MEMORANDUM — PRIVILEGED AND CONFIDENTIAL / ATTORNEY WORK PRODUCT
This memorandum is protected by the attorney-client privilege and the attorney work product doctrine. It is intended solely for the use of the individuals to whom it is addressed and contains confidential information. Any unauthorized review, use, disclosure, or distribution is prohibited. If you have received this memorandum in error, please notify the sender immediately and destroy all copies.
FROM: Sean Morrissey, Associate, Calderwood & Harkness LLP
TO: Miriam Calloway, Partner, Calderwood & Harkness LLP
CC: Christopher Aiken, Associate, Calderwood & Harkness LLP; Joel Strauss, Partner, Calderwood & Harkness LLP
DATE: July 5, 2023
RE: Satisfaction of Conditions Precedent to Closing — Master Clinical Trial Agreement between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. (Protocol PPC-4871-III / CLARION)
MATTER NO.: 1018-00004
Right-click to update Table of Contents
I. Executive Summary
The purpose of this memorandum is to confirm that all conditions precedent to the closing of the Master Clinical Trial Agreement (the "MCTA"), dated June 28, 2023, by and between Penterra Pharmaceuticals Corp., a Delaware corporation ("Penterra" or the "Sponsor"), and Veridian Health Research Network, Inc., a Delaware non-profit corporation ("Veridian" or the "Site Network"), have been satisfied or, where applicable, waived, as of July 5, 2023.
The MCTA governs the conduct of Protocol PPC-4871-III, known by the study acronym CLARION (Clinical Assessment of Response with Longitudinal Investigation in ONcology), a Phase III, randomized, double-blind, placebo-controlled clinical trial evaluating the safety and efficacy of penterafenib (PPC-4871) in adult patients with advanced hepatocellular carcinoma ("HCC") who have progressed on or are intolerant to first-line systemic therapy. The CLARION trial is planned to be conducted across thirty-eight (38) Veridian Network sites located in fourteen (14) states, with a planned enrollment of approximately 1,200 subjects and a total contractual deal value of Eighty Million Dollars ($80,000,000).
The MCTA was duly executed by both parties on June 28, 2023. Closing of the MCTA was conditioned upon the satisfaction of certain deliverables and conditions precedent as set forth in Article XII of the MCTA and the Closing Checklist attached thereto as Exhibit L. These conditions included, among other things: (i) the execution and delivery of signature pages by both parties and the lead site institution; (ii) delivery of certificates of insurance meeting specified minimum coverage thresholds; (iii) receipt of Institutional Review Board ("IRB") approvals for the two lead enrollment sites; (iv) execution and delivery of principal investigator agreements and investigator undertakings; (v) delivery of financial disclosure certifications in accordance with 21 C.F.R. Part 54; (vi) delivery of secretary's certificates and closing certificates by both parties; (vii) execution and delivery of ancillary agreements, including the intellectual Property Side Letter and Individual Site Agreements for the lead sites; and (viii) finalization and delivery of all exhibits and schedules to the MCTA.
As set forth in detail below, I have reviewed all deliverables received by Calderwood & Harkness LLP in connection with the closing and have confirmed with both the Penterra and Veridian engagement teams that each condition precedent has been satisfied. No conditions precedent remain outstanding. Accordingly, closing of the MCTA is confirmed effective as of July 5, 2023.
The Effective Date of the MCTA, as defined in Section 2.1 of the MCTA, will be July 18, 2023, which is the date following final administrative confirmation and the distribution of the closing binder to all parties and their respective counsel.
II. Background
A. The Parties
Penterra Pharmaceuticals Corp. ("Penterra" or the "Sponsor") is a Delaware corporation headquartered at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540. Penterra is a publicly traded biopharmaceutical company whose common stock is listed on the Nasdaq Global Select Market under the ticker symbol "PTRA." Penterra is engaged in the discovery, development, and commercialization of novel oncology therapeutics, with a pipeline focused on kinase inhibitors and immuno-oncology agents. Penterra serves as the Sponsor of Protocol PPC-4871-III under the MCTA and bears primary responsibility for study design, regulatory filings, drug supply, data ownership, and pharmacovigilance oversight.
Veridian Health Research Network, Inc. ("Veridian" or the "Site Network") is a Delaware non-profit corporation organized under Section 501(c)(3) of the Internal Revenue Code, headquartered at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104. Veridian operates a coordinated network of academic medical centers, community oncology practices, and hospital-based research programs across the United States. Veridian serves as the institutional counterparty and site network coordinator under the MCTA, responsible for the enrollment and management of participating clinical trial sites, coordination of IRB activities through its Central IRB framework, and oversight of site-level operational compliance.
B. The CLARION Trial
Protocol PPC-4871-III (CLARION) is a Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial designed to evaluate the safety and efficacy of penterafenib (PPC-4871), a selective, oral, multi-kinase inhibitor, in adult patients with advanced HCC who have received and progressed on at least one prior line of systemic therapy. The study employs a 2:1 randomization ratio, with approximately 800 subjects randomized to the treatment arm (penterafenib plus best supportive care) and approximately 400 subjects randomized to the control arm (matching placebo plus best supportive care), for a total planned enrollment of 1,200 subjects. The primary endpoint is overall survival; key secondary endpoints include progression-free survival, objective response rate per RECIST v1.1, duration of response, and patient-reported outcomes.
The CLARION trial is planned to be conducted across thirty-eight (38) Veridian Network sites located in fourteen (14) states. The enrollment period is estimated at forty-two (42) months, with a total anticipated study duration of sixty (60) months from first patient in to last patient last visit. The target date for first patient in ("FPI") is August 14, 2023.
