letter-transmitting-first-draft.docx

1018-00004 · Penterra Pharmaceuticals Corp · Correspondence

letter-transmitting-first-draft.docx DOCUMENT Finance & Banking

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CALDERWOOD & HARKNESS LLP Attorneys at Law 280 Park Avenue, 34th Floor New York, New York 10017 Telephone: (212) 540-7000 Facsimile: (212) 540-7001 www.calderwoodharkness.com

April 7, 2023

Via Email and First-Class Mail

Allison Whitmore, Esq. Whitmore, Jansen & Callahan LLP 1500 Market Street, Suite 3200 Philadelphia, PA 19102

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

Dear Ms. Whitmore:

We write on behalf of our client, Penterra Pharmaceuticals Corp. ("Penterra"), a Delaware corporation with principal offices at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540, whose common stock is publicly traded on the Nasdaq Stock Market under the ticker symbol PTRA. Calderwood & Harkness LLP represents Penterra in connection with the proposed Master Clinical Trial Agreement (the "MCTA") between Penterra and Veridian Health Research Network, Inc. ("Veridian"), and we understand that Whitmore, Jansen & Callahan LLP serves as legal counsel to Veridian in this matter. The purpose of this letter is to transmit, for Veridian's review and comment, Calderwood & Harkness's initial draft of the MCTA, a copy of which is enclosed herewith together with all exhibits and schedules as described more fully below.

The enclosed draft MCTA is intended to govern the terms and conditions of a multi-site clinical trial collaboration between Penterra and Veridian's research network for Penterra's Phase III clinical trial of penterafenib (PPC-4871), an oral multi-kinase inhibitor currently under clinical development. The trial will be conducted under Protocol PPC-4871-III, titled "CLARION" (Clinical Assessment of Response with Longitudinal Investigation in ONcology), and is designed as a randomized, double-blind, placebo-controlled study evaluating penterafenib as a second-line therapy in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression following prior systemic therapy. The trial is registered on ClinicalTrials.gov under Identifier NCT05928174, and Penterra holds the corresponding Investigational New Drug Application, IND 157823, which was filed with the United States Food and Drug Administration ("FDA"). The study design calls for planned enrollment of approximately 1,200 subjects, randomized in a 2:1 ratio — 800 subjects to the penterafenib treatment arm and 400 subjects to the placebo control arm — across 38 Veridian Health Research Network academic medical centers and affiliated research sites located in 14 states. The projected enrollment period is 42 months, with a target first patient in date of August 2023 and a total estimated study duration of approximately 60 months. The primary efficacy endpoint is overall survival (OS), with key secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, has been identified to serve as Global Principal Investigator for the CLARION trial, and Dr. Howard Matsuoka, M.D., Associate Professor of Hepatology & Oncology at Lakemont Medical Center, will serve as Co-Principal Investigator.

The total deal value contemplated under the MCTA is Eighty Million Dollars ($80,000,000), covering all Veridian Network sites over the projected life of the trial. The financial structure reflected in the enclosed draft, and detailed in Exhibit B (Budget and Payment Schedule), is summarized as follows:

(a) Per-Patient Site Fees: Fifty-Two Thousand Dollars ($52,000) per enrolled subject, multiplied by 1,200 subjects, for a total of Sixty-Two Million Four Hundred Thousand Dollars ($62,400,000). Per-patient site fees will be disbursed in four milestone-based installments of Thirteen Thousand Dollars ($13,000) each, payable at (i) randomization, (ii) completion of the Week 12 visit, (iii) completion of the Week 24 visit, and (iv) study completion or final visit, as applicable.

(b) Start-Up Fees: Seventy-Five Thousand Dollars ($75,000) per site, multiplied by 38 participating sites, for a total of Two Million Eight Hundred Fifty Thousand Dollars ($2,850,000). Start-up fees will be payable in two equal installments of Thirty-Seven Thousand Five Hundred Dollars ($37,500) each, with 50% due upon site activation and 50% due upon enrollment of the first patient at such site.

