1018-00004 · Penterra Pharmaceuticals Corp · Engagement

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MEMORANDUM — CONFIDENTIAL / ATTORNEY WORK PRODUCT

CALDERWOOD & HARKNESS LLP 280 Park Avenue, 34th Floor New York, New York 10017

Date: March 20, 2023

To: File — Matter No. 1018-00004

From: Miriam Calloway, Partner, Healthcare & Life Sciences Practice Group

Re: Matter Opening — Penterra Pharmaceuticals Corp. / Veridian Health Research Network, Inc. — Master Clinical Trial Agreement and Site-Network Agreements for Protocol PPC-4871-III (CLARION)

Classification: Internal / Privileged and Confidential

This memorandum is protected by the attorney-client privilege and the work product doctrine. It is intended solely for internal use by the attorneys and professional staff of Calderwood & Harkness LLP assigned to Matter No. 1018-00004. This memorandum and its contents should not be disclosed to any person outside the firm without the prior written authorization of the undersigned.

I. Purpose

This memorandum formally opens Matter No. 1018-00004 in the firm's matter management system and establishes the foundational record for the engagement described herein. Its purpose is to document the key facts, parties, transaction parameters, legal issues, engagement team composition, and anticipated timeline relevant to the matter so that all team members and firm administrative personnel have a consolidated reference document from which to work.

Calderwood & Harkness LLP has been retained by Penterra Pharmaceuticals Corp. ("Penterra" or "PPC") to represent the company as outside counsel in the negotiation, drafting, and finalization of a Master Clinical Trial Agreement ("MCTA") and associated site-network agreements with Veridian Health Research Network, Inc. ("Veridian" or "VHRN"). The engagement encompasses the full lifecycle of the transactional documents, from initial drafting through execution, closing, and delivery of all ancillary instruments, as more fully described in Section IX below.

The engagement arises from Penterra's planned Phase III multi-center clinical trial for its lead investigational compound penterafenib (PPC-4871), an oral next-generation multi-kinase inhibitor being developed for the treatment of advanced hepatocellular carcinoma (HCC) in the second-line setting. The Phase III trial, conducted under Protocol PPC-4871-III and bearing the short title "CLARION" (Clinical Assessment of Response with Longitudinal Investigation in ONcology), represents a pivotal registrational study and a critical milestone in Penterra's clinical development program for penterafenib. Veridian operates a research network of 38 academic medical centers across 14 states, all of which are anticipated to serve as clinical trial sites under the MCTA.

The engagement was confirmed by Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs at Penterra, who serves as the day-to-day legal contact for the MCTA negotiation. Ms. Liang's authorization to retain the firm was given with the express approval and authorization of Nathaniel Briggs, Esq., Vice President and General Counsel of Penterra, who will serve as the senior legal officer with oversight responsibility for the engagement on the client side.

The formal engagement letter was executed as of March 20, 2023. The retainer acknowledgment is pending countersignature from Penterra; Ms. Liang has indicated that countersignature will be forthcoming within approximately five business days following internal processing by Penterra's finance department. Upon receipt of the executed retainer acknowledgment, a copy will be placed in the matter file.

A comprehensive conflict check has been completed and cleared as of March 20, 2023. The results of that check, including all identified relationships and the basis for clearance, are documented in a separate Conflict Check Memorandum filed concurrently with this matter opening memorandum. No conflicts of interest or potential conflicts requiring client waiver were identified.

II. Client Information

The following information summarizes the key facts regarding the client for purposes of this engagement.

Full Legal Name: Penterra Pharmaceuticals Corp.

Short Names / Abbreviations Used in this Memorandum and Related Correspondence: Penterra; PPC.

Entity Type: Corporation, incorporated under the laws of the State of Delaware. Penterra was originally incorporated in Delaware in 2009 and has maintained its domicile in that jurisdiction since its founding. The company is in good standing with the Delaware Secretary of State as of the date of this memorandum.

Publicly Traded: Yes. Penterra's common stock is listed on the Nasdaq Global Select Market under the ticker symbol PTRA. As a Nasdaq-listed issuer, Penterra is subject to the periodic reporting requirements of the Securities Exchange Act of 1934, as amended, and the rules and regulations of the U.S. Securities and Exchange Commission ("SEC"). This status is relevant to the matter insofar as certain provisions of the MCTA (including confidentiality, publication rights, and material contract disclosure) may implicate Penterra's SEC disclosure obligations.

Headquarters: 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540. The Princeton headquarters serves as the company's principal executive office and houses its legal, clinical development, and corporate affairs functions.

Registered Agent in Delaware: Capitol Registered Agents, LLC, 1209 Orange Street, Wilmington, Delaware 19801.

Key Financial Data

The following financial data points are provided for context and for the purpose of assessing the materiality of the MCTA and related agreements to Penterra's overall financial position:

Given the total estimated deal value of approximately $80 million (as detailed in Section IV.D below), the MCTA represents a significant but not individually material commitment relative to Penterra's overall financial position, its annual R&D expenditure, or its current cash reserves. Nonetheless, the CLARION trial is understood to be a pivotal registrational study for penterafenib, and the successful prosecution of this trial is material to Penterra's long-term pipeline value and corporate strategy. The engagement team should be mindful of the potential for disclosure implications and should coordinate with Ms. Liang regarding any public disclosure requirements that may arise in connection with the execution of the MCTA.

Primary Client Contacts

The following individuals at Penterra are the primary points of contact for purposes of this engagement:

1. Nathaniel Briggs, Esq. — Vice President & General Counsel. Mr. Briggs exercises overall legal oversight over the MCTA negotiation and serves as an authorized signatory for Penterra on the executed agreement. Communications with Mr. Briggs should generally be routed through Ms. Liang unless the matter warrants direct escalation. Mr. Briggs's office is located at Penterra's Princeton headquarters.

2. Rebecca Liang, Esq. — Associate General Counsel, Clinical Affairs. Ms. Liang is the day-to-day legal contact for all matters relating to the MCTA negotiation and drafting. She will serve as the principal liaison between Penterra's in-house legal team and Calderwood & Harkness on all aspects of this engagement. Ms. Liang has extensive experience in clinical trial agreements and has worked with Veridian on prior transactions in connection with Penterra's earlier-stage clinical programs. All initial communications, document circulations, and negotiation updates should be directed to Ms. Liang.

3. Samantha Novak — Director, Clinical Contracts. Ms. Novak oversees contracts administration within Penterra's clinical operations function and will be responsible for the operational aspects of MCTA implementation, including site-level joinder agreements, budget negotiations at the site level, and coordination with Penterra's contract research organization. Ms. Novak's involvement will become more significant during the site-level agreement phase following execution of the master agreement.

Other Relevant Penterra Personnel

In addition to the primary contacts listed above, the following individuals at Penterra are relevant to the engagement and may participate in meetings, calls, or communications from time to time:

• Dr. Anand Raghavan, M.D., Ph.D. — Chief Executive Officer. Dr. Raghavan serves as the executive sponsor of the CLARION trial and is an authorized signatory for Penterra on the MCTA. His involvement will likely be limited to executive-level discussions and final signing.

• Dr. Elaine Whitford, M.D. — Chief Medical Officer. Dr. Whitford has medical oversight responsibility for the CLARION trial and will be involved in discussions relating to protocol-related provisions of the MCTA, including subject-injury indemnification, safety reporting, and protocol deviation liability allocation.

• Dr. Marcus Yun, M.D., M.P.H. — Senior Vice President, Clinical Development. Dr. Yun is the clinical development lead for the penterafenib program and may participate in discussions regarding the protocol synopsis, enrollment timelines, and site selection criteria.

• Jennifer Holt — Vice President, Clinical Operations. Ms. Holt is the operational lead for the CLARION trial and is responsible for day-to-day trial management, site activation, and coordination with Meridian CRO. She will be a key operational contact during the negotiation of site start-up, payment schedules, and operational provisions of the MCTA.

III. Counterparty Information

The following information summarizes the key facts regarding the counterparty to the MCTA.

Full Legal Name: Veridian Health Research Network, Inc.

Short Names / Abbreviations Used in this Memorandum and Related Correspondence: Veridian; VHRN.

Entity Type: Corporation, incorporated under the laws of the State of Delaware. Veridian is organized and operates as a tax-exempt organization under Section 501(c)(3) of the Internal Revenue Code. Veridian's tax-exempt status is relevant to the engagement in several respects, including the applicability of unrelated business income tax (UBIT) considerations for certain types of payments, the structural requirements of Veridian's organizational documents (which may impose restrictions on the scope of contractual commitments and indemnification obligations), and the generally more conservative negotiating posture that tax-exempt research networks typically adopt with respect to liability exposure.

Headquarters: 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104.

Employer Identification Number (EIN): 23-4178205.

Network Size: Veridian operates a research network comprising 38 academic medical centers and affiliated research institutions located across 14 states. The network is understood to include a mix of university-affiliated hospitals, independent academic medical centers, and research institutes, all of which have executed network participation agreements with Veridian granting Veridian authority to negotiate and enter into clinical trial agreements on behalf of the network. The scope and terms of Veridian's authority to bind individual network sites will be a key diligence point in the MCTA negotiation, and the engagement team should request and review copies of Veridian's standard network participation agreement and any relevant delegation-of-authority documentation.

Annual Research Volume: Veridian reports that its network conducts approximately $1.4 billion in sponsored research annually across all therapeutic areas and study phases. This figure positions Veridian as one of the larger academic research networks in the United States and reflects a substantial level of institutional experience with clinical trial agreements, regulatory compliance, and multi-site coordination.

Employees: Approximately 6,200 employees across the network's central administrative offices and member sites.

Key Counterparty Contacts

The following individuals at Veridian are the anticipated primary contacts for purposes of this engagement:

1. Dr. Franklin Osei, M.D., Ph.D. — President & Chief Executive Officer. Dr. Osei serves as the executive counterpart to Dr. Raghavan and is an authorized signatory for Veridian on the MCTA. Dr. Osei may participate in high-level discussions regarding the strategic framework of the agreement but is not expected to be involved in day-to-day negotiations.

2. Diane Prescott — Chief Operating Officer. Ms. Prescott is the operational counterpart to Jennifer Holt at Penterra and will likely be involved in discussions regarding operational provisions, site activation timelines, and network coordination logistics.

3. Dr. Lena Marchetti, Ph.D. — Senior Vice President, Research Administration. Dr. Marchetti oversees Veridian's research administration function and is responsible for budgetary and administrative matters relating to sponsored research agreements across the network.

4. Gregory Callahan, Esq. — Vice President, Legal & Compliance. Mr. Callahan is the legal lead for Veridian on the MCTA negotiation. He is expected to manage the legal review process on Veridian's side and to serve as the primary point of contact for counterpart communications with Calderwood & Harkness and with Veridian's outside counsel. (Note: Mr. Callahan shares a surname with the undersigned but there is no familial or personal relationship; this has been noted in the Conflict Check Memorandum.)

5. Patricia Dunne — Director, Sponsored Research Agreements. Ms. Dunne will handle the contracts negotiation at a working level on Veridian's side and will be the primary counterpart for Samantha Novak of Penterra on site-level budget and payment issues.

