Contract analysis

I. Executive Summary Calderwood & Harkness LLP ("C&H"), in coordination with Whitfield Bauer & Associates LLP ("Whitfield Bauer," regulatory co-counsel) and Tavrenis Stern Consulting Group LLC ("Tavrenis Stern," forensic consultant), conducted an internal investigation of certain promotional practices of Penterra Pharmaceuticals Corp. ("Penterra" or the "Company") relating to its product Zelvara® (trepivant sodium).

II. Scope and Methodology of the Investigation A. Scope Definition The scope of the internal investigation was established in the Internal Investigation Plan Memorandum prepared by C&H and delivered to Penterra's General Counsel, Margaret Tan, on November 8, 2023. The scope was designed to encompass all aspects of the Company's Zelvara® promotional practices that were reasonably related to the issues identified in th

1. Promotional Materials Review. A comprehensive review of all Zelvara®-related promotional materials approved by the Promotional Review Committee from January 1, 2023 through October 16, 2023, including but not limited to detail aids, digital advertisements, email campaigns, conference materials, leave-behind brochures, and speaker deck presentations.

2. PRC Meeting Minutes Review. A review of PRC meeting minutes for all meetings held between January 2023 and October 2023, with a focus on the approval deliberations for the three OPDP-cited materials, any dissenting opinions or objections raised during the review process, and the documentation of substantiation supporting promotional claims.

3. Forensic Review of Sales Representative Communications. A forensic review of CRM records, corporate email, and text messages associated with sales representatives identified as having distributed one or more of the OPDP-cited materials, with particular attention to evidence of off-label promotion, unapproved claims, or communications inconsistent with approved promotional content.

4. Witness Interviews. Interviews of key Penterra personnel and relevant third-party personnel involved in the development, approval, and dissemination of the OPDP-cited materials, as well as personnel with oversight responsibility for the Company's promotional compliance program. Each workstream was supervised by Jeffrey Park (Lead Associate, C&H), with day-to-day assistance from Audrey Zhou (Working Associate, C&H)

1. Derek Foss, Vice President, Commercial Operations & Marketing, Penterra — interviewed November 28, 2023. Mr. Foss was interviewed regarding his role in overseeing the Clarity Campaign, his interactions with Ridgeline Health Analytics LLC, his awareness of the PRC approval process for the cited materials, and his knowledge of sales-representative conduct in the field.

2. Alan Renwick, Director, Promotional Review Committee, Penterra — interviewed November 29, 2023. Mr. Renwick was interviewed regarding the PRC's review and approval of the three cited materials, the May 18, 2023 PRC meeting and vote, the PRC's standard operating procedures for resolving internal disagreements, and the documentation of evidentiary substantiation.

3. Dr. Lina Gerhardt, Pharm.D., Senior Director, Medical Affairs, Penterra — interviewed November 30, 2023. Dr. Gerhardt was interviewed regarding her objection to the truncated y-axis in ZVR-2023-EML-019, the Medical Affairs team's role in the PRC process, and her assessment of the scientific accuracy of the cited materials.

4. Monica Chu, Account Lead for Penterra, Ridgeline Health Analytics LLC — interviewed December 5, 2023. Ms. Chu's interview was conducted with Penterra's consent and Ridgeline's cooperation. Ms. Chu was interviewed regarding Ridgeline's creative development process for the Clarity Campaign, the origin of specific claims and data presentations in the cited materials, and Ridgeline's internal review procedures for reg

5. Three identified sales representatives (names withheld in this memorandum pending completion of HR consultation) — interviewed December 7–8, 2023. These three individuals were identified through the Tavrenis Stern forensic review as having made off-label verbal claims regarding Zelvara® and cluster headache. Each representative was interviewed regarding the specific CRM entries identified, the context in which the

6. Dr. Rajeev Anand, M.D., Ph.D., Chief Medical Officer, Penterra — interviewed December 11, 2023. Dr. Anand was interviewed regarding the general oversight of the Medical Affairs team's participation in the PRC process, his awareness of the off-label claims, and the Company's compliance infrastructure for promotional activities. Detailed interview summaries for each session are maintained in the privileged investiga

III. Background: The OPDP Inquiry and Cited Materials A. OPDP Inquiry Letter On October 12, 2023, FDA's Office of Prescription Drug Promotion issued an inquiry letter to Penterra Pharmaceuticals Corp. regarding certain promotional materials for Zelvara® (trepivant sodium). The letter was received by Penterra's Regulatory Affairs department on October 16, 2023 and was immediately escalated to General Counsel Margaret

1. Digital Banner Ad — Material ID ZVR-2023-BNR-044. A digital banner advertisement placed on the HCP-targeted medical-education platform MedLinkPro, containing the claim "Fastest Onset in Its Class" and omitting hepatotoxicity risk information.

2. Physician Email Blast — Material ID ZVR-2023-EML-019. A promotional email sent to approximately 42,000 neurologists and primary-care physicians, containing a bar chart with a truncated y-axis presenting Zelvara® 2-hour pain-freedom rates versus a comparator product (lasmiditan).

3. Sales Representative Detail Aid — Material ID ZVR-2023-DA-007. A detail aid distributed to Penterra's field sales force, containing a "real-world evidence" claim citing a Penterra-funded study without disclosing the funding source or the study's design limitations. Each of these materials and the specific compliance deficiencies identified therein are discussed in detail in Section IV.A below.

