1018-00004 · Penterra Pharmaceuticals Corp · Correspondence

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CALDERWOOD & HARKNESS LLP Counselors at Law

280 Park Avenue, 34th Floor New York, NY 10017 Telephone: (212) 554-7000 Facsimile: (212) 554-7001 www.calderwoodharkness.com

New York · Princeton · Washington, D.C. · Boston · San Francisco · London

Princeton Office: 101 Carnegie Center, Suite 500, Princeton, NJ 08540

July 18, 2023

Via Email and First Class Mail

Nathaniel Briggs, Esq. Vice President & General Counsel Penterra Pharmaceuticals Corp. 200 Biopharma Boulevard, Suite 1400 Princeton, NJ 08540

Re: Matter Closing Confirmation — Calderwood & Harkness Matter No. 1018-00004 Master Clinical Trial Agreement between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. Protocol PPC-4871-III (CLARION)

Dear Nathaniel:

1. Purpose and Effective Date Confirmation

I write to confirm the effective date of the Master Clinical Trial Agreement (the "MCTA") and the formal closing of Calderwood & Harkness LLP Matter No. 1018-00004. This letter serves as the firm's official matter closing confirmation and provides a comprehensive record of the transaction documents, conditions precedent, and ongoing post-closing obligations for Penterra Pharmaceuticals Corp.'s files.

We are pleased to confirm that the MCTA between Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware ("Penterra"), and Veridian Health Research Network, Inc., a nonprofit corporation organized and existing under the laws of the State of Delaware and recognized as a tax-exempt organization under Section 501(c)(3) of the Internal Revenue Code of 1986, as amended ("Veridian"), became effective as of July 18, 2023 (the "Effective Date"). The MCTA governs the conduct of the multi-center clinical trial conducted under Protocol PPC-4871-III, known by the short title CLARION (Clinical Assessment of Response with Longitudinal Investigation in ONcology) (the "Protocol" or the "CLARION Trial"). The investigational product subject to the MCTA is penterafenib (PPC-4871), Penterra's proprietary oral multi-kinase inhibitor under clinical development for the treatment of advanced hepatocellular carcinoma.

The aggregate deal value under the MCTA is Eighty Million Dollars ($80,000,000), encompassing site fees, per-patient milestone payments, investigator grants, and operational costs across thirty-eight (38) participating Veridian Network clinical sites located in fourteen (14) states throughout the United States, over a projected forty-two (42)-month enrollment period within a total anticipated study duration of sixty (60) months.

2. Summary of Transaction Timeline

For the benefit of your records, set forth below is a chronological summary of the key milestones achieved during the negotiation and execution of the MCTA and related ancillary agreements:

The above timeline reflects a negotiation period of approximately ninety (90) days from initial draft circulation through execution, which is consistent with the scope and complexity of a multi-site clinical trial agreement of this magnitude. We note that the negotiation process benefited significantly from the collaborative approach taken by all parties and their respective counsel throughout.

3. Summary of Executed Documents

The following is a comprehensive listing of all executed documents comprising the transaction, each of which has been included in the closing binder referenced in Section 5 below:

1. Master Clinical Trial Agreement (execution version, dated June 28, 2023), by and between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc.

2. MCTA Signature Pages — executed counterpart signature pages from Penterra Pharmaceuticals Corp. (executed by Nathaniel Briggs, Esq., Vice President & General Counsel), Veridian Health Research Network, Inc. (executed by Dr. Franklin Osei, President & Chief Executive Officer), and Graystone University Medical Center (executed by Dr. William Corwin, President, as lead site)

3. Exhibit A — Protocol Synopsis (PPC-4871-III / CLARION), providing a summary of the Protocol objectives, study design, endpoints, inclusion/exclusion criteria, and anticipated enrollment targets

4. Exhibit B — Budget and Payment Schedule, reflecting a total budget of $80,000,000, allocated as follows:

5. Exhibit C — Form of Individual Site Agreement (Joinder), the template agreement pursuant to which each participating Veridian Network site will join the MCTA and agree to be bound by its terms

6. Exhibit D — Subject-Injury Indemnification Provisions, including: (i) per-subject medical care cap of $500,000; (ii) aggregate cap of $15,000,000 for all subject-injury claims; (iii) uncapped indemnification for claims arising from product-defect or manufacturing-defect causes of action; and (iv) site indemnity capped at $5,000,000 per site, per occurrence, and $20,000,000 in the aggregate

7. Exhibit E — Insurance Requirements and Certificate Forms, specifying: (i) Penterra's clinical trial liability insurance of $25,000,000 per occurrence / $75,000,000 aggregate, provided by Briarcliff Mutual Insurance Company under Policy No. BM-CTL-2023-04182, with a subject-injury sublimit of $10,000,000 per occurrence / $50,000,000 aggregate; and (ii) Veridian/site insurance requirements of $5,000,000 per occurrence / $10,000,000 aggregate for general liability and professional liability coverage

8. Exhibit F — Confidentiality and Data Protection Provisions, establishing mutual confidentiality obligations with a ten (10)-year term from the date of disclosure of each item of Confidential Information

9. Exhibit G — Intellectual Property and Publication Rights, providing for Penterra's sixty (60)-day review period for proposed publications and a ninety (90)-day patent delay period to permit the filing of patent applications prior to public disclosure

10. Exhibit H — Regulatory Compliance Representations and Covenants, setting forth representations, warranties, and ongoing covenants regarding compliance with applicable federal and state regulatory requirements, including Good Clinical Practice (GCP), FDA regulations (21 CFR Parts 50, 56, 312, and 812), Anti-Kickback Statute, and the Physician Payments Sunshine Act

11. Exhibit I — Form of Investigator Undertaking, the template acknowledgment to be executed by each site investigator confirming acceptance of responsibilities under the Protocol and applicable regulations