(c) Annual Site Maintenance Fees: Forty Thousand Dollars ($40,000) per site per annum, multiplied by 38 sites over an average period of 3.5 years, for a total of Five Million Three Hundred Twenty Thousand Dollars ($5,320,000).

(d) Investigator Grants for Publication and Academic Support: One Million Five Hundred Thousand Dollars ($1,500,000), to be allocated in accordance with the publication and academic support provisions set forth in Exhibit G to the MCTA.

(e) Network Coordination/Administrative Fee to Veridian Central: Four Million Two Hundred Thousand Dollars ($4,200,000), calculated at Three Hundred Thousand Dollars ($300,000) per calendar quarter over 14 quarters, payable to Veridian's central administrative office for network coordination, administrative oversight, and governance support.

(f) Technology/EDC Integration Costs: One Million Two Hundred Thirty Thousand Dollars ($1,230,000), covering the integration, licensing, and maintenance of the electronic data capture (EDC) platform provided by Pinnacle Data Solutions, Inc., as further described in the MCTA and Exhibit K.

(g) Contingency/Change Order Reserve: Two Million Five Hundred Thousand Dollars ($2,500,000), to be held in reserve and accessed only upon mutual written agreement of the parties in connection with change orders, protocol amendments requiring additional site activities, or other unforeseen costs arising during the course of the trial.

All payments under the MCTA are subject to payment terms of Net 45 days from Penterra's receipt of a proper and complete invoice submitted in accordance with the invoicing procedures set forth in Exhibit B.

We wish to draw your attention to several key provisions in the enclosed draft that Calderwood & Harkness anticipates will be subjects of particular focus during the negotiation process. We have drafted these provisions to reflect Penterra's position while recognizing that the parties will need to reach consensus on a number of important commercial and risk-allocation issues:

Subject-Injury Indemnification (Exhibit D). The draft provides for sponsor indemnification of Veridian, each participating site institution, the principal investigators, sub-investigators, and site staff for third-party claims arising from the administration of the investigational product when administered in accordance with the Protocol, as well as claims arising from product defects, sponsor breach of the MCTA, and sponsor negligence or willful misconduct. This indemnification is subject to carve-outs for site or investigator negligence, unauthorized deviations from the Protocol, and site breach of the MCTA or any applicable Individual Site Agreement. The draft includes a per-subject medical care cap of Five Hundred Thousand Dollars ($500,000) and an aggregate medical care cap of Fifteen Million Dollars ($15,000,000) across all subjects and all sites. Indemnification claims are subject to a 30-calendar-day written notice requirement.

Reciprocal Site Indemnity (Exhibit D). The draft provides for reciprocal indemnification by Veridian and each participating site in favor of Penterra for claims arising from site staff negligence or willful misconduct, unauthorized protocol deviations, and site breach. The site indemnity is capped at Five Million Dollars ($5,000,000) per site per occurrence and Twenty Million Dollars ($20,000,000) in the aggregate across all sites.

Insurance Requirements (Exhibit E). Penterra is required to maintain clinical trial liability insurance with limits of not less than Twenty-Five Million Dollars ($25,000,000) per occurrence and Seventy-Five Million Dollars ($75,000,000) in the aggregate, including subject-injury sublimits, with Veridian and each participating site named as additional insureds on the policy. Veridian and each site are required to maintain general liability and professional liability coverage with limits of not less than Five Million Dollars ($5,000,000) per occurrence and Ten Million Dollars ($10,000,000) in the aggregate. Certificates of insurance are to be exchanged within 15 business days following execution of the MCTA.

Data Ownership and intellectual Property (Exhibit G). Penterra retains exclusive ownership of all clinical trial data generated under the MCTA and the Protocol. Each party retains ownership of its respective pre-existing intellectual property. Any joint inventions conceived or reduced to practice in the course of the trial will be governed by a separate intellectual Property Side Letter, which we intend to negotiate concurrently with the MCTA, as described further below. Sites are required to retain study records for a minimum of 15 years following completion of the study.

