1018-00002 · Penterra Pharmaceuticals Corp · Engagement

co-counsel-engagement-letter-whitfield-bauer.docx DOCUMENT M&A / Corporate

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CONFIDENTIAL — ATTORNEY-CLIENT PRIVILEGED

CALDERWOOD & HARKNESS LLP Attorneys at Law 600 Lexington Avenue New York, NY 10022

Telephone: (212) 554-7000 Facsimile: (212) 554-7001 www.calderwoodharkness.com

November 10, 2023

VIA EMAIL AND HAND DELIVERY

Dr. Hannah Whitfield, J.D., Ph.D. Partner Whitfield Bauer & Associates LLP 1330 Connecticut Avenue NW, Suite 500 Washington, DC 20036

Re: Engagement of Co-Counsel — FDA OPDP Inquiry OPDP-2023-1847; Penterra Pharmaceuticals Corp. / Zelvara® (trepivant sodium) Calderwood & Harkness Matter No. 1018-00002

Dear Dr. Whitfield:

We are pleased to write to you to formalize the engagement of Whitfield Bauer & Associates LLP ("Whitfield Bauer" or "WBA") as co-counsel to Calderwood & Harkness LLP ("C&H") in the above-referenced matter. This letter sets forth the terms and conditions of that engagement, including the scope of services to be provided, staffing arrangements, billing and fee arrangements, obligations with respect to privilege and confidentiality, and related matters. We ask that you review this letter carefully and, if the terms are acceptable, countersign a copy in the space provided below and return it to our offices at your earliest convenience.

1. Purpose and Background of Engagement

Calderwood & Harkness LLP represents Penterra Pharmaceuticals Corp. ("Penterra" or "PPC"), a Delaware corporation publicly traded on the New York Stock Exchange under the ticker symbol PTPH, with its principal offices located at 480 Overlook Drive, Suite 700, Summit, New Jersey 07901. Penterra is a specialty pharmaceutical company focused on the development and commercialization of therapies for neurological conditions, including migraine.

On October 12, 2023, the United States Food and Drug Administration's Office of Prescription Drug Promotion ("OPDP"), within the Center for Drug Evaluation and Research ("CDER"), issued a formal inquiry letter bearing reference number OPDP-2023-1847, addressed to Penterra's Vice President of Regulatory Affairs, Christine Holloway. The letter was received by Penterra's regulatory affairs department on October 16, 2023. The inquiry concerns allegedly misleading promotional materials and sales representative communications related to Penterra's migraine drug Zelvara® (trepivant sodium), available in 75 mg and 150 mg oral tablet formulations. Zelvara® was approved by the FDA on October 11, 2019, pursuant to New Drug Application ("NDA") No. 214-837, for the acute treatment of migraine with or without aura in adults.

C&H was formally engaged by Penterra on October 30, 2023, pursuant to an engagement letter executed by Margaret Tan, Executive Vice President and General Counsel of Penterra, to advise Penterra on responding to the OPDP inquiry, to conduct an internal review of Penterra's promotional practices with respect to Zelvara®, and to prepare a comprehensive written response to the FDA on Penterra's behalf. The engagement team at C&H for this matter consists of the following attorneys:

• Leonard Cross — Responsible Partner

• Nathaniel Bower — Billing Partner

• Jeffrey Park — Lead Associate

• Audrey Zhou — Working Associate

Given the specialized nature of the OPDP inquiry and the regulatory issues it presents, C&H seeks to engage Whitfield Bauer as FDA regulatory specialist co-counsel. As you know, Whitfield Bauer has established a preeminent reputation in FDA promotional-labeling compliance, OPDP response strategy, and related regulatory enforcement matters, and we believe that your firm's participation in this matter will be of significant benefit to our mutual client.

We note that Penterra, acting through its EVP and General Counsel Margaret Tan, has provided written consent to the engagement of Whitfield Bauer as co-counsel in this matter. A copy of Ms. Tan's written authorization, dated November 7, 2023, is on file with C&H and is available for your review upon request.

2. Description of the OPDP Inquiry

For purposes of establishing context for Whitfield Bauer's engagement, we summarize below the principal allegations set forth in the OPDP inquiry letter. We will provide the full text of the inquiry letter, together with copies of the cited promotional materials, under separate cover in accordance with the privilege protocol described in Section 6 of this letter.

2.1 Promotional Materials at Issue

The OPDP inquiry identifies three promotional materials that are the subject of the agency's concerns. All three materials were developed as part of a promotional initiative known internally at Penterra as the "Clarity Campaign." The Clarity Campaign was developed by Ridgeline Health Analytics LLC, a third-party promotional agency retained by Penterra, and was deployed during the second and third quarters of calendar year 2023. The three materials at issue are as follows:

(a) Digital Banner Ad (Material ID: ZVR-2023-BNR-044). This digital banner advertisement ran on MedLinkPro, a healthcare-professional-targeted digital platform, during the period from April 15 through August 31, 2023. The OPDP alleges that the banner ad included the claim "Fastest Onset in Its Class" without adequate substantiation and that the advertisement omitted material risk information, specifically information regarding the risk of hepatotoxicity associated with Zelvara®.

(b) Physician Email Blast (Material ID: ZVR-2023-EML-019). This email communication was sent on June 7, 2023, to a distribution list comprising approximately 42,000 neurologists and primary-care physicians. The OPDP alleges that the email included a bar chart presenting 2-hour pain-freedom rates derived from the SUMMIT-3 clinical trial, but that the bar chart utilized a truncated y-axis in a manner that exaggerated the apparent efficacy differential between Zelvara® and a named comparator, lasmiditan, thereby creating a misleading visual impression of Zelvara®'s relative efficacy.

(c) Sales Representative Detail Aid (Material ID: ZVR-2023-DA-007). This printed detail aid, which was approved by Penterra's internal Promotional Review Committee on March 22, 2023, cited an unpublished retrospective chart review authored by Harmon et al. and presented as a poster at the American Headache Society 2022 annual meeting. The OPDP alleges that the detail aid failed to disclose that the Harmon et al. study was funded by Penterra and that the study lacked a control arm, thereby presenting the data in a misleading manner.