12. Exhibit J — Safety Reporting Procedures, establishing: (i) Serious Adverse Event (SAE) reporting within twenty-four (24) hours of site awareness; and (ii) IND safety report submission timelines in accordance with 21 CFR § 312.32 (seven (7)-day reports for fatal or life-threatening unexpected adverse reactions; fifteen (15)-day reports for all other serious and unexpected adverse reactions)

13. Exhibit K — Approved Subcontractors List, identifying the following pre-approved subcontractors: (i) Meridian CRO (contract research organization services); (ii) Pinnacle Data Solutions (electronic data capture and data management); and (iii) Northbridge Bioanalytical Laboratories (bioanalytical and pharmacokinetic sample analysis)

14. Schedule 1 — List of 38 Participating Veridian Network Sites, identifying each site by site number, institution name, principal investigator, location, and applicable Institutional Review Board

15. Individual Site Agreement — Graystone University Medical Center (Site 001), with Principal Investigator Dr. Catherine Aldridge and IRB oversight by the Graystone University Institutional Review Board (IORG Registration No. IRB00012847)

16. Individual Site Agreement — Lakemont Medical Center (Site 002), with Co-Principal Investigator Dr. Howard Matsuoka and IRB oversight by the Veridian Central IRB

17. Individual Site Agreement — Haverford Regional Medical Center (Site 003)

18. Individual Site Agreement — Cedar Falls University Hospital (Site 004)

19. Individual Site Agreement — Weston Memorial Health System (Site 005)

20. Principal Investigator Agreement — Dr. Catherine Aldridge, designating Dr. Aldridge as Global Principal Investigator for the CLARION Trial

21. Co-Principal Investigator Agreement — Dr. Howard Matsuoka, designating Dr. Matsuoka as Co-Principal Investigator

22. intellectual Property Side Letter (execution version, dated June 28, 2023), supplementing the intellectual property provisions of the MCTA with respect to certain pre-existing Veridian intellectual property and biomarker-related inventions

23. Closing Certificate — Penterra Pharmaceuticals Corp., certifying satisfaction of conditions precedent and accuracy of representations and warranties as of the Effective Date

24. Closing Certificate — Veridian Health Research Network, Inc., certifying satisfaction of conditions precedent and accuracy of representations and warranties as of the Effective Date

25. Secretary's Certificate — Penterra Pharmaceuticals Corp., certifying board authorization of the MCTA and incumbency of Nathaniel Briggs, Esq. (Vice President & General Counsel) and Dr. Anand Raghavan (Senior Vice President, Clinical Development)

26. Secretary's Certificate — Veridian Health Research Network, Inc., certifying board authorization of the MCTA and incumbency of Dr. Franklin Osei (President & Chief Executive Officer) and Gregory Callahan (Senior Vice President & General Counsel)

27. Officer's Certificate — Penterra Pharmaceuticals Corp., confirming the bringdown of representations and warranties as of July 5, 2023, and certifying that no material adverse change has occurred since the date of execution

4. Conditions Precedent Satisfaction

We confirm that all conditions precedent to the effectiveness of the MCTA, as specified in Section 12.1 thereof, were satisfied in full as of July 5, 2023. Specifically, the following conditions were satisfied:

(a) Penterra Insurance Certificate. Delivery by Penterra of its certificate of insurance from Briarcliff Mutual Insurance Company (Policy No. BM-CTL-2023-04182), evidencing clinical trial liability coverage of $25,000,000 per occurrence / $75,000,000 aggregate, including the required additional insured endorsement naming Veridian Health Research Network, Inc. and each participating Veridian Network site as additional insureds thereunder.

(b) Site Insurance Certificates. Delivery of site insurance certificates from each of the initial participating Veridian Network sites (Sites 001 through 005) demonstrating general liability and professional liability coverage of at least $5,000,000 per occurrence / $10,000,000 aggregate, meeting the minimum insurance requirements specified in Exhibit E to the MCTA.

(c) Lead Site IRB Approval. Receipt of written IRB approval from the Graystone University Institutional Review Board (IORG Registration No. IRB00012847) for conduct of the CLARION Trial at the lead site (Graystone University Medical Center, Site 001).

(d) Central IRB Approval. Receipt of written IRB approval from the Veridian Central IRB for conduct of the CLARION Trial at all participating Veridian Network sites located outside the Commonwealth of Pennsylvania.

(e) Investigator Signature Pages. Receipt of fully executed investigator signature pages from Dr. Catherine Aldridge (Global Principal Investigator, Site 001) and Dr. Howard Matsuoka (Co-Principal Investigator, Site 002), including executed Investigator Undertaking forms.

(f) Secretary's and Officer's Certificates. Delivery of executed secretary's certificates and officer's certificates from both Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc., in each case in the forms set forth in the closing deliverables schedule to the MCTA.

No conditions precedent were waived by either party. All deliverables were received in complete and satisfactory form.

5. Delivery of Closing Binder

We confirm that the complete closing binder for this transaction has been compiled by this firm and is being delivered concurrently with this letter. The closing binder is organized by tab number in accordance with the enclosed Closing Binder Index and Table of Contents, which corresponds to the document listing set forth in Section 3 above. Each tab contains a fully executed original or conformed copy of the applicable document.

Three (3) hard copies of the closing binder are being delivered by hand and overnight courier to Penterra's headquarters at 200 Biopharma Boulevard, Suite 1400, Princeton, NJ 08540, to the attention of Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs. We ask that Ms. Liang confirm receipt of the closing binders upon delivery.

In addition, a complete electronic copy of the closing binder, in searchable PDF format, has been uploaded to the secure document repository maintained by Calderwood & Harkness LLP and accessible to the authorized members of the Penterra legal team. Access credentials for the electronic closing binder are being transmitted separately via secure encrypted email to Ms. Liang and to you.

