FINANCIAL DISCLOSURE CERTIFICATION FORM — CLINICAL INVESTIGATORS
Pursuant to 21 C.F.R. Part 54 — Financial Disclosure by Clinical Investigators
Protocol PPC-4871-III (CLARION — Clinical Assessment of Response with Longitudinal Investigation in ONcology)
Sponsor: Penterra Pharmaceuticals Corp. 200 Biopharma Boulevard, Suite 1400, Princeton, NJ 08540
IND Number: IND 157823 ClinicalTrials.gov Identifier: NCT05928174
Investigational Product: Penterafenib (PPC-4871), Oral Multi-Kinase Inhibitor Indication: Advanced Hepatocellular Carcinoma (HCC), Second-Line After Prior Systemic Therapy Phase: Phase III, Randomized, Double-Blind, Placebo-Controlled
Form Version Date: April 2023
Prepared by: Calderwood & Harkness LLP Matter No. 1018-00004
NOTE: This template form is to be completed by each clinical investigator (principal investigators, sub-investigators, and co-principal investigators) participating in Protocol PPC-4871-III at sites within the Veridian Health Research Network, Inc. Each investigator must complete and return this form to the Sponsor prior to site activation and first patient enrollment. Investigators should review all definitions and instructions carefully before completing this certification. Questions regarding this form should be directed to Penterra's Director of Clinical Contracts, Samantha Novak, or Associate General Counsel, Clinical Affairs, Rebecca Liang, Esq., at the address listed above.
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SECTION 1: PURPOSE AND REGULATORY BACKGROUND
This Financial Disclosure Certification Form is required under Title 21 of the Code of Federal Regulations, Part 54 ("21 C.F.R. Part 54"), to ensure adequate and timely disclosure of financial interests and arrangements held by clinical investigators that could affect the reliability of data submitted to the United States Food and Drug Administration ("FDA") in support of marketing applications for penterafenib (PPC-4871). The purpose of this form is to collect the financial information necessary for Penterra Pharmaceuticals Corp. ("Penterra" or the "Sponsor") to comply with its regulatory obligations under 21 C.F.R. Part 54, including the obligation to certify the absence of certain financial interests of clinical investigators or, where such interests exist, to disclose them to the FDA.
The FDA requires sponsors of covered clinical studies to collect financial disclosure information from all clinical investigators who participate in such studies and to submit this information as part of any marketing application, including a New Drug Application ("NDA"), Biologics License Application ("BLA"), or supplemental application filed with the Agency. The requirement reflects the FDA's recognition that financial interests held by clinical investigators may introduce bias — whether conscious or unconscious — into the design, conduct, reporting, or analysis of clinical studies. The purpose of the disclosure requirement is not to prohibit any particular financial arrangement, but to ensure transparency so that the FDA can evaluate the potential impact of any such arrangement on the integrity and reliability of the clinical data.
This form is designed to collect the information required under the following regulatory provisions:
• 21 C.F.R. § 54.4 — Certification and Disclosure Requirements. This section requires the sponsor to submit, for each clinical investigator who participated in a covered clinical study, either a certification that the investigator did not have specified disclosable financial interests or arrangements, or a disclosure of such interests.
• 21 C.F.R. § 54.5 — Agency Evaluation of Financial Interests. This section describes the FDA's process for evaluating the potential impact of disclosed financial interests on the reliability of clinical data, including the steps the Agency may take where a financial interest raises concerns about data integrity.
• 21 C.F.R. § 54.6 — Recordkeeping and Retention Requirements. This section requires the sponsor to maintain complete records of all financial disclosures and certifications for a period of two years after the date of approval of the marketing application, or, if the application is not approved, for two years after the date of the last submission to the FDA. The Master Clinical Trial Agreement ("MCTA") between Penterra and Veridian Health Research Network, Inc. ("Veridian") imposes a longer retention period.