IV. Findings A. Finding 1: Promotional Materials Review — Deficiencies Limited to Three OPDP-Cited Materials

1. Overview of Review Results As described in Section II.B, C&H reviewed all sixty-seven (67) Zelvara® promotional materials approved by the PRC during the period from January 1, 2023 through October 16, 2023. Each material was evaluated for compliance with the substantive requirements of 21 U.S.C. § 352(n), 21 C.F.R. § 202.1(e)(5) (fair balance and adequate risk information), and 21 C.F.R. § 202.1(e)(6) (substantiat

2. Digital Banner Ad — ZVR-2023-BNR-044 The Digital Banner Ad identified by Material ID ZVR-2023-BNR-044 was a promotional banner advertisement placed on the HCP-targeted medical-education platform MedLinkPro. The advertisement ran from April 15, 2023 through August 31, 2023. According to campaign analytics provided by Ridgeline, the banner ad received approximately 2.3 million impressions and generated approximately

3. Physician Email Blast — ZVR-2023-EML-019 The Physician Email Blast identified by Material ID ZVR-2023-EML-019 was a promotional email disseminated on June 7, 2023 to a distribution list of approximately 42,000 neurologists and primary-care physicians. The email was transmitted through Penterra's email marketing platform and was designed and formatted by Ridgeline Health Analytics LLC as part of the Clarity Campaig

4. Sales Representative Detail Aid — ZVR-2023-DA-007 The Sales Representative Detail Aid identified by Material ID ZVR-2023-DA-007 was approved by the PRC on March 22, 2023 and was subsequently distributed to Penterra's field sales force for use during physician detailing visits. The detail aid was a multi-page printed piece designed to guide sales representatives through key messages about Zelvara®'s clinical profil

1. The PRC Review Process for ZVR-2023-EML-019 The PRC convened on May 18, 2023 for its regularly scheduled monthly meeting. The meeting was attended by the full complement of PRC voting members, including representatives from Medical Affairs, Regulatory Affairs, Commercial Operations & Marketing, and Legal. The meeting was chaired by Alan Renwick, Director of the PRC. Among the materials presented for PRC review and

2. Significance. The May 18, 2023 PRC minutes are significant for several reasons: First, the minutes demonstrate that Penterra had internal notice that the email blast's graphical presentation was potentially misleading before the material was disseminated. An identified subject-matter expert within the Company — Dr. Gerhardt, who holds a Doctor of Pharmacy degree and serves as Senior Director of Medical Affairs — e

3. Interview Corroboration The PRC minutes and the significance of the May 18 vote were corroborated through witness interviews: Dr. Lina Gerhardt (November 30, 2023): Dr. Gerhardt confirmed that she raised the objection to the truncated y-axis at the May 18, 2023 PRC meeting, as documented in the minutes. She stated that she had also raised the concern informally with Alan Renwick before the meeting, during a prepar

1. Tavrenis Stern Forensic Review As described in Section II.D, Tavrenis Stern Consulting Group LLC, under C&H's direction and engagement (lead: Patricia Okoro; fixed fee: $87,500), collected and processed CRM records, corporate email, and text messages for fourteen (14) identified Northeast-region sales representatives who had been documented as distributing Detail Aid ZVR-2023-DA-007 during the data collection peri

2. Key Finding: Three Representatives Made Off-Label Claims The forensic review identified CRM call notes for three (3) of the fourteen (14) reviewed sales representatives that contained entries reflecting verbal statements to physicians suggesting that Zelvara® was effective for the treatment of cluster headache. Cluster headache is not an approved indication for Zelvara® under NDA 214-837, which covers only the acu

3. No Evidence of Systemic Direction The investigation did not identify evidence that the off-label claims were directed, encouraged, or condoned by Penterra management, including Derek Foss (VP, Commercial Operations & Marketing), Alan Renwick (Director, PRC), Dr. Lina Gerhardt (Senior Director, Medical Affairs), or any other management-level personnel. The review team specifically examined the following potential s

4. Regulatory Risk Assessment Off-label promotion by pharmaceutical company sales representatives constitutes a significant regulatory and legal risk. The legal and regulatory framework relevant to this finding includes the following: • Misbranding under 21 U.S.C. § 352: Promotional claims for unapproved uses can render a drug misbranded under the FDCA if the labeling or advertising is false or misleading or if it fa

5. Interview Findings The three identified sales representatives were interviewed on December 7–8, 2023, with each interview conducted separately. Each representative was provided with Upjohn / corporate-Miranda warnings, as described in Section II.E above, and each acknowledged understanding of the warnings before proceeding. The key findings from these interviews are as follows: • Each of the three representatives

1. SOW Review C&H reviewed the Statement of Work between Penterra and Ridgeline Health Analytics LLC for the Clarity Campaign, dated January 9, 2023, together with the relevant provisions of the Master Services Agreement between Penterra and Ridgeline dated March 15, 2021. The SOW defined Ridgeline's deliverables as creative concept development, content drafting (including copywriting, graphic design, and layout), di

2. Interview with Monica Chu (Ridgeline Account Lead) Monica Chu, the Ridgeline account lead for the Penterra engagement, was interviewed on December 5, 2023. The interview was conducted with Penterra's consent and Ridgeline's cooperation, and Ms. Chu was advised that the interview was being conducted in connection with an internal investigation directed by Penterra's counsel. Ms. Chu was cooperative and forthcoming

3. Significance. The absence of independent medical-legal review within Ridgeline's workflow, combined with the lack of a contractual obligation to conduct such review in either the SOW or the MSA, created a structural gap in Penterra's promotional compliance framework. Under this arrangement, materials with significant compliance deficiencies — including unsubstantiated comparative claims, misleading graphical prese