The Investigational New Drug Application for penterafenib is filed with the United States Food and Drug Administration ("FDA") under IND Number 157823. The trial is registered on ClinicalTrials.gov under Identifier NCT05928174.
C. Negotiation Timeline
The negotiation of the MCTA proceeded over an approximately twelve-week period, as summarized below:
• April 7, 2023: Calderwood & Harkness circulated the first draft of the MCTA, prepared on behalf of Penterra, to Whitmore, Jansen & Callahan LLP ("WJC"), outside counsel for Veridian.
• April 28, 2023: WJC returned a comprehensive counterparty markup of the MCTA on behalf of Veridian, with significant comments on indemnification, intellectual property, insurance requirements, and data protection provisions.
• May 5, 2023: The parties exchanged a term sheet addressing the indemnification and subject-injury provisions, following internal alignment discussions between Penterra's clinical operations and legal teams.
• May 19, 2023: Calderwood & Harkness circulated a second revised draft of the MCTA incorporating agreed-upon indemnification terms and reflecting further comments on insurance, regulatory compliance, and publication rights.
• June 9, 2023: An in-person negotiation session was held at WJC's offices in Philadelphia, Pennsylvania. Attendees included Miriam Calloway and Sean Morrissey of Calderwood & Harkness; Allison Whitmore and David Kesselman of WJC; Nathaniel Briggs and Rebecca Liang of Penterra; and Gregory Callahan and Dr. Franklin Osei of Veridian. The session resolved remaining open issues related to the intellectual property side letter, the scope of the additional insured endorsement, the Central IRB reliance framework, and the publication review timeline.
• June 16, 2023: Calderwood & Harkness circulated a near-final draft of the MCTA incorporating all resolutions from the June 9 session.
• June 23, 2023: The final agreed-upon draft of the MCTA was confirmed by both Calderwood & Harkness and WJC.
• June 28, 2023: The MCTA was duly executed by both Penterra and Veridian.
D. Outside Counsel and Key Contacts
Outside counsel for Veridian is Whitmore, Jansen & Callahan LLP, located at 1500 Market Street, Suite 3200, Philadelphia, Pennsylvania 19102, with the following attorneys of record on this matter: Allison Whitmore, Partner, and David Kesselman, Associate.
The contract research organization ("CRO") engaged by Penterra for the CLARION trial is Meridian Contract Research Organization, Inc. ("Meridian CRO"). Penterra and Meridian CRO are parties to a separate Master Services Agreement dated January 15, 2023, which governs the CRO's responsibilities for data management, biostatistics, regulatory submissions support, and clinical monitoring. The Meridian CRO MSA is not part of the MCTA closing but is referenced herein for coordination purposes, as certain operational responsibilities under the MCTA interface with Meridian CRO's scope of work.
III. Conditions Precedent — Summary Table
The following table provides a summary of all conditions precedent to closing of the MCTA, together with the responsible party, deliverable description, date received or confirmed, and current status. Each item is discussed in further detail in Section IV below.
IV. Detailed Analysis of Each Condition Precedent
A. Execution and Delivery of the MCTA and Signature Pages
Section 12.1(a) of the MCTA required the execution and delivery of the MCTA by each of the parties and by Graystone University Medical Center as the designated lead site institution.
The Execution Version of the MCTA was finalized and circulated to all parties for execution on June 26, 2023. Execution occurred on June 28, 2023, and Calderwood & Harkness has confirmed receipt of all required signature pages, as follows:
Penterra Pharmaceuticals Corp. Signature Page. The MCTA signature page on behalf of Penterra was signed by Nathaniel Briggs, Esq., Vice President and General Counsel, Penterra Pharmaceuticals Corp., dated June 28, 2023. Mr. Briggs was duly authorized to execute the MCTA on behalf of Penterra pursuant to the board resolutions referenced in the Secretary's Certificate discussed in Section IV.G below. The original wet-ink signature page was transmitted to Calderwood & Harkness via overnight delivery (Severin Partners LLC tracking no. 7749 2135 8841) and received at our New York office on June 29, 2023. A conformed copy was received via email on June 28, 2023.
Veridian Health Research Network, Inc. Signature Page. The MCTA signature page on behalf of Veridian was signed by Dr. Franklin Osei, M.D., Ph.D., President and Chief Executive Officer, Veridian Health Research Network, Inc., dated June 28, 2023. Dr. Osei was duly authorized to execute the MCTA on behalf of Veridian pursuant to the board resolutions referenced in the Veridian Secretary's Certificate discussed in Section IV.G below. A PDF copy of the executed signature page was transmitted to Calderwood & Harkness by Whitmore, Jansen & Callahan LLP via email on June 28, 2023, at approximately 4:47 p.m. Eastern Time. The original wet-ink signature page was transmitted via overnight delivery and received at our New York office on June 30, 2023.
Graystone University Medical Center Signature Page (Lead Site). The MCTA signature page on behalf of Graystone University Medical Center, in its capacity as the designated lead site institution under the MCTA, was signed by Dr. William Corwin, M.D., President, Graystone University Medical Center, dated June 28, 2023. The executed signature page was transmitted to Calderwood & Harkness by Veridian and WJC via email on June 29, 2023, with the original received by overnight delivery the same day.
All three required signature pages have been received in original form and matched against the execution version of the MCTA. No discrepancies or irregularities were noted.
Condition: Satisfied.