Publication Rights (Exhibit G). Investigators may publish or present study results subject to a 60-day review period in favor of Penterra for screening of confidential information and patentable subject matter, with Penterra holding the right to request an additional 90-day delay for the filing of patent applications.

Confidentiality (Exhibit F). Confidential information is subject to a 10-year confidentiality period from the date of disclosure. Permitted disclosures include those necessary for institutional review board (IRB) submissions, submissions to regulatory authorities, and disclosures to legal counsel in connection with the MCTA or the trial.

Regulatory Compliance (Exhibit H). The MCTA includes representations and covenants regarding compliance with 21 C.F.R. Parts 11 (electronic records and signatures), 50 (protection of human subjects), 54 (financial disclosure by clinical investigators), 56 (institutional review boards), and 312 (investigational new drug applications); the International Council for Harmonisation ("ICH") Guideline for Good Clinical Practice, E6(R2); the Health Insurance Portability and Accountability Act of 1996, as amended ("HIPAA"); the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)); and the Physician Payments Sunshine Act (Open Payments) provisions of the Affordable Care Act (42 U.S.C. § 1320a-7h).

Safety Reporting (Exhibit J). Serious adverse events (SAEs) must be reported to Penterra within 24 hours of site awareness. IND safety reports are to be submitted on 7-day timelines for fatal or life-threatening events and 15-day timelines for all other reportable events, in each case in accordance with 21 C.F.R. § 312.32. Safety reporting workflows will be coordinated with Meridian Contract Research Organization, Inc. ("Meridian CRO"), which Penterra has engaged as its contracted CRO for the CLARION trial.

Termination. The MCTA provides for a 120-day wind-down period following termination or expiration to ensure the orderly transition of enrolled subjects and the protection of subject safety. Subjects who are in active treatment at the time of termination will be either transitioned to appropriate clinical care or permitted to complete their current treatment cycle, as determined in consultation with the treating investigator and Penterra's medical monitor.

Governing Law and Dispute Resolution. The MCTA is governed by the laws of the State of New York, without regard to its conflicts-of-laws principles. Disputes are subject to a three-step escalation process consisting of (i) a 30-day good-faith negotiation period between designated senior representatives of the parties, (ii) a 60-day mediation administered by the American Arbitration Association ("AAA"), and (iii) binding arbitration under the rules of the AAA, to be conducted in New York, New York before a panel of three arbitrators. Notwithstanding the foregoing, either party may seek injunctive or other equitable relief in state or federal courts located in New York County, New York.

With respect to the IRB and regulatory framework, the enclosed draft contemplates that each participating site will obtain institutional review board approval prior to the enrollment of any subjects at that site. The lead sites — Graystone University Medical Center and Lakemont Medical Center — will each obtain individual IRB approval through their respective institutional review boards. We note for your reference that the Graystone University Medical Center IRB is registered with the Office for Human Research Protections under IRB Registration Number IRB00012847. The remaining Veridian Network sites may rely on the Veridian Central IRB under an IRB Authorization Agreement, consistent with the revised Common Rule requirements at 45 C.F.R. Part 46 (effective January 21, 2019). Penterra, as the IND holder (IND 157823), will retain full responsibility for all IND maintenance, annual reports, and communications with the FDA, with the assistance of regulatory counsel at Castleton & Hargrove LLP.

In addition to the body of the MCTA itself, the enclosed draft includes the following exhibits and schedules, each of which is transmitted herewith for Veridian's review:

Exhibit A — Protocol Synopsis (PPC-4871-III / CLARION)

Exhibit B — Budget and Payment Schedule

Exhibit C — Form of Individual Site Agreement (Joinder)

Exhibit D — Subject-Injury Indemnification Provisions

Exhibit E — Insurance Requirements and Certificate Forms

Exhibit F — Confidentiality and Data Protection Provisions

Exhibit G — Intellectual Property and Publication Rights

Exhibit H — Regulatory Compliance Representations and Covenants

Exhibit I — Form of Investigator Undertaking

Exhibit J — Safety Reporting Procedures

Exhibit K — Approved Subcontractors List (identifying Meridian Contract Research Organization, Inc., Pinnacle Data Solutions, Inc., and Northbridge Bioanalytical Laboratories, Inc.)