6. Key Terms Reminder — Governing Law and Dispute Resolution

For ease of reference, we provide the following brief reminder regarding the governing law and dispute resolution provisions of the MCTA, as set forth in Article XV thereof:

Governing Law. The MCTA is governed by and construed in accordance with the laws of the State of New York, without regard to conflicts of law principles that would result in the application of the laws of any other jurisdiction.

Dispute Resolution. The MCTA provides for a three-step dispute resolution escalation process, as follows:

Step 1 — Designated Representative Negotiation. In the event of any dispute, controversy, or claim arising out of or relating to the MCTA, the designated senior representatives of each party shall first attempt to resolve such dispute through good-faith negotiation for a period of thirty (30) days following written notice of the dispute.

Step 2 — Mediation. If the dispute is not resolved through negotiation within such thirty (30)-day period, the parties shall submit the dispute to mediation under the American Arbitration Association ("AAA") Commercial Mediation Rules for a period of sixty (60) days, or such longer period as the parties may agree.

Step 3 — Binding Arbitration. If the dispute is not resolved through mediation, either party may submit the dispute to final and binding arbitration in New York, New York under the AAA Commercial Arbitration Rules, before a panel of three (3) arbitrators selected in accordance with such rules.

Injunctive Relief. Notwithstanding the foregoing, either party may seek injunctive or other equitable relief from the state and federal courts located in New York County, New York, to protect its confidential information, intellectual property, or other rights for which monetary damages would be an inadequate remedy.

7. Ongoing Post-Closing Obligations and Action Items

Although the negotiation and execution of the MCTA and ancillary agreements is now complete, we wish to highlight the following ongoing post-closing obligations and near-term action items for Penterra's attention. While Calderwood & Harkness's active engagement on this matter is concluding, we believe it is prudent to memorialize these items for the benefit of Penterra's internal clinical contracts and legal teams.

Remaining Site Joinders. As of the Effective Date, Individual Site Agreements have been executed for five (5) of the thirty-eight (38) participating Veridian Network sites (Sites 001 through 005). Execution of Individual Site Agreements for the remaining thirty-three (33) sites is expected to occur on a rolling basis as each site completes its internal review and obtains the requisite IRB approval. This process is to be coordinated by Samantha Novak, Director of Clinical Contracts at Penterra, in collaboration with Patricia Dunne, Director of Sponsored Research Agreements at Veridian. We recommend that Penterra establish an internal tracking mechanism to monitor the status of each site joinder and to ensure that no site initiates study activities prior to the execution of its Individual Site Agreement.

Annual Insurance Renewals. The Briarcliff Mutual Insurance Company clinical trial liability policy (Policy No. BM-CTL-2023-04182) currently maintained by Penterra has a policy expiration date of March 31, 2024. Penterra must ensure timely renewal of such policy and delivery of updated certificates of insurance to Veridian annually throughout the duration of the CLARION Trial. Any lapse in coverage could constitute a material breach of the MCTA and could result in a suspension of study activities at participating sites. We recommend that Penterra's risk management group calendar the renewal date well in advance and coordinate with Briarcliff Mutual to ensure continuity of coverage.

Site Insurance Certificate Collection. Penterra has an ongoing obligation under Exhibit E of the MCTA to collect and maintain current certificates of insurance from all thirty-eight (38) participating Veridian Network sites, confirming that each site maintains general liability and professional liability coverage meeting the minimum thresholds specified in the MCTA ($5,000,000 per occurrence / $10,000,000 aggregate). We recommend that Penterra's clinical contracts team implement a centralized insurance certificate tracking system and establish annual reminder protocols for certificate renewals.

Payment Administration. The MCTA contemplates the following categories of payments, each subject to specified triggering events and administrative requirements:

• Per-Patient Milestone Payments: $13,000 per milestone × four (4) milestones per patient (Informed Consent, Randomization, Treatment Completion, and End-of-Study Visit), for a total per-patient payment of $52,000

• Start-Up Fee Second Installments: $37,500 per site, payable upon enrollment of the first patient at each site (the first installment of $37,500 per site having been paid upon execution of the applicable Individual Site Agreement)

• Quarterly Network Coordination Fees: $300,000 per quarter, payable to Veridian for network coordination and administrative services

• Annual Site Maintenance Fees: as set forth in Exhibit B, payable annually during the study period

• All payments are due net forty-five (45) days from receipt of a proper and complete invoice submitted by Veridian in accordance with the invoicing procedures set forth in Section 7.3 of the MCTA

IRB Maintenance. Each participating site must maintain active IRB approval throughout the duration of the CLARION Trial. IRB continuing review submissions must be filed no later than the applicable anniversary date of the initial IRB approval for each site. Penterra's clinical operations team should coordinate with Veridian to track IRB approval status across all thirty-eight (38) sites and to ensure that no site conducts study activities under a lapsed IRB approval.

Form FDA 1572 Collection. Penterra has an ongoing obligation to collect and maintain current FDA Form 1572 (Statement of Investigator) and financial disclosure certifications pursuant to 21 CFR Part 54 (Financial Disclosure by Clinical Investigators) from all site investigators. These forms must be updated as investigators are added or replaced and must be maintained in the regulatory trial master file.

Regulatory Compliance. Penterra must ensure ongoing compliance with applicable regulatory requirements throughout the CLARION Trial, including, without limitation: (i) the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)); (ii) the Physician Payments Sunshine Act and Open Payments reporting requirements (42 U.S.C. § 1320a-7h); and (iii) the Health Insurance Portability and Accountability Act of 1996 ("HIPAA") and its implementing regulations. We understand that Penterra is coordinating with Castleton & Hargrove LLP, specifically Dr. Priya Sundaram, on FDA regulatory matters, including the maintenance of IND 157823 and ongoing communications with the FDA's Division of Oncology Drug Products. We recommend continued close coordination between Penterra's clinical and regulatory teams and outside regulatory counsel throughout the study.

Document Retention. Pursuant to Section 14.2 of the MCTA and applicable FDA regulations, site records, including but not limited to source documents, case report forms, informed consent documents, IRB correspondence, and drug accountability records, must be retained for a minimum of fifteen (15) years following the completion or termination of the CLARION Trial.