B. Delivery of Sponsor Insurance Certificates
Section 12.1(b) of the MCTA required Penterra, as Sponsor, to deliver certificates of insurance evidencing clinical trial liability coverage meeting the minimum coverage requirements set forth in Exhibit E of the MCTA within fifteen (15) business days of the date of execution of the MCTA. Exhibit E specifies minimum per-occurrence and aggregate limits, requires clinical trial-specific coverage, includes a subject-injury sublimit, and mandates that Veridian and each participating Veridian Network site institution be named as additional insureds under the Sponsor's clinical trial liability policy.
Calderwood & Harkness coordinated with Penterra's insurance broker and underwriter to ensure timely delivery of the required certificate and endorsement. The following documentation was received and confirmed:
Certificate of Insurance. A certificate of insurance was received from Briarcliff Mutual Insurance Company, located at 55 Constitution Plaza, Hartford, Connecticut 06103, for Policy No. BM-CTL-2023-04182. The certificate was issued by Karen Tremblay, Vice President, Life Sciences Lines, Briarcliff Mutual Insurance Company. The key terms of the policy are as follows:
• Policy Period: April 1, 2023, through March 31, 2024 (renewable annually).
• Per-Occurrence Limit: Twenty-Five Million Dollars ($25,000,000).
• Aggregate Limit: Seventy-Five Million Dollars ($75,000,000).
• Subject-Injury Sublimit: Ten Million Dollars ($10,000,000) per occurrence; Fifty Million Dollars ($50,000,000) aggregate.
• Coverage Type: Clinical Trial Liability — Sponsor, including coverage for claims arising out of the administration and use of investigational products, protocol procedures, and trial-related medical interventions.
Calderwood & Harkness reviewed the certificate of insurance and confirmed that all coverage limits and terms meet or exceed the minimum requirements specified in Exhibit E of the MCTA.
Additional Insured Endorsement. Following execution of the MCTA, Calderwood & Harkness transmitted a letter to Briarcliff Mutual Insurance Company requesting the issuance of an additional insured endorsement naming Veridian Health Research Network, Inc. and each participating Veridian Network site institution as additional insureds under Policy No. BM-CTL-2023-04182. The endorsement was issued by Briarcliff Mutual and received by Calderwood & Harkness on July 1, 2023. The endorsement was reviewed and confirmed to name the required additional insured parties and to provide coverage consistent with the terms of Exhibit E.
Transmittal to Veridian. The certificate of insurance and additional insured endorsement were transmitted to Whitmore, Jansen & Callahan LLP, on behalf of Veridian, via a Certificate of Insurance Transmittal Letter prepared by Calderwood & Harkness, on July 3, 2023. This date falls within the fifteen (15) business day period following the June 28, 2023, date of MCTA execution.
WJC acknowledged receipt of the certificate and endorsement by email to Sean Morrissey on July 3, 2023, and confirmed that the certificate met the coverage requirements of the MCTA on behalf of Veridian.
Condition: Satisfied.
C. Delivery of Site Network Insurance Certificates
Section 12.1(c) of the MCTA required Veridian and each participating site institution to deliver certificates of insurance evidencing general liability and professional liability coverage of at least Five Million Dollars ($5,000,000) per occurrence and Ten Million Dollars ($10,000,000) in the aggregate within fifteen (15) business days of execution of the MCTA. With respect to the closing condition specifically, Section 12.1(c)(ii) required delivery of certificates for the Veridian network-level policy and for each of the two lead sites—Graystone University Medical Center (Site 001) and Lakemont Medical Center (Site 002)—as a condition to closing.
Calderwood & Harkness transmitted a letter to Gregory Callahan, Esq., Vice President, Legal & Compliance, Veridian Health Research Network, Inc., on June 29, 2023, requesting the delivery of site insurance certificates in accordance with the MCTA. The following certificates were received and reviewed:
Veridian Network-Level Certificate. Veridian provided a certificate of insurance evidencing network-level general liability and professional liability coverage through its institutional umbrella policy. The certificate was received by Calderwood & Harkness from WJC on July 3, 2023. Coverage limits were confirmed to meet or exceed the minimum thresholds specified in the MCTA.
Graystone University Medical Center (Site 001). A certificate of insurance was received from Graystone University Medical Center's institutional insurer, confirming general liability and professional liability coverage with per-occurrence limits of Five Million Dollars ($5,000,000) and aggregate limits of Ten Million Dollars ($10,000,000). The certificate was received from WJC on July 3, 2023. Coverage was confirmed to meet the thresholds specified in Exhibit E of the MCTA.
Lakemont Medical Center (Site 002). A certificate of insurance was received from Lakemont Medical Center's institutional insurer, confirming general liability and professional liability coverage with per-occurrence limits of Five Million Dollars ($5,000,000) and aggregate limits of Ten Million Dollars ($10,000,000). The certificate was received from WJC on July 5, 2023. Coverage was confirmed to meet the thresholds specified in Exhibit E of the MCTA.
Remaining Sites. Certificates from the remaining thirty-six (36) Veridian Network sites (Sites 003 through 038) were not required as conditions precedent to closing. Pursuant to Section 12.1(c)(iii) of the MCTA and as confirmed during the June 9, 2023, negotiation session, the parties agreed that delivery of certificates from the lead sites and the Veridian network-level certificate would be sufficient for closing purposes. Certificates from remaining sites are to be delivered on a rolling basis as each site executes its Individual Site Agreement (Joinder) pursuant to Exhibit C of the MCTA, with delivery due within fifteen (15) business days of each site joinder execution. This obligation is discussed further in Section V below as a post-closing deliverable.