Counterparty Outside Counsel

Veridian has retained Whitmore, Jansen & Callahan LLP ("WJC") as its outside counsel for the MCTA negotiation. WJC's relevant personnel and contact information are as follows:

• Firm: Whitmore, Jansen & Callahan LLP, 1500 Market Street, Suite 3200, Philadelphia, Pennsylvania 19102.

• Lead Partner: Allison Whitmore. Ms. Whitmore leads WJC's Life Sciences & Research Institutions Group and is understood to have significant experience representing academic medical centers and research networks in clinical trial agreements. The engagement team should be prepared for a detailed and thorough negotiation process, as WJC has a reputation for rigorous advocacy on behalf of its institutional clients.

• Associate: David Kesselman. Mr. Kesselman is expected to handle day-to-day drafting and redlining on WJC's side.

IV. Matter Description

A. Nature of the Matter

This matter involves the negotiation, drafting, and closing of a clinical trial agreement. Specifically, the engagement encompasses the preparation and negotiation of a Master Clinical Trial Agreement ("MCTA") and associated site-network agreements between Penterra Pharmaceuticals Corp. (as Sponsor) and Veridian Health Research Network, Inc. (as Site Network) for the conduct of Protocol PPC-4871-III (the CLARION study).

The MCTA is the principal contractual instrument governing the relationship between Penterra and Veridian with respect to the CLARION trial. It will establish the overarching terms and conditions applicable to all 38 Veridian Network sites participating in the study, including but not limited to the allocation of responsibilities between Sponsor and Site Network, the financial terms and payment structure, indemnification and insurance requirements, intellectual property and data ownership, confidentiality obligations, publication rights, regulatory compliance representations, and termination and wind-down procedures. Individual Veridian Network sites will participate in the CLARION trial through the execution of site-level joinder agreements, which will incorporate the terms of the MCTA by reference and will contain site-specific details such as site budgets, investigator designations, and local regulatory approvals.

The master agreement/joinder agreement structure is standard for multi-site clinical trials conducted through organized research networks such as Veridian. This structure allows the sponsor and network to negotiate the substantive terms of the relationship once, at the master agreement level, while preserving the flexibility to address site-specific matters at the joinder agreement level. The engagement team has substantial experience with this transactional structure and anticipates that the negotiation will follow a pattern consistent with prior comparable engagements.

B. The Investigational Product and Trial

The following information describes the investigational product and clinical trial that are the subject of the MCTA. This information is drawn from publicly available sources (including ClinicalTrials.gov and Penterra's SEC filings) as well as confidential information provided by the client. It is included here to provide the engagement team with sufficient context to negotiate the clinical and scientific provisions of the MCTA effectively.

Investigational Product: Penterafenib (PPC-4871) is an oral, next-generation multi-kinase inhibitor that has been designed to selectively target multiple receptor tyrosine kinases implicated in the pathogenesis and progression of hepatocellular carcinoma (HCC). Penterafenib represents Penterra's lead clinical-stage asset and is the subject of a comprehensive development program spanning multiple clinical trials and indications.

Indication: Advanced hepatocellular carcinoma (HCC) in the second-line setting, following failure of or intolerance to prior systemic therapy. HCC is the most common form of primary liver cancer and represents a significant area of unmet medical need, particularly in the second-line setting where treatment options remain limited. The commercial opportunity for a successful therapy in this indication is substantial, which underscores the strategic importance of the CLARION trial to Penterra.

IND Number: IND 157823, filed with the United States Food and Drug Administration ("FDA") in October 2021. The IND remains in good standing, and Penterra has not received any clinical hold notices or other regulatory actions that would restrict the initiation or conduct of the CLARION trial.

Phase II Results: The Phase II portion of the penterafenib development program was completed in January 2023. The Phase II trial demonstrated an objective response rate (ORR) of 38% in patients with advanced HCC who had progressed on or were intolerant to prior systemic therapy. These results were considered sufficiently promising to support the advancement of penterafenib into the pivotal Phase III CLARION trial, and Penterra has publicly announced its intention to proceed with the Phase III program.

Protocol Number: PPC-4871-III.

Protocol Short Title: CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology.

ClinicalTrials.gov Identifier: NCT05928174.

Study Design: Phase III, randomized, double-blind, placebo-controlled, multi-center study. The double-blind, placebo-controlled design is consistent with FDA expectations for a pivotal registrational trial in oncology and will require careful attention to blinding procedures, unblinding triggers, and data safety monitoring board (DSMB) provisions in the MCTA and associated protocol documents.

Planned Enrollment: 1,200 subjects, 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 substantial enrollment target reflects the statistical powering requirements for an overall survival (OS) endpoint in an oncology trial and will drive significant per-patient costs across the 38 participating sites.

Number of Sites under MCTA: 38 Veridian Network sites located across 14 states. A complete list of participating sites will be attached as an exhibit to the executed MCTA and will be updated from time to time as additional sites are activated or existing sites are deactivated.

Projected Enrollment Period: 42 months from the date of first-patient-in (FPI) at the first activated site.

Target First Patient In (FPI): August 14, 2023. This date is a critical milestone for Penterra's development timeline and is one of the principal drivers of the engagement timeline for this matter. The MCTA and all associated agreements must be executed and all conditions precedent satisfied in sufficient time to permit site activation and initiation activities in advance of the FPI target date.

Estimated Total Study Duration: 60 months, comprising a 42-month enrollment period followed by an 18-month follow-up period for all enrolled subjects. The substantial duration of the study will require particular attention to the MCTA's provisions regarding term, renewal, amendment, and termination, as well as provisions addressing changes in law, changes in standard of care, and investigator succession.

Primary Endpoint: Overall survival (OS), defined as the time from randomization to death from any cause. OS is the gold-standard endpoint in oncology clinical trials and is the endpoint most likely to support a regulatory approval application for penterafenib.

Key Secondary Endpoints:

• Progression-free survival (PFS), defined as the time from randomization to first documented disease progression or death from any cause.

• Objective response rate (ORR), defined as the proportion of subjects achieving a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 criteria.

• Duration of response (DOR), defined as the time from first documented response to first documented disease progression or death from any cause.

C. Lead Sites and Investigators

The following lead sites and investigators have been identified for the CLARION trial. These individuals and institutions will receive particular attention in the MCTA and in the preparation of site-level and investigator-level agreements.

Lead Site: Graystone University Medical Center, located at 1200 University Avenue, Philadelphia, Pennsylvania 19104. Graystone University Medical Center is a Pennsylvania nonprofit corporation and a member of the Veridian Health Research Network. Graystone is one of the nation's leading academic medical centers in oncology research and has a long history of participation in multi-center clinical trials. The institution is led by Dr. William Corwin, M.D., who serves as President. Graystone maintains its own Institutional Review Board (the "Graystone University Institutional Review Board"), which holds IRB Registration No. IRB00012847 with the Office for Human Research Protections (OHRP). The Graystone IRB will serve as the reviewing IRB for the lead site and may serve as the IRB of record for other participating sites that elect to rely on the Graystone IRB under an IRB reliance agreement, depending on the final IRB oversight structure adopted for the trial.

Global Principal Investigator: Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center. Dr. Aldridge is a nationally recognized expert in hepatocellular carcinoma and liver cancer therapeutics and has served as principal investigator on multiple Phase II and Phase III oncology trials. Dr. Aldridge will serve as the Global Principal Investigator for the CLARION trial across all participating sites and will bear overall responsibility for the scientific and medical conduct of the study. The engagement team should give particular attention to the investigator agreement with Dr. Aldridge, including provisions regarding her responsibilities, authority, compensation, publication rights, and financial disclosure obligations under 21 C.F.R. Part 54.

Key Secondary Site: Lakemont Medical Center, located at 4400 North Michigan Drive, Chicago, Illinois 60611. Lakemont Medical Center is an Illinois nonprofit corporation and a member of the Veridian Health Research Network. Lakemont is expected to be a high-enrolling site for the CLARION trial due to its large hepatology and oncology patient populations.

Co-Principal Investigator at Lakemont: Dr. Howard Matsuoka, M.D., Associate Professor of Hepatology & Oncology at Lakemont Medical Center. Dr. Matsuoka will serve as the Co-Principal Investigator at the Lakemont site and will have primary investigator responsibility at that location. Lakemont's IRB oversight for the CLARION trial will be provided through the Veridian Central IRB, a centralized IRB operated by Veridian for its network members.

D. Estimated Deal Value

The total estimated deal value for the MCTA and associated site-network agreements is approximately $80,000,000 (eighty million dollars), covering site fees, per-patient payments, investigator grants, network coordination fees, technology integration costs, and a contingency reserve over the projected life of the CLARION trial. This figure represents the aggregate financial commitment anticipated under the MCTA and is based on current enrollment assumptions, site counts, and projected study duration.

The breakdown of the estimated deal value by component is as follows:

The per-patient site fees represent the largest single component of the deal value and will be structured as milestone-based payments tied to specific study events (e.g., informed consent, randomization, treatment visits, end-of-treatment, follow-up visits, and study completion). The detailed payment schedule and milestone definitions will be set forth in the budget exhibit to the MCTA. The engagement team should ensure that the per-patient fee structure, the investigator grant amounts, and the network coordination fees are each supported by fair market value analyses to mitigate risk under the Anti-Kickback Statute, as discussed in Section VI below.

E. Key Third-Party Service Providers (Referenced but Out of Scope)

The following third-party service providers are relevant to the CLARION trial and may be referenced in the MCTA or its exhibits. However, the agreements with these service providers are not within the scope of this engagement. They are listed here for reference and to ensure that the engagement team has a complete picture of the contractual landscape surrounding the CLARION trial.

1. Meridian Contract Research Organization, Inc. ("Meridian CRO"). Meridian is Penterra's contracted CRO for the CLARION trial, responsible for clinical monitoring, data management, safety reporting, and biostatistics. Meridian is headquartered at 9200 Corporate Boulevard, Raleigh, North Carolina 27615, and is led by CEO Thomas Hartwell. Penterra and Meridian are parties to a separate Master Services Agreement dated January 15, 2023 (the "Meridian MSA"), which governs Meridian's engagement for the CLARION trial and is not in scope for this matter. The MCTA will need to address the relationship between Penterra's CRO and the Veridian Network sites, including provisions regarding CRO monitoring visits, access to site facilities and records, and the delineation of responsibilities between the CRO and the sites.

2. Briarcliff Mutual Insurance Company. Briarcliff is Penterra's clinical trial liability and subject-injury insurer. Briarcliff is located at 55 Constitution Plaza, Hartford, Connecticut 06103. The relevant policy information is as follows:

• Policy Number: BM-CTL-2023-04182

• Policy Period: April 1, 2023 through March 31, 2024 (renewable annually)

• Per-Occurrence Limit: $25,000,000

• Aggregate Limit: $75,000,000

• Subject-Injury Sublimit: $10,000,000 per occurrence / $50,000,000 aggregate

The MCTA will contain insurance requirements that must be satisfied by Penterra as Sponsor. The engagement team should review the current Briarcliff policy to confirm that its terms, limits, and coverage scope are consistent with the insurance requirements that Veridian is expected to demand. As noted in Section VI below, Veridian may seek higher per-occurrence limits, and the engagement team should be prepared to discuss with the client whether policy amendments, endorsements, or additional coverage may be necessary to satisfy Veridian's requirements.

