1018-00004 · Penterra Pharmaceuticals Corp · Closing

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CLOSING CERTIFICATE OF PENTERRA PHARMACEUTICALS CORP.

Delivered pursuant to Section 9.02(a)(iii) of the Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA"), by and between Penterra Pharmaceuticals Corp., a Delaware corporation ("Sponsor" or "Penterra"), and Veridian Health Research Network, Inc., a Delaware 501(c)(3) corporation ("Site Network" or "Veridian")

Protocol: PPC-4871-III (CLARION — CLinical Assessment of Response with Longitudinal Investigation in ONcology)

Date of Certificate: July 5, 2023

ClinicalTrials.gov Identifier: NCT05928174

IND Number: IND 157823

RECITALS

A. WHEREAS, Penterra Pharmaceuticals Corp., a corporation duly organized and validly existing under the laws of the State of Delaware, with its principal executive offices located at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540, and Veridian Health Research Network, Inc., a 501(c)(3) corporation duly organized and validly existing under the laws of the State of Delaware, with its principal executive offices located at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104, entered into that certain Master Clinical Trial Agreement dated as of June 28, 2023 (the "MCTA"), governing the conduct and administration of the clinical trial described therein;

B. WHEREAS, the MCTA governs the conduct of Protocol PPC-4871-III (the "CLARION" trial), 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"), to be conducted across thirty-eight (38) Veridian Network clinical trial sites located in fourteen (14) states across the United States, with a total aggregate deal value of Eighty Million United States Dollars ($80,000,000) over the anticipated duration of the trial;

C. WHEREAS, this Closing Certificate is delivered by Penterra to Veridian pursuant to and in satisfaction of the conditions precedent set forth in Article IX of the MCTA, which require, among other things, the delivery by Penterra of a duly executed closing certificate on or before the Closing Date (as defined in the MCTA), certifying as to the accuracy of representations and warranties, the performance of pre-closing covenants and obligations, and the satisfaction of all conditions precedent to the closing of the transactions contemplated by the MCTA; and

D. WHEREAS, except as otherwise defined herein, capitalized terms used but not defined in this Closing Certificate shall have the respective meanings ascribed to such terms in the MCTA, including any exhibits, schedules, annexes, and ancillary agreements attached thereto or delivered in connection therewith.

NOW, THEREFORE, the undersigned hereby certifies as follows:

SECTION 1: IDENTITY AND AUTHORITY OF CERTIFYING OFFICER

The undersigned, Nathaniel Briggs, Esq., hereby certifies that he serves as the Vice President and General Counsel of Penterra Pharmaceuticals Corp. and is a duly authorized officer of Penterra. The undersigned further certifies that he has been duly authorized by Penterra's Board of Directors and by the Chief Executive Officer of Penterra to execute and deliver this Closing Certificate on behalf of Penterra in connection with the MCTA and the transactions contemplated thereby.

This Closing Certificate is being delivered by the undersigned in his official capacity as Vice President and General Counsel of Penterra Pharmaceuticals Corp. and not in any individual or personal capacity. The undersigned shall have no personal liability whatsoever with respect to any of the certifications, representations, or statements made herein, all of which are made solely on behalf of Penterra.

The authority of the undersigned to execute and deliver this Closing Certificate is further confirmed by the Secretary's Certificate of Penterra Pharmaceuticals Corp. (the "Secretary's Certificate"), delivered concurrently herewith pursuant to Section 9.02(a)(ii) of the MCTA, which Secretary's Certificate certifies, among other things, the resolutions duly adopted by the Board of Directors of Penterra authorizing the execution, delivery, and performance of the MCTA and all ancillary agreements, and the incumbency and specimen signatures of each officer of Penterra authorized to execute documents on behalf of the company in connection with the CLARION trial.

SECTION 2: REPRESENTATIONS AND WARRANTIES — BRINGDOWN CERTIFICATION

The undersigned hereby certifies that all representations and warranties made by Penterra in the MCTA, including without limitation those representations and warranties set forth in Article IV of the MCTA and the Regulatory Compliance Representations and Covenants attached as Exhibit H to the MCTA, are true and correct in all material respects as of the date of this Closing Certificate (July 5, 2023), with the same force and effect as though each such representation and warranty had been originally made on and as of such date (except for any representations and warranties that by their terms speak as of a specific earlier date, which representations and warranties are true and correct in all material respects as of such earlier date).

Without limiting the generality of the foregoing certification, the undersigned specifically confirms that the following representations and warranties, among others, remain true and correct in all material respects as of the date hereof:

(a) Organization and Good Standing. Penterra is a corporation duly organized, validly existing, and in good standing under the laws of the State of Delaware. Penterra's registered agent in the State of Delaware is Capitol Registered Agents, LLC, located at 1209 Orange Street, Wilmington, Delaware 19801. Penterra is duly qualified to do business and is in good standing in each jurisdiction in which the ownership of its properties or the conduct of its business requires such qualification, including each state in which Veridian Network sites participating in the CLARION trial are located.

(b) Corporate Power and Authority. Penterra has all requisite corporate power and authority to execute, deliver, and perform its obligations under the MCTA and each ancillary agreement contemplated thereby, including without limitation the Individual Site Agreements for each of the thirty-eight (38) participating Veridian Network sites, the intellectual Property Side Letter dated June 28, 2023, the Principal Investigator Agreement with the Global Principal Investigator, and the Co-Principal Investigator Agreement. The execution, delivery, and performance of each such agreement by Penterra does not and will not conflict with, result in a breach of, or constitute a default under Penterra's certificate of incorporation, bylaws, or any material agreement, instrument, order, judgment, decree, or applicable law to which Penterra is a party or by which it is bound.

(c) Due Authorization. The execution, delivery, and performance of the MCTA and each ancillary agreement by Penterra have been duly authorized by all necessary corporate action on the part of Penterra, including approval by the Board of Directors of Penterra at a duly convened meeting at which a quorum was present. No further corporate action or approval, including any stockholder approval, is required for Penterra to consummate the transactions contemplated by the MCTA.