Condition: Satisfied (with respect to the closing condition; remaining site certificates are post-closing deliverables).
D. IRB Approvals for Lead Sites
Section 12.1(d) of the MCTA required receipt of IRB approval for Protocol PPC-4871-III (CLARION) at each of the two designated lead enrollment sites prior to closing. This condition was designed to confirm that the lead sites would be positioned to commence enrollment activities promptly following the Effective Date of the MCTA.
Graystone University Medical Center (Site 001). Graystone University Medical Center maintains its own IRB, the Graystone University Institutional Review Board (IRB Registration No. IRB00012847), registered with the Office for Human Research Protections ("OHRP"). IRB approval for Protocol PPC-4871-III (CLARION) was confirmed by letter from the Graystone University Institutional Review Board dated June 22, 2023. The approval letter was received by Calderwood & Harkness from Veridian and WJC on June 26, 2023. The scope of the IRB approval covers the following study documents:
• Protocol PPC-4871-III (CLARION), Version 3.0, dated May 15, 2023;
• Informed Consent Form, Version 2.1, dated May 22, 2023;
• Investigator's Brochure for Penterafenib (PPC-4871), Edition 7, dated March 1, 2023; and
• Subject Recruitment Materials, Version 1.0, dated April 10, 2023.
The approval is valid for a period of one (1) year from the date of issuance, subject to continuing review by the Graystone University Institutional Review Board in accordance with 21 C.F.R. Part 56 and the institution's Federalwide Assurance.
Lakemont Medical Center (Site 002). Lakemont Medical Center participates in the Veridian Central IRB reliance framework. Under this framework, Veridian Central IRB serves as the IRB of record for Veridian Network sites located outside of Pennsylvania, pursuant to reliance agreements executed between the Veridian Central IRB and each participating site's institutional signatory official. IRB approval for Protocol PPC-4871-III (CLARION) at Lakemont Medical Center was confirmed under the Veridian Central IRB reliance framework by approval letter dated June 30, 2023. The approval letter was received by Calderwood & Harkness from WJC on July 3, 2023.
Remaining Sites. IRB approvals for the remaining Veridian Network sites will be obtained on a rolling basis prior to each site's activation and enrollment of the first subject at that site. This is consistent with the multi-site IRB reliance structure described in Article VIII of the MCTA and the Memorandum on IRB Reliance for Multi-Site Trials circulated to the engagement team on May 12, 2023. The closing of the MCTA was conditioned only upon receipt of lead-site IRB approvals, and this condition has been met.
Condition: Satisfied.
E. Executed Investigator Signature Pages and Undertakings
Section 12.1(e) of the MCTA required the execution and delivery of principal investigator and co-principal investigator agreements and investigator undertaking forms (in the form attached as Exhibit I to the MCTA) prior to closing, with respect to the designated Global Principal Investigator and Co-Principal Investigator for the CLARION trial.
Dr. Catherine Aldridge, M.D., Ph.D. — Global Principal Investigator. Dr. Aldridge serves as the Global Principal Investigator for Protocol PPC-4871-III (CLARION). Dr. Aldridge is Professor of Oncology at Graystone University Medical Center, 1200 University Avenue, Philadelphia, Pennsylvania 19104, and is board-certified in Medical Oncology and Hematology. The following documents were executed and received:
• Principal Investigator Agreement: Executed by Dr. Aldridge, signed and dated June 27, 2023. The executed agreement was transmitted by WJC and received by Calderwood & Harkness on June 28, 2023.
• Investigator Undertaking (Exhibit I form): Executed by Dr. Aldridge, signed and dated June 27, 2023, in which Dr. Aldridge undertakes, among other things, to comply with the protocol, applicable regulations (including 21 C.F.R. Parts 50, 54, 56, and 312), ICH E6(R2) Good Clinical Practice guidelines, and the terms and conditions of the MCTA. The executed undertaking was received concurrently with the Principal Investigator Agreement.
Dr. Howard Matsuoka, M.D. — Co-Principal Investigator. Dr. Matsuoka serves as the Co-Principal Investigator for Protocol PPC-4871-III (CLARION). Dr. Matsuoka is Associate Professor of Hepatology and Oncology at Lakemont Medical Center, 4400 North Michigan Drive, Chicago, Illinois 60611. The following documents were executed and received:
• Co-Principal Investigator Agreement: Executed by Dr. Matsuoka, signed and dated June 28, 2023. The executed agreement was transmitted by WJC and received by Calderwood & Harkness on June 29, 2023.
• Investigator Undertaking (Exhibit I form): Executed by Dr. Matsuoka, signed and dated June 28, 2023, containing the same undertakings described above. The executed undertaking was received concurrently with the Co-Principal Investigator Agreement.
Remaining Investigators. Investigator signature pages and undertakings for sub-investigators and site principal investigators at the remaining thirty-six (36) Veridian Network sites will be collected on a rolling basis as Individual Site Agreements are executed. The preparation and collection of Form FDA 1572 (Statement of Investigator) for each site investigator is being coordinated pursuant to the Form 1572 Preparation Memorandum circulated to Penterra's clinical operations team (Jennifer Holt, Vice President, Clinical Operations, and Samantha Novak, Director, Clinical Contracts) on June 15, 2023. This coordination effort is a post-closing matter.
Condition: Satisfied.