It is important to note that Penterra Pharmaceuticals Corp. is a publicly traded company whose common stock is listed on the Nasdaq Stock Market under the ticker symbol "PTRA." As of the first quarter of 2023, Penterra's market capitalization is approximately $4.2 billion. The publicly traded status of the Sponsor makes equity interests and proprietary interest disclosures particularly relevant. Investigators who hold stock, stock options, warrants, or other equity instruments in Penterra, or whose spouses or dependent children hold such interests, must carefully evaluate whether these interests trigger the disclosure requirements set forth in this form.
This form covers the "Covered Period," which is defined as the period beginning one year prior to the date of the investigator's first participation in Protocol PPC-4871-III and extending through one year after the last patient's last visit under the protocol. Based on current study timelines, the projected date of the last patient's last visit is August 2028, such that the Covered Period may extend through approximately August 2029 for investigators who participate through study completion. Investigators who withdraw from participation earlier will have a correspondingly shorter Covered Period.
Each investigator is required to update this certification promptly if his or her financial circumstances change during participation in Protocol PPC-4871-III or during the one-year period following study completion. The obligation to update is ongoing and is not limited to changes that occur at the time of initial form submission. Specific instructions regarding the update process are set forth in Section 7 of this form.
SECTION 2: INVESTIGATOR IDENTIFICATION INFORMATION
Please complete all fields below in full. Use black ink if completing this form by hand. Fields marked with an asterisk (*) are required.
Full Legal Name of Investigator*:
First Name: ______________
Middle Name: ______________
Last Name: ______________
Suffix (if applicable): ______________
Title / Academic Rank*:
________________________________________
Institutional Affiliation*:
Institution Name: ______________
Street Address: ______________
City: ______ State: __ ZIP: ____
(e.g., Graystone University Medical Center, 1200 University Avenue, Philadelphia, PA 19104; Lakemont Medical Center, 4400 North Michigan Drive, Chicago, IL 60611; or other Veridian Health Research Network member institution)
Veridian Network Site Number*:
________________________________________
(e.g., Site 001, Site 002, etc. — refer to Schedule 1 of the Master Clinical Trial Agreement, which lists all 38 participating sites across 14 states)
Role in Study* (check one):
Principal Investigator
Sub-Investigator
Co-Principal Investigator
Medical License Number and State of Licensure*:
License Number: ______________
State of Licensure: ______________
Additional License(s) (if applicable): ______________
Board Certifications:
________________________________________
________________________________________
Business Mailing Address (if different from institutional address above):
________________________________________
________________________________________
Business Telephone*: ______________
Business Email*: ______________
Date of First Involvement in Protocol PPC-4871-III*: ______________
NOTE: For the Global Principal Investigator (Dr. Catherine Aldridge, M.D., Ph.D., Graystone University Medical Center, Site 001) and the Co-Principal Investigator (Dr. Howard Matsuoka, M.D., Lakemont Medical Center, Site 008), this form must be completed and submitted to the Sponsor prior to site activation. No site activation visit may occur, and no patients may be screened or enrolled, until the Sponsor has received and reviewed the completed Financial Disclosure Certification Form for the site's Principal Investigator or Co-Principal Investigator, as applicable.
SECTION 3: DEFINITIONS
For purposes of this Financial Disclosure Certification Form, the following terms have the meanings set forth below. These definitions are derived from and are consistent with the definitions contained in 21 C.F.R. § 54.2. Investigators are encouraged to review the full text of 21 C.F.R. Part 54 and to consult with their institutional conflict-of-interest offices or personal legal counsel if they have any questions about the applicability of these definitions to their individual circumstances.
"Covered Clinical Study" means, as defined in 21 C.F.R. § 54.2(e), any study of a drug or device in humans submitted in a marketing application or reclassification petition that the applicant or the FDA relies upon to establish that the product is effective (including studies that show equivalence to an effective product) or any study in which a single investigator makes a significant contribution to the demonstration of safety. A study is considered a covered clinical study regardless of whether it is ultimately included in a marketing application if, at the time the study is being conducted, it is intended to or could be relied upon to support such an application. For purposes of this form, Protocol PPC-4871-III (CLARION) is a covered clinical study. This Phase III, randomized, double-blind, placebo-controlled study is designed to generate pivotal efficacy and safety data intended to support an NDA submission for penterafenib (PPC-4871) for the treatment of advanced hepatocellular carcinoma (HCC) in adults who have received at least one prior line of systemic therapy.