Target Enrollment Milestones. The current projected timeline for the CLARION Trial is as follows:

• Target First Patient In: August 14, 2023

• Projected Last Patient In: February 2027

• Projected Study Completion: August 2028

8. Engagement Team and Ongoing Support

The Calderwood & Harkness LLP engagement team for Matter No. 1018-00004 was as follows:

• Miriam Calloway, Partner — Responsible Partner

• Joel Strauss, Partner — Billing Partner

• Sean Morrissey, Associate — Lead Associate

• Christopher Aiken, Associate — Working Associate

With the closing of Matter No. 1018-00004, Calderwood & Harkness LLP's engagement for the negotiation, drafting, and execution of the MCTA and ancillary agreements in connection with the CLARION Trial is now concluded. The firm's final invoice for this matter will be transmitted under separate cover.

We note that any future legal services related to the CLARION Trial — including, by way of example, amendment negotiations, dispute resolution, additional site joinder support, regulatory advisory services, or other legal matters arising under or in connection with the MCTA — would require either a separate engagement letter or a formal amendment to the existing engagement letter dated March 20, 2023. We would be pleased to discuss the scope and terms of any such future engagement at your convenience.

In the interim, we remain available for informal consultation on post-closing matters as they arise, and we encourage you to reach out to me or any member of the engagement team with any questions. We understand that Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, will serve as the day-to-day legal contact at Penterra for any follow-up questions related to the closing binder or the matters addressed in this letter.

9. Acknowledgment and Appreciation

We wish to express our sincere appreciation for the opportunity to represent Penterra Pharmaceuticals Corp. in connection with this significant and complex clinical trial transaction. The CLARION Trial represents a substantial commitment by Penterra to advancing the treatment of advanced hepatocellular carcinoma, and we are proud to have played a role in bringing the MCTA and the associated network of clinical trial agreements to a successful conclusion.

We would like to acknowledge the extraordinary collaborative efforts and dedication of the Penterra team throughout this engagement, including you, Nathaniel; Rebecca Liang, for her meticulous attention to the clinical contract details and closing deliverables; Jennifer Holt, for her contributions to the regulatory and compliance provisions; Samantha Novak, for her tireless work coordinating the site-level agreements and budget negotiations; and the clinical development team led by Dr. Marcus Yun and Dr. Elaine Whitford, whose scientific expertise was invaluable in ensuring that the MCTA accurately reflected the operational requirements of the CLARION Protocol.

We also wish to note the constructive and professional engagement with Veridian's counsel at Whitmore, Jansen & Callahan LLP, particularly Allison Whitmore and David Kesselman, whose pragmatic approach to the negotiations contributed meaningfully to the efficient resolution of open issues. Similarly, we appreciated the professionalism and responsiveness of Veridian's internal legal and administrative teams, including Gregory Callahan, Senior Vice President & General Counsel, and Patricia Dunne, Director of Sponsored Research Agreements.

We look forward to continuing to serve Penterra's legal needs and to supporting the important work of the CLARION program.

Very truly yours,

CALDERWOOD & HARKNESS LLP

By: ________

Miriam Calloway Partner Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 280 Park Avenue, 34th Floor New York, NY 10017 Telephone: (212) 554-7024

Email: m.calloway@calderwoodharkness.com

cc:

Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp. Joel Strauss, Partner, Calderwood & Harkness LLP Sean Morrissey, Associate, Calderwood & Harkness LLP Christopher Aiken, Associate, Calderwood & Harkness LLP

Enclosures:

1. Closing Binder (3 hard copies), with Closing Binder Index and Table of Contents

2. Electronic closing binder access credentials (transmitted separately via secure encrypted email)

Date	Milestone
March 20, 2023	Calderwood & Harkness matter opened (Matter No. 1018-00004); engagement confirmed by executed engagement letter
April 7, 2023	First draft of MCTA circulated to Whitmore, Jansen & Callahan LLP ("WJC"), counsel for Veridian
April 28, 2023	Receipt of Veridian/WJC initial markup of the MCTA with accompanying comments memorandum
May 5, 2023	Indemnification term sheet exchanged between the parties to facilitate resolution of open subject-injury indemnification and site liability provisions
May 19, 2023	Second draft of MCTA circulated with redline against the Veridian/WJC initial markup
June 2, 2023	Receipt of Veridian/WJC second markup and revised exhibit drafts
June 9, 2023	In-person negotiation session held at WJC's Philadelphia office (1500 Market Street, Suite 3200, Philadelphia, PA 19102), resulting in resolution of substantially all remaining open points, including indemnification caps, insurance thresholds, publication rights, and intellectual property provisions
June 16, 2023	Near-final draft of MCTA circulated incorporating all agreed resolutions from the June 9 negotiation session
June 23, 2023	Final agreed draft of MCTA and all exhibits and schedules confirmed by both parties
June 28, 2023	Execution of the MCTA; signature pages executed by Nathaniel Briggs, Esq. (Vice President & General Counsel, for Penterra), Dr. Franklin Osei (President & Chief Executive Officer, for Veridian), and Dr. William Corwin (President, for Graystone University Medical Center, as lead site)
July 5, 2023	All conditions precedent to effectiveness satisfied, including delivery of insurance certificates, receipt of IRB approvals for lead sites, and execution of investigator signature pages
July 18, 2023	Effective Date of the MCTA
Budget Category	Amount
Per-patient fees ($52,000 × 1,200 subjects)	$62,400,000
Start-up fees ($75,000 × 38 sites)	$2,850,000
Site maintenance fees	$5,320,000
Investigator grants	$1,500,000
Network coordination fee	$4,200,000
Technology/EDC integration	$1,230,000
Contingency	$2,500,000
Total	$80,000,000

