms, formulations, and placebo comparators supplied by the Sponsor for use in the Study.
(d) "Site" means Weston Memorial Health System, located at 1420 Peachtree Medical Drive NE, Atlanta, Georgia 30309, including all clinical research facilities operated by Weston Memorial Health System that are designated for use in connection with the Study.
(e) "Site Number" means Site 005, as assigned by the Sponsor for purposes of the Study.
(f) "IRB of Record" means the Veridian Central IRB, the central institutional review board designated by the Network to serve as the IRB of record for multi-site research conducted within the Veridian Health Research Network.
(g) "Site Principal Investigator" or "Site PI" means the individual physician identified in Schedule A to this Agreement who is responsible for the conduct of the Study at this Site, as that term is used in 21 C.F.R. § 312.53.
(h) "Site Activation" means the date on which the Sponsor confirms in writing that all regulatory, contractual, and logistical prerequisites for the initiation of the Study at this Site have been satisfied, including but not limited to IRB approval, execution of this Agreement, receipt of FDA Form 1572, and completion of site initiation activities.
Section 1.2 — Incorporation of MCTA Terms
(a) The terms and conditions of the MCTA are hereby incorporated by reference into this Individual Site Agreement as if fully set forth herein. The Site acknowledges that it has received, reviewed, and understands the MCTA and all Exhibits and Schedules thereto, and agrees to be bound by the terms and conditions thereof as if it were a direct party thereto, subject to the site-specific terms set forth herein.
(b) In the event of any conflict or inconsistency between any provision of this Individual Site Agreement and any provision of the MCTA, the terms of the MCTA shall control and govern, except to the extent that this Agreement expressly provides site-specific terms that are stated herein to supersede a corresponding provision of the MCTA. For avoidance of doubt, site-specific terms set forth in the Schedules to this Agreement that address matters of budget, enrollment allocation, and site-specific operational details shall not be deemed to conflict with the MCTA.
(c) The Exhibits and Schedules attached to this Agreement supplement, and do not replace, the corresponding Exhibits and Schedules to the MCTA. Where an Exhibit or Schedule to this Agreement addresses the same subject matter as an Exhibit or Schedule to the MCTA, the two documents shall be read together and, to the extent practicable, harmonized.
ARTICLE 2 — SITE INFORMATION
Section 2.1 — Site Identification
The following information identifies the Site for purposes of this Agreement and the Study:
The full site address and additional contact information are set forth in Schedule A to this Agreement.
Section 2.2 — Site Principal Investigator
(a) The Site Principal Investigator for the Study at this Site shall be the individual identified in Schedule A to this Agreement. The Site PI shall be responsible for the overall conduct of the Study at this Site and shall serve as the responsible individual investigator under 21 C.F.R. § 312.53.
(b) The Site PI must meet all qualifications set forth in Section 4.3 of the MCTA and shall execute the Form of Investigator Undertaking attached as Exhibit I to the MCTA prior to the initiation of any Study activities at this Site. The executed Form of Investigator Undertaking shall be maintained in the Site's regulatory binder and copies shall be provided to the Sponsor and Meridian CRO.
(c) The Site PI must have executed a completed FDA Form 1572 (Statement of Investigator) prior to Site Activation. The executed FDA Form 1572 shall be included in Schedule C to this Agreement and shall be updated as necessary to reflect changes in sub-investigators, study facilities, or IRB information during the course of the Study.
(d) The Site PI and all sub-investigators must have completed and submitted to the Sponsor the Financial Disclosure Certification required under 21 C.F.R. Part 54 prior to Site Activation, and shall update such certifications promptly during the Study and for one year following the completion of the Study, in accordance with the requirements of 21 C.F.R. § 54.4.
(e) In the event the Site PI is unable to continue to serve as the principal investigator at this Site for any reason, including but not limited to disability, departure from the Site Institution, regulatory disqualification, or voluntary withdrawal, the Site shall promptly notify the Sponsor and the Network, and the Parties shall cooperate in good faith to identify and approve a qualified replacement principal investigator. No Study activities shall be conducted at this Site during any period in which there is no approved Site PI, except as necessary to ensure the safety and well-being of enrolled subjects.
Section 2.3 — Sub-Investigators and Study Personnel
(a) A list of qualified sub-investigators and key study personnel authorized to conduct Study activities at this Site shall be identified in Schedule A to this Agreement. This list shall be updated by the Site as necessary to reflect additions, removals, or changes in study personnel, and all updates shall be communicated to the Sponsor and Meridian CRO in a timely manner.