2.2 Alleged Regulatory Violations

The OPDP inquiry alleges that the above-described materials constitute potential violations of the following provisions of federal law and regulation:

• Section 502(n) of the Federal Food, Drug, and Cosmetic Act ("FDCA"), codified at 21 U.S.C. § 352(n), which governs the advertising and labeling of prescription drugs and requires, among other things, that advertisements present a true statement of information in brief summary relating to the drug's side effects, contraindications, and effectiveness;

• 21 C.F.R. § 202.1(e)(5), which addresses the omission or minimization of risk information in prescription drug advertisements; and

• 21 C.F.R. § 202.1(e)(6), which prohibits misleading efficacy claims, including unsubstantiated superiority claims and the use of misleading graphical or visual presentations.

2.3 Response Deadline and Extension

The OPDP inquiry letter established an original response deadline of November 15, 2023, which was thirty (30) days from the date of Penterra's receipt of the inquiry on October 16, 2023. On November 1, 2023, Penterra, through C&H, submitted a written request for an extension of the response deadline. On November 8, 2023, the FDA granted a sixty (60)-day extension, establishing a new deadline for Penterra's formal written response of January 15, 2024.

2.4 Voluntary Withdrawal of Cited Materials

Penterra, on the advice of C&H and in consultation with Ms. Holloway and Ms. Tan, voluntarily withdrew all three cited promotional materials from circulation as of November 3, 2023. Confirmation of the withdrawal was communicated to Penterra's sales organization and to Ridgeline Health Analytics LLC on the same date. We anticipate that the voluntary withdrawal will be referenced in Penterra's formal response to the OPDP as evidence of the company's good-faith commitment to promotional compliance.

3. Scope of Whitfield Bauer's Engagement

Whitfield Bauer is engaged to serve as regulatory co-counsel and will provide services in the areas described below. The scope of this engagement is limited to the matters set forth in this Section 3, and any expansion of the scope of engagement shall require the prior written agreement of C&H and Whitfield Bauer and, as appropriate, the consent of Penterra.

3.1 OPDP Response Strategy

Whitfield Bauer will advise C&H and Penterra on the overall strategy for responding to the OPDP inquiry letter, reference number OPDP-2023-1847. This advisory role shall include, but not be limited to, the following:

(a) Assessing the nature and severity of the allegations contained in the OPDP inquiry letter and advising on the likelihood of escalation by the FDA, including the possibility that the OPDP inquiry could result in the issuance of a Warning Letter or an Untitled Letter, or that the matter could be referred to the U.S. Department of Justice ("DOJ") or the Office of Inspector General ("OIG") of the U.S. Department of Health and Human Services;

(b) Advising on the appropriate tone, structure, and substance of the formal written response to the OPDP, with a view toward demonstrating Penterra's cooperation, good faith, and commitment to corrective action while preserving Penterra's legal and factual positions as appropriate; and

(c) Drawing upon Whitfield Bauer's experience with prior OPDP inquiries and enforcement actions to inform the strategic approach to this engagement.

3.2 Promotional-Labeling Compliance Analysis

Whitfield Bauer will conduct a detailed legal and regulatory analysis of each of the three cited promotional materials against the applicable provisions of the FDCA and implementing regulations. This analysis shall specifically address:

(a) Compliance of each cited material with Section 502(n) of the FDCA (21 U.S.C. § 352(n)) and with the advertising and labeling requirements of 21 C.F.R. Part 202, including in particular §§ 202.1(e)(5) (omission or minimization of risk information) and 202.1(e)(6) (misleading efficacy claims and graphical presentations);

(b) Consistency of each cited material with applicable FDA guidance documents on promotional materials, including but not limited to FDA Draft Guidance for Industry, "Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements" (2018), and FDA Guidance for Industry, "Presenting Risk Information in Prescription Drug and Medical Device Promotion" (2009);

(c) An evaluation of the substantiation basis for the "Fastest Onset in Its Class" claim featured in the digital banner ad (Material ID: ZVR-2023-BNR-044), including a critical review of the indirect treatment comparison meta-analysis commissioned by Penterra and performed by Keswick Bioanalytics Inc. (the "Keswick ITC"), and an assessment of whether the Keswick ITC provides a level of substantiation that would be considered adequate by the FDA for a comparative onset-of-action claim in promotional materials;

(d) An analysis of the truncated y-axis graphical presentation of SUMMIT-3 trial data in the physician email blast (Material ID: ZVR-2023-EML-019). For reference, the SUMMIT-3 trial (Penterra's Phase III pivotal trial) reported a 2-hour pain-freedom rate of 23.7% for Zelvara® versus 14.2% for placebo (p < 0.001; n = 1,842 intent-to-treat population). Whitfield Bauer will advise on whether the truncated y-axis presentation, as used in the email blast, constitutes a misleading graphical presentation under applicable regulatory standards and will recommend appropriate corrective measures;

(e) An evaluation of the adequacy of disclosure in the sales representative detail aid (Material ID: ZVR-2023-DA-007) regarding the Harmon et al. poster, including the failure to disclose Penterra's financial sponsorship of the study and the absence of a control arm in the retrospective chart review, and the implications of citing an unpublished, uncontrolled study in promotional materials; and

(f) An assessment of risk-information disclosure deficiencies across the cited materials, with particular attention to the omission of hepatotoxicity risk information. As reflected in Zelvara®'s prescribing information, alanine aminotransferase ("ALT") elevations greater than three times the upper limit of normal (>3× ULN) were observed in 1.8% of clinical trial subjects receiving Zelvara®, and Whitfield Bauer will advise on whether the omission or minimization of this risk information in the cited materials constitutes a violation of the applicable regulatory requirements.

3.3 Review of Corrective Materials

Whitfield Bauer will review and advise on corrective materials and actions to be undertaken by Penterra in response to the OPDP inquiry, including the following:

(a) Reviewing and providing comments on a corrective "Dear Healthcare Provider" letter to be disseminated to the approximately 42,000 physicians (neurologists and primary-care physicians) who received the email blast (Material ID: ZVR-2023-EML-019) on June 7, 2023. The corrective letter will address the misleading graphical presentation and will provide corrected efficacy information in a manner that complies with applicable FDA requirements;

(b) Reviewing proposed revised versions of promotional materials for Zelvara® to ensure compliance with the FDCA, 21 C.F.R. Part 202, and applicable FDA guidance before the revised materials are submitted to Penterra's Promotional Review Committee for internal approval; and

(c) Advising on the corrective action plan elements to be included in the formal OPDP response, including steps taken and to be taken by Penterra to address the identified deficiencies and to prevent recurrence of similar promotional compliance issues.