CALDERWOOD & HARKNESS LLP Counselors at Law
280 Park Avenue, 34th Floor New York, NY 10017 Telephone: (212) 554-7000 Facsimile: (212) 554-7001 www.calderwoodharkness.com
New York · Princeton · Washington, D.C. · Boston · San Francisco · London
Princeton Office: 101 Carnegie Center, Suite 500, Princeton, NJ 08540 | Telephone: (609) 428-3300
July 18, 2023
Via Email and First Class Mail
Nathaniel Briggs, Esq. Vice President & General Counsel Penterra Pharmaceuticals Corp. 200 Biopharma Boulevard, Suite 1400 Princeton, NJ 08540
Re: Matter Closing Confirmation — Calderwood & Harkness Matter No. 1018-00004 Master Clinical Trial Agreement between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. Protocol PPC-4871-III (CLARION)
Dear Nathaniel:
1. Purpose and Effective Date Confirmation
I write to confirm the effective date of the Master Clinical Trial Agreement (the "MCTA") and the formal closing of Calderwood & Harkness LLP Matter No. 1018-00004. This letter serves as the firm's official matter closing confirmation and provides a comprehensive record of the transaction documents, conditions precedent, and ongoing post-closing obligations for Penterra Pharmaceuticals Corp.'s files.
We are pleased to confirm that the MCTA between Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware ("Penterra"), and Veridian Health Research Network, Inc., a nonprofit corporation organized and existing under the laws of the State of Delaware and recognized as a tax-exempt organization under Section 501(c)(3) of the Internal Revenue Code of 1986, as amended ("Veridian"), became effective as of July 18, 2023 (the "Effective Date"). The MCTA governs the conduct of the multi-center clinical trial conducted under Protocol PPC-4871-III, known by the short title CLARION (Clinical Assessment of Response with Longitudinal Investigation in ONcology) (the "Protocol" or the "CLARION Trial"). The investigational product subject to the MCTA is penterafenib (PPC-4871), Penterra's proprietary oral multi-kinase inhibitor under clinical development for the treatment of advanced hepatocellular carcinoma.
The aggregate deal value under the MCTA is Eighty Million Dollars ($80,000,000), encompassing site fees, per-patient milestone payments, investigator grants, and operational costs across thirty-eight (38) participating Veridian Network clinical sites located in fourteen (14) states throughout the United States, over a projected forty-two (42)-month enrollment period within a total anticipated study duration of sixty (60) months.
2. Summary of Transaction Timeline
For the benefit of your records, set forth below is a chronological summary of the key milestones achieved during the negotiation and execution of the MCTA and related ancillary agreements:
The above timeline reflects a negotiation period of approximately ninety (90) days from initial draft circulation through execution, which is consistent with the scope and complexity of a multi-site clinical trial agreement of this magnitude. We note that the negotiation process benefited significantly from the collaborative approach taken by all parties and their respective counsel throughout.
3. Summary of Executed Documents
The following is a comprehensive listing of all executed documents comprising the transaction, each of which has been included in the closing binder referenced in Section 5 below:
1. Master Clinical Trial Agreement (execution version, dated June 28, 2023), by and between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc.
2. MCTA Signature Pages — executed counterpart signature pages from Penterra Pharmaceuticals Corp. (executed by Nathaniel Briggs, Esq., Vice President & General Counsel), Veridian Health Research Network, Inc. (executed by Dr. Franklin Osei, President & Chief Executive Officer), and Graystone University Medical Center (executed by Dr. William Corwin, President, as lead site)
3. Exhibit A — Protocol Synopsis (PPC-4871-III / CLARION), providing a summary of the Protocol objectives, study design, endpoints, inclusion/exclusion criteria, and anticipated enrollment targets
4. Exhibit B — Budget and Payment Schedule, reflecting a total budget of $80,000,000, allocated as follows:
5. Exhibit C — Form of Individual Site Agreement (Joinder), the template agreement pursuant to which each participating Veridian Network site will join the MCTA and agree to be bound by its terms
6. Exhibit D — Subject-Injury Indemnification Provisions, including: (i) per-subject medical care cap of $500,000; (ii) aggregate cap of $15,000,000 for all subject-injury claims; (iii) uncapped indemnification for claims arising from product-defect or manufacturing-defect causes of action; and (iv) site indemnity capped at $5,000,000 per site, per occurrence, and $20,000,000 in the aggregate
7. Exhibit E — Insurance Requirements and Certificate Forms, specifying: (i) Penterra's clinical trial liability insurance of $25,000,000 per occurrence / $75,000,000 aggregate, provided by Briarcliff Mutual Insurance Company under Policy No. BM-CTL-2023-04182, with a subject-injury sublimit of $10,000,000 per occurrence / $50,000,000 aggregate; and (ii) Veridian/site insurance requirements of $5,000,000 per occurrence / $10,000,000 aggregate for general liability and professional liability coverage
8. Exhibit F — Confidentiality and Data Protection Provisions, establishing mutual confidentiality obligations with a ten (10)-year term from the date of disclosure of each item of Confidential Information
9. Exhibit G — Intellectual Property and Publication Rights, providing for Penterra's sixty (60)-day review period for proposed publications and a ninety (90)-day patent delay period to permit the filing of patent applications prior to public disclosure
10. Exhibit H — Regulatory Compliance Representations and Covenants, setting forth representations, warranties, and ongoing covenants regarding compliance with applicable federal and state regulatory requirements, including Good Clinical Practice (GCP), FDA regulations (21 CFR Parts 50, 56, 312, and 812), Anti-Kickback Statute, and the Physician Payments Sunshine Act
11. Exhibit I — Form of Investigator Undertaking, the template acknowledgment to be executed by each site investigator confirming acceptance of responsibilities under the Protocol and applicable regulations
12. Exhibit J — Safety Reporting Procedures, establishing: (i) Serious Adverse Event (SAE) reporting within twenty-four (24) hours of site awareness; and (ii) IND safety report submission timelines in accordance with 21 CFR § 312.32 (seven (7)-day reports for fatal or life-threatening unexpected adverse reactions; fifteen (15)-day reports for all other serious and unexpected adverse reactions)
