1018-00005 · Penterra Pharmaceuticals Corp · Matter Administration

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CALDERWOOD & HARKNESS LLP

INTERNAL MEMORANDUM — FILE PRESERVATION AND MATTER ADMINISTRATION

1. Dormancy Status

Pursuant to instruction received from Lisa Moritani, Esq., General Counsel and Corporate Secretary of Penterra Pharmaceuticals Corp. ("Penterra" or "PPC"), by email dated December 1, 2022, Matter No. 1018-00005 is hereby placed on dormant status effective December 1, 2022.

The client in this matter is Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware, publicly traded on the New York Stock Exchange under the ticker symbol PTRC, and headquartered at 900 Commons Way, Suite 400, Dralvecen, New Jersey 08807.

The matter involves the Firm's engagement as outside regulatory counsel to Penterra for the preparation and submission of a supplemental New Drug Application ("sNDA") to the United States Food and Drug Administration ("FDA") seeking approval to add a new indication — moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy — to the approved labeling for VELONATIB® (velonatib hydrochloride) tablets, NDA No. 215-847. The engagement encompassed regulatory strategy development, coordination with the FDA, preparation of draft labeling materials (including the United States Prescribing Information and Medication Guide), analysis of pediatric study requirements under the Pediatric Research Equity Act ("PREA"), Risk Evaluation and Mitigation Strategy ("REMS") assessment analysis, and coordination with Penterra's other outside advisors, including intellectual property counsel and regulatory consultants.

The decision to place the matter on dormant status was triggered by the failure of the CLARION-3 confirmatory Phase III clinical trial to meet its co-primary endpoint of PASI-90 at Week 16. Top-line results from CLARION-3 were announced by Penterra on November 17, 2022. The trial did not achieve statistical significance on the PASI-90 co-primary endpoint, with 43.9% of patients receiving velonatib achieving PASI-90 at Week 16 compared to 39.7% of patients receiving an adalimumab biosimilar as the active comparator (p = 0.174). As a result of these trial results, Penterra determined that it could not proceed with sNDA submission based on the existing clinical data package and informed this Firm that all work on the sNDA should be suspended pending completion of a redesigned confirmatory trial.

Penterra has communicated its intention to pursue a redesigned confirmatory trial, designated CLARION-3R, and anticipates reactivating the engagement with this Firm upon availability of CLARION-3R top-line data. Based on current projections communicated by the client, CLARION-3R top-line data are expected in the second half of 2024, though this timeline is subject to change based on enrollment progress, clinical operations, and regulatory developments.

Effective immediately, no further billable work is to be performed on this matter without prior written authorization from the client. All timekeepers assigned to this matter should close their time entries as of November 30, 2022, and should not enter any additional time against matter number 1018-00005. Any inquiries from the client or from third parties regarding this matter should be directed to the undersigned or to Joel Strauss in the first instance.

For the record, the engagement letter governing the Firm's representation of Penterra in this matter was executed on July 7, 2022, by Joel Strauss on behalf of the Firm and countersigned by Lisa Moritani on behalf of Penterra. The engagement was active from July 7, 2022 through November 30, 2022, a period of approximately five months.

2. Financial Summary

The following table sets forth a comprehensive financial reconciliation for the engagement through the effective date of dormancy. All figures have been confirmed with the Firm's Finance Department as of the date of this memorandum and reflect all time entries, invoices, and payments processed through November 30, 2022.

The billing arrangement for this matter, as set forth in the engagement letter dated July 7, 2022, provides for blended hourly rates as follows: partners at $1,175 per hour and associates at $725 per hour. Disbursements are billed at cost. Invoices were submitted monthly and were payable within thirty (30) days of the invoice date, in accordance with Penterra's standard outside counsel payment terms.