(b) All sub-investigators must execute the Form of Investigator Undertaking (Exhibit I to the MCTA) and complete the Financial Disclosure Certification under 21 C.F.R. Part 54 prior to participating in any Study activities at this Site.
(c) The Site is responsible for ensuring that all study personnel, including the Site PI, sub-investigators, study coordinators, research nurses, pharmacists, and other staff involved in the conduct of the Study, are adequately trained on the Protocol, Good Clinical Practice guidelines (ICH E6(R2)), and all applicable federal, state, and local regulations, including without limitation 21 C.F.R. Parts 11, 50, 54, 56, and 312. The Site shall maintain documentation of all training activities, including training logs, certificates of completion, and records of continuing education, and shall make such documentation available for inspection by the Sponsor, Meridian CRO, the FDA, and other regulatory authorities upon request.
(d) The Site shall ensure that all study personnel maintain current certifications in human subjects protection training (e.g., CITI Program or equivalent) throughout the duration of their participation in the Study.
Section 2.4 — Site Facilities and Capabilities
(a) The Site hereby certifies that it possesses adequate facilities, equipment, and qualified personnel to conduct the Study in accordance with the Protocol, ICH E6(R2) GCP Guidelines, and all applicable regulatory requirements. Without limiting the foregoing, the Site certifies that it has access to appropriate clinical space for subject screening, enrollment, and follow-up visits; an appropriately equipped and staffed research pharmacy for the receipt, storage, dispensation, and accountability of the Investigational Product; laboratory facilities or access to central laboratory services for the processing and shipment of study specimens; and imaging capabilities necessary for tumor assessments as required by the Protocol.
(b) The Site agrees to maintain such facilities, equipment, and qualified personnel throughout the enrollment period, the active treatment period, and the follow-up period of the Study, and to promptly notify the Sponsor and the Network of any material changes in the availability or condition of such facilities that could adversely affect the conduct of the Study at this Site.
(c) A description of the clinical research facilities available at this Site is set forth in Schedule A to this Agreement.
ARTICLE 3 — SCOPE OF WORK AND PROTOCOL COMPLIANCE
Section 3.1 — Conduct of the Study
(a) The Site shall conduct the Study at this Site in strict accordance with Protocol PPC-4871-III (CLARION), the ICH E6(R2) Good Clinical Practice Guidelines, the Declaration of Helsinki (as most recently amended), and all applicable federal, state, and local laws and regulations, including without limitation the Federal Food, Drug, and Cosmetic Act (21 U.S.C. §§ 301 et seq.) and the regulations promulgated thereunder.
(b) The Site shall enroll subjects in the Study in accordance with the Protocol's inclusion and exclusion criteria. The Site shall not enroll any subject who does not satisfy all inclusion criteria or who meets any exclusion criterion, except as may be expressly permitted by the Protocol or authorized in writing by the Sponsor. The Site shall use good faith efforts to meet the enrollment targets assigned to this Site as set forth in Schedule B to this Agreement.
(c) The Study is designed as a Phase III, randomized, double-blind, placebo-controlled trial with a planned total enrollment of approximately 1,200 subjects across all thirty-eight (38) Veridian Network sites participating in the Study. Subjects will be randomized in a 2:1 ratio, with approximately 800 subjects assigned to the penterafenib treatment arm and approximately 400 subjects assigned to the placebo control arm. The specific enrollment allocation for Site 005 is set forth in Schedule B to this Agreement.
(d) The Site shall participate in all Study-related activities as required by the Protocol and the MCTA, including but not limited to subject screening and enrollment, administration of the Investigational Product, collection of efficacy and safety data, processing and shipment of biological specimens, performance of imaging assessments, and conduct of follow-up visits through the end of the Study observation period.
Section 3.2 — Protocol Deviations
(a) The Site shall not deviate from the Protocol in any material respect except as: (i) authorized in writing by the Sponsor in advance of such deviation, including through Protocol amendments approved by the Veridian Central IRB; or (ii) necessary to protect the immediate safety, rights, or well-being of a study subject, in which case the deviation shall be documented as a medically necessary protocol deviation.