3.4 Drafting Support

Whitfield Bauer will provide drafting support in connection with the preparation of Penterra's formal response to the OPDP inquiry. Specifically:

(a) Whitfield Bauer will co-draft and review, in collaboration with the C&H engagement team, the formal written response letter to be submitted to the OPDP, addressed to Dr. Carla M. Witherspoon, Pharm.D., Regulatory Review Officer, OPDP, CDER, FDA. The response letter is due on or before January 15, 2024; and

(b) Whitfield Bauer will prepare or review supporting legal memoranda on promotional-labeling compliance issues as may be necessary or useful in connection with the preparation of the response or for the purpose of advising Penterra on related compliance matters.

3.5 Exclusions and Limitations

The scope of Whitfield Bauer's engagement under this letter is limited to the regulatory matters described in Sections 3.1 through 3.4 above. The following matters are expressly excluded from the scope of this engagement:

(a) Securities-disclosure advice, including advice regarding Penterra's obligations to disclose the OPDP inquiry or related matters in its periodic filings with the U.S. Securities and Exchange Commission or in any other public disclosures. Such advice, if needed, will be provided by C&H or by other counsel engaged by Penterra for that purpose;

(b) Internal employment matters relating to the discipline, termination, or reassignment of Penterra sales-force personnel in connection with the matters at issue in the OPDP inquiry; and

(c) Contract disputes or claims arising between Penterra and third-party vendors, including but not limited to Ridgeline Health Analytics LLC, whether related to the Clarity Campaign or otherwise.

In addition, and for the avoidance of doubt, Whitfield Bauer is not separately engaged by Penterra as outside counsel. Whitfield Bauer's engagement is as co-counsel to C&H in this matter, and all substantive communications with Penterra personnel shall be coordinated through C&H, as further described in Section 8 below.

4. Staffing

The following Whitfield Bauer attorneys are authorized to perform work on this matter:

Any additional Whitfield Bauer personnel — whether attorneys, paralegals, or other staff — who may be needed to assist with this matter must be approved in advance by Leonard Cross, Responsible Partner at C&H, and, as necessary and appropriate, by Margaret Tan, EVP and General Counsel of Penterra, prior to commencing any work. Whitfield Bauer shall provide C&H with the name, title, applicable hourly rate, and relevant qualifications of any proposed additional personnel for review and approval.

5. Billing and Fee Arrangements

5.1 Hourly Rates

The following hourly rates shall apply to work performed by Whitfield Bauer attorneys on this matter:

These rates are effective as of the date of this letter and shall remain in effect for the duration of this engagement unless modified by mutual written agreement of the parties. In the event that Whitfield Bauer implements a firm-wide rate increase during the term of this engagement, Whitfield Bauer shall provide C&H with not less than thirty (30) days' prior written notice of any proposed rate change, and any such increase shall be subject to C&H's approval and the consent of Penterra.

5.2 Billing Procedures

Whitfield Bauer will submit monthly invoices to Calderwood & Harkness LLP, attention Nathaniel Bower, Partner, at the address set forth above or by electronic transmission to such email address as Mr. Bower may designate. Invoices shall be submitted within fifteen (15) days following the close of each calendar month for services rendered during that month.

Each invoice shall include detailed time entries with contemporaneous task descriptions sufficient for client review, including the date of each service, the identity of the timekeeping attorney, the time expended (in increments of no greater than one-tenth of an hour), and a description of the work performed with sufficient detail to permit meaningful review by C&H and by Penterra.

C&H will review Whitfield Bauer's invoices for accuracy and reasonableness and will submit them to Penterra for payment as part of the consolidated billing for this matter. Alternatively, at the direction of Margaret Tan, C&H may arrange for direct payment of Whitfield Bauer's invoices by Penterra. In either case, C&H shall be responsible for coordinating the billing process and for communicating with Penterra regarding the status and amount of Whitfield Bauer's fees and expenses.

Please note that C&H's overall engagement with Penterra for this matter is subject to a fee cap of Four Hundred Fifty Thousand Dollars ($450,000.00) for C&H's own professional fees. Whitfield Bauer's fees are separate from and in addition to this fee cap, and Whitfield Bauer's fees will be invoiced and tracked independently from C&H's fees for purposes of Penterra's internal budgeting and cost management.

5.3 Expenses. Reasonable out-of-pocket expenses incurred by Whitfield Bauer in connection with this matter will be billed at cost without markup. Such expenses may include, but are not limited to, travel expenses (airfare, ground transportation, lodging, and meals), document reproduction and printing costs, electronic legal research charges (e.g., Westmark Data Systems, Sundial Solutions), overnight courier and delivery charges, and long-distance telephone charges.

Any single expense item exceeding One Thousand Dollars ($1,000.00) shall require the prior written approval of C&H before being incurred. Whitfield Bauer shall submit requests for approval of such expenses to Leonard Cross or Jeffrey Park by email, and approval shall be confirmed in writing prior to the expenditure being made.

6. Privilege and Confidentiality

The parties acknowledge and agree that all communications between C&H and Whitfield Bauer in connection with this matter are made for the purpose of providing coordinated legal advice to Penterra and are protected by the attorney-client privilege, the work-product doctrine, and the common-interest doctrine. Both firms are engaged to provide legal advice to Penterra with respect to the same matter — namely, the OPDP inquiry referenced above — and all communications, work product, documents, and information exchanged between the firms in furtherance of that representation are intended to be and shall remain privileged and confidential.

Whitfield Bauer shall treat all information received in connection with this engagement, whether received from C&H, from Penterra, or from any other source, as strictly confidential and subject to attorney-client privilege and work-product protection. Whitfield Bauer shall implement appropriate safeguards to protect the confidentiality of such information, including limiting access to the information to those Whitfield Bauer personnel who have been authorized to work on this matter and who have a need to know the information in connection with their work.

Whitfield Bauer shall comply with the Privilege and Work-Product Protection Protocol established by C&H for this matter, dated October 31, 2023 (the "Privilege Protocol"), a copy of which has been provided to you separately. The Privilege Protocol sets forth specific procedures for the marking, handling, storage, and transmission of privileged and confidential materials, and Whitfield Bauer's compliance with those procedures is a condition of this engagement.