F. Financial Disclosure Certifications (21 C.F.R. Part 54)
Section 12.1(f) of the MCTA required the completion and delivery of financial disclosure certification forms in accordance with 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators) for the Global Principal Investigator and the Co-Principal Investigator prior to closing. Financial disclosure certifications are required by FDA regulations to identify any financial interests or arrangements that could affect the reliability of data submitted in support of a marketing application.
Dr. Catherine Aldridge. Dr. Aldridge completed and submitted a Financial Disclosure Certification form dated June 27, 2023. The certification confirms compliance with the requirements of 21 C.F.R. Part 54, including certification that Dr. Aldridge does not hold any disqualifying financial interests in Penterra Pharmaceuticals Corp. or in penterafenib (PPC-4871), including but not limited to equity interests, significant payments exceeding $25,000, proprietary interests in the investigational product, or significant equity interests in the Sponsor. The completed certification was received by Calderwood & Harkness from WJC on June 28, 2023.
Dr. Howard Matsuoka. Dr. Matsuoka completed and submitted a Financial Disclosure Certification form dated June 28, 2023. The certification confirms compliance with the requirements of 21 C.F.R. Part 54 and confirms no disqualifying financial interests in Penterra or penterafenib. The completed certification was received by Calderwood & Harkness from WJC on June 29, 2023.
Calderwood & Harkness reviewed each certification for completeness and consistency with the form prescribed by the MCTA and confirmed that no disclosures of potentially disqualifying financial interests were made by either investigator. Copies of the certifications will be maintained in the closing binder and have been transmitted to Penterra's regulatory affairs team for inclusion in the IND file as required by 21 C.F.R. § 312.23(a)(11) and § 54.6.
Financial disclosure certifications for the remaining site investigators and sub-investigators will be completed as part of the Individual Site Agreement joinder process on a rolling basis. This is a post-closing deliverable.
Condition: Satisfied.
G. Secretary's Certificates and Corporate Authorization
Section 12.1(g) of the MCTA required the delivery by each party of a secretary's certificate confirming due corporate authorization of the MCTA and ancillary agreements.
Penterra Pharmaceuticals Corp. A Secretary's Certificate was received from Penterra, executed by the Secretary of Penterra Pharmaceuticals Corp. and dated June 28, 2023. The Secretary's Certificate certifies the following:
(i) That the Board of Directors of Penterra Pharmaceuticals Corp. duly adopted resolutions authorizing the execution, delivery, and performance of the MCTA and all ancillary agreements contemplated thereby, including the intellectual Property Side Letter and the Individual Site Agreements;
(ii) That the following individuals are duly elected or appointed officers of Penterra and are authorized signatories with respect to the MCTA and ancillary agreements: Nathaniel Briggs, Esq., Vice President and General Counsel, and Dr. Anand Raghavan, M.D., Ph.D., Chief Executive Officer; and
(iii) That attached to the Secretary's Certificate are true and correct copies of the bylaws and certificate of incorporation of Penterra Pharmaceuticals Corp., each as currently in effect.
The Secretary's Certificate was received by Calderwood & Harkness via email on June 28, 2023, with the original received by overnight delivery on June 29, 2023.
Veridian Health Research Network, Inc. A Secretary's Certificate was received from Veridian, transmitted by WJC and dated June 28, 2023. The Secretary's Certificate certifies the following:
(i) That the Board of Directors of Veridian Health Research Network, Inc. duly adopted resolutions authorizing the execution, delivery, and performance of the MCTA and all ancillary agreements contemplated thereby;
(ii) That the following individuals are duly elected or appointed officers of Veridian and are authorized signatories with respect to the MCTA and ancillary agreements: Dr. Franklin Osei, M.D., Ph.D., President and Chief Executive Officer, and Gregory Callahan, Esq., Vice President, Legal and Compliance; and
(iii) That attached to the Secretary's Certificate are true and correct copies of the relevant organizational documents of Veridian Health Research Network, Inc., each as currently in effect.
The Veridian Secretary's Certificate was received by Calderwood & Harkness via email from WJC on June 28, 2023, with the original received by overnight delivery on June 30, 2023.
Calderwood & Harkness reviewed both Secretary's Certificates and confirmed that each is in proper form, certifies the requisite corporate authorizations, and includes the incumbency confirmations and organizational documents required by Section 12.1(g) of the MCTA.
Condition: Satisfied.
H. Closing Certificates
Section 12.1(h) of the MCTA required the delivery by each party of a closing certificate, together with an officer's certificate providing a representations and warranties bringdown, as of the date of closing.
Penterra Closing Certificate. A closing certificate was received from Penterra, executed by Nathaniel Briggs, Esq., Vice President and General Counsel, on behalf of Penterra Pharmaceuticals Corp., dated July 5, 2023. The closing certificate certifies that: (a) all representations and warranties of Penterra set forth in Article IX of the MCTA remain true and correct in all material respects as of July 5, 2023 (with the same effect as though such representations and warranties had been made on and as of such date, except to the extent that such representations and warranties expressly relate to an earlier date, in which case they remain true and correct in all material respects as of such earlier date); and (b) Penterra has performed and complied with all covenants, obligations, and conditions required by the MCTA to be performed or complied with by Penterra prior to or on the closing date. The closing certificate was received by Calderwood & Harkness via email and overnight delivery on July 5, 2023.
Veridian Closing Certificate. A closing certificate was received from Veridian, executed by Dr. Franklin Osei, M.D., Ph.D., President and Chief Executive Officer, on behalf of Veridian Health Research Network, Inc., dated July 5, 2023. The closing certificate certifies that: (a) all representations and warranties of Veridian set forth in Article X of the MCTA remain true and correct in all material respects as of July 5, 2023; and (b) Veridian has performed and complied with all covenants, obligations, and conditions required by the MCTA to be performed or complied with by Veridian prior to or on the closing date. The closing certificate was received by Calderwood & Harkness from WJC via email on July 5, 2023, with the original to follow by overnight delivery.