Schedule 1 — List of Participating Veridian Network Sites (38 sites across 14 states)

Additionally, as noted above, Penterra intends to negotiate an intellectual Property Side Letter concurrently with the MCTA, and a form of that side letter will be provided to you separately in due course. Principal Investigator and Co-Principal Investigator agreements for Dr. Catherine Aldridge and Dr. Howard Matsuoka, respectively, will also be negotiated in parallel with the MCTA, and we anticipate circulating drafts of those agreements within the coming weeks.

For your reference, the primary contacts on Penterra's side for purposes of the MCTA negotiation and the CLARION trial are as follows:

Nathaniel Briggs, Esq., Vice President & General Counsel, Penterra Pharmaceuticals Corp.

Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp. — Ms. Liang will serve as Penterra's day-to-day legal contact for the MCTA negotiations.

Samantha Novak, Director, Clinical Contracts, Penterra Pharmaceuticals Corp. — Ms. Novak will serve as the contracts administration contact for invoicing, site activation, and budgetary matters.

Jennifer Holt, Vice President, Clinical Operations, Penterra Pharmaceuticals Corp. — Ms. Holt will serve as the operational lead for trial-related questions, site readiness, and enrollment matters.

At Calderwood & Harkness, the engagement team for this matter consists of:

Miriam Calloway, Partner (responsible partner)

Joel Strauss, Partner (billing partner)

Sean Morrissey, Associate (lead associate)

Christopher Aiken, Associate (working associate)

We respectfully ask that day-to-day correspondence relating to the MCTA be directed to Miriam Calloway (mcalloway@calderwoodharkness.com) and Sean Morrissey (smorrissey@calderwoodharkness.com).

We respectfully request that Veridian and Whitmore, Jansen & Callahan LLP provide their markup of the enclosed draft within three weeks of the date of this letter — that is, by no later than Friday, April 28, 2023. Maintaining this timeline is important to support the target first patient in date of August 14, 2023, and to allow sufficient time for the completion of all necessary regulatory submissions and IRB approval processes at each participating site in advance of enrollment. We are, of course, happy to schedule a call or in-person meeting at your and Veridian's convenience to discuss the draft and any preliminary questions or concerns prior to the delivery of a formal markup. Should you or Veridian require any additional background materials in the course of your review — including the full Protocol (PPC-4871-III), the Investigator's Brochure for penterafenib, or supporting insurance documentation — please do not hesitate to let us know and we will arrange to provide them promptly.

Please note that the enclosed draft MCTA and all accompanying exhibits and schedules are confidential and are being provided solely for purposes of the negotiation between the parties. We respectfully request that Veridian and Whitmore, Jansen & Callahan LLP treat all materials transmitted herewith as confidential and limit their distribution to those individuals within your respective organizations who have a need to review the materials in connection with this transaction.

We look forward to working with you and your team on this important engagement. Please do not hesitate to contact me or Sean Morrissey if you have any questions or if we can be of any further assistance as you begin your review.

Very truly yours,

CALDERWOOD & HARKNESS LLP

By: ________

Miriam Calloway Partner

280 Park Avenue, 34th Floor New York, NY 10017 Telephone: (212) 540-7214

Email: mcalloway@calderwoodharkness.com

Enclosures:

1. Draft Master Clinical Trial Agreement (First Draft) between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. — Protocol PPC-4871-III (CLARION), together with Exhibits A through K and Schedule 1

cc:

Nathaniel Briggs, Esq., Vice President & General Counsel, Penterra Pharmaceuticals Corp. Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp. Sean Morrissey, Calderwood & Harkness LLP Christopher Aiken, Calderwood & Harkness LLP David Kesselman, Esq., Whitmore, Jansen & Callahan LLP