3. Pinnacle Data Solutions, Inc. Pinnacle is Penterra's electronic data capture (EDC) and eClinical platform vendor for the CLARION trial. Pinnacle is located at 6000 Clearwater Drive, San Diego, California 92121. The MCTA will reference Pinnacle's EDC platform in connection with data entry, electronic signatures (21 C.F.R. Part 11 compliance), and the technology integration costs included in the deal value.

4. Northbridge Bioanalytical Laboratories, Inc. Northbridge serves as the central laboratory for the CLARION trial, responsible for pharmacokinetic/pharmacodynamic (PK/PD) analyses, biomarker assessments, and safety laboratory analyses. Northbridge is located at 2900 Commerce Way, Baltimore, Maryland 21224. The MCTA will address specimen handling, shipping, chain of custody, and the responsibilities of participating sites with respect to central laboratory procedures.

5. Castleton & Hargrove LLP. Castleton & Hargrove serves as FDA regulatory counsel to Penterra and is responsible for all regulatory strategy matters relating to the penterafenib program, including IND maintenance, FDA communications, and regulatory submissions. Castleton & Hargrove is located at 1100 Connecticut Avenue NW, Suite 900, Washington, DC 20036. The lead partner for the Penterra engagement is Dr. Priya Sundaram, Esq. FDA regulatory strategy matters are expressly excluded from the scope of this engagement.

V. Governing Law

The MCTA is expected to be governed by the laws of the State of New York, without regard to its conflicts of law principles. This choice of law is consistent with Penterra's standard contractual practice for clinical trial agreements and reflects the firm's location in New York as well as the well-developed body of New York commercial contract law that provides a predictable framework for interpreting the MCTA's provisions.

The MCTA is anticipated to include a three-step escalation procedure for the resolution of disputes arising under or in connection with the agreement, as follows:

1. Designated Representative Negotiation (30 days). In the first instance, any dispute will be referred to designated senior representatives of each party (anticipated to be individuals at the Vice President level or above) for good-faith negotiation and attempted resolution. The designated representatives will have a period of thirty (30) days from the date of referral to resolve the dispute through direct negotiation.

2. Mediation (60 days). If the dispute is not resolved through designated representative negotiation within the initial 30-day period, either party may refer the dispute to mediation administered by the American Arbitration Association ("AAA") under the AAA Commercial Mediation Rules then in effect. The mediation will be conducted in New York, New York, and the parties will have a period of sixty (60) days from the commencement of mediation to resolve the dispute through the mediation process.

3. Binding Arbitration. If the dispute is not resolved through mediation within the 60-day period, either party may submit the dispute to binding arbitration in New York, New York, administered by the AAA under the AAA Commercial Arbitration Rules then in effect. The arbitration will be conducted before a panel of three (3) arbitrators, with each party selecting one arbitrator and the two party-selected arbitrators selecting the third. The arbitrators' award will be final and binding on the parties and may be entered and enforced in any court of competent jurisdiction.

Notwithstanding the foregoing dispute resolution provisions, the MCTA is expected to preserve the right of either party to seek injunctive or other equitable relief in aid of arbitration or to prevent irreparable harm. For purposes of such proceedings, the parties will be expected to submit to the exclusive jurisdiction of the state and federal courts located in New York County, New York.

The engagement team should note that the application of New York governing law to a clinical trial agreement involving research sites located across 14 states raises a number of considerations, including the interplay between New York contract law and the regulatory and institutional frameworks governing clinical research in other jurisdictions. A separate analysis memorandum addressing the implications of New York governing law for multi-state clinical trial agreements will be prepared and circulated to the engagement team in connection with the initial MCTA drafting process.

VI. Key Legal Issues Anticipated

Based on the engagement team's initial review of the matter and its experience with comparable clinical trial agreements, the following legal issues are anticipated to be significant in the negotiation of the MCTA. This list is not exhaustive and will be updated as the negotiation progresses.

1. Subject-Injury Indemnification Scope and Caps. The scope and financial limits of the Sponsor's indemnification obligations for injuries suffered by clinical trial subjects will be a central issue in the MCTA negotiation. Veridian and its network sites will seek broad indemnification from Penterra for subject injuries arising from the investigational product, while Penterra will seek to limit its indemnification exposure through per-subject and aggregate caps, exclusions for injuries caused by site negligence or protocol deviations, and appropriate notice and cooperation requirements. The engagement team should develop an indemnification framework that balances these competing interests and is consistent with the coverage limits of the Briarcliff insurance policy.

2. Allocation of Liability for Protocol Deviations. The MCTA will need to clearly allocate liability between Penterra and Veridian (and its network sites) for protocol deviations, with particular attention to the distinction between medically necessary deviations (e.g., deviations undertaken for subject safety) and unauthorized deviations (e.g., deviations resulting from investigator error or negligence). The treatment of medically necessary deviations is frequently a contentious issue in clinical trial agreement negotiations, as sponsors typically resist indemnifying sites for the consequences of deviations that were not prospectively approved by the sponsor, while sites argue that investigators must retain clinical judgment to deviate from the protocol when subject safety requires it.

3. Insurance Adequacy. Veridian may demand higher per-occurrence limits than those provided under the current Briarcliff policy (which provides $25 million per occurrence and $75 million in the aggregate). Academic medical centers and research networks commonly require per-occurrence limits of $50 million or more for Phase III oncology trials with large enrollment targets. The engagement team should confer with the client regarding the feasibility of obtaining increased policy limits or supplemental excess coverage if Veridian's insurance requirements exceed the current Briarcliff policy terms. The subject-injury sublimit of $10 million per occurrence and $50 million in the aggregate should also be evaluated in light of the trial's enrollment size and the oncology patient population.

4. Data Ownership and intellectual Property Rights. Penterra will seek to retain exclusive ownership of all clinical trial data generated in connection with the CLARION trial, consistent with its position as the IND holder and regulatory sponsor. This position is standard in the pharmaceutical industry but may be resisted by Veridian and its academic investigators, who may seek co-ownership, access, or use rights with respect to the data for academic and research purposes. The engagement team should negotiate data ownership provisions that preserve Penterra's exclusive ownership rights while providing appropriate accommodations for academic use, subject to Penterra's review and approval rights and consistent with the publication rights framework described below.

5. Investigator Publication Rights and Academic Freedom vs. Sponsor Review/Patent Protection. The tension between investigators' academic freedom and desire to publish clinical trial results, on the one hand, and the sponsor's interest in reviewing proposed publications for accuracy, patent protection, and confidentiality, on the other hand, is a recurring issue in clinical trial agreements with academic institutions. Veridian will likely insist on publication rights for its investigators, including the right to publish individual site results as well as multi-center results, subject to a reasonable review period for the sponsor. The engagement team should draft publication provisions that grant investigators a right to publish subject to: (a) a review period of no less than 60 days (with the possibility of an additional 30-day extension for patent filing purposes); (b) removal of Penterra confidential information; and (c) review for scientific accuracy.

6. Termination Provisions and Wind-Down Period for Subject Safety. The MCTA must contain robust termination provisions that address both for-cause and without-cause termination, as well as termination due to safety concerns, regulatory action, or force majeure events. Of particular importance are the wind-down provisions that will apply following termination, including obligations to continue treating enrolled subjects through an appropriate transition period, data transfer and lock procedures, and the financial obligations of the parties during the wind-down period. Subject safety during the wind-down period is a non-negotiable priority for both parties and for regulatory compliance.

7. Regulatory Compliance Frameworks. The MCTA must address compliance with a number of federal and state regulatory frameworks, including but not limited to:

• The Federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)) and the safe harbor regulations thereunder, with particular attention to the fair market value of all payments to investigators and sites;

• The Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h) and the CMS Open Payments reporting requirements, including Penterra's obligations to report payments to covered recipients;

• The Health Insurance Portability and Accountability Act of 1996 ("HIPAA") and its implementing regulations (45 C.F.R. Parts 160 and 164), including the Privacy Rule and the Security Rule, with particular attention to the handling of protected health information (PHI) in connection with clinical trial data;

• FDA regulations at 21 C.F.R. Part 11 (Electronic Records; Electronic Signatures), 21 C.F.R. Part 50 (Protection of Human Subjects), 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators), 21 C.F.R. Part 56 (Institutional Review Boards), and 21 C.F.R. Part 312 (Investigational New Drug Application);

• The International Council for Harmonisation (ICH) E6(R2) Guideline for Good Clinical Practice (GCP), which sets forth the international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials.

8. Fair Market Value of Investigator Compensation and Site Payments. As noted above, all payments to investigators and sites under the MCTA must be established at fair market value to mitigate risk under the Anti-Kickback Statute. The engagement team should coordinate with Penterra to obtain or commission a fair market value assessment of all payment components, including per-patient fees, start-up fees, maintenance fees, investigator grants, and any other compensation provided to investigators or sites in connection with the CLARION trial.

9. IRB Oversight Structure. The MCTA negotiation will need to address the IRB oversight structure for the CLARION trial, including the use of the Graystone University Institutional Review Board and the Veridian Central IRB. The parties will need to determine whether the trial will use a single central IRB for all participating sites (with individual sites entering into IRB reliance agreements) or whether some sites will maintain their own IRB oversight. The adoption of the 2018 Revised Common Rule (45 C.F.R. Part 46), which requires single-IRB review for federally funded multi-site research, may inform but does not mandate the IRB structure for this industry-sponsored trial. The engagement team should prepare an analysis of the available IRB oversight models and their legal and practical implications.

10. Confidentiality. The MCTA is expected to include a confidentiality provision with a term of ten (10) years, which is standard for clinical trial agreements in the pharmaceutical industry. The confidentiality provisions will need to address the definition of confidential information, permitted disclosures (including disclosures required by law, regulation, or court order, and disclosures in connection with regulatory submissions), return and destruction of confidential information, and remedies for breach. The interaction between the confidentiality provisions and the publication rights provisions will require careful coordination.

11. Safety Reporting Procedures. The MCTA will establish the safety reporting obligations of the parties, including: (a) reporting of serious adverse events (SAEs) by investigators to the sponsor within 24 hours of awareness; (b) the sponsor's obligations with respect to IND safety reports to the FDA on 7-day timelines (for fatal or life-threatening unexpected suspected adverse reactions) and 15-day timelines (for other serious and unexpected suspected adverse reactions); and (c) distribution of safety information to investigators, IRBs, and regulatory authorities. The safety reporting provisions must be consistent with 21 C.F.R. § 312.32 and ICH E6(R2) requirements.

12. Site Document Retention. The MCTA will establish document retention requirements for participating sites. The current expectation is that sites will be required to retain all study-related documents for a minimum of fifteen (15) years following the completion of the study. This retention period exceeds the FDA's minimum requirements under 21 C.F.R. § 312.62 and is consistent with Penterra's standard contractual practice and the extended timelines associated with post-marketing surveillance and potential regulatory actions.

VII. Engagement Team

The following attorneys and professional staff of Calderwood & Harkness LLP are assigned to this engagement.

