Contract analysis

I. Purpose and Executive Summary This memorandum establishes the plan, scope, methodology, timeline, budget, and deliverables for Calderwood & Harkness LLP's ("C&H") internal investigation of the promotional practices of Penterra Pharmaceuticals Corp. ("Penterra" or "PPC") relating to its flagship migraine drug Zelvara® (trepivant sodium, NDA #214-837). The investigation has been undertaken at the direction of Penter

1. Scope Determination. Determine the full scope of any promotional-compliance deficiencies beyond the three materials specifically cited in the OPDP inquiry letter, including whether additional Zelvara® promotional materials developed in 2023 contain similar or related issues.

2. Root-Cause Analysis. Identify the root causes of the compliance deficiencies, including any failures in Penterra's Promotional Review Committee ("PRC") process, inadequacies in the medical-legal review of promotional claims, and breakdowns in the oversight of the external agency responsible for campaign development.

3. Off-Label Promotion Assessment. Assess whether off-label promotion occurred in the field through sales-representative interactions with healthcare providers, including any verbal claims promoting Zelvara® for indications beyond its FDA-approved labeling (i.e., acute treatment of migraine with or without aura in adults).

4. Factual Record Development. Develop a comprehensive and well-documented factual record to support Penterra's formal FDA response, to inform the development of a corrective action plan, and to position Penterra favorably in any subsequent regulatory or enforcement proceedings. To accomplish these objectives, the investigation is organized around four principal workstreams, each described in detail in Section III be

II. Background A. The OPDP Inquiry On October 12, 2023, OPDP issued an inquiry letter to Penterra Pharmaceuticals Corp. bearing reference number OPDP-2023-1847. The letter was signed by Dr. Carla M. Witherspoon, Pharm.D., Regulatory Review Officer in the Division of Drug Marketing, Advertising, and Communications within the Office of Prescription Drug Promotion, CDER, FDA. Penterra received the inquiry letter at its

1. Digital Banner Ad (Material ID: ZVR-2023-BNR-044). This digital banner advertisement ran on MedLinkPro, a healthcare-professional-targeted medical-education platform, from April 15 through August 31, 2023. OPDP's inquiry letter states that the banner ad contained the claim "Fastest Onset in Its Class" without adequate substantiation. The letter further alleges that the banner ad omitted any reference to the risk o

2. Physician Email Blast (Material ID: ZVR-2023-EML-019). This email communication was sent on June 7, 2023, to a distribution list of approximately 42,000 neurologists and primary-care physicians. The email featured a bar chart comparing the 2-hour pain-freedom rates of Zelvara® versus placebo, drawn from data in the SUMMIT-3 clinical trial (23.7% vs. 14.2% for placebo, p < 0.001, n = 1,842). OPDP's inquiry letter s

3. Sales Representative Detail Aid (Material ID: ZVR-2023-DA-007). This printed detail aid was approved by Penterra's PRC on March 22, 2023 and was subsequently distributed to the company's field sales force for use in physician-office visits. OPDP's inquiry letter states that the detail aid cited an unpublished retrospective chart review (Harmon et al., poster presentation at the American Headache Society annual mee

III. Scope of Investigation A. Workstream 1 — Review of Zelvara® Promotional Materials The first workstream of the investigation consists of a comprehensive review of all Zelvara® promotional materials approved by Penterra's PRC during the period from January 1, 2023 through October 16, 2023 (the date on which Penterra received the OPDP inquiry letter). Penterra's Regulatory Affairs team, under the direction of Chris

1. Derek Foss — Vice President, Commercial Operations & Marketing, Penterra Pharmaceuticals Corp. Mr. Foss is the senior Penterra executive with direct responsibility for the company's commercial marketing activities, including the oversight and direction of external agencies such as Ridgeline Health Analytics. The interview with Mr. Foss will focus on the following topics: • His role in developing and approving the

2. Alan Renwick — Director, Promotional Review Committee, Penterra Pharmaceuticals Corp. Mr. Renwick chairs the PRC and is responsible for the committee's procedures, agenda, and documentation. The interview with Mr. Renwick will focus on the following topics: • The PRC's standard procedures for reviewing and approving promotional materials, including the committee's SOPs, the substantiation standards applied to effi

3. Dr. Lina Gerhardt, Pharm.D. — Senior Director, Medical Affairs, Penterra Pharmaceuticals Corp. Dr. Gerhardt leads the Medical Affairs function at Penterra and is understood to have been the most senior Medical Affairs representative involved in the PRC's review of the Clarity Campaign materials. Preliminary information indicates that Dr. Gerhardt and her team raised objections to the truncated y-axis in the email