CALDERWOOD & HARKNESS LLP Attorneys at Law 280 Park Avenue, 34th Floor New York, New York 10017 Telephone: (212) 540-7000 Facsimile: (212) 540-7001 www.calderwoodharkness.com
April 7, 2023
Via Email and First-Class Mail
Allison Whitmore, Esq. Whitmore, Jansen & Callahan LLP 1500 Market Street, Suite 3200 Philadelphia, PA 19102
Re: Master Clinical Trial Agreement Between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. — Protocol PPC-4871-III (CLARION) Calderwood & Harkness Matter No. 1018-00004
Dear Ms. Whitmore:
We write on behalf of our client, Penterra Pharmaceuticals Corp. ("Penterra"), a Delaware corporation with principal offices at 200 Biopharma Boulevard, Suite 1400, Princeton, New Jersey 08540, whose common stock is publicly traded on the Nasdaq Stock Market under the ticker symbol PTRA. Calderwood & Harkness LLP represents Penterra in connection with the proposed Master Clinical Trial Agreement (the "MCTA") between Penterra and Veridian Health Research Network, Inc. ("Veridian"), and we understand that Whitmore, Jansen & Callahan LLP serves as legal counsel to Veridian in this matter. The purpose of this letter is to transmit, for Veridian's review and comment, Calderwood & Harkness's initial draft of the MCTA, a copy of which is enclosed herewith together with all exhibits and schedules as described more fully below.
The enclosed draft MCTA is intended to govern the terms and conditions of a multi-site clinical trial collaboration between Penterra and Veridian's research network for Penterra's Phase III clinical trial of penterafenib (PPC-4871), an oral multi-kinase inhibitor currently under clinical development. The trial will be conducted under Protocol PPC-4871-III, titled "CLARION" (Clinical Assessment of Response with Longitudinal Investigation in ONcology), and is designed as a randomized, double-blind, placebo-controlled study evaluating penterafenib as a second-line therapy in patients with advanced hepatocellular carcinoma (HCC) who have experienced disease progression following prior systemic therapy. The trial is registered on ClinicalTrials.gov under Identifier NCT05928174, and Penterra holds the corresponding Investigational New Drug Application, IND 157823, which was filed with the United States Food and Drug Administration ("FDA"). The study design calls for planned enrollment of approximately 1,200 subjects, randomized in a 2:1 ratio — 800 subjects to the penterafenib treatment arm and 400 subjects to the placebo control arm — across 38 Veridian Health Research Network academic medical centers and affiliated research sites located in 14 states. The projected enrollment period is 42 months, with a target first patient in date of August 2023 and a total estimated study duration of approximately 60 months. The primary efficacy endpoint is overall survival (OS), with key secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR). Dr. Catherine Aldridge, M.D., Ph.D., Professor of Oncology at Graystone University Medical Center, has been identified to serve as Global Principal Investigator for the CLARION trial, and Dr. Howard Matsuoka, M.D., Associate Professor of Hepatology & Oncology at Lakemont Medical Center, will serve as Co-Principal Investigator.
The total deal value contemplated under the MCTA is Eighty Million Dollars ($80,000,000), covering all Veridian Network sites over the projected life of the trial. The financial structure reflected in the enclosed draft, and detailed in Exhibit B (Budget and Payment Schedule), is summarized as follows:
(a) Per-Patient Site Fees: Fifty-Two Thousand Dollars ($52,000) per enrolled subject, multiplied by 1,200 subjects, for a total of Sixty-Two Million Four Hundred Thousand Dollars ($62,400,000). Per-patient site fees will be disbursed in four milestone-based installments of Thirteen Thousand Dollars ($13,000) each, payable at (i) randomization, (ii) completion of the Week 12 visit, (iii) completion of the Week 24 visit, and (iv) study completion or final visit, as applicable.
(b) Start-Up Fees: Seventy-Five Thousand Dollars ($75,000) per site, multiplied by 38 participating sites, for a total of Two Million Eight Hundred Fifty Thousand Dollars ($2,850,000). Start-up fees will be payable in two equal installments of Thirty-Seven Thousand Five Hundred Dollars ($37,500) each, with 50% due upon site activation and 50% due upon enrollment of the first patient at such site.
(c) Annual Site Maintenance Fees: Forty Thousand Dollars ($40,000) per site per annum, multiplied by 38 sites over an average period of 3.5 years, for a total of Five Million Three Hundred Twenty Thousand Dollars ($5,320,000).