Responsible Partner: Miriam Calloway, Partner, Healthcare & Life Sciences Practice Group. Ms. Calloway will serve as the Responsible Partner for the engagement, with overall responsibility for the quality and timeliness of all work product, the management of the client relationship, and the supervision of all attorneys working on the matter. Ms. Calloway is located at the firm's New York office at 280 Park Avenue, 34th Floor, New York, New York 10017.

Billing Partner: Joel Strauss, Partner, Healthcare & Life Sciences Practice Group. Mr. Strauss will serve as the Billing Partner for the engagement and will be responsible for billing administration, fee estimates, and client communications regarding fees and expenses. Mr. Strauss is also located at the firm's New York office at 280 Park Avenue, 34th Floor, New York, New York 10017. Mr. Strauss brings substantial experience in clinical trial agreements for oncology programs and will be available to assist with substantive issues as needed.

Lead Associate: Sean Morrissey, Associate, Healthcare & Life Sciences Practice Group. Mr. Morrissey will serve as the Lead Associate on the engagement, with primary responsibility for drafting the MCTA and all associated agreements and exhibits, managing the day-to-day workflow, and serving as the principal point of contact with counterparty counsel for document exchanges and negotiation sessions. Mr. Morrissey has significant experience in clinical trial agreement transactions and has worked on prior matters involving academic research networks.

Working Associate: Christopher Aiken, Associate, Healthcare & Life Sciences Practice Group. Mr. Aiken will support Mr. Morrissey in the drafting and negotiation process, with particular responsibility for regulatory compliance analysis, fair market value analysis, and the preparation of ancillary documents including site joinder agreements, investigator agreements, and closing deliverables.

Additional Resources: The firm's Princeton office, located at 101 Carnegie Center, Suite 500, Princeton, New Jersey 08540, is available for in-person meetings with the client given Penterra's headquarters location in Princeton. The engagement team anticipates that certain meetings with Penterra's in-house team may be held at the Princeton office for the convenience of the client. Conference facilities and videoconferencing capabilities are available at both the New York and Princeton locations.

Detailed staffing plans and budget estimates for the engagement will be addressed in a separate Staffing & Budget Estimate Memorandum, which will be prepared and circulated to the Responsible Partner and Billing Partner for review and approval prior to submission to the client.

VIII. Projected Timeline and Key Milestones

The following timeline sets forth the key milestones and target dates for the engagement. These dates are based on the client's stated objective of achieving a target first-patient-in (FPI) date of August 14, 2023, and reflect the engagement team's assessment of a realistic but aggressive schedule for the negotiation and closing of the MCTA.

The engagement team notes that the period between the target MCTA execution date (late June 2023) and the target FPI date (August 14, 2023) is approximately six to seven weeks, which is a compressed timeline for the completion of all closing conditions, site activation procedures, and pre-study initiation activities. The team will work closely with the client and with Veridian to identify and address any potential impediments to timely closing and site activation as early as possible in the negotiation process.

The projected study completion date of August 2028 reflects the anticipated total study duration of 60 months (42-month enrollment period plus 18-month follow-up period). While the engagement team's active involvement in the matter is expected to be concentrated in the period from March through July 2023 (covering the drafting, negotiation, and closing phases), the team should be available for post-closing support as needed throughout the life of the trial, including support for MCTA amendments, site additions or removals, protocol amendments, dispute resolution, and any other matters arising under the MCTA.

IX. Scope of Representation

The scope of Calderwood & Harkness's representation of Penterra in this matter encompasses the following work streams and deliverables:

1. Master Clinical Trial Agreement. Drafting and negotiation of the Master Clinical Trial Agreement between Penterra (as Sponsor) and Veridian (as Site Network), including all substantive terms and conditions governing the conduct of the CLARION trial across the 38 participating Veridian Network sites.

2. MCTA Exhibits and Schedules. Drafting of all exhibits and schedules to the MCTA, which are anticipated to include the following:

(a) Protocol Synopsis (Exhibit A);

(b) Budget and Payment Schedule (Exhibit B);

(d) Subject-Injury Indemnification Provisions (Exhibit D);

(e) Insurance Requirements (Exhibit E);

(f) Confidentiality and Data Protection Provisions (Exhibit F);

(g) intellectual Property and Publication Rights (Exhibit G);

(h) Regulatory Compliance Representations and Warranties (Exhibit H);

(i) Investigator Undertaking Form (Exhibit I);

(j) Safety Reporting Procedures (Exhibit J);

(k) Approved Subcontractors List (Exhibit K);

(l) List of Participating Sites (Exhibit L).

3. Site Joinder Agreements. Preparation of individual site agreements (joinder agreements) for each of the 38 Veridian Network sites, incorporating the terms of the MCTA by reference and containing site-specific information including local budgets, investigator designations, and local regulatory approvals.

4. Principal Investigator and Co-Principal Investigator Agreements. Preparation of investigator-level agreements for Dr. Catherine Aldridge (Global Principal Investigator) and Dr. Howard Matsuoka (Co-Principal Investigator at Lakemont Medical Center), as well as template investigator agreements for use at other participating sites.

5. intellectual Property Side Letter. Negotiation and execution of an intellectual property side letter addressing any matters not covered by the IP provisions of the MCTA, including any pre-existing IP rights of the investigators or Veridian Network sites, background IP, and any specific inventions or discoveries that may arise during the conduct of the CLARION trial.

6. Closing Deliverables. Preparation of all closing deliverables required for the MCTA closing, including closing certificates, secretary's certificates (certifying organizational authority), officer's certificates (certifying representations and warranties), and any other instruments required to satisfy the conditions precedent to the effectiveness of the MCTA.

7. Insurance Coordination. Coordination with Penterra's insurance broker and with Briarcliff Mutual Insurance Company regarding additional insured endorsement requests, certificate of insurance exchanges, and any policy amendments or supplemental coverage that may be required to satisfy Veridian's insurance requirements under the MCTA.

8. Regulatory Compliance Analysis Memoranda. Preparation of one or more legal memoranda analyzing the regulatory compliance implications of the MCTA and the CLARION trial, including analysis under the Anti-Kickback Statute, the Physician Payments Sunshine Act / Open Payments, HIPAA (45 C.F.R. Parts 160 and 164), and the FDA financial disclosure requirements under 21 C.F.R. Part 54.

9. Fair Market Value Analysis. Preparation or coordination of a fair market value analysis for investigator compensation and site payment amounts under the MCTA, to support compliance with the Anti-Kickback Statute and applicable safe harbor provisions.

10. IRB Reliance / Central IRB Structure Analysis. Analysis of the available IRB oversight models for the CLARION trial, including the use of the Graystone University IRB, the Veridian Central IRB, and individual site IRBs, and preparation of recommendations regarding the optimal IRB oversight structure.

Matters Not in Scope

The following matters are expressly excluded from the scope of this engagement and are being handled by other counsel or advisors:

• CRO Agreement. The Master Services Agreement with Meridian Contract Research Organization, Inc. (dated January 15, 2023) is separately handled and is not within the scope of this engagement.

• FDA Regulatory Strategy. All matters relating to FDA regulatory strategy for penterafenib, including IND maintenance, FDA communications, and regulatory submissions, are handled by Castleton & Hargrove LLP and are not within the scope of this engagement.

• Financial Advisory Matters. Financial advisory matters relating to Penterra are handled by Ridgeline Capital Markets LLC and are not within the scope of this engagement.

• Audit Matters. Audit and accounting matters relating to Penterra are handled by Townsend Independent Auditors LLP and are not within the scope of this engagement.

X. Administrative Information

The following administrative information is recorded for the purpose of matter management and firm operations.

Document Management: All documents generated or received in connection with this matter are to be filed under Matter No. 1018-00004 in the firm's document management system. Team members should follow the firm's standard document naming conventions and filing protocols. All privileged and confidential documents should be appropriately marked.

Retention Notes: Document retention for this matter shall be governed by the firm's standard document retention policy as well as any specific instructions received from the client. The engagement team should note that clinical trial site records are subject to a minimum retention period of fifteen (15) years following the completion of the study, as discussed in Section VI above. While the firm's retention obligations with respect to its own work product may differ from the site-level retention requirements, the team should be aware of the extended retention expectations and should coordinate with the client regarding any specific retention instructions applicable to the firm's files.

XI. Distribution

This memorandum is designated for internal distribution only within Calderwood & Harkness LLP. It is not to be provided to the client, counterparty, or any third party without the prior written authorization of the Responsible Partner.

Internal Distribution:

• Miriam Calloway, Partner

• Joel Strauss, Partner

• Sean Morrissey, Associate

• Christopher Aiken, Associate

Copy to File: Matter No. 1018-00004.

PREPARED BY:

________________________________________

Miriam Calloway Partner, Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 280 Park Avenue, 34th Floor New York, New York 10017

Date: March 20, 2023

CONFIDENTIAL — ATTORNEY WORK PRODUCT — PRIVILEGED AND CONFIDENTIAL This memorandum has been prepared by Calderwood & Harkness LLP for internal use in connection with Matter No. 1018-00004. It is protected by the attorney-client privilege and the work product doctrine. Unauthorized reproduction, distribution, or disclosure of this memorandum or its contents is strictly prohibited.

Metric	Value
Market Capitalization (Q1 2023)	Approximately $4.2 billion
FY2022 Total Revenue	$1.87 billion
FY2022 Research & Development Expenditure	$612 million
Cash and Cash Equivalents (Q1 2023)	$890 million
Component	Unit Cost	Units	Subtotal
Per-patient site fees (screen-to-completion)	$52,000/subject	1,200 subjects	$62,400,000
Start-up fees	$75,000/site	38 sites	$2,850,000
Annual site maintenance fees	$40,000/site/year	38 sites × 3.5 years (avg.)	$5,320,000
Investigator grants (publication & academic support)	—	—	$1,500,000
Network coordination/administrative fee to Veridian central	$300,000/quarter	14 quarters	$4,200,000
Technology/EDC integration costs (Pinnacle Data Solutions)	—	—	$1,230,000
Contingency/change order reserve	—	—	$2,500,000
Total	$80,000,000
Milestone	Target Date
Matter Opened	March 20, 2023
Target First Draft MCTA Circulation (to client for review)	Early April 2023 (target: April 7, 2023)
Anticipated Negotiation Period (with Veridian/WJC)	April – June 2023
Target Execution / Signing Date (MCTA)	Late June 2023
Conditions Precedent / Closing (delivery of insurance certificates, IRB approvals for lead sites, executed investigator signature pages)	Early July 2023
Target Effective Date (MCTA)	Mid-July 2023
Target First Patient In (FPI)	August 14, 2023
Projected Last Patient In	February 2027
Projected Study Completion	August 2028
Field	Detail

Matter Number	1018-00004
Client Number	Per firm internal records — Penterra Pharmaceuticals Corp.
Practice Group	Healthcare & Life Sciences
Primary Office	New York (280 Park Avenue, 34th Floor, New York, NY 10017)
Secondary Office	Princeton (101 Carnegie Center, Suite 500, Princeton, NJ 08540) — available for client meetings
Billing Arrangement	Per engagement letter dated March 20, 2023; hourly rates as set forth therein
Conflicts Cleared	March 20, 2023 (see separate Conflict Check Memorandum)