Whitfield Bauer shall not disclose any confidential information received in connection with this engagement to any third party — including any other client of Whitfield Bauer, any regulatory authority, any court, or any other person or entity — without the prior written consent of both C&H and Penterra. In the event that Whitfield Bauer receives a subpoena, court order, or other legal process seeking the production of information received in connection with this engagement, Whitfield Bauer shall promptly notify C&H and shall cooperate with C&H in asserting all applicable privileges and protections.

7. Conflicts of Interest

Whitfield Bauer confirms that it has conducted a thorough conflicts-of-interest check in accordance with its standard conflicts procedures and with the requirements of the applicable Rules of Professional Conduct. Based on that conflicts check, Whitfield Bauer represents and warrants as follows:

(a) Whitfield Bauer has identified no conflicts of interest, whether actual or potential, that would prevent it from serving as co-counsel in this matter;

(b) Whitfield Bauer does not currently represent any party adverse to Penterra Pharmaceuticals Corp. in any matter, whether related or unrelated to the subject matter of this engagement;

(c) Whitfield Bauer does not currently represent and has not within the preceding twelve (12) months represented the United States Food and Drug Administration, the Office of Prescription Drug Promotion, or any other FDA component, nor does it represent any entity or individual whose interests are or may be adverse to Penterra in connection with the matters at issue in the OPDP inquiry; and

(d) Whitfield Bauer is not aware of any facts or circumstances that could reasonably be expected to give rise to a conflict of interest during the course of this engagement.

Whitfield Bauer agrees to promptly notify C&H, in writing, if at any time during the course of this engagement Whitfield Bauer becomes aware of any actual or potential conflict of interest that could affect its ability to continue serving as co-counsel. In the event that a conflict arises that cannot be resolved through appropriate conflict-waiver procedures, the parties will discuss the matter in good faith and determine the appropriate course of action, which may include the termination of Whitfield Bauer's engagement.

8. Key Client Contacts

The primary client contacts at Penterra Pharmaceuticals Corp. for this matter are as follows:

• Margaret Tan, Executive Vice President & General Counsel

• Christine Holloway, Vice President, Regulatory Affairs

• Dr. Rajeev Anand, M.D., Ph.D., Chief Medical Officer

All substantive communications with Penterra personnel regarding the OPDP inquiry or any other aspect of this matter shall be coordinated through Jeffrey Park, Lead Associate at C&H, or Leonard Cross, Responsible Partner at C&H. Whitfield Bauer personnel shall not initiate direct substantive communications with Penterra personnel without first consulting with and obtaining the approval of Mr. Park or Mr. Cross. This coordination requirement is intended to ensure consistency and efficiency in the representation and is not intended to impede the timely flow of information; C&H will endeavor to facilitate all necessary communications promptly.

9. Duration and Termination

This engagement shall commence upon the execution of this letter by both parties and shall continue until (a) the matter is resolved to the satisfaction of Penterra and C&H, (b) the engagement is terminated by either C&H or Whitfield Bauer upon written notice to the other party, or (c) Penterra directs the termination of Whitfield Bauer's engagement as co-counsel. In the event of termination, Whitfield Bauer shall be entitled to compensation for all services rendered and expenses incurred through the effective date of termination, and shall promptly return to C&H all documents, work product, and confidential information in its possession relating to the matter.

Based on the current status of the matter, the engagement is expected to conclude upon the FDA's acknowledgment of Penterra's corrective action plan following Penterra's submission of its formal written response to the OPDP. The response deadline is January 15, 2024. However, the parties acknowledge that the duration of the engagement may be affected by the nature and timing of the FDA's response to Penterra's submission, and the engagement may continue beyond the submission of the response if additional work is needed to address follow-up inquiries or other developments.

10. Governing Law

This engagement letter shall be governed by and construed in accordance with the laws of the State of New York, without regard to principles of conflicts of law. Both parties consent to the jurisdiction of the courts of the State of New York, and of the federal courts located in the Southern District of New York, for the resolution of any dispute arising out of or relating to this engagement letter.

11. Acceptance

We look forward to working with you and your team on this matter. If the foregoing terms are acceptable, please indicate Whitfield Bauer's acceptance of this engagement by signing this letter in the space provided below and returning a signed copy to our offices. An executed copy may be returned by hand, by overnight courier, or by email (as a PDF scan) to Leonard Cross at lcross@calderwoodharkness.com.

Please do not hesitate to contact me directly at (212) 554-7120 or lcross@calderwoodharkness.com if you have any questions regarding the terms of this letter or any other aspect of the engagement. We are grateful for your firm's willingness to assist with this important matter and are confident that your regulatory expertise will be invaluable to the representation.

Very truly yours,

CALDERWOOD & HARKNESS LLP

By: ________

Name: Leonard Cross

Title: Partner

Calderwood & Harkness LLP 600 Lexington Avenue New York, NY 10022

ACCEPTED AND AGREED

The undersigned, on behalf of Whitfield Bauer & Associates LLP, hereby accepts and agrees to the terms of the foregoing engagement letter, effective as of the date set forth below.

WHITFIELD BAUER & ASSOCIATES LLP

By: ________

Name: Dr. Hannah Whitfield, J.D., Ph.D.

Title: Partner

Whitfield Bauer & Associates LLP 1330 Connecticut Avenue NW, Suite 500 Washington, DC 20036

Date: ________

Enclosure: Copy of OPDP Inquiry Letter dated October 12, 2023 (OPDP-2023-1847) [to be provided under separate cover subject to Privilege and Work-Product Protection Protocol dated October 31, 2023]

cc: Margaret Tan, EVP & General Counsel, Penterra Pharmaceuticals Corp. Nathaniel Bower, Partner, Calderwood & Harkness LLP Jeffrey Park, Associate, Calderwood & Harkness LLP

Attorney	Role	Primary Responsibilities
Dr. Hannah Whitfield, J.D., Ph.D.	Lead Partner	Regulatory strategy, OPDP response review, senior-level advisory
Thomas Crane	Senior Associate	Research, drafting, compliance analysis support
Attorney	Hourly Rate
Dr. Hannah Whitfield, J.D., Ph.D.	$950.00
Thomas Crane	$625.00

