Contract analysis

I. Executive Summary The purpose of this memorandum is to provide Penterra Pharmaceuticals Corp. ("Penterra" or the "Company") legal and regulatory leadership with Calderwood & Harkness LLP's ("C&H" or "we") preliminary legal analysis of the inquiry letter issued by the U.S. Food and Drug Administration's Office of Prescription Drug Promotion ("OPDP"), dated October 12, 2023, received by Penterra on October 16, 2023,

1. Voluntary Withdrawal of All Three Cited Materials. Complete and document the withdrawal of all three promotional materials identified in the OPDP Inquiry, which Penterra initiated on November 3, 2023.

2. Engagement of FDA-Specialist Regulatory Co-Counsel. Retain Whitfield Bauer & Associates LLP ("Whitfield Bauer"), a Washington, DC-based firm specializing in FDA regulatory matters and OPDP response strategy, as co-counsel to Calderwood & Harkness for purposes of this matter.

3. Commencement of Internal Investigation. Initiate a comprehensive internal investigation, conducted under attorney-client privilege and work-product protection, to assess the full scope of any promotional compliance issues related to the Clarity Campaign and, potentially, other Zelvara® promotional materials.

4. Development of a Comprehensive FDA Response. Develop and submit to OPDP a comprehensive written response addressing each allegation raised in the Inquiry, accompanied by a detailed corrective action plan and supporting documentation. We further note that Penterra submitted a 60-day extension request to FDA on November 1, 2023, seeking to extend the response deadline from November 15, 2023, to January 15, 2024. As

II. Background A. Zelvara® Product Overview Zelvara® (trepivant sodium) is an oral prescription medication marketed by Penterra Pharmaceuticals Corp. for the acute treatment of migraine with or without aura in adults. The product is available in two dosage strengths — 75 mg and 150 mg oral tablets — and was approved by the FDA on October 11, 2019, under New Drug Application ("NDA") No. 214-837. The approval of Zelvar

1. Digital Banner Ad (Material ID: ZVR-2023-BNR-044);

2. Physician Email Blast (Material ID: ZVR-2023-EML-019); and

3. Sales Representative Detail Aid (Material ID: ZVR-2023-DA-007). Each of these materials is analyzed in detail in Sections III through V below.

III. Analysis of Material 1: Digital Banner Ad (ZVR-2023-BNR-044) A. Description of Material The first material cited in the OPDP Inquiry is a branded digital banner advertisement bearing Material ID ZVR-2023-BNR-044. The banner ad was displayed on MedLinkPro, a healthcare-professional-targeted medical-education platform, during the period from April 15, 2023, through August 31, 2023 — a distribution window of approx

IV. Analysis of Material 2: Physician Email Blast (ZVR-2023-EML-019) A. Description of Material The second material cited in the OPDP Inquiry is a branded email communication to healthcare providers bearing Material ID ZVR-2023-EML-019. The email was sent on June 7, 2023, to a distribution list of approximately 42,000 neurologists and primary-care physicians. The scope of this distribution is significant — 42,000 phy

V. Analysis of Material 3: Sales Representative Detail Aid (ZVR-2023-DA-007) A. Description of Material The third material cited in the OPDP Inquiry is a detail aid — available in both printed and digital formats — bearing Material ID ZVR-2023-DA-007. The detail aid was designed for use by Penterra's field sales representatives during physician office visits ("detailing" visits) and was approved by the PRC on March 2

VI. Statutory and Regulatory Framework Summary This section provides a summary of the principal statutory and regulatory provisions implicated by the OPDP Inquiry, together with an overview of the enforcement framework within which the Inquiry is situated. A. 21 U.S.C. § 352(n) — Misbranding

Section 502(n) of the Federal Food, Drug, and Cosmetic Act ("FDCA"), codified at 21 U.S.C. § 352(n), provides the foundational statutory authority for the regulation of prescription drug advertising. Under this provision, a drug is deemed misbranded if its labeling or advertising is "false or misleading in any particular." The misbranding prohibition encompasses both affirmative misstatements — i.e., statements that

Section 202.1(e)(6) is directly applicable to all three materials cited in the OPDP Inquiry: • Digital Banner Ad (ZVR-2023-BNR-044): The "Fastest Onset in Its Class" claim is based on an unpublished indirect treatment comparison with acknowledged methodological limitations, which is insufficient to support a superiority claim under Section 202.1(e)(6)(i). • Physician Email Blast (ZVR-2023-EML-019): The truncated y-ax

VII. Preliminary Risk Assessment and Materiality Considerations A. Legal Exposure Based on our preliminary analysis set forth in Sections III through V above, it is our assessment that all three materials cited in the OPDP Inquiry present non-trivial compliance deficiencies under the applicable FDA promotional regulations. While the specific nature and severity of the deficiencies varies across the three materials, n

1. The unsubstantiated superiority claim in the digital banner ad (ZVR-2023-BNR-044), which relies on an unpublished indirect treatment comparison with acknowledged methodological limitations in the absence of any head-to-head clinical data.

2. The truncated y-axis graphical presentation in the physician email blast (ZVR-2023-EML-019), which is a well-established and frequently enforced OPDP concern with extensive precedent and which is exacerbated by the internal PRC override of Medical Affairs' objection.

3. The undisclosed funding and uncontrolled study design of the Harmon et al. data cited in the detail aid (ZVR-2023-DA-007), which combines multiple independent compliance deficiencies — lack of a control arm, non-peer-reviewed status, and undisclosed company funding — in a single material. Several factors serve to mitigate Penterra's overall exposure: • Penterra's prompt engagement of outside counsel (Calderwood &

VIII. Recommended Immediate Actions Based on our preliminary analysis, we recommend the following immediate actions. We respectfully request that Margaret Tan and Christine Holloway confirm their authorization to proceed on each item at the earliest opportunity. A. Voluntary Withdrawal of Cited Materials We recommend the immediate and complete cessation of use and distribution of all three promotional materials cited

1. Review of all Zelvara® promotional materials approved by the Promotional Review Committee from January 1, 2023, through October 16, 2023 (the date of receipt of the OPDP Inquiry). Based on preliminary information provided by Penterra, we estimate that the total number of approved promotional materials during this period is approximately 67 pieces. Each of these materials will be reviewed for compliance with applic

2. Review of PRC meeting minutes from January through October 2023 (an estimated nine meetings). This review will focus on the PRC's decision-making processes, including the identification of any other instances in which Medical Affairs objections were overridden by the commercial function, and the adequacy of the PRC's governance procedures and voting protocols.

3. Forensic review of CRM records, emails, and text messages of the 14 identified sales representatives in the Northeast region who utilized the cited detail aid (ZVR-2023-DA-007). This review will assess whether sales representatives made any verbal claims — whether during detailing visits or in written communications with physicians — that exceeded or diverged from the approved content of the detail aid, with parti

4. Witness interviews of key Penterra personnel involved in the development, review, and approval of the Clarity Campaign materials, including Derek Foss (VP, Commercial Operations & Marketing), Alan Renwick (Director, PRC), and Dr. Lina Gerhardt (Senior Director, Medical Affairs). Depending on the findings of the document review, we may also recommend interviews of additional personnel, including representatives fro