(d) IND Status. Penterra holds a valid Investigational New Drug Application bearing IND Number 157823 ("IND 157823") filed with the United States Food and Drug Administration (the "FDA") for the investigational product penterafenib (PPC-4871). IND 157823 is in good standing with the FDA, has not been placed on clinical hold (full or partial), and is not the subject of any pending or, to the knowledge of the undersigned, threatened FDA enforcement action. All required IND amendments, annual reports, and safety reports have been timely submitted to the FDA in accordance with applicable regulations.

(e) Protocol Compliance and Registration. The Protocol (PPC-4871-III / CLARION), bearing ClinicalTrials.gov Identifier NCT05928174, has been duly registered on ClinicalTrials.gov in accordance with 42 U.S.C. § 282(j) and the applicable requirements of the FDA Amendments Act of 2007. The Protocol is, and the conduct of the CLARION trial thereunder will be, in compliance in all material respects with applicable FDA requirements, including without limitation those set forth in 21 C.F.R. Part 11 (Electronic Records; Electronic Signatures), 21 C.F.R. Part 50 (Protection of Human Subjects), 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators), 21 C.F.R. Part 56 (Institutional Review Boards), and 21 C.F.R. Part 312 (Investigational New Drug Application), as well as with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice E6(R2) (the "ICH-GCP Guidelines").

(f) Absence of Material Adverse Events or Proceedings. Penterra is not aware of any material adverse event, proceeding, governmental investigation, or regulatory action that would prevent or materially impair its ability to perform its obligations under the MCTA or that would reasonably be expected to have a material adverse effect on the conduct of the CLARION trial. There are no pending or, to the knowledge of the undersigned, threatened proceedings or investigations by the FDA, the Department of Justice, the Office of Inspector General of the Department of Health and Human Services, or any other governmental authority that relate to or could reasonably be expected to affect the CLARION trial, the investigational product, or Penterra's ability to perform its obligations under the MCTA.

(g) Healthcare Regulatory Compliance. All representations made by Penterra in the MCTA and in Exhibit H thereto regarding compliance with applicable healthcare laws and regulations remain true and correct in all material respects, including without limitation representations regarding compliance with the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)), the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h) and the Open Payments reporting requirements thereunder, the federal False Claims Act (31 U.S.C. §§ 3729–3733), and the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act (collectively, "HIPAA"), including the Standards for Privacy of Individually Identifiable Health Information and the Security Standards for the Protection of Electronic Protected Health Information set forth in 45 C.F.R. Parts 160 and 164. Penterra has established and maintains policies and procedures reasonably designed to ensure compliance with the foregoing laws and regulations in connection with the CLARION trial.

(h) Fair Market Value of Compensation. The compensation structure under the MCTA, including (i) per-patient site fees of Fifty-Two Thousand United States Dollars ($52,000) per enrolled subject (totaling Sixty-Two Million Four Hundred Thousand United States Dollars ($62,400,000) for the planned enrollment of one thousand two hundred (1,200) subjects), (ii) investigator grants in the aggregate amount of One Million Five Hundred Thousand United States Dollars ($1,500,000), (iii) start-up and site activation fees, (iv) institutional overhead and indirect cost allocations, and (v) all other payments and consideration to be provided by Penterra under the MCTA and the ancillary agreements, reflects fair market value for the services to be rendered by Veridian and the participating Veridian Network sites and investigators in connection with the CLARION trial, as determined by a contemporaneous fair market value assessment conducted by an independent third-party valuation firm, and such compensation has not been determined in a manner that takes into account the volume or value of any referrals or business otherwise generated between the parties.

SECTION 3: PERFORMANCE OF PRE-CLOSING OBLIGATIONS AND COVENANTS

The undersigned hereby certifies that Penterra has performed and complied in all material respects with all agreements, covenants, conditions, and obligations required by the MCTA to be performed or complied with by Penterra on or before the Closing Date of July 5, 2023, including without limitation the following:

(a) Insurance Delivery. Penterra has obtained and delivered to Veridian a certificate of insurance evidencing clinical trial liability insurance coverage maintained by Penterra through Briarcliff Mutual Insurance Company, under Policy Number BM-CTL-2023-04182, with a policy period of April 1, 2023 through March 31, 2024. Such clinical trial liability insurance provides minimum coverage of Twenty-Five Million United States Dollars ($25,000,000) per occurrence and Seventy-Five Million United States Dollars ($75,000,000) in the aggregate. The policy further includes a subject-injury sublimit of Ten Million United States Dollars ($10,000,000) per occurrence and Fifty Million United States Dollars ($50,000,000) in the aggregate. The policy names Veridian Health Research Network, Inc., each participating Veridian Network site, and their respective officers, directors, employees, and agents as additional insureds, in each case as required by the insurance provisions set forth in Exhibit E to the MCTA. Penterra has further confirmed that such insurance coverage meets or exceeds all minimum coverage thresholds and requirements specified in Section 7.04 and Exhibit E of the MCTA. A copy of the certificate of insurance, together with the additional insured endorsement, has been delivered to Veridian's Office of Sponsored Programs concurrent with the delivery of this Closing Certificate.

(b) Execution and Delivery of Ancillary Agreements. Penterra has duly executed and delivered, or caused to be duly executed and delivered, each of the following ancillary documents and agreements required to be executed and delivered by Penterra on or before the Closing Date:

(i) The intellectual Property Side Letter dated June 28, 2023, between Penterra and Veridian, governing the allocation of intellectual property rights, invention disclosures, publication rights, and data ownership and licensing in connection with the CLARION trial;

(ii) The Principal Investigator Agreement dated June 28, 2023, between Penterra and Dr. Catherine Aldridge, M.D., Ph.D., appointed as the Global Principal Investigator for the CLARION trial, affiliated with Graystone University Medical Center, Philadelphia, Pennsylvania;

(iii) The Co-Principal Investigator Agreement dated June 28, 2023, between Penterra and Dr. Howard Matsuoka, M.D., appointed as the Co-Principal Investigator for the CLARION trial, affiliated with Lakemont Medical Center, Lakemont, Pennsylvania;

(iv) The Individual Site Agreement — Graystone University Medical Center (designated as Site 001), executed by Penterra, Veridian (on behalf of the Veridian Network), and an authorized representative of Graystone University Medical Center, governing the site-specific terms, budget, and operational requirements for the conduct of the CLARION trial at Site 001; and

(v) The Individual Site Agreement — Lakemont Medical Center (designated as Site 002), executed by Penterra, Veridian (on behalf of the Veridian Network), and an authorized representative of Lakemont Medical Center, governing the site-specific terms, budget, and operational requirements for the conduct of the CLARION trial at Site 002.