CONFIDENTIAL — ATTORNEY-CLIENT PRIVILEGED
CALDERWOOD & HARKNESS LLP Attorneys at Law 600 Lexington Avenue New York, NY 10022
Telephone: (212) 554-7000 Facsimile: (212) 554-7001 www.calderwoodharkness.com
November 10, 2023
VIA EMAIL AND HAND DELIVERY
Dr. Hannah Whitfield, J.D., Ph.D. Partner Whitfield Bauer & Associates LLP 1330 Connecticut Avenue NW, Suite 500 Washington, DC 20036
Re: Engagement of Co-Counsel — FDA OPDP Inquiry OPDP-2023-1847; Penterra Pharmaceuticals Corp. / Zelvara® (trepivant sodium) Calderwood & Harkness Matter No. 1018-00002
Dear Dr. Whitfield:
We are pleased to write to you to formalize the engagement of Whitfield Bauer & Associates LLP ("Whitfield Bauer" or "WBA") as co-counsel to Calderwood & Harkness LLP ("C&H") in the above-referenced matter. This letter sets forth the terms and conditions of that engagement, including the scope of services to be provided, staffing arrangements, billing and fee arrangements, obligations with respect to privilege and confidentiality, and related matters. We ask that you review this letter carefully and, if the terms are acceptable, countersign a copy in the space provided below and return it to our offices at your earliest convenience.
1. Purpose and Background of Engagement
Calderwood & Harkness LLP represents Penterra Pharmaceuticals Corp. ("Penterra" or "PPC"), a Delaware corporation publicly traded on the New York Stock Exchange under the ticker symbol PTPH, with its principal offices located at 480 Overlook Drive, Suite 700, Summit, New Jersey 07901. Penterra is a specialty pharmaceutical company focused on the development and commercialization of therapies for neurological conditions, including migraine.
On October 12, 2023, the United States Food and Drug Administration's Office of Prescription Drug Promotion ("OPDP"), within the Center for Drug Evaluation and Research ("CDER"), issued a formal inquiry letter bearing reference number OPDP-2023-1847, addressed to Penterra's Vice President of Regulatory Affairs, Christine Holloway. The letter was received by Penterra's regulatory affairs department on October 16, 2023. The inquiry concerns allegedly misleading promotional materials and sales representative communications related to Penterra's migraine drug Zelvara® (trepivant sodium), available in 75 mg and 150 mg oral tablet formulations. Zelvara® was approved by the FDA on October 11, 2019, pursuant to New Drug Application ("NDA") No. 214-837, for the acute treatment of migraine with or without aura in adults.
C&H was formally engaged by Penterra on October 30, 2023, pursuant to an engagement letter executed by Margaret Tan, Executive Vice President and General Counsel of Penterra, to advise Penterra on responding to the OPDP inquiry, to conduct an internal review of Penterra's promotional practices with respect to Zelvara®, and to prepare a comprehensive written response to the FDA on Penterra's behalf. The engagement team at C&H for this matter consists of the following attorneys:
•  Leonard Cross — Responsible Partner
•  Nathaniel Bower — Billing Partner
•  Jeffrey Park — Lead Associate
•  Audrey Zhou — Working Associate
Given the specialized nature of the OPDP inquiry and the regulatory issues it presents, C&H seeks to engage Whitfield Bauer as FDA regulatory specialist co-counsel. As you know, Whitfield Bauer has established a preeminent reputation in FDA promotional-labeling compliance, OPDP response strategy, and related regulatory enforcement matters, and we believe that your firm's participation in this matter will be of significant benefit to our mutual client.
We note that Penterra, acting through its EVP and General Counsel Margaret Tan, has provided written consent to the engagement of Whitfield Bauer as co-counsel in this matter. A copy of Ms. Tan's written authorization, dated November 7, 2023, is on file with C&H and is available for your review upon request.
2. Description of the OPDP Inquiry
For purposes of establishing context for Whitfield Bauer's engagement, we summarize below the principal allegations set forth in the OPDP inquiry letter. We will provide the full text of the inquiry letter, together with copies of the cited promotional materials, under separate cover in accordance with the privilege protocol described in Section 6 of this letter.
2.1 Promotional Materials at Issue
The OPDP inquiry identifies three promotional materials that are the subject of the agency's concerns. All three materials were developed as part of a promotional initiative known internally at Penterra as the "Clarity Campaign." The Clarity Campaign was developed by Ridgeline Health Analytics LLC, a third-party promotional agency retained by Penterra, and was deployed during the second and third quarters of calendar year 2023. The three materials at issue are as follows:
(a) Digital Banner Ad (Material ID: ZVR-2023-BNR-044). This digital banner advertisement ran on MedLinkPro, a healthcare-professional-targeted digital platform, during the period from April 15 through August 31, 2023. The OPDP alleges that the banner ad included the claim "Fastest Onset in Its Class" without adequate substantiation and that the advertisement omitted material risk information, specifically information regarding the risk of hepatotoxicity associated with Zelvara®.
(b) Physician Email Blast (Material ID: ZVR-2023-EML-019). This email communication was sent on June 7, 2023, to a distribution list comprising approximately 42,000 neurologists and primary-care physicians. The OPDP alleges that the email included a bar chart presenting 2-hour pain-freedom rates derived from the SUMMIT-3 clinical trial, but that the bar chart utilized a truncated y-axis in a manner that exaggerated the apparent efficacy differential between Zelvara® and a named comparator, lasmiditan, thereby creating a misleading visual impression of Zelvara®'s relative efficacy.
(c) Sales Representative Detail Aid (Material ID: ZVR-2023-DA-007). This printed detail aid, which was approved by Penterra's internal Promotional Review Committee on March 22, 2023, cited an unpublished retrospective chart review authored by Harmon et al. and presented as a poster at the American Headache Society 2022 annual meeting. The OPDP alleges that the detail aid failed to disclose that the Harmon et al. study was funded by Penterra and that the study lacked a control arm, thereby presenting the data in a misleading manner.
2.2 Alleged Regulatory Violations
The OPDP inquiry alleges that the above-described materials constitute potential violations of the following provisions of federal law and regulation:
•  Section 502(n) of the Federal Food, Drug, and Cosmetic Act ("FDCA"), codified at 21 U.S.C. § 352(n), which governs the advertising and labeling of prescription drugs and requires, among other things, that advertisements present a true statement of information in brief summary relating to the drug's side effects, contraindications, and effectiveness;
•  21 C.F.R. § 202.1(e)(5), which addresses the omission or minimization of risk information in prescription drug advertisements; and
•  21 C.F.R. § 202.1(e)(6), which prohibits misleading efficacy claims, including unsubstantiated superiority claims and the use of misleading graphical or visual presentations.