"Clinical Investigator" means, as defined in 21 C.F.R. § 54.2(d), the listed or identified investigator or sub-investigator who is directly involved in the treatment or evaluation of research subjects. This includes any individual listed on the FDA Form 1572 (Statement of Investigator) for Protocol PPC-4871-III, whether designated as a principal investigator, co-principal investigator, or sub-investigator. Individuals who serve solely in an administrative or coordinating capacity and who do not directly treat or evaluate research subjects are generally not considered clinical investigators for purposes of this regulation; however, if there is any question regarding an individual's status, the Sponsor should be consulted.
"Sponsor" means Penterra Pharmaceuticals Corp., a Delaware corporation with principal offices at 200 Biopharma Boulevard, Suite 1400, Princeton, NJ 08540 (Nasdaq: PTRA). For purposes of 21 C.F.R. Part 54, the term "sponsor" includes any entity that has entered into an arrangement with the sponsor to act on its behalf in the conduct of the study, although the financial disclosure obligations run to the sponsor itself.
"Investigational Product" means penterafenib (PPC-4871), an oral multi-kinase inhibitor currently under investigation for the treatment of advanced hepatocellular carcinoma (HCC). The investigational product is the subject of IND 157823 and ClinicalTrials.gov registration NCT05928174.
"Significant Equity Interest" means, as defined in 21 C.F.R. § 54.2(b):
(a) Any ownership interest, stock options, or other financial interest whose value cannot be readily determined through reference to public prices (such as combinated ownership interest in a privately held company, or non-publicly traded stock options); or
(b) Any equity interest in a publicly traded company that exceeds $50,000 in value at any time during the period the clinical investigator is carrying out the study and for one year following completion of the study.
For purposes of this form, because Penterra Pharmaceuticals Corp. is publicly traded on the Nasdaq Stock Market, a significant equity interest exists if the investigator, the investigator's spouse, or any dependent child of the investigator holds equity interests in Penterra (including common stock, preferred stock, stock options, warrants, or convertible securities) with a value exceeding $50,000 at any time during the Covered Period.
"Proprietary Interest" means, as defined in 21 C.F.R. § 54.2(a), property or other financial interest in the tested product, including but not limited to a patent, trademark, copyright, or licensing agreement relating to the investigational product. A proprietary interest may exist regardless of whether the investigator derives current revenue from the interest. Investigators who are named as inventors on patents or patent applications relating to penterafenib (PPC-4871) or its methods of use, or who are parties to licensing agreements relating to the investigational product, hold a proprietary interest.
"Significant Payments of Other Sorts" means, as defined in 21 C.F.R. § 54.2(f), payments made by the sponsor of a covered study to the investigator or the investigator's institution to support activities of the investigator that have a monetary value of more than $25,000 during the Covered Period, exclusive of the costs of conducting the clinical study or other clinical studies (i.e., per-patient fees and other direct costs of study conduct), and exclusive of payments that are fair market value for legitimate services (such as fair market value consulting fees for bona fide consulting arrangements). The threshold of $25,000 is an aggregate amount calculated over the entire Covered Period, not per payment or per annum.
"Covered Period" means the period beginning one year prior to the date of the investigator's first participation in Protocol PPC-4871-III and extending through one year after the last patient's last visit under the protocol. Based on current study timelines, the projected date of the last patient's last visit is August 2028. The Covered Period may be adjusted if the study completion date changes. For investigators who withdraw from the study before its completion, the Covered Period ends one year after the investigator's last involvement in study activities.