MEMORANDUM — CONFIDENTIAL / ATTORNEY WORK PRODUCT
CALDERWOOD & HARKNESS LLP 280 Park Avenue, 34th Floor New York, New York 10017
Date: March 20, 2023
To: File — Matter No. 1018-00004
From: Miriam Calloway, Partner, Healthcare & Life Sciences Practice Group
Re: Matter Opening — Penterra Pharmaceuticals Corp. / Veridian Health Research Network, Inc. — Master Clinical Trial Agreement and Site-Network Agreements for Protocol PPC-4871-III (CLARION)
Classification: Internal / Privileged and Confidential
This memorandum is protected by the attorney-client privilege and the work product doctrine. It is intended solely for internal use by the attorneys and professional staff of Calderwood & Harkness LLP assigned to Matter No. 1018-00004. This memorandum and its contents should not be disclosed to any person outside the firm without the prior written authorization of the undersigned.
I. Purpose
This memorandum formally opens Matter No. 1018-00004 in the firm's matter management system and establishes the foundational record for the engagement described herein. Its purpose is to document the key facts, parties, transaction parameters, legal issues, engagement team composition, and anticipated timeline relevant to the matter so that all team members and firm administrative personnel have a consolidated reference document from which to work.
Calderwood & Harkness LLP has been retained by Penterra Pharmaceuticals Corp. ("Penterra" or "PPC") to represent the company as outside counsel in the negotiation, drafting, and finalization of a Master Clinical Trial Agreement ("MCTA") and associated site-network agreements with Veridian Health Research Network, Inc. ("Veridian" or "VHRN"). The engagement encompasses the full lifecycle of the transactional documents, from initial drafting through execution, closing, and delivery of all ancillary instruments, as more fully described in Section IX below.
The engagement arises from Penterra's planned Phase III multi-center clinical trial for its lead investigational compound penterafenib (PPC-4871), an oral next-generation multi-kinase inhibitor being developed for the treatment of advanced hepatocellular carcinoma (HCC) in the second-line setting. The Phase III trial, conducted under Protocol PPC-4871-III and bearing the short title "CLARION" (Clinical Assessment of Response with Longitudinal Investigation in ONcology), represents a pivotal registrational study and a critical milestone in Penterra's clinical development program for penterafenib. Veridian operates a research network of 38 academic medical centers across 14 states, all of which are anticipated to serve as clinical trial sites under the MCTA.
The engagement was confirmed by Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs at Penterra, who serves as the day-to-day legal contact for the MCTA negotiation. Ms. Liang's authorization to retain the firm was given with the express approval and authorization of Nathaniel Briggs, Esq., Vice President and General Counsel of Penterra, who will serve as the senior legal officer with oversight responsibility for the engagement on the client side.
The formal engagement letter was executed as of March 20, 2023. The retainer acknowledgment is pending countersignature from Penterra; Ms. Liang has indicated that countersignature will be forthcoming within approximately five business days following internal processing by Penterra's finance department. Upon receipt of the executed retainer acknowledgment, a copy will be placed in the matter file.
A comprehensive conflict check has been completed and cleared as of March 20, 2023. The results of that check, including all identified relationships and the basis for clearance, are documented in a separate Conflict Check Memorandum filed concurrently with this matter opening memorandum. No conflicts of interest or potential conflicts requiring client waiver were identified.
II. Client Information
The following information summarizes the key facts regarding the client for purposes of this engagement.
Full Legal Name: Penterra Pharmaceuticals Corp.
Short Names / Abbreviations Used in this Memorandum and Related Correspondence: Penterra; PPC.
Entity Type: Corporation, incorporated under the laws of the State of Delaware. Penterra was originally incorporated in Delaware in 2009 and has maintained its domicile in that jurisdiction since its founding. The company is in good standing with the Delaware Secretary of State as of the date of this memorandum.
Publicly Traded: Yes. Penterra's common stock is listed on the Nasdaq Global Select Market under the ticker symbol PTRA. As a Nasdaq-listed issuer, Penterra is subject to the periodic reporting requirements of the Securities Exchange Act of 1934, as amended, and the rules and regulations of the U.S. Securities and Exchange Commission ("SEC"). This status is relevant to the matter insofar as certain provisions of the MCTA (including confidentiality, publication rights, and material contract disclosure) may implicate Penterra's SEC disclosure obligations.
Headquarters: 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540. The Princeton headquarters serves as the company's principal executive office and houses its legal, clinical development, and corporate affairs functions.
Registered Agent in Delaware: Capitol Registered Agents, LLC, 1209 Orange Street, Wilmington, Delaware 19801.
Key Financial Data
The following financial data points are provided for context and for the purpose of assessing the materiality of the MCTA and related agreements to Penterra's overall financial position:
Given the total estimated deal value of approximately $80 million (as detailed in Section IV.D below), the MCTA represents a significant but not individually material commitment relative to Penterra's overall financial position, its annual R&D expenditure, or its current cash reserves. Nonetheless, the CLARION trial is understood to be a pivotal registrational study for penterafenib, and the successful prosecution of this trial is material to Penterra's long-term pipeline value and corporate strategy. The engagement team should be mindful of the potential for disclosure implications and should coordinate with Ms. Liang regarding any public disclosure requirements that may arise in connection with the execution of the MCTA.
Primary Client Contacts
The following individuals at Penterra are the primary points of contact for purposes of this engagement:
1.  Nathaniel Briggs, Esq. — Vice President & General Counsel. Mr. Briggs exercises overall legal oversight over the MCTA negotiation and serves as an authorized signatory for Penterra on the executed agreement. Communications with Mr. Briggs should generally be routed through Ms. Liang unless the matter warrants direct escalation. Mr. Briggs's office is located at Penterra's Princeton headquarters.
2.  Rebecca Liang, Esq. — Associate General Counsel, Clinical Affairs. Ms. Liang is the day-to-day legal contact for all matters relating to the MCTA negotiation and drafting. She will serve as the principal liaison between Penterra's in-house legal team and Calderwood & Harkness on all aspects of this engagement. Ms. Liang has extensive experience in clinical trial agreements and has worked with Veridian on prior transactions in connection with Penterra's earlier-stage clinical programs. All initial communications, document circulations, and negotiation updates should be directed to Ms. Liang.
3.  Samantha Novak — Director, Clinical Contracts. Ms. Novak oversees contracts administration within Penterra's clinical operations function and will be responsible for the operational aspects of MCTA implementation, including site-level joinder agreements, budget negotiations at the site level, and coordination with Penterra's contract research organization. Ms. Novak's involvement will become more significant during the site-level agreement phase following execution of the master agreement.
Other Relevant Penterra Personnel
In addition to the primary contacts listed above, the following individuals at Penterra are relevant to the engagement and may participate in meetings, calls, or communications from time to time:
•  Dr. Anand Raghavan, M.D., Ph.D. — Chief Executive Officer. Dr. Raghavan serves as the executive sponsor of the CLARION trial and is an authorized signatory for Penterra on the MCTA. His involvement will likely be limited to executive-level discussions and final signing.
•  Dr. Elaine Whitford, M.D. — Chief Medical Officer. Dr. Whitford has medical oversight responsibility for the CLARION trial and will be involved in discussions relating to protocol-related provisions of the MCTA, including subject-injury indemnification, safety reporting, and protocol deviation liability allocation.
•  Dr. Marcus Yun, M.D., M.P.H. — Senior Vice President, Clinical Development. Dr. Yun is the clinical development lead for the penterafenib program and may participate in discussions regarding the protocol synopsis, enrollment timelines, and site selection criteria.
•  Jennifer Holt — Vice President, Clinical Operations. Ms. Holt is the operational lead for the CLARION trial and is responsible for day-to-day trial management, site activation, and coordination with Meridian CRO. She will be a key operational contact during the negotiation of site start-up, payment schedules, and operational provisions of the MCTA.
III. Counterparty Information
The following information summarizes the key facts regarding the counterparty to the MCTA.
Full Legal Name: Veridian Health Research Network, Inc.
Short Names / Abbreviations Used in this Memorandum and Related Correspondence: Veridian; VHRN.
Entity Type: Corporation, incorporated under the laws of the State of Delaware. Veridian is organized and operates as a tax-exempt organization under Section 501(c)(3) of the Internal Revenue Code. Veridian's tax-exempt status is relevant to the engagement in several respects, including the applicability of unrelated business income tax (UBIT) considerations for certain types of payments, the structural requirements of Veridian's organizational documents (which may impose restrictions on the scope of contractual commitments and indemnification obligations), and the generally more conservative negotiating posture that tax-exempt research networks typically adopt with respect to liability exposure.
Headquarters: 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104.
Employer Identification Number (EIN): 23-4178205.
Network Size: Veridian operates a research network comprising 38 academic medical centers and affiliated research institutions located across 14 states. The network is understood to include a mix of university-affiliated hospitals, independent academic medical centers, and research institutes, all of which have executed network participation agreements with Veridian granting Veridian authority to negotiate and enter into clinical trial agreements on behalf of the network. The scope and terms of Veridian's authority to bind individual network sites will be a key diligence point in the MCTA negotiation, and the engagement team should request and review copies of Veridian's standard network participation agreement and any relevant delegation-of-authority documentation.
Annual Research Volume: Veridian reports that its network conducts approximately $1.4 billion in sponsored research annually across all therapeutic areas and study phases. This figure positions Veridian as one of the larger academic research networks in the United States and reflects a substantial level of institutional experience with clinical trial agreements, regulatory compliance, and multi-site coordination.
Employees: Approximately 6,200 employees across the network's central administrative offices and member sites.
Key Counterparty Contacts
The following individuals at Veridian are the anticipated primary contacts for purposes of this engagement:
1.  Dr. Franklin Osei, M.D., Ph.D. — President & Chief Executive Officer. Dr. Osei serves as the executive counterpart to Dr. Raghavan and is an authorized signatory for Veridian on the MCTA. Dr. Osei may participate in high-level discussions regarding the strategic framework of the agreement but is not expected to be involved in day-to-day negotiations.
2.  Diane Prescott — Chief Operating Officer. Ms. Prescott is the operational counterpart to Jennifer Holt at Penterra and will likely be involved in discussions regarding operational provisions, site activation timelines, and network coordination logistics.
3.  Dr. Lena Marchetti, Ph.D. — Senior Vice President, Research Administration. Dr. Marchetti oversees Veridian's research administration function and is responsible for budgetary and administrative matters relating to sponsored research agreements across the network.
4.  Gregory Callahan, Esq. — Vice President, Legal & Compliance. Mr. Callahan is the legal lead for Veridian on the MCTA negotiation. He is expected to manage the legal review process on Veridian's side and to serve as the primary point of contact for counterpart communications with Calderwood & Harkness and with Veridian's outside counsel. (Note: Mr. Callahan shares a surname with the undersigned but there is no familial or personal relationship; this has been noted in the Conflict Check Memorandum.)
5.  Patricia Dunne — Director, Sponsored Research Agreements. Ms. Dunne will handle the contracts negotiation at a working level on Veridian's side and will be the primary counterpart for Samantha Novak of Penterra on site-level budget and payment issues.
Counterparty Outside Counsel
Veridian has retained Whitmore, Jansen & Callahan LLP ("WJC") as its outside counsel for the MCTA negotiation. WJC's relevant personnel and contact information are as follows:
•  Firm: Whitmore, Jansen & Callahan LLP, 1500 Market Street, Suite 3200, Philadelphia, Pennsylvania 19102.