2.3 Response Deadline and Extension
The OPDP inquiry letter established an original response deadline of November 15, 2023, which was thirty (30) days from the date of Penterra's receipt of the inquiry on October 16, 2023. On November 1, 2023, Penterra, through C&H, submitted a written request for an extension of the response deadline. On November 8, 2023, the FDA granted a sixty (60)-day extension, establishing a new deadline for Penterra's formal written response of January 15, 2024.
2.4 Voluntary Withdrawal of Cited Materials
Penterra, on the advice of C&H and in consultation with Ms. Holloway and Ms. Tan, voluntarily withdrew all three cited promotional materials from circulation as of November 3, 2023. Confirmation of the withdrawal was communicated to Penterra's sales organization and to Ridgeline Health Analytics LLC on the same date. We anticipate that the voluntary withdrawal will be referenced in Penterra's formal response to the OPDP as evidence of the company's good-faith commitment to promotional compliance.
3. Scope of Whitfield Bauer's Engagement
Whitfield Bauer is engaged to serve as regulatory co-counsel and will provide services in the areas described below. The scope of this engagement is limited to the matters set forth in this Section 3, and any expansion of the scope of engagement shall require the prior written agreement of C&H and Whitfield Bauer and, as appropriate, the consent of Penterra.
3.1 OPDP Response Strategy
Whitfield Bauer will advise C&H and Penterra on the overall strategy for responding to the OPDP inquiry letter, reference number OPDP-2023-1847. This advisory role shall include, but not be limited to, the following:
(a) Assessing the nature and severity of the allegations contained in the OPDP inquiry letter and advising on the likelihood of escalation by the FDA, including the possibility that the OPDP inquiry could result in the issuance of a Warning Letter or an Untitled Letter, or that the matter could be referred to the U.S. Department of Justice ("DOJ") or the Office of Inspector General ("OIG") of the U.S. Department of Health and Human Services;
(b) Advising on the appropriate tone, structure, and substance of the formal written response to the OPDP, with a view toward demonstrating Penterra's cooperation, good faith, and commitment to corrective action while preserving Penterra's legal and factual positions as appropriate; and
(c) Drawing upon Whitfield Bauer's experience with prior OPDP inquiries and enforcement actions to inform the strategic approach to this engagement.
3.2 Promotional-Labeling Compliance Analysis
Whitfield Bauer will conduct a detailed legal and regulatory analysis of each of the three cited promotional materials against the applicable provisions of the FDCA and implementing regulations. This analysis shall specifically address:
(a) Compliance of each cited material with Section 502(n) of the FDCA (21 U.S.C. § 352(n)) and with the advertising and labeling requirements of 21 C.F.R. Part 202, including in particular §§ 202.1(e)(5) (omission or minimization of risk information) and 202.1(e)(6) (misleading efficacy claims and graphical presentations);
(b) Consistency of each cited material with applicable FDA guidance documents on promotional materials, including but not limited to FDA Draft Guidance for Industry, "Presenting Quantitative Efficacy and Risk Information in Direct-to-Consumer Promotional Labeling and Advertisements" (2018), and FDA Guidance for Industry, "Presenting Risk Information in Prescription Drug and Medical Device Promotion" (2009);
(c) An evaluation of the substantiation basis for the "Fastest Onset in Its Class" claim featured in the digital banner ad (Material ID: ZVR-2023-BNR-044), including a critical review of the indirect treatment comparison meta-analysis commissioned by Penterra and performed by Keswick Bioanalytics Inc. (the "Keswick ITC"), and an assessment of whether the Keswick ITC provides a level of substantiation that would be considered adequate by the FDA for a comparative onset-of-action claim in promotional materials;
(d) An analysis of the truncated y-axis graphical presentation of SUMMIT-3 trial data in the physician email blast (Material ID: ZVR-2023-EML-019). For reference, the SUMMIT-3 trial (Penterra's Phase III pivotal trial) reported a 2-hour pain-freedom rate of 23.7% for Zelvara® versus 14.2% for placebo (p < 0.001; n = 1,842 intent-to-treat population). Whitfield Bauer will advise on whether the truncated y-axis presentation, as used in the email blast, constitutes a misleading graphical presentation under applicable regulatory standards and will recommend appropriate corrective measures;
(e) An evaluation of the adequacy of disclosure in the sales representative detail aid (Material ID: ZVR-2023-DA-007) regarding the Harmon et al. poster, including the failure to disclose Penterra's financial sponsorship of the study and the absence of a control arm in the retrospective chart review, and the implications of citing an unpublished, uncontrolled study in promotional materials; and
(f) An assessment of risk-information disclosure deficiencies across the cited materials, with particular attention to the omission of hepatotoxicity risk information. As reflected in Zelvara®'s prescribing information, alanine aminotransferase ("ALT") elevations greater than three times the upper limit of normal (>3× ULN) were observed in 1.8% of clinical trial subjects receiving Zelvara®, and Whitfield Bauer will advise on whether the omission or minimization of this risk information in the cited materials constitutes a violation of the applicable regulatory requirements.
3.3 Review of Corrective Materials
Whitfield Bauer will review and advise on corrective materials and actions to be undertaken by Penterra in response to the OPDP inquiry, including the following:
(a) Reviewing and providing comments on a corrective "Dear Healthcare Provider" letter to be disseminated to the approximately 42,000 physicians (neurologists and primary-care physicians) who received the email blast (Material ID: ZVR-2023-EML-019) on June 7, 2023. The corrective letter will address the misleading graphical presentation and will provide corrected efficacy information in a manner that complies with applicable FDA requirements;
(b) Reviewing proposed revised versions of promotional materials for Zelvara® to ensure compliance with the FDCA, 21 C.F.R. Part 202, and applicable FDA guidance before the revised materials are submitted to Penterra's Promotional Review Committee for internal approval; and
(c) Advising on the corrective action plan elements to be included in the formal OPDP response, including steps taken and to be taken by Penterra to address the identified deficiencies and to prevent recurrence of similar promotional compliance issues.
3.4 Drafting Support
Whitfield Bauer will provide drafting support in connection with the preparation of Penterra's formal response to the OPDP inquiry. Specifically:
(a) Whitfield Bauer will co-draft and review, in collaboration with the C&H engagement team, the formal written response letter to be submitted to the OPDP, addressed to Dr. Carla M. Witherspoon, Pharm.D., Regulatory Review Officer, OPDP, CDER, FDA. The response letter is due on or before January 15, 2024; and
(b) Whitfield Bauer will prepare or review supporting legal memoranda on promotional-labeling compliance issues as may be necessary or useful in connection with the preparation of the response or for the purpose of advising Penterra on related compliance matters.
3.5 Exclusions and Limitations
The scope of Whitfield Bauer's engagement under this letter is limited to the regulatory matters described in Sections 3.1 through 3.4 above. The following matters are expressly excluded from the scope of this engagement:
(a) Securities-disclosure advice, including advice regarding Penterra's obligations to disclose the OPDP inquiry or related matters in its periodic filings with the U.S. Securities and Exchange Commission or in any other public disclosures. Such advice, if needed, will be provided by C&H or by other counsel engaged by Penterra for that purpose;
(b) Internal employment matters relating to the discipline, termination, or reassignment of Penterra sales-force personnel in connection with the matters at issue in the OPDP inquiry; and
(c) Contract disputes or claims arising between Penterra and third-party vendors, including but not limited to Ridgeline Health Analytics LLC, whether related to the Clarity Campaign or otherwise.
In addition, and for the avoidance of doubt, Whitfield Bauer is not separately engaged by Penterra as outside counsel. Whitfield Bauer's engagement is as co-counsel to C&H in this matter, and all substantive communications with Penterra personnel shall be coordinated through C&H, as further described in Section 8 below.
4. Staffing
The following Whitfield Bauer attorneys are authorized to perform work on this matter:
Any additional Whitfield Bauer personnel — whether attorneys, paralegals, or other staff — who may be needed to assist with this matter must be approved in advance by Leonard Cross, Responsible Partner at C&H, and, as necessary and appropriate, by Margaret Tan, EVP and General Counsel of Penterra, prior to commencing any work. Whitfield Bauer shall provide C&H with the name, title, applicable hourly rate, and relevant qualifications of any proposed additional personnel for review and approval.
5. Billing and Fee Arrangements
5.1 Hourly Rates
The following hourly rates shall apply to work performed by Whitfield Bauer attorneys on this matter:
These rates are effective as of the date of this letter and shall remain in effect for the duration of this engagement unless modified by mutual written agreement of the parties. In the event that Whitfield Bauer implements a firm-wide rate increase during the term of this engagement, Whitfield Bauer shall provide C&H with not less than thirty (30) days' prior written notice of any proposed rate change, and any such increase shall be subject to C&H's approval and the consent of Penterra.
5.2 Billing Procedures
Whitfield Bauer will submit monthly invoices to Calderwood & Harkness LLP, attention Nathaniel Bower, Partner, at the address set forth above or by electronic transmission to such email address as Mr. Bower may designate. Invoices shall be submitted within fifteen (15) days following the close of each calendar month for services rendered during that month.
Each invoice shall include detailed time entries with contemporaneous task descriptions sufficient for client review, including the date of each service, the identity of the timekeeping attorney, the time expended (in increments of no greater than one-tenth of an hour), and a description of the work performed with sufficient detail to permit meaningful review by C&H and by Penterra.
C&H will review Whitfield Bauer's invoices for accuracy and reasonableness and will submit them to Penterra for payment as part of the consolidated billing for this matter. Alternatively, at the direction of Margaret Tan, C&H may arrange for direct payment of Whitfield Bauer's invoices by Penterra. In either case, C&H shall be responsible for coordinating the billing process and for communicating with Penterra regarding the status and amount of Whitfield Bauer's fees and expenses.
Please note that C&H's overall engagement with Penterra for this matter is subject to a fee cap of Four Hundred Fifty Thousand Dollars ($450,000.00) for C&H's own professional fees. Whitfield Bauer's fees are separate from and in addition to this fee cap, and Whitfield Bauer's fees will be invoiced and tracked independently from C&H's fees for purposes of Penterra's internal budgeting and cost management.
5.3 Expenses.  Reasonable out-of-pocket expenses incurred by Whitfield Bauer in connection with this matter will be billed at cost without markup. Such expenses may include, but are not limited to, travel expenses (airfare, ground transportation, lodging, and meals), document reproduction and printing costs, electronic legal research charges (e.g., Westmark Data Systems, Sundial Solutions), overnight courier and delivery charges, and long-distance telephone charges.
Any single expense item exceeding One Thousand Dollars ($1,000.00) shall require the prior written approval of C&H before being incurred. Whitfield Bauer shall submit requests for approval of such expenses to Leonard Cross or Jeffrey Park by email, and approval shall be confirmed in writing prior to the expenditure being made.
6. Privilege and Confidentiality
The parties acknowledge and agree that all communications between C&H and Whitfield Bauer in connection with this matter are made for the purpose of providing coordinated legal advice to Penterra and are protected by the attorney-client privilege, the work-product doctrine, and the common-interest doctrine. Both firms are engaged to provide legal advice to Penterra with respect to the same matter — namely, the OPDP inquiry referenced above — and all communications, work product, documents, and information exchanged between the firms in furtherance of that representation are intended to be and shall remain privileged and confidential.
Whitfield Bauer shall treat all information received in connection with this engagement, whether received from C&H, from Penterra, or from any other source, as strictly confidential and subject to attorney-client privilege and work-product protection. Whitfield Bauer shall implement appropriate safeguards to protect the confidentiality of such information, including limiting access to the information to those Whitfield Bauer personnel who have been authorized to work on this matter and who have a need to know the information in connection with their work.
Whitfield Bauer shall comply with the Privilege and Work-Product Protection Protocol established by C&H for this matter, dated October 31, 2023 (the "Privilege Protocol"), a copy of which has been provided to you separately. The Privilege Protocol sets forth specific procedures for the marking, handling, storage, and transmission of privileged and confidential materials, and Whitfield Bauer's compliance with those procedures is a condition of this engagement.