(b) In the event of a medically necessary protocol deviation undertaken to protect the safety of a study subject, the Site PI shall report such deviation to the Sponsor and Meridian CRO within twenty-four (24) hours of the occurrence of the deviation. The Site PI shall document the deviation in the subject's source documents and in the electronic data capture system, including a description of the circumstances necessitating the deviation, the actions taken, and any impact on the subject's continued participation in the Study.
(c) The Site shall maintain a log of all protocol deviations occurring at this Site, whether major or minor, and shall make such log available for inspection by the Sponsor, Meridian CRO, and the Veridian Central IRB upon request. Protocol deviations classified as major deviations shall be reported to the Veridian Central IRB in accordance with the IRB's reporting requirements.
(d) Liability for unauthorized protocol deviations that are not medically necessary shall be allocated in accordance with the indemnification provisions set forth in Exhibit D to the MCTA and Article 6 of this Agreement.
Section 3.3 — Regulatory Compliance
(a) The Site shall comply with all applicable provisions of the Code of Federal Regulations, including without limitation:
(i) 21 C.F.R. Part 11 (Electronic Records; Electronic Signatures);
(ii) 21 C.F.R. Part 50 (Protection of Human Subjects);
(iii) 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators);
(iv) 21 C.F.R. Part 56 (Institutional Review Boards); and
(v) 21 C.F.R. Part 312 (Investigational New Drug Application).
(b) The Site shall comply with the Health Insurance Portability and Accountability Act of 1996, as amended ("HIPAA"), and the regulations promulgated thereunder at 45 C.F.R. Parts 160 and 164, with respect to all protected health information ("PHI") collected, used, or disclosed in connection with the Study. The Site shall ensure that a HIPAA-compliant authorization is obtained from each study subject prior to the collection, use, or disclosure of any individually identifiable health information in connection with the Study.
(c) The Site shall comply with the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)) and all applicable state anti-kickback and self-referral laws. The Site shall ensure that all investigator compensation is consistent with fair market value and does not take into account the volume or value of referrals or other business generated between the Parties.
(d) The Site shall comply with the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h) and the Open Payments reporting requirements administered by the Centers for Medicare & Medicaid Services ("CMS"), including by providing the Sponsor with all information necessary for the Sponsor to fulfill its reporting obligations under the Open Payments program with respect to transfers of value to the Site and its covered recipients.
Section 3.4 — Use of Approved Subcontractors
(a) The Sponsor has approved the following subcontractors for the performance of specified Study-related functions, as set forth in Exhibit K to the MCTA:
(i) Meridian Contract Research Organization, Inc. ("Meridian CRO"), serving as the Sponsor's contracted CRO for clinical monitoring, data management, pharmacovigilance, and regulatory affairs;
(ii) Pinnacle Data Solutions, Inc., serving as the provider of the electronic data capture (EDC) platform for the Study; and
(iii) Northbridge Bioanalytical Laboratories, Inc., serving as the central laboratory for the processing and analysis of study specimens.
(b) The Site shall cooperate with each approved subcontractor in the performance of its respective functions as required by the Protocol and the MCTA. Without limiting the foregoing, the Site shall accommodate monitoring visits by Meridian CRO representatives, respond to data queries generated through the Pinnacle EDC platform, and comply with specimen collection, processing, and shipment procedures established by Northbridge Bioanalytical Laboratories, Inc.
(c) The Site shall not engage any additional subcontractors to perform Study-related activities without the prior written approval of the Sponsor.
ARTICLE 4 — IRB OVERSIGHT
Section 4.1 — IRB of Record
(a) The Veridian Central IRB shall serve as the IRB of record for Site 005 for purposes of the Study. The Site acknowledges and agrees that the Veridian Central IRB will provide initial and continuing review and approval of the Study at this Site, including review of the Protocol, informed consent documents, investigator brochure, recruitment materials, and other study-related documents.
(b) The Site operates under an IRB Authorization Agreement (also known as a reliance agreement or IRB of Record agreement) between Weston Memorial Health System and Veridian Health Research Network, Inc., executed in accordance with the requirements of the 2018 revised Common Rule (45 C.F.R. Part 46, Subpart A) for single-IRB review of cooperative (multi-site) research. Under this IRB Authorization Agreement, the institutional review board of Weston Memorial Health System has agreed to cede review of multi-site research conducted within the Veridian Network to the Veridian Central IRB, while retaining the authority to disapprove research that the Veridian Central IRB has approved, in accordance with applicable regulations.