Each of the foregoing ancillary agreements has been executed by a duly authorized officer of Penterra and delivered to Veridian in accordance with the requirements of the MCTA. Penterra acknowledges that Individual Site Agreements for the remaining thirty-six (36) Veridian Network sites will be executed on a rolling basis in accordance with the site activation schedule set forth in Exhibit C to the MCTA.

(c) Secretary's Certificate. Penterra has delivered its Secretary's Certificate, executed by Sarah T. Novak, Corporate Secretary of Penterra Pharmaceuticals Corp., certifying (i) the resolutions duly adopted by the Board of Directors of Penterra authorizing the execution, delivery, and performance of the MCTA and all ancillary agreements, (ii) the incumbency and specimen signatures of each officer of Penterra authorized to execute documents in connection with the MCTA and the CLARION trial, and (iii) attaching true and correct copies of Penterra's Amended and Restated Certificate of Incorporation (as filed with the Secretary of State of the State of Delaware) and Penterra's Amended and Restated Bylaws, each as currently in effect.

(d) Investigational Product Readiness. Penterra has confirmed the availability of the investigational product, penterafenib (PPC-4871), and matching placebo, in quantities sufficient for the initial phase of site activation and subject enrollment, for distribution to activated Veridian Network sites in accordance with the Protocol, the Investigator's Brochure (Edition 5, dated March 2023), and the Pharmacy Manual (Version 2.0, dated May 2023). The investigational product and matching placebo have been manufactured in accordance with current Good Manufacturing Practices ("cGMP") as set forth in 21 C.F.R. Parts 210 and 211, and certificates of analysis for each manufactured lot have been made available to Veridian's designated pharmacist at each activated site. The investigational product supply chain, including temperature-controlled storage and distribution logistics, has been coordinated through Penterra's designated clinical supply vendor, and all interactive response technology ("IRT") systems for drug assignment and inventory management are operational.

(e) CRO Coordination. Penterra has confirmed that Meridian Contract Research Organization, Inc., a contract research organization headquartered in Raleigh, North Carolina, which has been engaged by Penterra pursuant to that certain Master Services Agreement dated January 15, 2023 (the "CRO MSA"), is prepared to commence the provision of monitoring, data management, safety reporting, medical monitoring, pharmacovigilance, and biostatistical services for the CLARION trial at each activated Veridian Network site. Meridian has completed all required training of its clinical research associates, has finalized the monitoring plan, and has confirmed its readiness to conduct site initiation visits at Sites 001 and 002 in accordance with the study timeline. Penterra remains responsible for the acts and omissions of Meridian in connection with the CLARION trial to the extent provided in the MCTA.

(f) EDC and Central Lab Coordination. Penterra has confirmed the operational readiness of each of the following approved subcontractors, as listed in Exhibit K to the MCTA:

(i) Pinnacle Data Solutions, Inc. ("Pinnacle"), which has been engaged by Penterra to provide the electronic data capture ("EDC") platform for the CLARION trial. Pinnacle has completed system build, user acceptance testing, and database validation in accordance with 21 C.F.R. Part 11, and EDC user accounts have been provisioned for authorized personnel at Sites 001 and 002; and

(ii) Northbridge Bioanalytical Laboratories, Inc. ("Northbridge"), which has been engaged by Penterra to serve as the central laboratory for the CLARION trial. Northbridge has completed laboratory kit assembly, validated all protocol-specified assays (including serum alpha-fetoprotein, liver function panels, and circulating tumor DNA analysis), and established courier and specimen logistics for each activated site. Northbridge's laboratory operations are in compliance with applicable Clinical Laboratory Improvement Amendments ("CLIA") requirements and College of American Pathologists ("CAP") accreditation standards.

(g) Regulatory Filings. All required regulatory filings, notifications, and submissions related to the commencement and conduct of the CLARION trial at Veridian Network sites have been completed or are in process consistent with the Protocol timeline and the regulatory milestones set forth in Exhibit D to the MCTA. This includes, without limitation, the submission of all required IND amendments and protocol amendments to the FDA, the submission of IND safety reports as applicable, and coordination with Veridian and its participating sites to ensure that all Institutional Review Board ("IRB") submissions, informed consent form reviews, and site-specific regulatory binder documentation are on track for the target first-patient-in date of August 14, 2023. Penterra has further confirmed that it has submitted or is in the process of submitting all required financial disclosure forms (FDA Form 3455) from participating investigators, and that all pre-study regulatory requirements identified in the site activation checklist (Exhibit L to the MCTA) for Sites 001 and 002 have been completed.

SECTION 4: CONDITIONS PRECEDENT — ACKNOWLEDGMENT OF SATISFACTION

The undersigned hereby acknowledges and certifies that, to the knowledge of the undersigned after due inquiry, all conditions precedent to the obligations of both parties under the MCTA, as set forth in Article IX thereof, have been satisfied or, where applicable, waived in writing by the appropriate party, as of the Closing Date of July 5, 2023. Without limiting the generality of the foregoing, the undersigned specifically acknowledges satisfaction of the following conditions precedent:

(a) Insurance Certificates. Certificates of insurance have been delivered by both Penterra and Veridian (on behalf of itself and its participating Veridian Network sites) within the required timeframe of fifteen (15) business days following the execution of the MCTA on June 28, 2023, in accordance with Section 7.04 and Exhibit E of the MCTA. Penterra has reviewed the certificate of insurance delivered by Veridian and confirms that it meets the minimum coverage requirements set forth in the MCTA.