Whitfield Bauer shall not disclose any confidential information received in connection with this engagement to any third party — including any other client of Whitfield Bauer, any regulatory authority, any court, or any other person or entity — without the prior written consent of both C&H and Penterra. In the event that Whitfield Bauer receives a subpoena, court order, or other legal process seeking the production of information received in connection with this engagement, Whitfield Bauer shall promptly notify C&H and shall cooperate with C&H in asserting all applicable privileges and protections.
7. Conflicts of Interest
Whitfield Bauer confirms that it has conducted a thorough conflicts-of-interest check in accordance with its standard conflicts procedures and with the requirements of the applicable Rules of Professional Conduct. Based on that conflicts check, Whitfield Bauer represents and warrants as follows:
(a) Whitfield Bauer has identified no conflicts of interest, whether actual or potential, that would prevent it from serving as co-counsel in this matter;
(b) Whitfield Bauer does not currently represent any party adverse to Penterra Pharmaceuticals Corp. in any matter, whether related or unrelated to the subject matter of this engagement;
(c) Whitfield Bauer does not currently represent and has not within the preceding twelve (12) months represented the United States Food and Drug Administration, the Office of Prescription Drug Promotion, or any other FDA component, nor does it represent any entity or individual whose interests are or may be adverse to Penterra in connection with the matters at issue in the OPDP inquiry; and
(d) Whitfield Bauer is not aware of any facts or circumstances that could reasonably be expected to give rise to a conflict of interest during the course of this engagement.
Whitfield Bauer agrees to promptly notify C&H, in writing, if at any time during the course of this engagement Whitfield Bauer becomes aware of any actual or potential conflict of interest that could affect its ability to continue serving as co-counsel. In the event that a conflict arises that cannot be resolved through appropriate conflict-waiver procedures, the parties will discuss the matter in good faith and determine the appropriate course of action, which may include the termination of Whitfield Bauer's engagement.
8. Key Client Contacts
The primary client contacts at Penterra Pharmaceuticals Corp. for this matter are as follows:
•  Margaret Tan, Executive Vice President & General Counsel
•  Christine Holloway, Vice President, Regulatory Affairs
•  Dr. Rajeev Anand, M.D., Ph.D., Chief Medical Officer
All substantive communications with Penterra personnel regarding the OPDP inquiry or any other aspect of this matter shall be coordinated through Jeffrey Park, Lead Associate at C&H, or Leonard Cross, Responsible Partner at C&H. Whitfield Bauer personnel shall not initiate direct substantive communications with Penterra personnel without first consulting with and obtaining the approval of Mr. Park or Mr. Cross. This coordination requirement is intended to ensure consistency and efficiency in the representation and is not intended to impede the timely flow of information; C&H will endeavor to facilitate all necessary communications promptly.
9. Duration and Termination
This engagement shall commence upon the execution of this letter by both parties and shall continue until (a) the matter is resolved to the satisfaction of Penterra and C&H, (b) the engagement is terminated by either C&H or Whitfield Bauer upon written notice to the other party, or (c) Penterra directs the termination of Whitfield Bauer's engagement as co-counsel. In the event of termination, Whitfield Bauer shall be entitled to compensation for all services rendered and expenses incurred through the effective date of termination, and shall promptly return to C&H all documents, work product, and confidential information in its possession relating to the matter.
Based on the current status of the matter, the engagement is expected to conclude upon the FDA's acknowledgment of Penterra's corrective action plan following Penterra's submission of its formal written response to the OPDP. The response deadline is January 15, 2024. However, the parties acknowledge that the duration of the engagement may be affected by the nature and timing of the FDA's response to Penterra's submission, and the engagement may continue beyond the submission of the response if additional work is needed to address follow-up inquiries or other developments.
10. Governing Law
This engagement letter shall be governed by and construed in accordance with the laws of the State of New York, without regard to principles of conflicts of law. Both parties consent to the jurisdiction of the courts of the State of New York, and of the federal courts located in the Southern District of New York, for the resolution of any dispute arising out of or relating to this engagement letter.
11. Acceptance
We look forward to working with you and your team on this matter. If the foregoing terms are acceptable, please indicate Whitfield Bauer's acceptance of this engagement by signing this letter in the space provided below and returning a signed copy to our offices. An executed copy may be returned by hand, by overnight courier, or by email (as a PDF scan) to Leonard Cross at lcross@calderwoodharkness.com.
Please do not hesitate to contact me directly at (212) 554-7120 or lcross@calderwoodharkness.com if you have any questions regarding the terms of this letter or any other aspect of the engagement. We are grateful for your firm's willingness to assist with this important matter and are confident that your regulatory expertise will be invaluable to the representation.
Very truly yours,
CALDERWOOD & HARKNESS LLP
By: ________
Name: Leonard Cross
Title: Partner
Calderwood & Harkness LLP 600 Lexington Avenue New York, NY 10022
ACCEPTED AND AGREED
The undersigned, on behalf of Whitfield Bauer & Associates LLP, hereby accepts and agrees to the terms of the foregoing engagement letter, effective as of the date set forth below.
WHITFIELD BAUER & ASSOCIATES LLP
By: ________
Name: Dr. Hannah Whitfield, J.D., Ph.D.
Title: Partner
Whitfield Bauer & Associates LLP 1330 Connecticut Avenue NW, Suite 500 Washington, DC 20036
Date: ________
Enclosure: Copy of OPDP Inquiry Letter dated October 12, 2023 (OPDP-2023-1847) [to be provided under separate cover subject to Privilege and Work-Product Protection Protocol dated October 31, 2023]
cc: Margaret Tan, EVP & General Counsel, Penterra Pharmaceuticals Corp. Nathaniel Bower, Partner, Calderwood & Harkness LLP Jeffrey Park, Associate, Calderwood & Harkness LLP
Attorney | Role | Primary Responsibilities
Dr. Hannah Whitfield, J.D., Ph.D. | Lead Partner | Regulatory strategy, OPDP response review, senior-level advisory
Thomas Crane | Senior Associate | Research, drafting, compliance analysis support
Attorney | Hourly Rate
Dr. Hannah Whitfield, J.D., Ph.D. | $950.00
Thomas Crane | $625.00

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CALDERWOOD & HARKNESS LLP

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WHITFIELD BAUER & ASSOCIATES LLP

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