(d) Investigator Grants for Publication and Academic Support: One Million Five Hundred Thousand Dollars ($1,500,000), to be allocated in accordance with the publication and academic support provisions set forth in Exhibit G to the MCTA.
(e) Network Coordination/Administrative Fee to Veridian Central: Four Million Two Hundred Thousand Dollars ($4,200,000), calculated at Three Hundred Thousand Dollars ($300,000) per calendar quarter over 14 quarters, payable to Veridian's central administrative office for network coordination, administrative oversight, and governance support.
(f) Technology/EDC Integration Costs: One Million Two Hundred Thirty Thousand Dollars ($1,230,000), covering the integration, licensing, and maintenance of the electronic data capture (EDC) platform provided by Pinnacle Data Solutions, Inc., as further described in the MCTA and Exhibit K.
(g) Contingency/Change Order Reserve: Two Million Five Hundred Thousand Dollars ($2,500,000), to be held in reserve and accessed only upon mutual written agreement of the parties in connection with change orders, protocol amendments requiring additional site activities, or other unforeseen costs arising during the course of the trial.
All payments under the MCTA are subject to payment terms of Net 45 days from Penterra's receipt of a proper and complete invoice submitted in accordance with the invoicing procedures set forth in Exhibit B.
We wish to draw your attention to several key provisions in the enclosed draft that Calderwood & Harkness anticipates will be subjects of particular focus during the negotiation process. We have drafted these provisions to reflect Penterra's position while recognizing that the parties will need to reach consensus on a number of important commercial and risk-allocation issues:
Subject-Injury Indemnification (Exhibit D). The draft provides for sponsor indemnification of Veridian, each participating site institution, the principal investigators, sub-investigators, and site staff for third-party claims arising from the administration of the investigational product when administered in accordance with the Protocol, as well as claims arising from product defects, sponsor breach of the MCTA, and sponsor negligence or willful misconduct. This indemnification is subject to carve-outs for site or investigator negligence, unauthorized deviations from the Protocol, and site breach of the MCTA or any applicable Individual Site Agreement. The draft includes a per-subject medical care cap of Five Hundred Thousand Dollars ($500,000) and an aggregate medical care cap of Fifteen Million Dollars ($15,000,000) across all subjects and all sites. Indemnification claims are subject to a 30-calendar-day written notice requirement.
Reciprocal Site Indemnity (Exhibit D). The draft provides for reciprocal indemnification by Veridian and each participating site in favor of Penterra for claims arising from site staff negligence or willful misconduct, unauthorized protocol deviations, and site breach. The site indemnity is capped at Five Million Dollars ($5,000,000) per site per occurrence and Twenty Million Dollars ($20,000,000) in the aggregate across all sites.
Insurance Requirements (Exhibit E). Penterra is required to maintain clinical trial liability insurance with limits of not less than Twenty-Five Million Dollars ($25,000,000) per occurrence and Seventy-Five Million Dollars ($75,000,000) in the aggregate, including subject-injury sublimits, with Veridian and each participating site named as additional insureds on the policy. Veridian and each site are required to maintain general liability and professional liability coverage with limits of not less than Five Million Dollars ($5,000,000) per occurrence and Ten Million Dollars ($10,000,000) in the aggregate. Certificates of insurance are to be exchanged within 15 business days following execution of the MCTA.
Data Ownership and intellectual Property (Exhibit G). Penterra retains exclusive ownership of all clinical trial data generated under the MCTA and the Protocol. Each party retains ownership of its respective pre-existing intellectual property. Any joint inventions conceived or reduced to practice in the course of the trial will be governed by a separate intellectual Property Side Letter, which we intend to negotiate concurrently with the MCTA, as described further below. Sites are required to retain study records for a minimum of 15 years following completion of the study.