(b) IRB Approvals. Penterra has received confirmation that the following Institutional Review Board approvals have been obtained for the initial lead sites:

(i) Approval by the Graystone University Institutional Review Board (IRB Registration Number: IRB00012847, registered with the Office for Human Research Protections) for the conduct of the CLARION trial at Graystone University Medical Center (Site 001), including approval of the Protocol (Version 3.0, dated May 15, 2023), the informed consent form (Version 2.1, dated June 1, 2023), and all subject-facing materials; and

(ii) Approval by the Veridian Central IRB (operating as the IRB of record pursuant to a reliance agreement under the NIH Single IRB Policy and in accordance with 45 C.F.R. Part 46) for the conduct of the CLARION trial at Lakemont Medical Center (Site 002) and other non-Pennsylvania Veridian Network sites for which the Veridian Central IRB serves as the reviewing IRB.

(c) Investigator Signature Pages. Duly executed investigator signature pages for the Protocol (PPC-4871-III / CLARION, Version 3.0, dated May 15, 2023) and the FDA Form 1572 (Statement of Investigator) have been received from each of the following investigators:

(i) Dr. Catherine Aldridge, M.D., Ph.D., Global Principal Investigator, Graystone University Medical Center (Site 001); and

(ii) Dr. Howard Matsuoka, M.D., Co-Principal Investigator, Lakemont Medical Center (Site 002).

(d) Closing Certificates. This Closing Certificate is being delivered by Penterra concurrently with the Closing Date. The undersigned acknowledges that Veridian has delivered, or is delivering concurrently herewith, its own closing certificate pursuant to Section 9.02(b)(iii) of the MCTA, certifying as to the accuracy of Veridian's representations and warranties and the satisfaction of Veridian's pre-closing obligations.

SECTION 5: NO MATERIAL ADVERSE CHANGE

The undersigned hereby certifies that, since the date of execution of the MCTA on June 28, 2023, there has been no material adverse change in the business, financial condition, operations, results of operations, assets, liabilities, or prospects of Penterra that would, individually or in the aggregate, materially impair Penterra's ability to perform its obligations under the MCTA or that would reasonably be expected to have a material adverse effect on the conduct or completion of the CLARION trial.

In support of the foregoing certification, the undersigned notes that Penterra is a publicly traded company, with its common stock listed on the Nasdaq Global Select Market under the ticker symbol "PTRA." As of the most recently reported quarter (Q1 2023, ended March 31, 2023), Penterra reported approximately Eight Hundred Ninety Million United States Dollars ($890,000,000) in cash, cash equivalents, and short-term investments on its consolidated balance sheet. Penterra reported full-year fiscal year 2022 revenues of approximately One Billion Eight Hundred Seventy Million United States Dollars ($1,870,000,000) and fiscal year 2022 research and development expenditures of approximately Six Hundred Twelve Million United States Dollars ($612,000,000). Based on Penterra's current financial position and its approved budgets for the CLARION trial program, Penterra has sufficient financial resources and liquidity to fund the Eighty Million Dollar ($80,000,000) total deal value under the MCTA over the anticipated duration of the trial.

No event has occurred since June 28, 2023 that constitutes, or would reasonably be expected to constitute, a "Material Adverse Change" as defined in Section 1.01 of the MCTA.

SECTION 6: NO LITIGATION OR PROCEEDINGS

The undersigned hereby certifies that, as of the date of this Closing Certificate, there is no action, suit, claim, proceeding, arbitration, or investigation pending or, to the knowledge of the undersigned after due inquiry, threatened against Penterra or any of its affiliates, officers, directors, or employees, by or before any court, arbitral tribunal, governmental authority, or regulatory body, that (a) challenges the validity or enforceability of the MCTA or any ancillary agreement delivered in connection therewith, (b) questions Penterra's right, power, or authority to execute, deliver, or perform its obligations under the MCTA or any such ancillary agreement, (c) seeks to restrain, enjoin, or prohibit the consummation of the transactions contemplated by the MCTA, or (d) could reasonably be expected to result in a material adverse effect on Penterra's ability to perform its obligations under the MCTA or on the conduct of the CLARION trial.

The undersigned further certifies that Penterra has not received any written notice of, and is not otherwise aware of, any pending or threatened investigation by the FDA, the Department of Health and Human Services (including the Office of Inspector General), the Department of Justice, or any state attorney general that relates to the CLARION trial, penterafenib (PPC-4871), or Penterra's clinical trial activities generally.

SECTION 7: GOVERNING LAW

This Closing Certificate shall be governed by and construed in accordance with the laws of the State of New York, without giving effect to any choice-of-law or conflict-of-law rules or provisions that would cause the application of the laws of any other jurisdiction, consistent with and pursuant to the governing law provisions set forth in Section 12.08 of the MCTA. Any dispute arising out of or relating to this Closing Certificate shall be resolved in accordance with the dispute resolution provisions of the MCTA.

IN WITNESS WHEREOF, the undersigned has duly executed and delivered this Closing Certificate as of the date first set forth above.

PENTERRA PHARMACEUTICALS CORP.

By: ________

Name: Nathaniel Briggs, Esq.

Title: Vice President and General Counsel

Date: July 5, 2023

Address for Notices: 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540 Telephone: (609) 555-4200

Email: legal@penterrapharma.com

ACKNOWLEDGMENT OF RECEIPT

The undersigned hereby acknowledges receipt of this Closing Certificate delivered by Penterra Pharmaceuticals Corp. pursuant to Section 9.02(a)(iii) of the MCTA.

VERIDIAN HEALTH RESEARCH NETWORK, INC.

Received and acknowledged by:

By: ________

Name: Dr. Franklin Osei, M.D., Ph.D.