(c) Notwithstanding the foregoing, the Site retains responsibility for ensuring compliance with any local institutional requirements, ancillary committee reviews (e.g., pharmacy and therapeutics committee, radiation safety committee, biosafety committee), and state or local laws applicable to the conduct of the Study at this Site that are not addressed by the Veridian Central IRB's review.
Section 4.2 — IRB Approval as Condition Precedent
(a) The Site shall not enroll any subjects in the Study, administer the Investigational Product to any subject, or initiate any other Study-related procedures involving human subjects until the Veridian Central IRB has granted initial approval for the conduct of the Study at this Site. IRB approval must encompass the Protocol, the informed consent form (including any site-specific modifications), and all recruitment materials to be used at this Site.
(b) Documentation of IRB approval, including the IRB approval letter, the approved Protocol version, and the IRB-stamped informed consent form, must be provided to the Sponsor and Meridian CRO prior to Site Activation. The Site shall not be deemed activated for purposes of enrollment or any fee payments under this Agreement until such documentation has been received and confirmed by the Sponsor.
Section 4.3 — Continuing Review and Amendments
(a) The Site shall ensure that continuing IRB review and approval of the Study is maintained at all times during the conduct of the Study at this Site, as required by 21 C.F.R. Part 56 and the policies of the Veridian Central IRB. The Site shall provide documentation of each continuing review approval to the Sponsor and Meridian CRO promptly upon receipt.
(b) Protocol amendments issued by the Sponsor shall not be implemented at this Site until approved by the Veridian Central IRB, except for amendments that are necessary to eliminate an immediate hazard to study subjects. In the case of amendments necessary to eliminate an immediate hazard, the Site PI may implement the amendment immediately, provided that the Veridian Central IRB is notified of the amendment and the reasons for its immediate implementation within five (5) business days, and formal IRB approval is obtained as soon as practicable thereafter.
(c) The Site shall promptly report to the Veridian Central IRB all unanticipated problems involving risks to subjects or others, protocol deviations that may affect subject safety or data integrity, and any other events or information required to be reported under the IRB's policies and applicable regulations.
ARTICLE 5 — BUDGET AND PAYMENT
Section 5.1 — Budget
The site-specific budget for the conduct of the Study at Site 005 is set forth in Schedule B to this Agreement. The budget has been prepared in accordance with and is consistent with the master budget framework set forth in Exhibit B to the MCTA. The key components of the site-specific budget are as follows:
All amounts set forth in the budget are inclusive of the Site's costs for personnel, facilities, and routine operational expenses associated with the conduct of the Study at this Site, including but not limited to the costs of the Site PI, sub-investigators, study coordinators, research nurses, pharmacy personnel, data entry, source document management, and routine overhead. The budget does not include costs for Investigational Product, central laboratory analyses, or EDC platform access, which are the responsibility of the Sponsor or its designated subcontractors as set forth in the MCTA.
Section 5.2 — Payment Milestones (Per-Patient Fees)
Payment of per-patient fees shall be made in four (4) equal milestone installments of Thirteen Thousand Dollars ($13,000) each per enrolled subject, as follows:
(a) Milestone 1 — Randomization: Twenty-five percent (25%) of the per-patient fee ($13,000) shall be payable upon confirmation of a subject's randomization in the Study;
(b) Milestone 2 — Week 12 Assessment: Twenty-five percent (25%) of the per-patient fee ($13,000) shall be payable upon completion of the Week 12 assessment for the subject;
(c) Milestone 3 — Week 24 Assessment: Twenty-five percent (25%) of the per-patient fee ($13,000) shall be payable upon completion of the Week 24 assessment for the subject; and
(d) Milestone 4 — Study Completion / Final Visit: Twenty-five percent (25%) of the per-patient fee ($13,000) shall be payable upon completion of the study completion visit or final visit for the subject.
For subjects who withdraw from the Study prior to completion of all four milestones, payment shall be made for all milestones achieved through the date of withdrawal. No payment shall be made for milestones not achieved due to subject withdrawal, unless otherwise agreed in writing by the Sponsor. If a subject is randomized but subsequently determined to be ineligible (e.g., due to a screening error), the Sponsor shall pay the Milestone 1 fee but shall have no obligation to pay subsequent milestone fees unless the subject continues in the Study with the Sponsor's written approval.