Officer's Certificate — Penterra (Representations and Warranties Bringdown). In addition to the Penterra closing certificate, Section 12.1(h)(iii) of the MCTA required delivery of a separate officer's certificate from an authorized officer of Penterra specifically confirming that the representations and warranties of Penterra contained in Article IX of the MCTA are true and correct in all material respects as of the closing date. This officer's certificate was executed by an authorized officer of Penterra on July 5, 2023, and was received by Calderwood & Harkness on July 5, 2023. The officer's certificate is consistent in scope and substance with the Penterra closing certificate and provides the required bringdown confirmation.
Calderwood & Harkness reviewed each closing certificate and the officer's certificate for compliance with the form and substantive requirements of Section 12.1(h) of the MCTA and confirmed that each is in proper form and contains the required certifications.
Condition: Satisfied.
I. Execution and Delivery of Ancillary Agreements
Section 12.1(i) of the MCTA required the execution and delivery of certain ancillary agreements as conditions precedent to closing, including the intellectual Property Side Letter and Individual Site Agreements for the two designated lead sites.
intellectual Property Side Letter. The intellectual Property Side Letter was executed concurrently with the MCTA on June 28, 2023. The IP Side Letter was signed by authorized signatories of both Penterra and Veridian. The IP Side Letter governs the ownership and licensing of inventions and other intellectual property arising during the conduct of the CLARION trial, including provisions addressing:
• Retention of pre-existing intellectual property by each party;
• Penterra's exclusive ownership of all clinical data and trial results;
• Allocation of rights in joint inventions conceived or first reduced to practice during the trial, with Penterra holding a worldwide, exclusive, royalty-bearing license to any such joint inventions, subject to Veridian's retained right to use joint inventions for non-commercial academic research purposes;
• Patent prosecution procedures, including Penterra's right of first refusal to file and prosecute patent applications on joint inventions; and
• Publication review and patent delay rights, as further specified in Exhibit G of the MCTA.
The executed IP Side Letter was received by Calderwood & Harkness on June 28, 2023.
Individual Site Agreement — Graystone University Medical Center (Site 001). The Individual Site Agreement for Graystone University Medical Center (Site 001) was executed in the form of Joinder attached as Exhibit C to the MCTA. The Joinder was signed by Dr. William Corwin, M.D., President of Graystone University Medical Center, dated June 28, 2023. The Joinder identifies Dr. Catherine Aldridge, M.D., Ph.D. as the site principal investigator and the Graystone University Institutional Review Board (IRB Registration No. IRB00012847) as the IRB of record for Site 001. The executed Joinder was received by Calderwood & Harkness from Veridian and WJC on June 29, 2023.
Individual Site Agreement — Lakemont Medical Center (Site 002). The Individual Site Agreement for Lakemont Medical Center (Site 002) was executed in the form of Joinder attached as Exhibit C to the MCTA. The Joinder was signed by the authorized institutional signatory of Lakemont Medical Center, dated June 28, 2023. The Joinder identifies Dr. Howard Matsuoka, M.D. as the site co-principal investigator and Veridian Central IRB as the IRB of record for Site 002 under the Central IRB reliance framework. The executed Joinder was received by Calderwood & Harkness from WJC on June 29, 2023.
Remaining Sites. Individual Site Agreements for the remaining thirty-six (36) sites (Sites 003 through 038) will be executed on a rolling basis as sites are activated for the CLARION trial. Representative joinder agreements have been prepared in the form of Exhibit C for the following sites, with execution expected in the weeks following closing:
• Haverford Regional Medical Center (Site 003), Boston, Massachusetts;
• Cedar Falls University Hospital (Site 004), Denver, Colorado; and
• Weston Memorial Health System (Site 005), Atlanta, Georgia.
Execution of Individual Site Agreements for the remaining sites is not a condition precedent to closing and is addressed as a post-closing deliverable in Section V below.
Condition: Satisfied (with respect to lead-site joinders required at closing).
J. Delivery of MCTA Exhibits and Schedules
Section 12.1(j) of the MCTA required that all exhibits and schedules to the MCTA be finalized and delivered in their final, agreed-upon form as of the closing date. Calderwood & Harkness has confirmed that each of the following exhibits and schedules has been finalized, agreed to by both parties, and delivered as part of the execution version of the MCTA:
Exhibit A — Protocol Synopsis (PPC-4871-III / CLARION). A summary of the key design elements of Protocol PPC-4871-III, including study objectives, endpoints, eligibility criteria, randomization scheme, treatment arms, dosing regimen, and statistical analysis plan overview. Finalized and delivered as of June 28, 2023.
Exhibit B — Budget and Payment Schedule. The Budget and Payment Schedule sets forth the total deal value of the MCTA at Eighty Million Dollars ($80,000,000), allocated as follows:
• Per-patient fees: $52,000 per subject × 1,200 subjects = $62,400,000
• Site start-up fees: $75,000 per site × 38 sites = $2,850,000
• Site maintenance fees: $40,000 per site per year × 38 sites × 3.5 years = $5,320,000
• Investigator grants: $1,500,000
• Network coordination fee: $300,000 per quarter × 14 quarters = $4,200,000
• Technology and EDC integration: $1,230,000
• Contingency reserve: $2,500,000
• Total: $80,000,000
The Budget and Payment Schedule was finalized following the June 9, 2023, negotiation session and delivered as of June 28, 2023.