Title: President and Chief Executive Officer

Date: July 5, 2023

Address for Notices: 750 Research Parkway, 8th Floor Philadelphia, Pennsylvania 19104 Telephone: (215) 555-8300

Email: legal@veridianresearch.org

CLOSING CERTIFICATE OF PENTERRA PHARMACEUTICALS CORP.
Delivered pursuant to Section 9.02(a)(iii) of the Master Clinical Trial Agreement dated June 28, 2023 (the "MCTA"), by and between Penterra Pharmaceuticals Corp., a Delaware corporation ("Sponsor" or "Penterra"), and Veridian Health Research Network, Inc., a Delaware 501(c)(3) corporation ("Site Network" or "Veridian")
Protocol: PPC-4871-III (CLARION — CLinical Assessment of Response with Longitudinal Investigation in ONcology)
Date of Certificate: July 5, 2023
ClinicalTrials.gov Identifier: NCT05928174
IND Number: IND 157823
RECITALS
A. WHEREAS, Penterra Pharmaceuticals Corp., a corporation duly organized and validly existing under the laws of the State of Delaware, with its principal executive offices located at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540, and Veridian Health Research Network, Inc., a 501(c)(3) corporation duly organized and validly existing under the laws of the State of Delaware, with its principal executive offices located at 750 Research Parkway, 8th Floor, Philadelphia, Pennsylvania 19104, entered into that certain Master Clinical Trial Agreement dated as of June 28, 2023 (the "MCTA"), governing the conduct and administration of the clinical trial described therein;
B. WHEREAS, the MCTA governs the conduct of Protocol PPC-4871-III (the "CLARION" trial), 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"), to be conducted across thirty-eight (38) Veridian Network clinical trial sites located in fourteen (14) states across the United States, with a total aggregate deal value of Eighty Million United States Dollars ($80,000,000) over the anticipated duration of the trial;
C. WHEREAS, this Closing Certificate is delivered by Penterra to Veridian pursuant to and in satisfaction of the conditions precedent set forth in Article IX of the MCTA, which require, among other things, the delivery by Penterra of a duly executed closing certificate on or before the Closing Date (as defined in the MCTA), certifying as to the accuracy of representations and warranties, the performance of pre-closing covenants and obligations, and the satisfaction of all conditions precedent to the closing of the transactions contemplated by the MCTA; and
D. WHEREAS, except as otherwise defined herein, capitalized terms used but not defined in this Closing Certificate shall have the respective meanings ascribed to such terms in the MCTA, including any exhibits, schedules, annexes, and ancillary agreements attached thereto or delivered in connection therewith.
NOW, THEREFORE, the undersigned hereby certifies as follows:
SECTION 1: IDENTITY AND AUTHORITY OF CERTIFYING OFFICER
The undersigned, Nathaniel Briggs, Esq., hereby certifies that he serves as the Vice President and General Counsel of Penterra Pharmaceuticals Corp. and is a duly authorized officer of Penterra. The undersigned further certifies that he has been duly authorized by Penterra's Board of Directors and by the Chief Executive Officer of Penterra to execute and deliver this Closing Certificate on behalf of Penterra in connection with the MCTA and the transactions contemplated thereby.
This Closing Certificate is being delivered by the undersigned in his official capacity as Vice President and General Counsel of Penterra Pharmaceuticals Corp. and not in any individual or personal capacity. The undersigned shall have no personal liability whatsoever with respect to any of the certifications, representations, or statements made herein, all of which are made solely on behalf of Penterra.
The authority of the undersigned to execute and deliver this Closing Certificate is further confirmed by the Secretary's Certificate of Penterra Pharmaceuticals Corp. (the "Secretary's Certificate"), delivered concurrently herewith pursuant to Section 9.02(a)(ii) of the MCTA, which Secretary's Certificate certifies, among other things, the resolutions duly adopted by the Board of Directors of Penterra authorizing the execution, delivery, and performance of the MCTA and all ancillary agreements, and the incumbency and specimen signatures of each officer of Penterra authorized to execute documents on behalf of the company in connection with the CLARION trial.
SECTION 2: REPRESENTATIONS AND WARRANTIES — BRINGDOWN CERTIFICATION
The undersigned hereby certifies that all representations and warranties made by Penterra in the MCTA, including without limitation those representations and warranties set forth in Article IV of the MCTA and the Regulatory Compliance Representations and Covenants attached as Exhibit H to the MCTA, are true and correct in all material respects as of the date of this Closing Certificate (July 5, 2023), with the same force and effect as though each such representation and warranty had been originally made on and as of such date (except for any representations and warranties that by their terms speak as of a specific earlier date, which representations and warranties are true and correct in all material respects as of such earlier date).
Without limiting the generality of the foregoing certification, the undersigned specifically confirms that the following representations and warranties, among others, remain true and correct in all material respects as of the date hereof:
(a) Organization and Good Standing. Penterra is a corporation duly organized, validly existing, and in good standing under the laws of the State of Delaware. Penterra's registered agent in the State of Delaware is Capitol Registered Agents, LLC, located at 1209 Orange Street, Wilmington, Delaware 19801. Penterra is duly qualified to do business and is in good standing in each jurisdiction in which the ownership of its properties or the conduct of its business requires such qualification, including each state in which Veridian Network sites participating in the CLARION trial are located.
(b) Corporate Power and Authority. Penterra has all requisite corporate power and authority to execute, deliver, and perform its obligations under the MCTA and each ancillary agreement contemplated thereby, including without limitation the Individual Site Agreements for each of the thirty-eight (38) participating Veridian Network sites, the intellectual Property Side Letter dated June 28, 2023, the Principal Investigator Agreement with the Global Principal Investigator, and the Co-Principal Investigator Agreement. The execution, delivery, and performance of each such agreement by Penterra does not and will not conflict with, result in a breach of, or constitute a default under Penterra's certificate of incorporation, bylaws, or any material agreement, instrument, order, judgment, decree, or applicable law to which Penterra is a party or by which it is bound.