Publication Rights (Exhibit G). Investigators may publish or present study results subject to a 60-day review period in favor of Penterra for screening of confidential information and patentable subject matter, with Penterra holding the right to request an additional 90-day delay for the filing of patent applications.
Confidentiality (Exhibit F). Confidential information is subject to a 10-year confidentiality period from the date of disclosure. Permitted disclosures include those necessary for institutional review board (IRB) submissions, submissions to regulatory authorities, and disclosures to legal counsel in connection with the MCTA or the trial.
Regulatory Compliance (Exhibit H). The MCTA includes representations and covenants regarding compliance with 21 C.F.R. Parts 11 (electronic records and signatures), 50 (protection of human subjects), 54 (financial disclosure by clinical investigators), 56 (institutional review boards), and 312 (investigational new drug applications); the International Council for Harmonisation ("ICH") Guideline for Good Clinical Practice, E6(R2); the Health Insurance Portability and Accountability Act of 1996, as amended ("HIPAA"); the federal Anti-Kickback Statute (42 U.S.C. § 1320a-7b(b)); and the Physician Payments Sunshine Act (Open Payments) provisions of the Affordable Care Act (42 U.S.C. § 1320a-7h).
Safety Reporting (Exhibit J). Serious adverse events (SAEs) must be reported to Penterra within 24 hours of site awareness. IND safety reports are to be submitted on 7-day timelines for fatal or life-threatening events and 15-day timelines for all other reportable events, in each case in accordance with 21 C.F.R. § 312.32. Safety reporting workflows will be coordinated with Meridian Contract Research Organization, Inc. ("Meridian CRO"), which Penterra has engaged as its contracted CRO for the CLARION trial.
Termination. The MCTA provides for a 120-day wind-down period following termination or expiration to ensure the orderly transition of enrolled subjects and the protection of subject safety. Subjects who are in active treatment at the time of termination will be either transitioned to appropriate clinical care or permitted to complete their current treatment cycle, as determined in consultation with the treating investigator and Penterra's medical monitor.
Governing Law and Dispute Resolution. The MCTA is governed by the laws of the State of New York, without regard to its conflicts-of-laws principles. Disputes are subject to a three-step escalation process consisting of (i) a 30-day good-faith negotiation period between designated senior representatives of the parties, (ii) a 60-day mediation administered by the American Arbitration Association ("AAA"), and (iii) binding arbitration under the rules of the AAA, to be conducted in New York, New York before a panel of three arbitrators. Notwithstanding the foregoing, either party may seek injunctive or other equitable relief in state or federal courts located in New York County, New York.
With respect to the IRB and regulatory framework, the enclosed draft contemplates that each participating site will obtain institutional review board approval prior to the enrollment of any subjects at that site. The lead sites — Graystone University Medical Center and Lakemont Medical Center — will each obtain individual IRB approval through their respective institutional review boards. We note for your reference that the Graystone University Medical Center IRB is registered with the Office for Human Research Protections under IRB Registration Number IRB00012847. The remaining Veridian Network sites may rely on the Veridian Central IRB under an IRB Authorization Agreement, consistent with the revised Common Rule requirements at 45 C.F.R. Part 46 (effective January 21, 2019). Penterra, as the IND holder (IND 157823), will retain full responsibility for all IND maintenance, annual reports, and communications with the FDA, with the assistance of regulatory counsel at Castleton & Hargrove LLP.
In addition to the body of the MCTA itself, the enclosed draft includes the following exhibits and schedules, each of which is transmitted herewith for Veridian's review:
Exhibit A — Protocol Synopsis (PPC-4871-III / CLARION)
Exhibit B — Budget and Payment Schedule
Exhibit C — Form of Individual Site Agreement (Joinder)
Exhibit D — Subject-Injury Indemnification Provisions
Exhibit E — Insurance Requirements and Certificate Forms
Exhibit F — Confidentiality and Data Protection Provisions
Exhibit G — Intellectual Property and Publication Rights
Exhibit H — Regulatory Compliance Representations and Covenants