SECTION 4: FINANCIAL INTEREST CERTIFICATION — PART A
(Certification of No Disclosable Financial Interests)
INSTRUCTIONS: This section permits the investigator to certify that he or she does not have any of the financial interests or arrangements that must be disclosed under 21 C.F.R. Part 54. To complete Part A, the investigator must be able to truthfully check each of the four boxes below (Sections 4.1 through 4.4). If the investigator is unable to check even one of the four boxes, the investigator must not sign Part A and must instead complete Part B (Section 5) of this form, providing full disclosure of the relevant financial interest(s).
The investigator should carefully review the definitions in Section 3 before completing this section. The certifications below apply to the investigator, and where specified, to the investigator's spouse and dependent children.
4.1 Compensation Arrangements Affected by Study Outcome
"I certify that I have NOT entered into any financial arrangement with Penterra Pharmaceuticals Corp. or any agent of the Sponsor whereby the value of the compensation to the investigator for conducting the study could be affected by the outcome of the study."
This certification addresses arrangements in which the investigator's compensation for participating in Protocol PPC-4871-III is contingent upon, or would increase or decrease based upon, the results of the study, including but not limited to milestone bonuses tied to favorable efficacy outcomes, success fees payable upon regulatory approval of the investigational product, or royalty arrangements linked to the commercial success of penterafenib (PPC-4871). Fixed per-patient fees paid at fair market value under the Master Clinical Trial Agreement or Individual Site Agreement are not considered compensation affected by the study outcome.
If you cannot make this certification, do NOT check the box above. Proceed to Part B (Section 5.1) to disclose the relevant arrangement.
4.2 Significant Equity Interest in Sponsor
"I certify that I do NOT hold, and my spouse and each dependent child do NOT hold, a significant equity interest (as defined in Section 3 above) in Penterra Pharmaceuticals Corp. (Nasdaq: PTRA), including stocks, stock options, warrants, convertible securities, or other equity instruments, with a value exceeding $50,000, at any time during the Covered Period."
This certification applies to all forms of equity ownership in the Sponsor, including direct and indirect holdings, beneficial ownership through trusts or investment vehicles, shares held in brokerage accounts, retirement accounts, or managed portfolios, and any stock options, warrants, restricted stock units, or other equity-linked instruments. Because Penterra is publicly traded on the Nasdaq Stock Market, the relevant threshold is $50,000 in aggregate value at any time during the Covered Period. Investigators should review their brokerage statements, retirement account holdings, and any managed portfolio holdings to determine whether they or their spouses or dependent children hold equity in Penterra.
If you cannot make this certification, do NOT check the box above. Proceed to Part B (Section 5.2) to disclose the relevant equity interest.
4.3 Proprietary Interest in the Investigational Product
"I certify that I do NOT hold any proprietary interest in penterafenib (PPC-4871), including any patent, patent application, trademark, copyright, or licensing agreement relating to the investigational product."
This certification covers any property or financial interest in the investigational product itself, as distinguished from an equity interest in the Sponsor. Investigators who have been involved in the preclinical or early-phase clinical development of penterafenib (PPC-4871) should carefully evaluate whether they hold any patent rights, are named as inventors on any patent application, or are parties to any licensing, royalty, or other proprietary arrangement relating to the investigational product or its formulation, method of use, or synthesis.
If you cannot make this certification, do NOT check the box above. Proceed to Part B (Section 5.3) to disclose the relevant proprietary interest.
4.4 Significant Payments of Other Sorts
"I certify that I have NOT received, and my institution has NOT received on my behalf, significant payments of other sorts (as defined in Section 3 above, exceeding $25,000 in aggregate during the Covered Period) from Penterra Pharmaceuticals Corp., exclusive of the costs of conducting the clinical study and exclusive of payments representing fair market value for legitimate services."
This certification addresses payments made by the Sponsor to the investigator or the investigator's institution that are not directly related to the costs of conducting Protocol PPC-4871-III or other clinical studies. Examples of payments that may trigger disclosure include honoraria, consulting fees in excess of fair market value, unrestricted educational grants, equipment or material grants, endowment funding, or other transfers of value.