Section 5.3 — Start-Up Fees
The start-up fee for this Site shall be Seventy-Five Thousand Dollars ($75,000), payable in two (2) equal installments as follows:
(a) Fifty percent (50%) of the start-up fee (Thirty-Seven Thousand Five Hundred Dollars ($37,500)) shall be payable upon Site Activation; and
(b) Fifty percent (50%) of the start-up fee (Thirty-Seven Thousand Five Hundred Dollars ($37,500)) shall be payable upon the enrollment of the first subject at this Site (i.e., the date on which the first subject at this Site signs the informed consent form and is screened for eligibility).
The start-up fee is intended to compensate the Site for costs incurred in connection with the preparation and activation of the Site for participation in the Study, including but not limited to regulatory submissions, IRB coordination, staff training, facility preparation, and establishment of study-specific procedures and systems.
Section 5.4 — Annual Site Maintenance Fees
The annual site maintenance fee for this Site shall be Forty Thousand Dollars ($40,000) per year, payable annually in advance on each anniversary of Site Activation. For partial years at the beginning or end of the Study, the annual site maintenance fee shall be prorated on a per-diem basis based on a 365-day year. The annual site maintenance fee is intended to compensate the Site for ongoing costs associated with maintaining the Site's readiness and capacity to conduct the Study, including storage and accountability of the Investigational Product, regulatory file maintenance, and continued staff training and certification.
Section 5.5 — Payment Terms
All payments under this Agreement shall be made Net Forty-Five (45) days from the Sponsor's receipt of a proper and complete invoice submitted by Veridian on behalf of the Site in accordance with the invoicing procedures set forth in the MCTA. Payments shall be made by wire transfer or automated clearing house (ACH) transfer to the bank account designated by Veridian. The Sponsor shall not be obligated to make any payment for which the Sponsor has not received a proper and complete invoice, and the Sponsor shall notify Veridian within ten (10) business days of receipt of any invoice that the Sponsor disputes or considers incomplete or improper, specifying the basis for such dispute or deficiency.
Section 5.6 — Invoicing
(a) Veridian shall submit invoices to the Sponsor on behalf of this Site in accordance with the invoicing procedures set forth in Article 7 of the MCTA. Invoices shall be submitted on a monthly basis, or at such other frequency as may be agreed by the Parties, and shall include sufficient detail to identify the milestone payments, start-up fees, and site maintenance fees to which each invoice relates.
(b) The Site shall provide Veridian with all documentation necessary to support each milestone payment, including but not limited to source verification of subject randomization dates, visit completion dates, and study completion or withdrawal dates. Veridian shall not submit an invoice on behalf of this Site unless it has received adequate supporting documentation from the Site.
(c) Invoicing contact information:
Veridian Health Research Network, Inc.
Attn: Patricia Dunne, Director, Sponsored Research Agreements
750 Research Parkway, 8th Floor Philadelphia, Pennsylvania 19104
Email: pdunne@veridianresearch.org
ARTICLE 6 — INDEMNIFICATION
Section 6.1 — Sponsor Indemnification of Site
(a) Penterra Pharmaceuticals Corp. shall indemnify, defend, and hold harmless Weston Memorial Health System, its Site Principal Investigator, sub-investigators, study coordinators, research nurses, and other site staff participating in the Study (collectively, the "Site Indemnitees"), from and against any and all claims, damages, losses, liabilities, costs, and expenses (including reasonable attorneys' fees and costs of litigation or arbitration) arising out of or relating to:
(i) Any injury, illness, or death of a study subject caused by the Investigational Product (penterafenib or placebo) when administered in accordance with the Protocol;
(ii) Any defect in the design, manufacture, formulation, packaging, labeling, or supply of the Investigational Product;
(iii) Any breach by the Sponsor of the MCTA, this Individual Site Agreement, or the Protocol; and
(iv) Any negligence or willful misconduct of the Sponsor, its employees, agents, or subcontractors (including Meridian CRO) in connection with the Study.
(b) The Sponsor's indemnification obligations under this Section 6.1 shall be subject to the following caps and limitations as set forth in Exhibit D to the MCTA:
(i) Subject Medical Care Costs: The Sponsor's liability for medical care costs arising from Study-related injuries to individual subjects shall be capped at Five Hundred Thousand Dollars ($500,000) per subject, with an aggregate cap across all participating sites in the Study of Fifteen Million Dollars ($15,000,000); and
(ii) Product-Defect Claims: The Sponsor's indemnification obligations with respect to claims arising from defects in the Investigational Product shall be uncapped.