13. Exhibit K — Approved Subcontractors List, identifying the following pre-approved subcontractors: (i) Meridian CRO (contract research organization services); (ii) Pinnacle Data Solutions (electronic data capture and data management); and (iii) Northbridge Bioanalytical Laboratories (bioanalytical and pharmacokinetic sample analysis)
14. Schedule 1 — List of 38 Participating Veridian Network Sites, identifying each site by site number, institution name, principal investigator, location, and applicable Institutional Review Board
15. Individual Site Agreement — Graystone University Medical Center (Site 001), with Principal Investigator Dr. Catherine Aldridge and IRB oversight by the Graystone University Institutional Review Board (IORG Registration No. IRB00012847)
16. Individual Site Agreement — Lakemont Medical Center (Site 002), with Co-Principal Investigator Dr. Howard Matsuoka and IRB oversight by the Veridian Central IRB
17. Individual Site Agreement — Haverford Regional Medical Center (Site 003)
18. Individual Site Agreement — Cedar Falls University Hospital (Site 004)
19. Individual Site Agreement — Weston Memorial Health System (Site 005)
20. Principal Investigator Agreement — Dr. Catherine Aldridge, designating Dr. Aldridge as Global Principal Investigator for the CLARION Trial
21. Co-Principal Investigator Agreement — Dr. Howard Matsuoka, designating Dr. Matsuoka as Co-Principal Investigator
22. intellectual Property Side Letter (execution version, dated June 28, 2023), supplementing the intellectual property provisions of the MCTA with respect to certain pre-existing Veridian intellectual property and biomarker-related inventions
23. Closing Certificate — Penterra Pharmaceuticals Corp., certifying satisfaction of conditions precedent and accuracy of representations and warranties as of the Effective Date
24. Closing Certificate — Veridian Health Research Network, Inc., certifying satisfaction of conditions precedent and accuracy of representations and warranties as of the Effective Date
25. Secretary's Certificate — Penterra Pharmaceuticals Corp., certifying board authorization of the MCTA and incumbency of Nathaniel Briggs, Esq. (Vice President & General Counsel) and Dr. Anand Raghavan (Senior Vice President, Clinical Development)
26. Secretary's Certificate — Veridian Health Research Network, Inc., certifying board authorization of the MCTA and incumbency of Dr. Franklin Osei (President & Chief Executive Officer) and Gregory Callahan (Senior Vice President & General Counsel)
27. Officer's Certificate — Penterra Pharmaceuticals Corp., confirming the bringdown of representations and warranties as of July 5, 2023, and certifying that no material adverse change has occurred since the date of execution
4. Conditions Precedent Satisfaction
We confirm that all conditions precedent to the effectiveness of the MCTA, as specified in Section 12.1 thereof, were satisfied in full as of July 5, 2023. Specifically, the following conditions were satisfied:
(a) Penterra Insurance Certificate. Delivery by Penterra of its certificate of insurance from Briarcliff Mutual Insurance Company (Policy No. BM-CTL-2023-04182), evidencing clinical trial liability coverage of $25,000,000 per occurrence / $75,000,000 aggregate, including the required additional insured endorsement naming Veridian Health Research Network, Inc. and each participating Veridian Network site as additional insureds thereunder.
(b) Site Insurance Certificates. Delivery of site insurance certificates from each of the initial participating Veridian Network sites (Sites 001 through 005) demonstrating general liability and professional liability coverage of at least $5,000,000 per occurrence / $10,000,000 aggregate, meeting the minimum insurance requirements specified in Exhibit E to the MCTA.
(c) Lead Site IRB Approval. Receipt of written IRB approval from the Graystone University Institutional Review Board (IORG Registration No. IRB00012847) for conduct of the CLARION Trial at the lead site (Graystone University Medical Center, Site 001).
(d) Central IRB Approval. Receipt of written IRB approval from the Veridian Central IRB for conduct of the CLARION Trial at all participating Veridian Network sites located outside the Commonwealth of Pennsylvania.
(e) Investigator Signature Pages. Receipt of fully executed investigator signature pages from Dr. Catherine Aldridge (Global Principal Investigator, Site 001) and Dr. Howard Matsuoka (Co-Principal Investigator, Site 002), including executed Investigator Undertaking forms.
(f) Secretary's and Officer's Certificates. Delivery of executed secretary's certificates and officer's certificates from both Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc., in each case in the forms set forth in the closing deliverables schedule to the MCTA.
No conditions precedent were waived by either party. All deliverables were received in complete and satisfactory form.
5. Delivery of Closing Binder
We confirm that the complete closing binder for this transaction has been compiled by this firm and is being delivered concurrently with this letter. The closing binder is organized by tab number in accordance with the enclosed Closing Binder Index and Table of Contents, which corresponds to the document listing set forth in Section 3 above. Each tab contains a fully executed original or conformed copy of the applicable document.
Three (3) hard copies of the closing binder are being delivered by hand and overnight courier to Penterra's headquarters at 200 Biopharma Boulevard, Suite 1400, Princeton, NJ 08540, to the attention of Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs. We ask that Ms. Liang confirm receipt of the closing binders upon delivery.
In addition, a complete electronic copy of the closing binder, in searchable PDF format, has been uploaded to the secure document repository maintained by Calderwood & Harkness LLP and accessible to the authorized members of the Penterra legal team. Access credentials for the electronic closing binder are being transmitted separately via secure encrypted email to Ms. Liang and to you.
6. Key Terms Reminder — Governing Law and Dispute Resolution
For ease of reference, we provide the following brief reminder regarding the governing law and dispute resolution provisions of the MCTA, as set forth in Article XV thereof:
Governing Law. The MCTA is governed by and construed in accordance with the laws of the State of New York, without regard to conflicts of law principles that would result in the application of the laws of any other jurisdiction.
Dispute Resolution. The MCTA provides for a three-step dispute resolution escalation process, as follows:
Step 1 — Designated Representative Negotiation. In the event of any dispute, controversy, or claim arising out of or relating to the MCTA, the designated senior representatives of each party shall first attempt to resolve such dispute through good-faith negotiation for a period of thirty (30) days following written notice of the dispute.
Step 2 — Mediation. If the dispute is not resolved through negotiation within such thirty (30)-day period, the parties shall submit the dispute to mediation under the American Arbitration Association ("AAA") Commercial Mediation Rules for a period of sixty (60) days, or such longer period as the parties may agree.
Step 3 — Binding Arbitration. If the dispute is not resolved through mediation, either party may submit the dispute to final and binding arbitration in New York, New York under the AAA Commercial Arbitration Rules, before a panel of three (3) arbitrators selected in accordance with such rules.
Injunctive Relief. Notwithstanding the foregoing, either party may seek injunctive or other equitable relief from the state and federal courts located in New York County, New York, to protect its confidential information, intellectual property, or other rights for which monetary damages would be an inadequate remedy.
7. Ongoing Post-Closing Obligations and Action Items
Although the negotiation and execution of the MCTA and ancillary agreements is now complete, we wish to highlight the following ongoing post-closing obligations and near-term action items for Penterra's attention. While Calderwood & Harkness's active engagement on this matter is concluding, we believe it is prudent to memorialize these items for the benefit of Penterra's internal clinical contracts and legal teams.
Remaining Site Joinders. As of the Effective Date, Individual Site Agreements have been executed for five (5) of the thirty-eight (38) participating Veridian Network sites (Sites 001 through 005). Execution of Individual Site Agreements for the remaining thirty-three (33) sites is expected to occur on a rolling basis as each site completes its internal review and obtains the requisite IRB approval. This process is to be coordinated by Samantha Novak, Director of Clinical Contracts at Penterra, in collaboration with Patricia Dunne, Director of Sponsored Research Agreements at Veridian. We recommend that Penterra establish an internal tracking mechanism to monitor the status of each site joinder and to ensure that no site initiates study activities prior to the execution of its Individual Site Agreement.
Annual Insurance Renewals. The Briarcliff Mutual Insurance Company clinical trial liability policy (Policy No. BM-CTL-2023-04182) currently maintained by Penterra has a policy expiration date of March 31, 2024. Penterra must ensure timely renewal of such policy and delivery of updated certificates of insurance to Veridian annually throughout the duration of the CLARION Trial. Any lapse in coverage could constitute a material breach of the MCTA and could result in a suspension of study activities at participating sites. We recommend that Penterra's risk management group calendar the renewal date well in advance and coordinate with Briarcliff Mutual to ensure continuity of coverage.
Site Insurance Certificate Collection. Penterra has an ongoing obligation under Exhibit E of the MCTA to collect and maintain current certificates of insurance from all thirty-eight (38) participating Veridian Network sites, confirming that each site maintains general liability and professional liability coverage meeting the minimum thresholds specified in the MCTA ($5,000,000 per occurrence / $10,000,000 aggregate). We recommend that Penterra's clinical contracts team implement a centralized insurance certificate tracking system and establish annual reminder protocols for certificate renewals.
Payment Administration. The MCTA contemplates the following categories of payments, each subject to specified triggering events and administrative requirements:
• Per-Patient Milestone Payments: $13,000 per milestone × four (4) milestones per patient (Informed Consent, Randomization, Treatment Completion, and End-of-Study Visit), for a total per-patient payment of $52,000
• Start-Up Fee Second Installments: $37,500 per site, payable upon enrollment of the first patient at each site (the first installment of $37,500 per site having been paid upon execution of the applicable Individual Site Agreement)
• Quarterly Network Coordination Fees: $300,000 per quarter, payable to Veridian for network coordination and administrative services
• Annual Site Maintenance Fees: as set forth in Exhibit B, payable annually during the study period
• All payments are due net forty-five (45) days from receipt of a proper and complete invoice submitted by Veridian in accordance with the invoicing procedures set forth in Section 7.3 of the MCTA
IRB Maintenance. Each participating site must maintain active IRB approval throughout the duration of the CLARION Trial. IRB continuing review submissions must be filed no later than the applicable anniversary date of the initial IRB approval for each site. Penterra's clinical operations team should coordinate with Veridian to track IRB approval status across all thirty-eight (38) sites and to ensure that no site conducts study activities under a lapsed IRB approval.
Form FDA 1572 Collection. Penterra has an ongoing obligation to collect and maintain current FDA Form 1572 (Statement of Investigator) and financial disclosure certifications pursuant to 21 CFR Part 54 (Financial Disclosure by Clinical Investigators) from all site investigators. These forms must be updated as investigators are added or replaced and must be maintained in the regulatory trial master file.
Regulatory Compliance. Penterra must ensure ongoing compliance with applicable regulatory requirements throughout the CLARION Trial, including, without limitation: (i) the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)); (ii) the Physician Payments Sunshine Act and Open Payments reporting requirements (42 U.S.C. § 1320a-7h); and (iii) the Health Insurance Portability and Accountability Act of 1996 ("HIPAA") and its implementing regulations. We understand that Penterra is coordinating with Castleton & Hargrove LLP, specifically Dr. Priya Sundaram, on FDA regulatory matters, including the maintenance of IND 157823 and ongoing communications with the FDA's Division of Oncology Drug Products. We recommend continued close coordination between Penterra's clinical and regulatory teams and outside regulatory counsel throughout the study.