(c) Due Authorization. The execution, delivery, and performance of the MCTA and each ancillary agreement by Penterra have been duly authorized by all necessary corporate action on the part of Penterra, including approval by the Board of Directors of Penterra at a duly convened meeting at which a quorum was present. No further corporate action or approval, including any stockholder approval, is required for Penterra to consummate the transactions contemplated by the MCTA.
(d) IND Status. Penterra holds a valid Investigational New Drug Application bearing IND Number 157823 ("IND 157823") filed with the United States Food and Drug Administration (the "FDA") for the investigational product penterafenib (PPC-4871). IND 157823 is in good standing with the FDA, has not been placed on clinical hold (full or partial), and is not the subject of any pending or, to the knowledge of the undersigned, threatened FDA enforcement action. All required IND amendments, annual reports, and safety reports have been timely submitted to the FDA in accordance with applicable regulations.
(e) Protocol Compliance and Registration. The Protocol (PPC-4871-III / CLARION), bearing ClinicalTrials.gov Identifier NCT05928174, has been duly registered on ClinicalTrials.gov in accordance with 42 U.S.C. § 282(j) and the applicable requirements of the FDA Amendments Act of 2007. The Protocol is, and the conduct of the CLARION trial thereunder will be, in compliance in all material respects with applicable FDA requirements, including without limitation those set forth in 21 C.F.R. Part 11 (Electronic Records; Electronic Signatures), 21 C.F.R. Part 50 (Protection of Human Subjects), 21 C.F.R. Part 54 (Financial Disclosure by Clinical Investigators), 21 C.F.R. Part 56 (Institutional Review Boards), and 21 C.F.R. Part 312 (Investigational New Drug Application), as well as with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice E6(R2) (the "ICH-GCP Guidelines").
(f) Absence of Material Adverse Events or Proceedings. Penterra is not aware of any material adverse event, proceeding, governmental investigation, or regulatory action that would prevent or materially impair its ability to perform its obligations under the MCTA or that would reasonably be expected to have a material adverse effect on the conduct of the CLARION trial. There are no pending or, to the knowledge of the undersigned, threatened proceedings or investigations by the FDA, the Department of Justice, the Office of Inspector General of the Department of Health and Human Services, or any other governmental authority that relate to or could reasonably be expected to affect the CLARION trial, the investigational product, or Penterra's ability to perform its obligations under the MCTA.
(g) Healthcare Regulatory Compliance. All representations made by Penterra in the MCTA and in Exhibit H thereto regarding compliance with applicable healthcare laws and regulations remain true and correct in all material respects, including without limitation representations regarding compliance with the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)), the Physician Payments Sunshine Act (42 U.S.C. § 1320a-7h) and the Open Payments reporting requirements thereunder, the federal False Claims Act (31 U.S.C. §§ 3729–3733), and the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology for Economic and Clinical Health Act (collectively, "HIPAA"), including the Standards for Privacy of Individually Identifiable Health Information and the Security Standards for the Protection of Electronic Protected Health Information set forth in 45 C.F.R. Parts 160 and 164. Penterra has established and maintains policies and procedures reasonably designed to ensure compliance with the foregoing laws and regulations in connection with the CLARION trial.
(h) Fair Market Value of Compensation. The compensation structure under the MCTA, including (i) per-patient site fees of Fifty-Two Thousand United States Dollars ($52,000) per enrolled subject (totaling Sixty-Two Million Four Hundred Thousand United States Dollars ($62,400,000) for the planned enrollment of one thousand two hundred (1,200) subjects), (ii) investigator grants in the aggregate amount of One Million Five Hundred Thousand United States Dollars ($1,500,000), (iii) start-up and site activation fees, (iv) institutional overhead and indirect cost allocations, and (v) all other payments and consideration to be provided by Penterra under the MCTA and the ancillary agreements, reflects fair market value for the services to be rendered by Veridian and the participating Veridian Network sites and investigators in connection with the CLARION trial, as determined by a contemporaneous fair market value assessment conducted by an independent third-party valuation firm, and such compensation has not been determined in a manner that takes into account the volume or value of any referrals or business otherwise generated between the parties.
SECTION 3: PERFORMANCE OF PRE-CLOSING OBLIGATIONS AND COVENANTS
The undersigned hereby certifies that Penterra has performed and complied in all material respects with all agreements, covenants, conditions, and obligations required by the MCTA to be performed or complied with by Penterra on or before the Closing Date of July 5, 2023, including without limitation the following:
(a) Insurance Delivery. Penterra has obtained and delivered to Veridian a certificate of insurance evidencing clinical trial liability insurance coverage maintained by Penterra through Briarcliff Mutual Insurance Company, under Policy Number BM-CTL-2023-04182, with a policy period of April 1, 2023 through March 31, 2024. Such clinical trial liability insurance provides minimum coverage of Twenty-Five Million United States Dollars ($25,000,000) per occurrence and Seventy-Five Million United States Dollars ($75,000,000) in the aggregate. The policy further includes a subject-injury sublimit of Ten Million United States Dollars ($10,000,000) per occurrence and Fifty Million United States Dollars ($50,000,000) in the aggregate. The policy names Veridian Health Research Network, Inc., each participating Veridian Network site, and their respective officers, directors, employees, and agents as additional insureds, in each case as required by the insurance provisions set forth in Exhibit E to the MCTA. Penterra has further confirmed that such insurance coverage meets or exceeds all minimum coverage thresholds and requirements specified in Section 7.04 and Exhibit E of the MCTA. A copy of the certificate of insurance, together with the additional insured endorsement, has been delivered to Veridian's Office of Sponsored Programs concurrent with the delivery of this Closing Certificate.
(b) Execution and Delivery of Ancillary Agreements. Penterra has duly executed and delivered, or caused to be duly executed and delivered, each of the following ancillary documents and agreements required to be executed and delivered by Penterra on or before the Closing Date:
(i) The intellectual Property Side Letter dated June 28, 2023, between Penterra and Veridian, governing the allocation of intellectual property rights, invention disclosures, publication rights, and data ownership and licensing in connection with the CLARION trial;