Exhibit C — Form of Individual Site Agreement (Joinder). The template joinder agreement to be executed by each participating Veridian Network site institution. Finalized and delivered as of June 28, 2023.
Exhibit D — Subject-Injury Indemnification Provisions. Exhibit D sets forth the indemnification framework for subject injuries arising in connection with the CLARION trial, including the following key terms:
• Sponsor indemnification for subject injury with a per-subject medical care cap of Five Hundred Thousand Dollars ($500,000) and an aggregate cap of Fifteen Million Dollars ($15,000,000);
• Uncapped indemnification for product-defect claims (i.e., claims arising from defects in the manufacture, formulation, labeling, or packaging of penterafenib);
• Carve-outs from sponsor indemnification for injuries resulting from investigator negligence, unauthorized protocol deviations, or material breach by the site;
• Reciprocal site indemnity of Five Million Dollars ($5,000,000) per site per occurrence, with an aggregate cap of Twenty Million Dollars ($20,000,000);
• Thirty (30) day notice requirement for indemnification claims.
Finalized and delivered as of June 28, 2023.
Exhibit E — Insurance Requirements and Certificate Forms. Specifies the minimum insurance coverage requirements for both the Sponsor and the Site Network, together with forms for certificates of insurance. Finalized and delivered as of June 28, 2023.
Exhibit F — Confidentiality and Data Protection Provisions. Sets forth the confidentiality obligations of both parties with a ten (10) year confidentiality term from the date of disclosure. Includes provisions governing the handling of protected health information in compliance with HIPAA and applicable state privacy laws. Finalized and delivered as of June 28, 2023.
Exhibit G — Intellectual Property and Publication Rights. Confirms Penterra's exclusive ownership of all clinical data generated during the trial. Provides Penterra with a sixty (60) day review period and an additional ninety (90) day patent delay right with respect to any proposed publications by investigators or Veridian personnel. Requires fifteen (15) year document retention by both parties. Finalized and delivered as of June 28, 2023.
Exhibit H — Regulatory Compliance Representations and Covenants. Sets forth the regulatory compliance framework applicable to the CLARION trial, including representations and covenants regarding compliance with 21 C.F.R. Parts 11 (Electronic Records; Electronic Signatures), 50 (Protection of Human Subjects), 54 (Financial Disclosure by Clinical Investigators), 56 (Institutional Review Boards), and 312 (Investigational New Drug Application), as well as ICH E6(R2) Good Clinical Practice guidelines, the Anti-Kickback Statute (42 U.S.C. § 1320a-7b), the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h), and the Health Insurance Portability and Accountability Act of 1996, as amended ("HIPAA"). Finalized and delivered as of June 28, 2023.
Exhibit I — Form of Investigator Undertaking. The template form of undertaking to be executed by each principal investigator, co-principal investigator, and sub-investigator participating in the CLARION trial. Finalized and delivered as of June 28, 2023.
Exhibit J — Safety Reporting Procedures. Establishes the safety reporting framework for the CLARION trial, including requirements for reporting serious adverse events ("SAEs") within twenty-four (24) hours of awareness, and procedures for submission of IND safety reports within seven (7) days (for fatal or life-threatening unexpected adverse reactions) or fifteen (15) days (for other serious, unexpected adverse reactions), in accordance with 21 C.F.R. § 312.32. Finalized and delivered as of June 28, 2023.
Exhibit K — Approved Subcontractors List. Identifies the approved subcontractors for the CLARION trial:
• Meridian Contract Research Organization, Inc. (CRO — data management, biostatistics, regulatory submissions support, and clinical monitoring);
• Pinnacle Data Solutions (electronic data capture and database development); and
• Northbridge Bioanalytical Laboratories (pharmacokinetic and biomarker sample analysis).
Finalized and delivered as of June 28, 2023.
Schedule 1 — List of Participating Veridian Network Sites. Identifies all thirty-eight (38) participating Veridian Network sites across fourteen (14) states, including site identification numbers, site names, addresses, anticipated principal investigators, and IRB designations. Finalized and delivered as of June 28, 2023.
Calderwood & Harkness has confirmed that each exhibit and schedule listed above has been finalized and delivered in the form agreed to by both parties and that no revisions to any exhibit or schedule remain outstanding.
Condition: Satisfied.
V. Post-Closing Obligations and Remaining Deliverables
Although all conditions precedent to closing have been satisfied as of July 5, 2023, several items remain outstanding as post-closing obligations under the MCTA. These items were not conditions to closing but are required to be delivered on a rolling basis or at specified intervals following the Effective Date. The engagement team will monitor the delivery of each post-closing item and will report to Penterra's legal and clinical operations teams as appropriate.
1. Remaining Site Insurance Certificates. Certificates of insurance from the remaining thirty-six (36) Veridian Network sites (i.e., all sites beyond Graystone University Medical Center and Lakemont Medical Center) are required to be delivered as each site executes its Individual Site Agreement (Joinder) pursuant to Exhibit C of the MCTA. Each certificate is due within fifteen (15) business days of the date of execution of the applicable site joinder. Calderwood & Harkness will maintain a tracking log of received certificates and will follow up with WJC as needed.