(c) The indemnification obligations of the Sponsor under this Section 6.1 are in accordance with and subject to the terms and conditions of Exhibit D to the MCTA, which sets forth the detailed procedures, conditions, and limitations applicable to indemnification claims.
Section 6.2 — Carve-Outs from Sponsor Indemnification
The Sponsor's indemnification obligations under Section 6.1 shall not extend to, and the Sponsor shall have no obligation to indemnify any Site Indemnitee against, any claims, damages, losses, liabilities, costs, or expenses to the extent arising from or attributable to:
(i) The negligence, recklessness, or willful misconduct of the Site, the Site PI, any sub-investigator, or any other site personnel in connection with the conduct of the Study;
(ii) Protocol deviations committed by the Site, the Site PI, or any site personnel that were not authorized by the Sponsor in writing and were not reasonably necessary to protect the immediate safety, rights, or well-being of a study subject; or
(iii) Any breach by the Site or the Network of the MCTA, this Individual Site Agreement, or applicable law, including but not limited to failure to obtain or maintain IRB approval, failure to obtain valid informed consent, or failure to comply with applicable HIPAA requirements.
In the event that a claim involves a combination of actions or omissions attributable to both the Sponsor and one or more Site Indemnitees, the respective indemnification obligations of the Parties shall be allocated in accordance with each Party's proportionate share of fault, as determined through the dispute resolution procedures set forth in Article 14 of this Agreement.
Section 6.3 — Site Indemnification of Sponsor
(a) Weston Memorial Health System and Veridian Health Research Network, Inc. shall, jointly and severally, indemnify, defend, and hold harmless Penterra Pharmaceuticals Corp., its officers, directors, employees, agents, affiliates, and successors (collectively, the "Sponsor Indemnitees"), from and against any and all claims, damages, losses, liabilities, costs, and expenses (including reasonable attorneys' fees and costs of litigation or arbitration) arising out of or relating to:
(i) Any negligence, recklessness, or willful misconduct of the Site, the Site PI, any sub-investigator, or any other site personnel in connection with the conduct of the Study at this Site;
(ii) Unauthorized protocol deviations committed by the Site, the Site PI, or any site personnel that were not required for the protection of subject safety; and
(iii) Any breach by the Site or the Network of the MCTA, this Individual Site Agreement, or applicable law.
(b) The indemnification obligations of the Site and the Network under this Section 6.3 shall be subject to the following caps:
(i) Per-Site Cap: Five Million Dollars ($5,000,000) per site per occurrence; and
(ii) Aggregate Cap: Twenty Million Dollars ($20,000,000) in the aggregate across all Veridian Network sites participating in the Study.
Section 6.4 — Notice of Claims
(a) Any Party seeking indemnification under this Article 6 (the "Indemnified Party") shall provide written notice to the Party from whom indemnification is sought (the "Indemnifying Party") within thirty (30) calendar days of becoming aware of any claim, demand, action, or proceeding for which indemnification may be sought (a "Claim"). Such notice shall include a description of the Claim, the factual basis therefor (to the extent then known), and an estimate of the amount of damages or losses involved (to the extent reasonably ascertainable).
(b) The failure of the Indemnified Party to provide timely written notice as required by this Section 6.4 shall not relieve the Indemnifying Party of its indemnification obligations hereunder, except to the extent that the Indemnifying Party is materially prejudiced by the delay in receiving such notice. The burden of demonstrating material prejudice shall rest with the Indemnifying Party.
Section 6.5 — Defense and Settlement
The procedures for the defense and settlement of indemnified Claims, including the Indemnifying Party's right to assume the defense of any Claim, the Indemnified Party's right to participate in such defense at its own expense, and the conditions under which settlement may be effected with or without the consent of the Indemnified Party, shall be as set forth in Exhibit D to the MCTA, which provisions are incorporated herein by reference. Neither Party shall settle any Claim for which indemnification is sought without the prior written consent of the other Party, which consent shall not be unreasonably withheld, conditioned, or delayed.
ARTICLE 7 — INSURANCE
Section 7.1 — Sponsor Insurance
(a) The Sponsor represents that it maintains clinical trial liability insurance coverage through Briarcliff Mutual Insurance Company under Policy No. BM-CTL-2023-04182, with a policy period of April 1, 2023 through March 31, 2024, renewable annually. Such policy provides the following coverage limits:
(b) Weston Memorial Health System shall be named as an additional insured under the Sponsor's clinical trial liability insurance policy for the duration of the Study at this Site, including any wind-down period following termination of this Agreement.