Document Retention. Pursuant to Section 14.2 of the MCTA and applicable FDA regulations, site records, including but not limited to source documents, case report forms, informed consent documents, IRB correspondence, and drug accountability records, must be retained for a minimum of fifteen (15) years following the completion or termination of the CLARION Trial.
Target Enrollment Milestones. The current projected timeline for the CLARION Trial is as follows:
• Target First Patient In: August 14, 2023
• Projected Last Patient In: February 2027
• Projected Study Completion: August 2028
8. Engagement Team and Ongoing Support
The Calderwood & Harkness LLP engagement team for Matter No. 1018-00004 was as follows:
• Miriam Calloway, Partner — Responsible Partner
• Joel Strauss, Partner — Billing Partner
• Sean Morrissey, Associate — Lead Associate
• Christopher Aiken, Associate — Working Associate
With the closing of Matter No. 1018-00004, Calderwood & Harkness LLP's engagement for the negotiation, drafting, and execution of the MCTA and ancillary agreements in connection with the CLARION Trial is now concluded. The firm's final invoice for this matter will be transmitted under separate cover.
We note that any future legal services related to the CLARION Trial — including, by way of example, amendment negotiations, dispute resolution, additional site joinder support, regulatory advisory services, or other legal matters arising under or in connection with the MCTA — would require either a separate engagement letter or a formal amendment to the existing engagement letter dated March 20, 2023. We would be pleased to discuss the scope and terms of any such future engagement at your convenience.
In the interim, we remain available for informal consultation on post-closing matters as they arise, and we encourage you to reach out to me or any member of the engagement team with any questions. We understand that Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, will serve as the day-to-day legal contact at Penterra for any follow-up questions related to the closing binder or the matters addressed in this letter.
9. Acknowledgment and Appreciation
We wish to express our sincere appreciation for the opportunity to represent Penterra Pharmaceuticals Corp. in connection with this significant and complex clinical trial transaction. The CLARION Trial represents a substantial commitment by Penterra to advancing the treatment of advanced hepatocellular carcinoma, and we are proud to have played a role in bringing the MCTA and the associated network of clinical trial agreements to a successful conclusion.
We would like to acknowledge the extraordinary collaborative efforts and dedication of the Penterra team throughout this engagement, including you, Nathaniel; Rebecca Liang, for her meticulous attention to the clinical contract details and closing deliverables; Jennifer Holt, for her contributions to the regulatory and compliance provisions; Samantha Novak, for her tireless work coordinating the site-level agreements and budget negotiations; and the clinical development team led by Dr. Marcus Yun and Dr. Elaine Whitford, whose scientific expertise was invaluable in ensuring that the MCTA accurately reflected the operational requirements of the CLARION Protocol.
We also wish to note the constructive and professional engagement with Veridian's counsel at Whitmore, Jansen & Callahan LLP, particularly Allison Whitmore and David Kesselman, whose pragmatic approach to the negotiations contributed meaningfully to the efficient resolution of open issues. Similarly, we appreciated the professionalism and responsiveness of Veridian's internal legal and administrative teams, including Gregory Callahan, Senior Vice President & General Counsel, and Patricia Dunne, Director of Sponsored Research Agreements.
We look forward to continuing to serve Penterra's legal needs and to supporting the important work of the CLARION program.
Very truly yours,
CALDERWOOD & HARKNESS LLP
By: ________
Miriam Calloway Partner Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 280 Park Avenue, 34th Floor New York, NY 10017 Telephone: (212) 554-7024
Email: m.calloway@calderwoodharkness.com
cc:
Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp. Joel Strauss, Partner, Calderwood & Harkness LLP Sean Morrissey, Associate, Calderwood & Harkness LLP Christopher Aiken, Associate, Calderwood & Harkness LLP
Enclosures:
1. Closing Binder (3 hard copies), with Closing Binder Index and Table of Contents
2. Electronic closing binder access credentials (transmitted separately via secure encrypted email)
Date | Milestone
March 20, 2023 | Calderwood & Harkness matter opened (Matter No. 1018-00004); engagement confirmed by executed engagement letter
April 7, 2023 | First draft of MCTA circulated to Whitmore, Jansen & Callahan LLP ("WJC"), counsel for Veridian
April 28, 2023 | Receipt of Veridian/WJC initial markup of the MCTA with accompanying comments memorandum
May 5, 2023 | Indemnification term sheet exchanged between the parties to facilitate resolution of open subject-injury indemnification and site liability provisions
May 19, 2023 | Second draft of MCTA circulated with redline against the Veridian/WJC initial markup
June 2, 2023 | Receipt of Veridian/WJC second markup and revised exhibit drafts
June 9, 2023 | In-person negotiation session held at WJC's Philadelphia office (1500 Market Street, Suite 3200, Philadelphia, PA 19102), resulting in resolution of substantially all remaining open points, including indemnification caps, insurance thresholds, publication rights, and intellectual property provisions
June 16, 2023 | Near-final draft of MCTA circulated incorporating all agreed resolutions from the June 9 negotiation session
June 23, 2023 | Final agreed draft of MCTA and all exhibits and schedules confirmed by both parties
June 28, 2023 | Execution of the MCTA; signature pages executed by Nathaniel Briggs, Esq. (Vice President & General Counsel, for Penterra), Dr. Franklin Osei (President & Chief Executive Officer, for Veridian), and Dr. William Corwin (President, for Graystone University Medical Center, as lead site)
July 5, 2023 | All conditions precedent to effectiveness satisfied, including delivery of insurance certificates, receipt of IRB approvals for lead sites, and execution of investigator signature pages
July 18, 2023 | Effective Date of the MCTA
Budget Category | Amount
Per-patient fees ($52,000 × 1,200 subjects) | $62,400,000
Start-up fees ($75,000 × 38 sites) | $2,850,000
Site maintenance fees | $5,320,000
Investigator grants | $1,500,000
Network coordination fee | $4,200,000
Technology/EDC integration | $1,230,000
Contingency | $2,500,000
Total | $80,000,000

CALDERWOOD & HARKNESS LLP Counselors at Law

CALDERWOOD & HARKNESS LLP

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