4. Monica Chu — Account Lead (Penterra Account), Ridgeline Health Analytics LLC Ms. Chu served as the primary Ridgeline contact for the Clarity Campaign and was involved in the development of the promotional materials cited by OPDP. Because Ms. Chu is employed by a third party, her participation in the interview is voluntary, and the interview must be coordinated with Ridgeline's outside counsel if Ridgeline is separ

IV. Privilege and Work-Product Protections Maintaining the integrity of the attorney-client privilege and the work-product doctrine is of paramount importance throughout this investigation. The investigation is being conducted at the direction of Penterra's legal department and in anticipation of regulatory proceedings and potential litigation. Accordingly, all investigation activities, communications, and work produ

V. Timeline and Milestones The following table sets forth the key dates, milestones, and deadlines for the investigation, from the approval of this investigation plan through the target submission of Penterra's formal response to OPDP: The timeline is designed to provide adequate time for a thorough and methodical investigation while ensuring that Penterra's formal response to OPDP is submitted well in advance of the

VI. Budget and Staffing A. Calderwood & Harkness LLP — Internal Costs The investigation will be staffed as follows within C&H: • Jeffrey Park (Lead Associate, Litigation (General)) — Lead Associate for all four workstreams; primary interviewer for Workstream 4; primary reviewer for Workstreams 1, 2, and 3; principal author of the Investigation Findings Memorandum and contributor to the FDA response letter. • Audrey Z

VII. Deliverables The investigation will produce the following deliverables:

1. Weekly Status Reports. Jeffrey Park will provide informal email updates on a weekly basis to Leonard Cross and Margaret Tan summarizing the progress across all four workstreams. Each weekly status report will identify key activities completed during the preceding week, significant findings or developments, any obstacles or delays encountered, anticipated activities for the following week, and any issues requiring

2. Interim Findings Summaries. Upon the completion of each workstream, or earlier if material findings are identified that warrant immediate attention, Jeffrey Park will provide an oral briefing to Leonard Cross and Margaret Tan. Interim findings summaries are designed to ensure that the investigation team, the supervising partner, and the client's legal department are aligned on the trajectory of the investigation a

3. Internal Investigation Findings Memorandum. The principal deliverable of the investigation will be a comprehensive privileged memorandum documenting all findings, conclusions, and recommendations arising from the four workstreams. The Investigation Findings Memorandum will include: (a) a detailed factual record of the compliance deficiencies identified in the OPDP-cited materials and any additional materials; (b)

4. Privilege Log. A privilege log will be maintained throughout the investigation documenting all privileged materials generated or reviewed in connection with the investigation, including interview memoranda, attorney work-product analyses, privileged communications, and any responsive documents identified during the forensic review that are withheld on privilege grounds. The privilege log will be maintained in a fo

5. Contribution to FDA Response. The investigation findings will be incorporated into the formal FDA response letter and corrective action plan to be submitted to OPDP. Jeffrey Park and Audrey Zhou, in coordination with Thomas Crane and Dr. Hannah Whitfield at Whitfield Bauer, will contribute the factual and analytical sections of the response letter, while the strategic framing and remediation commitments will be de

VIII. Coordination with Penterra and Co-Counsel Effective coordination among C&H, Penterra, and co-counsel is essential to the efficient conduct of the investigation and the integrity of the resulting factual record. Primary Penterra Contacts. The primary contacts at Penterra for all aspects of this investigation are Margaret Tan, Executive Vice President & General Counsel, and Christine Holloway, Vice President, Reg

IX. Risk Factors and Contingencies The investigation plan set forth in this memorandum is based on the information currently available to C&H and reflects certain assumptions about the scope, complexity, and trajectory of the investigation. The following risk factors and contingencies have been identified:

1. Expanded Scope of Compliance Issues. The investigation may reveal compliance deficiencies in Zelvara® promotional materials beyond the three materials cited by OPDP. If such additional deficiencies are identified, the scope of the corrective action plan will need to be expanded accordingly, and consideration will need to be given to whether voluntary withdrawal of additional materials is appropriate. In the most a

2. Off-Label Promotion by Sales Representatives. The current preliminary intelligence suggests that three of the 14 Northeast-region sales representatives may have made off-label claims regarding cluster headache. The forensic review in Workstream 3 may reveal that off-label promotion was more widespread than currently suspected — either involving additional representatives within the Northeast region or extending to

3. Ridgeline Cooperation. As a third party, Ridgeline Health Analytics LLC is not compelled to cooperate with this investigation or to make its personnel, including Monica Chu, available for interviews. While C&H anticipates that Ridgeline will cooperate in the interest of maintaining its commercial relationship with Penterra, the investigation plan includes a contingency for proceeding without Ridgeline testimony if