2. Remaining Individual Site Agreements (Joinders). Individual Site Agreements for Sites 003 through 038 are to be executed on a rolling basis as sites are activated for the CLARION trial. As noted in Section IV.I above, representative joinder agreements are in preparation for Haverford Regional Medical Center (Site 003, Boston, MA), Cedar Falls University Hospital (Site 004, Denver, CO), and Weston Memorial Health System (Site 005, Atlanta, GA), with execution expected in the weeks following closing. Calderwood & Harkness will coordinate with WJC on the execution and delivery of all remaining joinders.
3. Remaining Investigator Signature Pages, Undertakings, and Financial Disclosure Certifications. Principal Investigator Agreements, Investigator Undertakings (Exhibit I forms), and Financial Disclosure Certifications (21 C.F.R. Part 54) for sub-investigators and site principal investigators at all thirty-eight (38) sites are to be collected as part of the site activation process. Calderwood & Harkness will coordinate with Penterra's clinical operations team on the tracking and collection of these documents.
4. Form FDA 1572 Collection. The preparation and collection of Form FDA 1572 (Statement of Investigator) for each site investigator is being coordinated by Penterra's clinical operations team, specifically Jennifer Holt, Vice President, Clinical Operations, and Samantha Novak, Director, Clinical Contracts. Guidance has been provided in the Form 1572 Preparation Memorandum circulated on June 15, 2023. Calderwood & Harkness will provide legal support as needed in connection with the Form 1572 process.
5. Annual Insurance Certificate Renewal. Pursuant to Exhibit E of the MCTA, both parties are required to exchange updated certificates of insurance on an annual basis. The current Briarcliff Mutual policy (Policy No. BM-CTL-2023-04182) expires on March 31, 2024, and is renewable annually. Calderwood & Harkness will calendar the renewal date and coordinate with Penterra to ensure timely delivery of updated certificates to Veridian. A corresponding obligation applies to Veridian with respect to its network-level and site-level insurance coverages.
6. Closing Binder Assembly. Christopher Aiken, Associate, Calderwood & Harkness LLP, will be responsible for finalizing the closing binder containing all executed documents, certificates, exhibits, schedules, and ancillary agreements. The target date for completion and distribution of the closing binder is July 18, 2023, which will also serve as the Effective Date of the MCTA.
VI. Governing Law and Dispute Resolution Confirmation
For completeness, this memorandum confirms the governing law and dispute resolution provisions of the MCTA, as set forth in Article XIV thereof.
Governing Law. The MCTA is governed by and shall be construed in accordance with the laws of the State of New York, without giving effect to any choice-of-law or conflicts-of-law rules or provisions that would cause the application of the laws of any other jurisdiction.
Dispute Resolution. The MCTA provides for a three-tiered dispute resolution mechanism, as follows:
(1) Negotiation. In the event of any dispute, controversy, or claim arising out of or relating to the MCTA, the parties shall first attempt to resolve the matter through good-faith negotiation between designated senior representatives of each party. The negotiation period shall continue for a period of thirty (30) days from the date on which one party provides written notice of the dispute to the other party.
(2) Mediation. If the dispute is not resolved through negotiation within the thirty (30) day period, either party may submit the dispute to mediation administered by the American Arbitration Association ("AAA") under its Commercial Mediation Rules. The mediation shall be conducted in New York, New York, and shall continue for a period not to exceed sixty (60) days from the commencement of mediation, unless the parties mutually agree to extend such period.
(3) Binding Arbitration. If the dispute is not resolved through mediation, either party may submit the dispute to binding arbitration administered by the AAA under its Commercial Arbitration Rules. The arbitration shall be conducted in New York, New York, before a panel of three (3) arbitrators. The decision of the arbitrators shall be final and binding upon the parties and may be entered and enforced in any court of competent jurisdiction.
Injunctive Relief. Notwithstanding the foregoing, each party retains the right to seek injunctive or other equitable relief in the state and federal courts located in New York County, New York, to prevent irreparable harm, including in connection with breaches of confidentiality obligations, intellectual property rights, or other provisions for which monetary damages would be inadequate.
VII. Conclusion and Recommendation
Based upon the analysis set forth above, all conditions precedent to the closing of the Master Clinical Trial Agreement between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc., dated June 28, 2023, have been satisfied as of July 5, 2023. No conditions precedent remain outstanding, and no waivers were required.
Accordingly, closing of the MCTA is confirmed effective as of July 5, 2023.
The Effective Date of the MCTA is anticipated to be July 18, 2023, upon the completion of administrative close-out procedures and the distribution of the closing binder to all parties and their respective counsel.
The following post-closing deliverables will be monitored by the Calderwood & Harkness engagement team on an ongoing basis: (i) remaining Individual Site Agreements (Joinders) for Sites 003 through 038; (ii) remaining site insurance certificates; (iii) remaining investigator signature pages, undertakings, and financial disclosure certifications; (iv) Form FDA 1572 collection; and (v) annual insurance certificate renewals. The engagement team will provide periodic status updates to Penterra's legal and clinical operations teams as these deliverables are received.
The target date for first patient in ("FPI") for Protocol PPC-4871-III (CLARION) remains August 14, 2023. The closing of the MCTA and the anticipated July 18, 2023, Effective Date position the parties to proceed with site activation activities in advance of the FPI target.
I recommend notifying the following Penterra client contacts of the confirmed closing and next steps:
• Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp.
• Nathaniel Briggs, Esq., Vice President and General Counsel, Penterra Pharmaceuticals Corp.
A copy of this memorandum will be retained in Calderwood & Harkness LLP Matter File No. 1018-00004.
•
Please let me know if you have any questions or require any further analysis.
Respectfully submitted,
Sean Morrissey Associate Calderwood & Harkness LLP