•  Lead Partner: Allison Whitmore. Ms. Whitmore leads WJC's Life Sciences & Research Institutions Group and is understood to have significant experience representing academic medical centers and research networks in clinical trial agreements. The engagement team should be prepared for a detailed and thorough negotiation process, as WJC has a reputation for rigorous advocacy on behalf of its institutional clients.
•  Associate: David Kesselman. Mr. Kesselman is expected to handle day-to-day drafting and redlining on WJC's side.
IV. Matter Description
A. Nature of the Matter
This matter involves the negotiation, drafting, and closing of a clinical trial agreement. Specifically, the engagement encompasses the preparation and negotiation of a Master Clinical Trial Agreement ("MCTA") and associated site-network agreements between Penterra Pharmaceuticals Corp. (as Sponsor) and Veridian Health Research Network, Inc. (as Site Network) for the conduct of Protocol PPC-4871-III (the CLARION study).
The MCTA is the principal contractual instrument governing the relationship between Penterra and Veridian with respect to the CLARION trial. It will establish the overarching terms and conditions applicable to all 38 Veridian Network sites participating in the study, including but not limited to the allocation of responsibilities between Sponsor and Site Network, the financial terms and payment structure, indemnification and insurance requirements, intellectual property and data ownership, confidentiality obligations, publication rights, regulatory compliance representations, and termination and wind-down procedures. Individual Veridian Network sites will participate in the CLARION trial through the execution of site-level joinder agreements, which will incorporate the terms of the MCTA by reference and will contain site-specific details such as site budgets, investigator designations, and local regulatory approvals.
The master agreement/joinder agreement structure is standard for multi-site clinical trials conducted through organized research networks such as Veridian. This structure allows the sponsor and network to negotiate the substantive terms of the relationship once, at the master agreement level, while preserving the flexibility to address site-specific matters at the joinder agreement level. The engagement team has substantial experience with this transactional structure and anticipates that the negotiation will follow a pattern consistent with prior comparable engagements.
B. The Investigational Product and Trial
The following information describes the investigational product and clinical trial that are the subject of the MCTA. This information is drawn from publicly available sources (including ClinicalTrials.gov and Penterra's SEC filings) as well as confidential information provided by the client. It is included here to provide the engagement team with sufficient context to negotiate the clinical and scientific provisions of the MCTA effectively.
Investigational Product: Penterafenib (PPC-4871) is an oral, next-generation multi-kinase inhibitor that has been designed to selectively target multiple receptor tyrosine kinases implicated in the pathogenesis and progression of hepatocellular carcinoma (HCC). Penterafenib represents Penterra's lead clinical-stage asset and is the subject of a comprehensive development program spanning multiple clinical trials and indications.
Indication: Advanced hepatocellular carcinoma (HCC) in the second-line setting, following failure of or intolerance to prior systemic therapy. HCC is the most common form of primary liver cancer and represents a significant area of unmet medical need, particularly in the second-line setting where treatment options remain limited. The commercial opportunity for a successful therapy in this indication is substantial, which underscores the strategic importance of the CLARION trial to Penterra.
IND Number: IND 157823, filed with the United States Food and Drug Administration ("FDA") in October 2021. The IND remains in good standing, and Penterra has not received any clinical hold notices or other regulatory actions that would restrict the initiation or conduct of the CLARION trial.
Phase II Results: The Phase II portion of the penterafenib development program was completed in January 2023. The Phase II trial demonstrated an objective response rate (ORR) of 38% in patients with advanced HCC who had progressed on or were intolerant to prior systemic therapy. These results were considered sufficiently promising to support the advancement of penterafenib into the pivotal Phase III CLARION trial, and Penterra has publicly announced its intention to proceed with the Phase III program.
Protocol Number: PPC-4871-III.
Protocol Short Title: CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology.
ClinicalTrials.gov Identifier: NCT05928174.
Study Design: Phase III, randomized, double-blind, placebo-controlled, multi-center study. The double-blind, placebo-controlled design is consistent with FDA expectations for a pivotal registrational trial in oncology and will require careful attention to blinding procedures, unblinding triggers, and data safety monitoring board (DSMB) provisions in the MCTA and associated protocol documents.
Planned Enrollment: 1,200 subjects, 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 substantial enrollment target reflects the statistical powering requirements for an overall survival (OS) endpoint in an oncology trial and will drive significant per-patient costs across the 38 participating sites.
Number of Sites under MCTA: 38 Veridian Network sites located across 14 states. A complete list of participating sites will be attached as an exhibit to the executed MCTA and will be updated from time to time as additional sites are activated or existing sites are deactivated.
Projected Enrollment Period: 42 months from the date of first-patient-in (FPI) at the first activated site.
Target First Patient In (FPI): August 14, 2023. This date is a critical milestone for Penterra's development timeline and is one of the principal drivers of the engagement timeline for this matter. The MCTA and all associated agreements must be executed and all conditions precedent satisfied in sufficient time to permit site activation and initiation activities in advance of the FPI target date.
Estimated Total Study Duration: 60 months, comprising a 42-month enrollment period followed by an 18-month follow-up period for all enrolled subjects. The substantial duration of the study will require particular attention to the MCTA's provisions regarding term, renewal, amendment, and termination, as well as provisions addressing changes in law, changes in standard of care, and investigator succession.
Primary Endpoint: Overall survival (OS), defined as the time from randomization to death from any cause. OS is the gold-standard endpoint in oncology clinical trials and is the endpoint most likely to support a regulatory approval application for penterafenib.
Key Secondary Endpoints:
•  Progression-free survival (PFS), defined as the time from randomization to first documented disease progression or death from any cause.
•  Objective response rate (ORR), defined as the proportion of subjects achieving a confirmed complete response (CR) or partial response (PR) per RECIST v1.1 criteria.
•  Duration of response (DOR), defined as the time from first documented response to first documented disease progression or death from any cause.
C. Lead Sites and Investigators
The following lead sites and investigators have been identified for the CLARION trial. These individuals and institutions will receive particular attention in the MCTA and in the preparation of site-level and investigator-level agreements.
Lead Site: Graystone University Medical Center, located at 1200 University Avenue, Philadelphia, Pennsylvania 19104. Graystone University Medical Center is a Pennsylvania nonprofit corporation and a member of the Veridian Health Research Network. Graystone is one of the nation's leading academic medical centers in oncology research and has a long history of participation in multi-center clinical trials. The institution is led by Dr. William Corwin, M.D., who serves as President. Graystone maintains its own Institutional Review Board (the "Graystone University Institutional Review Board"), which holds IRB Registration No. IRB00012847 with the Office for Human Research Protections (OHRP). The Graystone IRB will serve as the reviewing IRB for the lead site and may serve as the IRB of record for other participating sites that elect to rely on the Graystone IRB under an IRB reliance agreement, depending on the final IRB oversight structure adopted for the trial.
Global Principal Investigator: Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center. Dr. Aldridge is a nationally recognized expert in hepatocellular carcinoma and liver cancer therapeutics and has served as principal investigator on multiple Phase II and Phase III oncology trials. Dr. Aldridge will serve as the Global Principal Investigator for the CLARION trial across all participating sites and will bear overall responsibility for the scientific and medical conduct of the study. The engagement team should give particular attention to the investigator agreement with Dr. Aldridge, including provisions regarding her responsibilities, authority, compensation, publication rights, and financial disclosure obligations under 21 C.F.R. Part 54.
Key Secondary Site: Lakemont Medical Center, located at 4400 North Michigan Drive, Chicago, Illinois 60611. Lakemont Medical Center is an Illinois nonprofit corporation and a member of the Veridian Health Research Network. Lakemont is expected to be a high-enrolling site for the CLARION trial due to its large hepatology and oncology patient populations.
Co-Principal Investigator at Lakemont: Dr. Howard Matsuoka, M.D., Associate Professor of Hepatology & Oncology at Lakemont Medical Center. Dr. Matsuoka will serve as the Co-Principal Investigator at the Lakemont site and will have primary investigator responsibility at that location. Lakemont's IRB oversight for the CLARION trial will be provided through the Veridian Central IRB, a centralized IRB operated by Veridian for its network members.
D. Estimated Deal Value
The total estimated deal value for the MCTA and associated site-network agreements is approximately $80,000,000 (eighty million dollars), covering site fees, per-patient payments, investigator grants, network coordination fees, technology integration costs, and a contingency reserve over the projected life of the CLARION trial. This figure represents the aggregate financial commitment anticipated under the MCTA and is based on current enrollment assumptions, site counts, and projected study duration.
The breakdown of the estimated deal value by component is as follows:
The per-patient site fees represent the largest single component of the deal value and will be structured as milestone-based payments tied to specific study events (e.g., informed consent, randomization, treatment visits, end-of-treatment, follow-up visits, and study completion). The detailed payment schedule and milestone definitions will be set forth in the budget exhibit to the MCTA. The engagement team should ensure that the per-patient fee structure, the investigator grant amounts, and the network coordination fees are each supported by fair market value analyses to mitigate risk under the Anti-Kickback Statute, as discussed in Section VI below.
E. Key Third-Party Service Providers (Referenced but Out of Scope)
The following third-party service providers are relevant to the CLARION trial and may be referenced in the MCTA or its exhibits. However, the agreements with these service providers are not within the scope of this engagement. They are listed here for reference and to ensure that the engagement team has a complete picture of the contractual landscape surrounding the CLARION trial.
1.  Meridian Contract Research Organization, Inc. ("Meridian CRO"). Meridian is Penterra's contracted CRO for the CLARION trial, responsible for clinical monitoring, data management, safety reporting, and biostatistics. Meridian is headquartered at 9200 Corporate Boulevard, Raleigh, North Carolina 27615, and is led by CEO Thomas Hartwell. Penterra and Meridian are parties to a separate Master Services Agreement dated January 15, 2023 (the "Meridian MSA"), which governs Meridian's engagement for the CLARION trial and is not in scope for this matter. The MCTA will need to address the relationship between Penterra's CRO and the Veridian Network sites, including provisions regarding CRO monitoring visits, access to site facilities and records, and the delineation of responsibilities between the CRO and the sites.
2.  Briarcliff Mutual Insurance Company. Briarcliff is Penterra's clinical trial liability and subject-injury insurer. Briarcliff is located at 55 Constitution Plaza, Hartford, Connecticut 06103. The relevant policy information is as follows:
•  Policy Number: BM-CTL-2023-04182
•  Policy Period: April 1, 2023 through March 31, 2024 (renewable annually)
•  Per-Occurrence Limit: $25,000,000
•  Aggregate Limit: $75,000,000
•  Subject-Injury Sublimit: $10,000,000 per occurrence / $50,000,000 aggregate
The MCTA will contain insurance requirements that must be satisfied by Penterra as Sponsor. The engagement team should review the current Briarcliff policy to confirm that its terms, limits, and coverage scope are consistent with the insurance requirements that Veridian is expected to demand. As noted in Section VI below, Veridian may seek higher per-occurrence limits, and the engagement team should be prepared to discuss with the client whether policy amendments, endorsements, or additional coverage may be necessary to satisfy Veridian's requirements.