NOTE: Per-patient site fees under the Master Clinical Trial Agreement (currently $52,000 per evaluable subject, paid on a milestone basis as specified in Exhibit C of the MCTA) and investigator grants for publication support are structured at fair market value, as determined by independent fair market value assessments conducted by an independent third-party valuation firm, and are excluded from this calculation. This structuring is consistent with applicable Anti-Kickback Statute (42 U.S.C. § 1320a-7b) safe harbor requirements for bona fide payments for research services. If the investigator has questions regarding whether a particular payment is excluded from this calculation, the investigator should contact Penterra's Director of Clinical Contracts (Samantha Novak) or Associate General Counsel, Clinical Affairs (Rebecca Liang, Esq.).
If you cannot make this certification, do NOT check the box above. Proceed to Part B (Section 5.4) to disclose the relevant payments.
4.5 Combined Certification
INSTRUCTIONS: If the investigator was able to check ALL FOUR boxes above (Sections 4.1 through 4.4), the investigator should sign and date this section below. Upon signing, the investigator should proceed directly to Section 6 (Institutional Financial Interests) and Section 7 (Ongoing Obligations), and then to Section 9 (Certification Signatures and Attestation) for final execution.
If the investigator was unable to check ANY ONE OR MORE of the boxes above, the investigator must NOT sign this section. Instead, the investigator must proceed to Part B (Section 5) and provide full disclosure of each financial interest or arrangement that prevented certification.
By signing below, I certify under penalty of perjury under the laws of the United States of America that all of the above statements in Part A (Sections 4.1 through 4.4) are true and correct to the best of my knowledge, information, and belief. I understand that any material misstatement or omission in this certification may constitute a violation of federal law and may result in regulatory action, including but not limited to rejection of clinical data, debarment, or referral for enforcement proceedings.
Printed Name of Investigator: ________
Signature: ________
Date: ________
Institution / Veridian Network Site Number: ________
SECTION 5: FINANCIAL DISCLOSURE — PART B
(Disclosure of Financial Interests)
INSTRUCTIONS: Complete this section ONLY if you were unable to make one or more of the certifications in Part A (Section 4). Provide detailed disclosure of each applicable financial interest or arrangement. Complete only those subsections (5.1 through 5.5) that correspond to the certification(s) in Part A that you were unable to make. If you were able to certify all items in Part A, skip this section entirely.
All information provided in this section will be treated as confidential in accordance with the confidentiality provisions of the MCTA. However, the Sponsor is required by federal law to submit this information to the FDA as part of any marketing application for penterafenib (PPC-4871), and such submissions are subject to applicable FDA disclosure policies.
5.1 Compensation Affected by Study Outcome
(Complete this subsection only if you were unable to check the box in Section 4.1.)
Description of Financial Arrangement: Provide a full description of any financial arrangement with Penterra Pharmaceuticals Corp. or any agent of the Sponsor whereby the value of your compensation for conducting Protocol PPC-4871-III could be affected by the outcome of the study:
________________________________________
________________________________________
________________________________________
________________________________________
Nature of the Arrangement (check all that apply):
Milestone bonus tied to study outcome
Success fee contingent upon regulatory approval
Royalty arrangement linked to commercial success of penterafenib
Other (describe): ______________
Monetary Value or Estimated Value:
________________________________________
5.2 Significant Equity Interest
(Complete this subsection only if you were unable to check the box in Section 4.2.)
Description of Equity Interest in Penterra Pharmaceuticals Corp. (Nasdaq: PTRA):
________________________________________
________________________________________
Type of Interest (check all that apply):
Common stock
Preferred stock
Stock options (vested or unvested)
Warrants
Convertible securities
Restricted stock units
Other (describe): ______________
Number of Shares or Units: ______________
Approximate Current Value (as of date of completion of this form): $ ______________
NOTE: Penterra's market capitalization as of Q1 2023 is approximately $4.2 billion. Investigators may reference the closing stock price on the Nasdaq Stock Market on the date of completion of this form to calculate the approximate value of their equity holdings.