(c) The Sponsor shall provide a certificate of insurance evidencing the coverage described in this Section 7.1 to the Site and the Network within fifteen (15) business days of execution of this Agreement and annually thereafter during the term of the Study. The Sponsor shall provide the Site with at least thirty (30) days' prior written notice of any cancellation, material modification, or non-renewal of such insurance coverage.
Section 7.2 — Site Insurance
(a) Weston Memorial Health System shall maintain, at its own expense, general liability insurance and professional liability (medical malpractice) insurance coverage throughout the term of the Study at this Site, with minimum coverage limits of not less than Five Million Dollars ($5,000,000) per occurrence and Ten Million Dollars ($10,000,000) in the aggregate. Such coverage shall extend to the acts and omissions of the Site PI, sub-investigators, and all other site personnel participating in the Study.
(b) The Site shall deliver a certificate of insurance evidencing the coverage required by this Section 7.2 to the Sponsor and the Network within fifteen (15) business days of execution of this Agreement. Thereafter, the Site shall deliver updated certificates of insurance to the Sponsor and the Network annually during the term of the Study, and promptly upon any material change in coverage. The Site shall provide the Sponsor with at least thirty (30) days' prior written notice of any cancellation, material modification, or non-renewal of such insurance coverage.
Section 7.3 — Certificate Exchange
The Parties shall exchange certificates of insurance within fifteen (15) business days of execution of this Agreement and annually thereafter during the term of the Study, as further detailed in Sections 7.1(c) and 7.2(b) above. Each Party shall cooperate with the other Parties in providing such additional information regarding its insurance coverage as may be reasonably requested.
ARTICLE 8 — SAFETY REPORTING
Section 8.1 — SAE Reporting
(a) The Site shall report all serious adverse events ("SAEs") occurring at this Site to the Sponsor and Meridian CRO within twenty-four (24) hours of the Site's awareness of the SAE, in accordance with the reporting procedures set forth in Exhibit J to the MCTA. For purposes of this Agreement, a serious adverse event is any adverse event that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is a medically important event that may jeopardize the subject or may require medical or surgical intervention to prevent one of the outcomes listed above, as defined in 21 C.F.R. § 312.32(a).
(b) Initial SAE reports shall be submitted using the SAE reporting form provided by Meridian CRO and shall include all available information regarding the event, including the subject identifier, the date of onset, the nature and severity of the event, the relationship to the Investigational Product (as assessed by the Site PI), the outcome of the event, and any corrective actions taken. Follow-up reports shall be submitted as additional information becomes available, until the event is resolved or the subject's condition has stabilized.
(c) The Site PI shall exercise medical judgment in assessing the seriousness, severity, and causality of all adverse events, and shall document such assessments in the subject's source documents and in the electronic data capture system.
Section 8.2 — IND Safety Reports
(a) The Sponsor is responsible for the preparation and submission of IND safety reports to the FDA and to all participating investigators in accordance with 21 C.F.R. § 312.32, including:
(i) Seven (7) calendar day reports for suspected adverse reactions that are both serious and unexpected and are fatal or life-threatening; and
(ii) Fifteen (15) calendar day reports for all other suspected adverse reactions that are both serious and unexpected.
(b) The Site shall cooperate with the Sponsor and Meridian CRO in providing all information necessary for the timely preparation and submission of IND safety reports, including prompt responses to follow-up queries and requests for additional clinical data.
(c) Upon receipt of IND safety reports from the Sponsor, the Site PI shall review such reports and take any actions necessary to protect the safety and well-being of subjects enrolled at this Site, including, if appropriate, modification of the informed consent document and re-consent of enrolled subjects.
Section 8.3 — Coordination with Meridian CRO
(a) Meridian Contract Research Organization, Inc. serves as the Sponsor's contracted CRO for the Study, with responsibility for clinical monitoring, data management, pharmacovigilance, and regulatory affairs support. The Site acknowledges and agrees that Meridian CRO acts on behalf of the Sponsor in the performance of these functions.
(b) The Site shall cooperate fully with Meridian CRO in connection with monitoring visits, including providing access to source documents, study records, regulatory files, and Investigational Product accountability records. The Site shall accommodate on-site monitoring visits at intervals determined by the Sponsor and Meridian CRO in accordance with the monitoring plan, and shall respond to data queries and requests for clarification in a timely manner.