3.  Pinnacle Data Solutions, Inc. Pinnacle is Penterra's electronic data capture (EDC) and eClinical platform vendor for the CLARION trial. Pinnacle is located at 6000 Clearwater Drive, San Diego, California 92121. The MCTA will reference Pinnacle's EDC platform in connection with data entry, electronic signatures (21 C.F.R. Part 11 compliance), and the technology integration costs included in the deal value.
4.  Northbridge Bioanalytical Laboratories, Inc. Northbridge serves as the central laboratory for the CLARION trial, responsible for pharmacokinetic/pharmacodynamic (PK/PD) analyses, biomarker assessments, and safety laboratory analyses. Northbridge is located at 2900 Commerce Way, Baltimore, Maryland 21224. The MCTA will address specimen handling, shipping, chain of custody, and the responsibilities of participating sites with respect to central laboratory procedures.
5.  Castleton & Hargrove LLP. Castleton & Hargrove serves as FDA regulatory counsel to Penterra and is responsible for all regulatory strategy matters relating to the penterafenib program, including IND maintenance, FDA communications, and regulatory submissions. Castleton & Hargrove is located at 1100 Connecticut Avenue NW, Suite 900, Washington, DC 20036. The lead partner for the Penterra engagement is Dr. Priya Sundaram, Esq. FDA regulatory strategy matters are expressly excluded from the scope of this engagement.
V. Governing Law
The MCTA is expected to be governed by the laws of the State of New York, without regard to its conflicts of law principles. This choice of law is consistent with Penterra's standard contractual practice for clinical trial agreements and reflects the firm's location in New York as well as the well-developed body of New York commercial contract law that provides a predictable framework for interpreting the MCTA's provisions.
The MCTA is anticipated to include a three-step escalation procedure for the resolution of disputes arising under or in connection with the agreement, as follows:
1.  Designated Representative Negotiation (30 days). In the first instance, any dispute will be referred to designated senior representatives of each party (anticipated to be individuals at the Vice President level or above) for good-faith negotiation and attempted resolution. The designated representatives will have a period of thirty (30) days from the date of referral to resolve the dispute through direct negotiation.
2.  Mediation (60 days). If the dispute is not resolved through designated representative negotiation within the initial 30-day period, either party may refer the dispute to mediation administered by the American Arbitration Association ("AAA") under the AAA Commercial Mediation Rules then in effect. The mediation will be conducted in New York, New York, and the parties will have a period of sixty (60) days from the commencement of mediation to resolve the dispute through the mediation process.
3.  Binding Arbitration. If the dispute is not resolved through mediation within the 60-day period, either party may submit the dispute to binding arbitration in New York, New York, administered by the AAA under the AAA Commercial Arbitration Rules then in effect. The arbitration will be conducted before a panel of three (3) arbitrators, with each party selecting one arbitrator and the two party-selected arbitrators selecting the third. The arbitrators' award will be final and binding on the parties and may be entered and enforced in any court of competent jurisdiction.
Notwithstanding the foregoing dispute resolution provisions, the MCTA is expected to preserve the right of either party to seek injunctive or other equitable relief in aid of arbitration or to prevent irreparable harm. For purposes of such proceedings, the parties will be expected to submit to the exclusive jurisdiction of the state and federal courts located in New York County, New York.
The engagement team should note that the application of New York governing law to a clinical trial agreement involving research sites located across 14 states raises a number of considerations, including the interplay between New York contract law and the regulatory and institutional frameworks governing clinical research in other jurisdictions. A separate analysis memorandum addressing the implications of New York governing law for multi-state clinical trial agreements will be prepared and circulated to the engagement team in connection with the initial MCTA drafting process.
VI. Key Legal Issues Anticipated
Based on the engagement team's initial review of the matter and its experience with comparable clinical trial agreements, the following legal issues are anticipated to be significant in the negotiation of the MCTA. This list is not exhaustive and will be updated as the negotiation progresses.
1. Subject-Injury Indemnification Scope and Caps. The scope and financial limits of the Sponsor's indemnification obligations for injuries suffered by clinical trial subjects will be a central issue in the MCTA negotiation. Veridian and its network sites will seek broad indemnification from Penterra for subject injuries arising from the investigational product, while Penterra will seek to limit its indemnification exposure through per-subject and aggregate caps, exclusions for injuries caused by site negligence or protocol deviations, and appropriate notice and cooperation requirements. The engagement team should develop an indemnification framework that balances these competing interests and is consistent with the coverage limits of the Briarcliff insurance policy.
2. Allocation of Liability for Protocol Deviations. The MCTA will need to clearly allocate liability between Penterra and Veridian (and its network sites) for protocol deviations, with particular attention to the distinction between medically necessary deviations (e.g., deviations undertaken for subject safety) and unauthorized deviations (e.g., deviations resulting from investigator error or negligence). The treatment of medically necessary deviations is frequently a contentious issue in clinical trial agreement negotiations, as sponsors typically resist indemnifying sites for the consequences of deviations that were not prospectively approved by the sponsor, while sites argue that investigators must retain clinical judgment to deviate from the protocol when subject safety requires it.
3. Insurance Adequacy. Veridian may demand higher per-occurrence limits than those provided under the current Briarcliff policy (which provides $25 million per occurrence and $75 million in the aggregate). Academic medical centers and research networks commonly require per-occurrence limits of $50 million or more for Phase III oncology trials with large enrollment targets. The engagement team should confer with the client regarding the feasibility of obtaining increased policy limits or supplemental excess coverage if Veridian's insurance requirements exceed the current Briarcliff policy terms. The subject-injury sublimit of $10 million per occurrence and $50 million in the aggregate should also be evaluated in light of the trial's enrollment size and the oncology patient population.
4. Data Ownership and intellectual Property Rights. Penterra will seek to retain exclusive ownership of all clinical trial data generated in connection with the CLARION trial, consistent with its position as the IND holder and regulatory sponsor. This position is standard in the pharmaceutical industry but may be resisted by Veridian and its academic investigators, who may seek co-ownership, access, or use rights with respect to the data for academic and research purposes. The engagement team should negotiate data ownership provisions that preserve Penterra's exclusive ownership rights while providing appropriate accommodations for academic use, subject to Penterra's review and approval rights and consistent with the publication rights framework described below.
5. Investigator Publication Rights and Academic Freedom vs. Sponsor Review/Patent Protection. The tension between investigators' academic freedom and desire to publish clinical trial results, on the one hand, and the sponsor's interest in reviewing proposed publications for accuracy, patent protection, and confidentiality, on the other hand, is a recurring issue in clinical trial agreements with academic institutions. Veridian will likely insist on publication rights for its investigators, including the right to publish individual site results as well as multi-center results, subject to a reasonable review period for the sponsor. The engagement team should draft publication provisions that grant investigators a right to publish subject to: (a) a review period of no less than 60 days (with the possibility of an additional 30-day extension for patent filing purposes); (b) removal of Penterra confidential information; and (c) review for scientific accuracy.
6. Termination Provisions and Wind-Down Period for Subject Safety. The MCTA must contain robust termination provisions that address both for-cause and without-cause termination, as well as termination due to safety concerns, regulatory action, or force majeure events. Of particular importance are the wind-down provisions that will apply following termination, including obligations to continue treating enrolled subjects through an appropriate transition period, data transfer and lock procedures, and the financial obligations of the parties during the wind-down period. Subject safety during the wind-down period is a non-negotiable priority for both parties and for regulatory compliance.
7. Regulatory Compliance Frameworks. The MCTA must address compliance with a number of federal and state regulatory frameworks, including but not limited to:
•  The Federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)) and the safe harbor regulations thereunder, with particular attention to the fair market value of all payments to investigators and sites;
•  The Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h) and the CMS Open Payments reporting requirements, including Penterra's obligations to report payments to covered recipients;
•  The Health Insurance Portability and Accountability Act of 1996 ("HIPAA") and its implementing regulations (45 C.F.R. Parts 160 and 164), including the Privacy Rule and the Security Rule, with particular attention to the handling of protected health information (PHI) in connection with clinical trial data;
•  FDA regulations at 21 C.F.R. Part 11 (Electronic Records; Electronic Signatures), 21 C.F.R. Part 50 (Protection of Human Subjects), 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators), 21 C.F.R. Part 56 (Institutional Review Boards), and 21 C.F.R. Part 312 (Investigational New Drug Application);
•  The International Council for Harmonisation (ICH) E6(R2) Guideline for Good Clinical Practice (GCP), which sets forth the international ethical and scientific quality standard for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials.
8. Fair Market Value of Investigator Compensation and Site Payments. As noted above, all payments to investigators and sites under the MCTA must be established at fair market value to mitigate risk under the Anti-Kickback Statute. The engagement team should coordinate with Penterra to obtain or commission a fair market value assessment of all payment components, including per-patient fees, start-up fees, maintenance fees, investigator grants, and any other compensation provided to investigators or sites in connection with the CLARION trial.
9. IRB Oversight Structure. The MCTA negotiation will need to address the IRB oversight structure for the CLARION trial, including the use of the Graystone University Institutional Review Board and the Veridian Central IRB. The parties will need to determine whether the trial will use a single central IRB for all participating sites (with individual sites entering into IRB reliance agreements) or whether some sites will maintain their own IRB oversight. The adoption of the 2018 Revised Common Rule (45 C.F.R. Part 46), which requires single-IRB review for federally funded multi-site research, may inform but does not mandate the IRB structure for this industry-sponsored trial. The engagement team should prepare an analysis of the available IRB oversight models and their legal and practical implications.
10. Confidentiality. The MCTA is expected to include a confidentiality provision with a term of ten (10) years, which is standard for clinical trial agreements in the pharmaceutical industry. The confidentiality provisions will need to address the definition of confidential information, permitted disclosures (including disclosures required by law, regulation, or court order, and disclosures in connection with regulatory submissions), return and destruction of confidential information, and remedies for breach. The interaction between the confidentiality provisions and the publication rights provisions will require careful coordination.
11. Safety Reporting Procedures. The MCTA will establish the safety reporting obligations of the parties, including: (a) reporting of serious adverse events (SAEs) by investigators to the sponsor within 24 hours of awareness; (b) the sponsor's obligations with respect to IND safety reports to the FDA on 7-day timelines (for fatal or life-threatening unexpected suspected adverse reactions) and 15-day timelines (for other serious and unexpected suspected adverse reactions); and (c) distribution of safety information to investigators, IRBs, and regulatory authorities. The safety reporting provisions must be consistent with 21 C.F.R. § 312.32 and ICH E6(R2) requirements.