Exhibit I — Form of Investigator Undertaking
Exhibit J — Safety Reporting Procedures
Exhibit K — Approved Subcontractors List (identifying Meridian Contract Research Organization, Inc., Pinnacle Data Solutions, Inc., and Northbridge Bioanalytical Laboratories, Inc.)
Schedule 1 — List of Participating Veridian Network Sites (38 sites across 14 states)
Additionally, as noted above, Penterra intends to negotiate an intellectual Property Side Letter concurrently with the MCTA, and a form of that side letter will be provided to you separately in due course. Principal Investigator and Co-Principal Investigator agreements for Dr. Catherine Aldridge and Dr. Howard Matsuoka, respectively, will also be negotiated in parallel with the MCTA, and we anticipate circulating drafts of those agreements within the coming weeks.
For your reference, the primary contacts on Penterra's side for purposes of the MCTA negotiation and the CLARION trial are as follows:
Nathaniel Briggs, Esq., Vice President & General Counsel, Penterra Pharmaceuticals Corp.
Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp. — Ms. Liang will serve as Penterra's day-to-day legal contact for the MCTA negotiations.
Samantha Novak, Director, Clinical Contracts, Penterra Pharmaceuticals Corp. — Ms. Novak will serve as the contracts administration contact for invoicing, site activation, and budgetary matters.
Jennifer Holt, Vice President, Clinical Operations, Penterra Pharmaceuticals Corp. — Ms. Holt will serve as the operational lead for trial-related questions, site readiness, and enrollment matters.
At Calderwood & Harkness, the engagement team for this matter consists of:
Miriam Calloway, Partner (responsible partner)
Joel Strauss, Partner (billing partner)
Sean Morrissey, Associate (lead associate)
Christopher Aiken, Associate (working associate)
We respectfully ask that day-to-day correspondence relating to the MCTA be directed to Miriam Calloway (mcalloway@calderwoodharkness.com) and Sean Morrissey (smorrissey@calderwoodharkness.com).
We respectfully request that Veridian and Whitmore, Jansen & Callahan LLP provide their markup of the enclosed draft within three weeks of the date of this letter — that is, by no later than Friday, April 28, 2023. Maintaining this timeline is important to support the target first patient in date of August 14, 2023, and to allow sufficient time for the completion of all necessary regulatory submissions and IRB approval processes at each participating site in advance of enrollment. We are, of course, happy to schedule a call or in-person meeting at your and Veridian's convenience to discuss the draft and any preliminary questions or concerns prior to the delivery of a formal markup. Should you or Veridian require any additional background materials in the course of your review — including the full Protocol (PPC-4871-III), the Investigator's Brochure for penterafenib, or supporting insurance documentation — please do not hesitate to let us know and we will arrange to provide them promptly.
Please note that the enclosed draft MCTA and all accompanying exhibits and schedules are confidential and are being provided solely for purposes of the negotiation between the parties. We respectfully request that Veridian and Whitmore, Jansen & Callahan LLP treat all materials transmitted herewith as confidential and limit their distribution to those individuals within your respective organizations who have a need to review the materials in connection with this transaction.
We look forward to working with you and your team on this important engagement. Please do not hesitate to contact me or Sean Morrissey if you have any questions or if we can be of any further assistance as you begin your review.
Very truly yours,
CALDERWOOD & HARKNESS LLP
By: ________
Miriam Calloway Partner
280 Park Avenue, 34th Floor New York, NY 10017 Telephone: (212) 540-7214
Email: mcalloway@calderwoodharkness.com
Enclosures:
1. Draft Master Clinical Trial Agreement (First Draft) between Penterra Pharmaceuticals Corp. and Veridian Health Research Network, Inc. — Protocol PPC-4871-III (CLARION), together with Exhibits A through K and Schedule 1
cc:
Nathaniel Briggs, Esq., Vice President & General Counsel, Penterra Pharmaceuticals Corp. Rebecca Liang, Esq., Associate General Counsel, Clinical Affairs, Penterra Pharmaceuticals Corp. Sean Morrissey, Calderwood & Harkness LLP Christopher Aiken, Calderwood & Harkness LLP David Kesselman, Esq., Whitmore, Jansen & Callahan LLP

CALDERWOOD & HARKNESS LLP

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