(c) The Site shall designate a primary point of contact for communication with Meridian CRO regarding Study-related matters and shall ensure that such contact person is available during normal business hours.
ARTICLE 9 — DATA AND RECORDS
Section 9.1 — Data Ownership
(a) Penterra Pharmaceuticals Corp. retains exclusive ownership of all clinical trial data generated at this Site in connection with the Study, including without limitation all case report forms, electronic data capture records, source data transcribed into the Study database, laboratory results, imaging data, biospecimen analyses, pharmacokinetic data, and any other data collected pursuant to the Protocol (collectively, "Study Data"), as set forth in Exhibit G to the MCTA.
(b) The Site acknowledges that Study Data constitutes confidential and proprietary information of the Sponsor and shall not disclose, publish, or otherwise make available any Study Data except as expressly permitted under the MCTA, this Agreement, or with the prior written consent of the Sponsor.
(c) Notwithstanding the foregoing, the Site shall retain ownership of the original source documents maintained at this Site in accordance with the Site's institutional records retention policies and applicable law. The Sponsor's ownership of Study Data shall not be construed to confer upon the Sponsor any ownership interest in the original medical records of study subjects.
Section 9.2 — Electronic Data Capture
(a) The Site shall enter all Study data into the electronic data capture (EDC) platform provided by Pinnacle Data Solutions, Inc., in accordance with the Protocol, the data management plan, and the requirements of 21 C.F.R. Part 11 governing electronic records and electronic signatures.
(b) The Site shall ensure that all study personnel who access or enter data into the EDC platform have been appropriately trained on the use of the system and have been assigned unique user identification credentials. The Site shall maintain the security and confidentiality of all EDC access credentials and shall promptly notify Meridian CRO in the event of any suspected unauthorized access to the EDC platform.
(c) Data shall be entered into the EDC platform within the timelines specified in the data management plan, and data queries shall be resolved within the timelines specified by Meridian CRO.
Section 9.3 — Source Document Retention
(a) The Site shall retain all source documents, study records, regulatory files, and other documentation related to the conduct of the Study at this Site for a minimum period of fifteen (15) years following the completion, termination, or discontinuation of the Study, or for such longer period as may be required by applicable federal, state, or local law, whichever period is longer.
(b) The Site shall not destroy or dispose of any source documents or study records without the prior written consent of the Sponsor. In the event the Site determines that it is unable or unwilling to continue to maintain source documents and study records for the required retention period, the Site shall notify the Sponsor in writing at least six (6) months in advance and shall cooperate with the Sponsor to arrange for the transfer of such documents and records to the Sponsor or its designee.
Section 9.4 — Access to Records
The Sponsor, Meridian CRO, the FDA, and other regulatory authorities having jurisdiction over the Study shall have the right, upon reasonable notice, to access, review, and copy all records, source documents, regulatory files, and other documentation related to the conduct of the Study at this Site, including but not limited to subject medical records (to the extent permitted by applicable law and subject authorizations), case report forms, laboratory records, pharmacy records, IRB correspondence, and financial records related to Study payments. The Site shall cooperate fully with all inspections, audits, and reviews conducted by the Sponsor, Meridian CRO, or regulatory authorities.
ARTICLE 10 — CONFIDENTIALITY
Section 10.1 — Confidentiality Obligations
(a) The confidentiality provisions of the MCTA, as set forth in Exhibit F thereto, are hereby incorporated into this Agreement by reference and shall apply to all Confidential Information disclosed to or received by the Site in connection with the Study.
(b) The term of the confidentiality obligations shall be ten (10) years from the date of each disclosure of Confidential Information.
(c) For purposes of this Agreement, "Confidential Information" includes, without limitation, all Protocol-related information, Investigational Product specifications and formulations, pharmacological and toxicological data, clinical study data and results, manufacturing processes, regulatory filings and correspondence, business plans and strategies, financial terms and conditions of this Agreement and the MCTA, and any other information designated as confidential by the disclosing Party or that, by its nature, should reasonably be understood to be confidential.
(d) The Site shall restrict access to Confidential Information to those employees, agents, and contractors of the Site who have a need to know such information in connection with the performance of the Site's obligations under this Agreement and the MCTA, and who are bound by obligations of confidentiality no less restrictive than those set forth herein.