12. Site Document Retention. The MCTA will establish document retention requirements for participating sites. The current expectation is that sites will be required to retain all study-related documents for a minimum of fifteen (15) years following the completion of the study. This retention period exceeds the FDA's minimum requirements under 21 C.F.R. § 312.62 and is consistent with Penterra's standard contractual practice and the extended timelines associated with post-marketing surveillance and potential regulatory actions.
VII. Engagement Team
The following attorneys and professional staff of Calderwood & Harkness LLP are assigned to this engagement.
Responsible Partner: Miriam Calloway, Partner, Healthcare & Life Sciences Practice Group. Ms. Calloway will serve as the Responsible Partner for the engagement, with overall responsibility for the quality and timeliness of all work product, the management of the client relationship, and the supervision of all attorneys working on the matter. Ms. Calloway is located at the firm's New York office at 280 Park Avenue, 34th Floor, New York, New York 10017.
Billing Partner: Joel Strauss, Partner, Healthcare & Life Sciences Practice Group. Mr. Strauss will serve as the Billing Partner for the engagement and will be responsible for billing administration, fee estimates, and client communications regarding fees and expenses. Mr. Strauss is also located at the firm's New York office at 280 Park Avenue, 34th Floor, New York, New York 10017. Mr. Strauss brings substantial experience in clinical trial agreements for oncology programs and will be available to assist with substantive issues as needed.
Lead Associate: Sean Morrissey, Associate, Healthcare & Life Sciences Practice Group. Mr. Morrissey will serve as the Lead Associate on the engagement, with primary responsibility for drafting the MCTA and all associated agreements and exhibits, managing the day-to-day workflow, and serving as the principal point of contact with counterparty counsel for document exchanges and negotiation sessions. Mr. Morrissey has significant experience in clinical trial agreement transactions and has worked on prior matters involving academic research networks.
Working Associate: Christopher Aiken, Associate, Healthcare & Life Sciences Practice Group. Mr. Aiken will support Mr. Morrissey in the drafting and negotiation process, with particular responsibility for regulatory compliance analysis, fair market value analysis, and the preparation of ancillary documents including site joinder agreements, investigator agreements, and closing deliverables.
Additional Resources: The firm's Princeton office, located at 101 Carnegie Center, Suite 500, Princeton, New Jersey 08540, is available for in-person meetings with the client given Penterra's headquarters location in Princeton. The engagement team anticipates that certain meetings with Penterra's in-house team may be held at the Princeton office for the convenience of the client. Conference facilities and videoconferencing capabilities are available at both the New York and Princeton locations.
Detailed staffing plans and budget estimates for the engagement will be addressed in a separate Staffing & Budget Estimate Memorandum, which will be prepared and circulated to the Responsible Partner and Billing Partner for review and approval prior to submission to the client.
VIII. Projected Timeline and Key Milestones
The following timeline sets forth the key milestones and target dates for the engagement. These dates are based on the client's stated objective of achieving a target first-patient-in (FPI) date of August 14, 2023, and reflect the engagement team's assessment of a realistic but aggressive schedule for the negotiation and closing of the MCTA.
The engagement team notes that the period between the target MCTA execution date (late June 2023) and the target FPI date (August 14, 2023) is approximately six to seven weeks, which is a compressed timeline for the completion of all closing conditions, site activation procedures, and pre-study initiation activities. The team will work closely with the client and with Veridian to identify and address any potential impediments to timely closing and site activation as early as possible in the negotiation process.
The projected study completion date of August 2028 reflects the anticipated total study duration of 60 months (42-month enrollment period plus 18-month follow-up period). While the engagement team's active involvement in the matter is expected to be concentrated in the period from March through July 2023 (covering the drafting, negotiation, and closing phases), the team should be available for post-closing support as needed throughout the life of the trial, including support for MCTA amendments, site additions or removals, protocol amendments, dispute resolution, and any other matters arising under the MCTA.
IX. Scope of Representation
The scope of Calderwood & Harkness's representation of Penterra in this matter encompasses the following work streams and deliverables:
1.  Master Clinical Trial Agreement. Drafting and negotiation of the Master Clinical Trial Agreement between Penterra (as Sponsor) and Veridian (as Site Network), including all substantive terms and conditions governing the conduct of the CLARION trial across the 38 participating Veridian Network sites.
2.  MCTA Exhibits and Schedules. Drafting of all exhibits and schedules to the MCTA, which are anticipated to include the following:
(a) Protocol Synopsis (Exhibit A);
(b) Budget and Payment Schedule (Exhibit B);
(c) Site Joinder Form (Exhibit C);
(d) Subject-Injury Indemnification Provisions (Exhibit D);
(e) Insurance Requirements (Exhibit E);
(f) Confidentiality and Data Protection Provisions (Exhibit F);
(g) intellectual Property and Publication Rights (Exhibit G);
(h) Regulatory Compliance Representations and Warranties (Exhibit H);
(i) Investigator Undertaking Form (Exhibit I);
(j) Safety Reporting Procedures (Exhibit J);
(k) Approved Subcontractors List (Exhibit K);
(l) List of Participating Sites (Exhibit L).
3.  Site Joinder Agreements. Preparation of individual site agreements (joinder agreements) for each of the 38 Veridian Network sites, incorporating the terms of the MCTA by reference and containing site-specific information including local budgets, investigator designations, and local regulatory approvals.
4.  Principal Investigator and Co-Principal Investigator Agreements. Preparation of investigator-level agreements for Dr. Catherine Aldridge (Global Principal Investigator) and Dr. Howard Matsuoka (Co-Principal Investigator at Lakemont Medical Center), as well as template investigator agreements for use at other participating sites.
5.  intellectual Property Side Letter. Negotiation and execution of an intellectual property side letter addressing any matters not covered by the IP provisions of the MCTA, including any pre-existing IP rights of the investigators or Veridian Network sites, background IP, and any specific inventions or discoveries that may arise during the conduct of the CLARION trial.
6.  Closing Deliverables. Preparation of all closing deliverables required for the MCTA closing, including closing certificates, secretary's certificates (certifying organizational authority), officer's certificates (certifying representations and warranties), and any other instruments required to satisfy the conditions precedent to the effectiveness of the MCTA.
7.  Insurance Coordination. Coordination with Penterra's insurance broker and with Briarcliff Mutual Insurance Company regarding additional insured endorsement requests, certificate of insurance exchanges, and any policy amendments or supplemental coverage that may be required to satisfy Veridian's insurance requirements under the MCTA.
8.  Regulatory Compliance Analysis Memoranda. Preparation of one or more legal memoranda analyzing the regulatory compliance implications of the MCTA and the CLARION trial, including analysis under the Anti-Kickback Statute, the Physician Payments Sunshine Act / Open Payments, HIPAA (45 C.F.R. Parts 160 and 164), and the FDA financial disclosure requirements under 21 C.F.R. Part 54.
9.  Fair Market Value Analysis. Preparation or coordination of a fair market value analysis for investigator compensation and site payment amounts under the MCTA, to support compliance with the Anti-Kickback Statute and applicable safe harbor provisions.
10.  IRB Reliance / Central IRB Structure Analysis. Analysis of the available IRB oversight models for the CLARION trial, including the use of the Graystone University IRB, the Veridian Central IRB, and individual site IRBs, and preparation of recommendations regarding the optimal IRB oversight structure.
Matters Not in Scope
The following matters are expressly excluded from the scope of this engagement and are being handled by other counsel or advisors:
•  CRO Agreement. The Master Services Agreement with Meridian Contract Research Organization, Inc. (dated January 15, 2023) is separately handled and is not within the scope of this engagement.
•  FDA Regulatory Strategy. All matters relating to FDA regulatory strategy for penterafenib, including IND maintenance, FDA communications, and regulatory submissions, are handled by Castleton & Hargrove LLP and are not within the scope of this engagement.
•  Financial Advisory Matters. Financial advisory matters relating to Penterra are handled by Ridgeline Capital Markets LLC and are not within the scope of this engagement.
•  Audit Matters. Audit and accounting matters relating to Penterra are handled by Townsend Independent Auditors LLP and are not within the scope of this engagement.
X. Administrative Information
The following administrative information is recorded for the purpose of matter management and firm operations.
Document Management: All documents generated or received in connection with this matter are to be filed under Matter No. 1018-00004 in the firm's document management system. Team members should follow the firm's standard document naming conventions and filing protocols. All privileged and confidential documents should be appropriately marked.
Retention Notes: Document retention for this matter shall be governed by the firm's standard document retention policy as well as any specific instructions received from the client. The engagement team should note that clinical trial site records are subject to a minimum retention period of fifteen (15) years following the completion of the study, as discussed in Section VI above. While the firm's retention obligations with respect to its own work product may differ from the site-level retention requirements, the team should be aware of the extended retention expectations and should coordinate with the client regarding any specific retention instructions applicable to the firm's files.
XI. Distribution
This memorandum is designated for internal distribution only within Calderwood & Harkness LLP. It is not to be provided to the client, counterparty, or any third party without the prior written authorization of the Responsible Partner.
Internal Distribution:
•  Miriam Calloway, Partner
•  Joel Strauss, Partner
•  Sean Morrissey, Associate
•  Christopher Aiken, Associate
Copy to File: Matter No. 1018-00004.
PREPARED BY:
________________________________________
Miriam Calloway Partner, Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 280 Park Avenue, 34th Floor New York, New York 10017
Date: March 20, 2023
CONFIDENTIAL — ATTORNEY WORK PRODUCT — PRIVILEGED AND CONFIDENTIAL This memorandum has been prepared by Calderwood & Harkness LLP for internal use in connection with Matter No. 1018-00004. It is protected by the attorney-client privilege and the work product doctrine. Unauthorized reproduction, distribution, or disclosure of this memorandum or its contents is strictly prohibited.
Metric | Value
Market Capitalization (Q1 2023) | Approximately $4.2 billion
FY2022 Total Revenue | $1.87 billion
FY2022 Research & Development Expenditure | $612 million
Cash and Cash Equivalents (Q1 2023) | $890 million
Component | Unit Cost | Units | Subtotal
Per-patient site fees (screen-to-completion) | $52,000/subject | 1,200 subjects | $62,400,000
Start-up fees | $75,000/site | 38 sites | $2,850,000
Annual site maintenance fees | $40,000/site/year | 38 sites × 3.5 years (avg.) | $5,320,000
Investigator grants (publication & academic support) | — | — | $1,500,000
Network coordination/administrative fee to Veridian central | $300,000/quarter | 14 quarters | $4,200,000
Technology/EDC integration costs (Pinnacle Data Solutions) | — | — | $1,230,000
Contingency/change order reserve | — | — | $2,500,000
Total | $80,000,000
Milestone | Target Date
Matter Opened | March 20, 2023
Target First Draft MCTA Circulation (to client for review) | Early April 2023 (target: April 7, 2023)
Anticipated Negotiation Period (with Veridian/WJC) | April – June 2023
Target Execution / Signing Date (MCTA) | Late June 2023
Conditions Precedent / Closing (delivery of insurance certificates, IRB approvals for lead sites, executed investigator signature pages) | Early July 2023
Target Effective Date (MCTA) | Mid-July 2023
Target First Patient In (FPI) | August 14, 2023
Projected Last Patient In | February 2027
Projected Study Completion | August 2028
Field | Detail
Matter Number | 1018-00004
Client Number | Per firm internal records — Penterra Pharmaceuticals Corp.
Practice Group | Healthcare & Life Sciences
Primary Office | New York (280 Park Avenue, 34th Floor, New York, NY 10017)
Secondary Office | Princeton (101 Carnegie Center, Suite 500, Princeton, NJ 08540) — available for client meetings
Billing Arrangement | Per engagement letter dated March 20, 2023; hourly rates as set forth therein
Conflicts Cleared | March 20, 2023 (see separate Conflict Check Memorandum)

MEMORANDUM — CONFIDENTIAL / ATTORNEY WORK PRODUCT

PREPARED BY:

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