(ii) The Principal Investigator Agreement dated June 28, 2023, between Penterra and Dr. Catherine Aldridge, M.D., Ph.D., appointed as the Global Principal Investigator for the CLARION trial, affiliated with Graystone University Medical Center, Philadelphia, Pennsylvania;
(iii) The Co-Principal Investigator Agreement dated June 28, 2023, between Penterra and Dr. Howard Matsuoka, M.D., appointed as the Co-Principal Investigator for the CLARION trial, affiliated with Lakemont Medical Center, Lakemont, Pennsylvania;
(iv) The Individual Site Agreement — Graystone University Medical Center (designated as Site 001), executed by Penterra, Veridian (on behalf of the Veridian Network), and an authorized representative of Graystone University Medical Center, governing the site-specific terms, budget, and operational requirements for the conduct of the CLARION trial at Site 001; and
(v) The Individual Site Agreement — Lakemont Medical Center (designated as Site 002), executed by Penterra, Veridian (on behalf of the Veridian Network), and an authorized representative of Lakemont Medical Center, governing the site-specific terms, budget, and operational requirements for the conduct of the CLARION trial at Site 002.
Each of the foregoing ancillary agreements has been executed by a duly authorized officer of Penterra and delivered to Veridian in accordance with the requirements of the MCTA. Penterra acknowledges that Individual Site Agreements for the remaining thirty-six (36) Veridian Network sites will be executed on a rolling basis in accordance with the site activation schedule set forth in Exhibit C to the MCTA.
(c) Secretary's Certificate. Penterra has delivered its Secretary's Certificate, executed by Sarah T. Novak, Corporate Secretary of Penterra Pharmaceuticals Corp., certifying (i) the resolutions duly adopted by the Board of Directors of Penterra authorizing the execution, delivery, and performance of the MCTA and all ancillary agreements, (ii) the incumbency and specimen signatures of each officer of Penterra authorized to execute documents in connection with the MCTA and the CLARION trial, and (iii) attaching true and correct copies of Penterra's Amended and Restated Certificate of Incorporation (as filed with the Secretary of State of the State of Delaware) and Penterra's Amended and Restated Bylaws, each as currently in effect.
(d) Investigational Product Readiness. Penterra has confirmed the availability of the investigational product, penterafenib (PPC-4871), and matching placebo, in quantities sufficient for the initial phase of site activation and subject enrollment, for distribution to activated Veridian Network sites in accordance with the Protocol, the Investigator's Brochure (Edition 5, dated March 2023), and the Pharmacy Manual (Version 2.0, dated May 2023). The investigational product and matching placebo have been manufactured in accordance with current Good Manufacturing Practices ("cGMP") as set forth in 21 C.F.R. Parts 210 and 211, and certificates of analysis for each manufactured lot have been made available to Veridian's designated pharmacist at each activated site. The investigational product supply chain, including temperature-controlled storage and distribution logistics, has been coordinated through Penterra's designated clinical supply vendor, and all interactive response technology ("IRT") systems for drug assignment and inventory management are operational.
(e) CRO Coordination. Penterra has confirmed that Meridian Contract Research Organization, Inc., a contract research organization headquartered in Raleigh, North Carolina, which has been engaged by Penterra pursuant to that certain Master Services Agreement dated January 15, 2023 (the "CRO MSA"), is prepared to commence the provision of monitoring, data management, safety reporting, medical monitoring, pharmacovigilance, and biostatistical services for the CLARION trial at each activated Veridian Network site. Meridian has completed all required training of its clinical research associates, has finalized the monitoring plan, and has confirmed its readiness to conduct site initiation visits at Sites 001 and 002 in accordance with the study timeline. Penterra remains responsible for the acts and omissions of Meridian in connection with the CLARION trial to the extent provided in the MCTA.
(f) EDC and Central Lab Coordination. Penterra has confirmed the operational readiness of each of the following approved subcontractors, as listed in Exhibit K to the MCTA:
(i) Pinnacle Data Solutions, Inc. ("Pinnacle"), which has been engaged by Penterra to provide the electronic data capture ("EDC") platform for the CLARION trial. Pinnacle has completed system build, user acceptance testing, and database validation in accordance with 21 C.F.R. Part 11, and EDC user accounts have been provisioned for authorized personnel at Sites 001 and 002; and
(ii) Northbridge Bioanalytical Laboratories, Inc. ("Northbridge"), which has been engaged by Penterra to serve as the central laboratory for the CLARION trial. Northbridge has completed laboratory kit assembly, validated all protocol-specified assays (including serum alpha-fetoprotein, liver function panels, and circulating tumor DNA analysis), and established courier and specimen logistics for each activated site. Northbridge's laboratory operations are in compliance with applicable Clinical Laboratory Improvement Amendments ("CLIA") requirements and College of American Pathologists ("CAP") accreditation standards.
(g) Regulatory Filings. All required regulatory filings, notifications, and submissions related to the commencement and conduct of the CLARION trial at Veridian Network sites have been completed or are in process consistent with the Protocol timeline and the regulatory milestones set forth in Exhibit D to the MCTA. This includes, without limitation, the submission of all required IND amendments and protocol amendments to the FDA, the submission of IND safety reports as applicable, and coordination with Veridian and its participating sites to ensure that all Institutional Review Board ("IRB") submissions, informed consent form reviews, and site-specific regulatory binder documentation are on track for the target first-patient-in date of August 14, 2023. Penterra has further confirmed that it has submitted or is in the process of submitting all required financial disclosure forms (FDA Form 3455) from participating investigators, and that all pre-study regulatory requirements identified in the site activation checklist (Exhibit L to the MCTA) for Sites 001 and 002 have been completed.
SECTION 4: CONDITIONS PRECEDENT — ACKNOWLEDGMENT OF SATISFACTION
The undersigned hereby acknowledges and certifies that, to the knowledge of the undersigned after due inquiry, all conditions precedent to the obligations of both parties under the MCTA, as set forth in Article IX thereof, have been satisfied or, where applicable, waived in writing by the appropriate party, as of the Closing Date of July 5, 2023. Without limiting the generality of the foregoing, the undersigned specifically acknowledges satisfaction of the following conditions precedent:
(a) Insurance Certificates. Certificates of insurance have been delivered by both Penterra and Veridian (on behalf of itself and its participating Veridian Network sites) within the required timeframe of fifteen (15) business days following the execution of the MCTA on June 28, 2023, in accordance with Section 7.04 and Exhibit E of the MCTA. Penterra has reviewed the certificate of insurance delivered by Veridian and confirms that it meets the minimum coverage requirements set forth in the MCTA.
(b) IRB Approvals. Penterra has received confirmation that the following Institutional Review Board approvals have been obtained for the initial lead sites:
(i) Approval by the Graystone University Institutional Review Board (IRB Registration Number: IRB00012847, registered with the Office for Human Research Protections) for the conduct of the CLARION trial at Graystone University Medical Center (Site 001), including approval of the Protocol (Version 3.0, dated May 15, 2023), the informed consent form (Version 2.1, dated June 1, 2023), and all subject-facing materials; and
(ii) Approval by the Veridian Central IRB (operating as the IRB of record pursuant to a reliance agreement under the NIH Single IRB Policy and in accordance with 45 C.F.R. Part 46) for the conduct of the CLARION trial at Lakemont Medical Center (Site 002) and other non-Pennsylvania Veridian Network sites for which the Veridian Central IRB serves as the reviewing IRB.
(c) Investigator Signature Pages. Duly executed investigator signature pages for the Protocol (PPC-4871-III / CLARION, Version 3.0, dated May 15, 2023) and the FDA Form 1572 (Statement of Investigator) have been received from each of the following investigators:
(i) Dr. Catherine Aldridge, M.D., Ph.D., Global Principal Investigator, Graystone University Medical Center (Site 001); and
(ii) Dr. Howard Matsuoka, M.D., Co-Principal Investigator, Lakemont Medical Center (Site 002).
(d) Closing Certificates. This Closing Certificate is being delivered by Penterra concurrently with the Closing Date. The undersigned acknowledges that Veridian has delivered, or is delivering concurrently herewith, its own closing certificate pursuant to Section 9.02(b)(iii) of the MCTA, certifying as to the accuracy of Veridian's representations and warranties and the satisfaction of Veridian's pre-closing obligations.
SECTION 5: NO MATERIAL ADVERSE CHANGE
The undersigned hereby certifies that, since the date of execution of the MCTA on June 28, 2023, there has been no material adverse change in the business, financial condition, operations, results of operations, assets, liabilities, or prospects of Penterra that would, individually or in the aggregate, materially impair Penterra's ability to perform its obligations under the MCTA or that would reasonably be expected to have a material adverse effect on the conduct or completion of the CLARION trial.
In support of the foregoing certification, the undersigned notes that Penterra is a publicly traded company, with its common stock listed on the Nasdaq Global Select Market under the ticker symbol "PTRA." As of the most recently reported quarter (Q1 2023, ended March 31, 2023), Penterra reported approximately Eight Hundred Ninety Million United States Dollars ($890,000,000) in cash, cash equivalents, and short-term investments on its consolidated balance sheet. Penterra reported full-year fiscal year 2022 revenues of approximately One Billion Eight Hundred Seventy Million United States Dollars ($1,870,000,000) and fiscal year 2022 research and development expenditures of approximately Six Hundred Twelve Million United States Dollars ($612,000,000). Based on Penterra's current financial position and its approved budgets for the CLARION trial program, Penterra has sufficient financial resources and liquidity to fund the Eighty Million Dollar ($80,000,000) total deal value under the MCTA over the anticipated duration of the trial.
No event has occurred since June 28, 2023 that constitutes, or would reasonably be expected to constitute, a "Material Adverse Change" as defined in Section 1.01 of the MCTA.
SECTION 6: NO LITIGATION OR PROCEEDINGS
The undersigned hereby certifies that, as of the date of this Closing Certificate, there is no action, suit, claim, proceeding, arbitration, or investigation pending or, to the knowledge of the undersigned after due inquiry, threatened against Penterra or any of its affiliates, officers, directors, or employees, by or before any court, arbitral tribunal, governmental authority, or regulatory body, that (a) challenges the validity or enforceability of the MCTA or any ancillary agreement delivered in connection therewith, (b) questions Penterra's right, power, or authority to execute, deliver, or perform its obligations under the MCTA or any such ancillary agreement, (c) seeks to restrain, enjoin, or prohibit the consummation of the transactions contemplated by the MCTA, or (d) could reasonably be expected to result in a material adverse effect on Penterra's ability to perform its obligations under the MCTA or on the conduct of the CLARION trial.
The undersigned further certifies that Penterra has not received any written notice of, and is not otherwise aware of, any pending or threatened investigation by the FDA, the Department of Health and Human Services (including the Office of Inspector General), the Department of Justice, or any state attorney general that relates to the CLARION trial, penterafenib (PPC-4871), or Penterra's clinical trial activities generally.
SECTION 7: GOVERNING LAW
This Closing Certificate shall be governed by and construed in accordance with the laws of the State of New York, without giving effect to any choice-of-law or conflict-of-law rules or provisions that would cause the application of the laws of any other jurisdiction, consistent with and pursuant to the governing law provisions set forth in Section 12.08 of the MCTA. Any dispute arising out of or relating to this Closing Certificate shall be resolved in accordance with the dispute resolution provisions of the MCTA.
IN WITNESS WHEREOF, the undersigned has duly executed and delivered this Closing Certificate as of the date first set forth above.
PENTERRA PHARMACEUTICALS CORP.
By: ________
Name: Nathaniel Briggs, Esq.
Title: Vice President and General Counsel
Date: July 5, 2023
Address for Notices: 200 Biopharma Boulevard, Suite 1400 Princeton, New Jersey 08540 Telephone: (609) 555-4200
Email: legal@penterrapharma.com
ACKNOWLEDGMENT OF RECEIPT
The undersigned hereby acknowledges receipt of this Closing Certificate delivered by Penterra Pharmaceuticals Corp. pursuant to Section 9.02(a)(iii) of the MCTA.
VERIDIAN HEALTH RESEARCH NETWORK, INC.
Received and acknowledged by:
By: ________
Name: Dr. Franklin Osei, M.D., Ph.D.
Title: President and Chief Executive Officer
Date: July 5, 2023
Address for Notices: 750 Research Parkway, 8th Floor Philadelphia, Pennsylvania 19104 Telephone: (215) 555-8300
Email: legal@veridianresearch.org