Date Acquired: ______________
Held By (check all that apply):
Investigator (self)
Spouse (name): ______________
Dependent child (name): ______________
5.3 Proprietary Interest in Investigational Product
(Complete this subsection only if you were unable to check the box in Section 4.3.)
Description of Proprietary Interest in Penterafenib (PPC-4871):
________________________________________
________________________________________
________________________________________
Type of Interest (check all that apply):
Patent (issued)
Patent application (pending)
Licensing agreement
Trademark
Copyright
Other (describe): ______________
Patent or Application Number (if applicable): ______________
Estimated Value or Revenue Derived: $ ______________
5.4 Significant Payments of Other Sorts
(Complete this subsection only if you were unable to check the box in Section 4.4.)
Description of Payments Exceeding $25,000 Received from Penterra Pharmaceuticals Corp. During the Covered Period: (Exclusive of clinical study costs and fair market value payments for legitimate services.)
________________________________________
________________________________________
________________________________________
Source of Payment: (Identify the department within Penterra or related entity from which payment was received.)
________________________________________
Purpose of Payment (check all that apply):
Consulting fees
Advisory board participation
Speaking fees / honoraria
Unrestricted educational grant
Equipment or material grant
Other (describe): ______________
Total Amount Received During Covered Period: $ ______________
Dates of Payment(s): ______________
5.5 Other Relevant Financial Interests
(Complete this subsection if you hold any other financial interests, relationships, or arrangements involving Penterra Pharmaceuticals Corp., the investigational product, or any entity that could benefit from the outcome of Protocol PPC-4871-III that have not been addressed in Sections 5.1 through 5.4 above.)
Description of Other Financial Interests, Relationships, or Arrangements:
________________________________________
________________________________________
________________________________________
________________________________________
INSTRUCTION: In completing this subsection, investigators should consider and, if applicable, disclose any financial relationships with the following entities involved in the conduct of Protocol PPC-4871-III:
• Meridian Contract Research Organization, Inc. (Penterra's CRO for Protocol PPC-4871-III)
• Pinnacle Data Solutions, Inc. (electronic data capture vendor)
• Northbridge Bioanalytical Laboratories, Inc. (central laboratory)
While 21 C.F.R. Part 54 specifically addresses financial interests involving the Sponsor and the investigational product, disclosure of other relevant financial relationships supports the overall integrity of the study and is requested by the Sponsor for internal conflict-of-interest review purposes.
5.6 Disclosure Certification
INSTRUCTIONS: If you have completed any portion of Part B (Sections 5.1 through 5.5), sign and date this section below to certify the completeness and accuracy of your disclosures.
By signing below, I certify that the disclosures provided in Part B (Sections 5.1 through 5.5, as applicable) are complete and accurate to the best of my knowledge, information, and belief. I understand that any material omission or misstatement in these disclosures may constitute a violation of federal law and may result in regulatory action by the FDA.
Printed Name of Investigator: ________
Signature: ________
Date: ________
Institution / Veridian Network Site Number: ________
SECTION 6: INSTITUTIONAL FINANCIAL INTERESTS
INSTRUCTIONS: All investigators must complete this section, regardless of whether they completed Part A or Part B above. If you are aware of any financial interest held by your institution (e.g., Graystone University Medical Center, Lakemont Medical Center, or other Veridian Health Research Network member institution) in Penterra Pharmaceuticals Corp. or the investigational product, you must disclose such interest below. If you are not aware of any such institutional interest, indicate "No" in each field below. Investigators are encouraged to contact their institutional conflict-of-interest office, sponsored research office, or technology transfer office to confirm their institution's financial interests before completing this section.
Does your institution hold an equity interest in Penterra Pharmaceuticals Corp.?
Yes No
If Yes, provide details:
________________________________________
________________________________________
________________________________________
Does your institution hold any proprietary interest in penterafenib (PPC-4871)?
Yes No
If Yes, provide details (including any patents, patent applications, or licensing agreements relating to the investigational product):
________________________________________
________________________________________