The original estimated fee range for the full scope of the engagement (i.e., from regulatory strategy development through sNDA assembly, submission, and initial FDA correspondence related to filing review) was $475,000 to $625,000. The fees actually incurred during the active engagement period ($287,450.00) represent approximately 46% to 60% of the original budget estimate. This reflects the fact that the engagement progressed through the pre-submission phase — including strategy development, FDA meeting preparation and analysis, draft labeling preparation, pediatric deferral analysis, REMS assessment analysis, and coordination with co-counsel and consultants — but was halted prior to sNDA assembly and filing. The remaining budgeted work, including final sNDA document assembly, electronic Common Technical Document ("eCTD") review, pre-submission preparation, and post-submission support, was not performed.

No further invoices are to be submitted during the dormancy period unless specific services are requested by the client in writing. In the event the client requests limited advisory services during the dormancy period (e.g., review of a pediatric deferral annual progress report or analysis of a new FDA guidance), such work will be billed in accordance with the existing engagement terms and will be invoiced separately upon completion.

3. Staffing Record

The following timekeepers billed to Matter No. 1018-00005 during the active engagement period (July 7, 2022 through November 30, 2022):

No additional attorneys, of-counsel, paralegals, or other professional staff were assigned to this matter during the active engagement period. All substantive work was performed by the four timekeepers identified above. Joel Strauss served as the primary relationship partner and lead regulatory strategist; Miriam Calloway served as billing partner with periodic substantive involvement; Sean Morrissey served as lead associate responsible for day-to-day drafting, research, and client coordination; and Christopher Aiken served as working associate supporting research, drafting, and document preparation.

4. File Preservation — Inventory of Work Product

All physical and electronic files for Matter No. 1018-00005 are to be preserved in accordance with the Firm's document retention policy (most recently updated October 2021) and the client's specific preservation instruction, as communicated in the December 1, 2022 email from Lisa Moritani directing that all work product and correspondence be retained by the Firm pending potential reactivation of the engagement. No files are to be destroyed, archived to off-site storage, or purged from the Firm's document management system without express written authorization from both the billing partner and the client.

The following table provides a detailed inventory of all key work-product items currently on file for this matter:

The following additional notes apply to the inventory listed above:

Items 11 and 12 — FDA Type B Pre-sNDA Meeting Materials. The FDA Type B Pre-sNDA meeting (Meeting ID: FDA-2022-M-1743) was held on May 4, 2022, prior to the commencement of the Calderwood & Harkness engagement. However, the Firm received copies of both the briefing document and the official FDA meeting minutes during the engagement period. The briefing document (Item 11) was originally prepared by Penterra's internal regulatory affairs team and the Callendar Baines Group LLC, and was provided to the Firm for review and comment on April 18, 2022 (prior to engagement execution, at the request of the client, as part of the pre-engagement scoping process). The Firm's review comments were incorporated by the client team. The FDA meeting minutes (Item 12) were received from the FDA on or about May 19, 2022 and were provided to the Firm following engagement execution; the Firm prepared annotations to the minutes identifying key FDA positions and action items relevant to the sNDA filing strategy.

Items 6 and 7 — Draft USPI and Draft Medication Guide. Draft USPI Rev. 3 (Item 6) and Draft Medication Guide Rev. 2 (Item 7) were prepared by Sean Morrissey and Christopher Aiken in coordination with Dr. Karen Hessler, Senior Vice President, Regulatory Affairs, Penterra Pharmaceuticals Corp., and the Callendar Baines Group LLC (regulatory and clinical strategy consultancy), specifically Dr. Priya Sundaram (Managing Director) and Dr. Neil Oxborough (Principal Consultant). Both documents were placed on hold effective November 22, 2022, at the direction of Dr. Hessler following the announcement of the CLARION-3 top-line results, and remain in draft form pending future reactivation and updating.

Item 5 — Patent Coordination Email. The patent coordination email (Item 5) involved communication with Whitfield & Grange LLP, outside intellectual property and patent counsel to Penterra. The primary contacts at Whitfield & Grange for purposes of this matter are Dr. Eleanor Cassidy (Lead Partner) and Brian Takata (Senior Associate). The coordination concerned Orange Book listing considerations for the following patents: U.S. Patent No. 10,412,XXX (compound patent, expiration February 2034) and U.S. Patent No. 10,891,XXX (formulation patent, expiration August 2036), as well as a provisional patent application (U.S. Provisional Application No. 63/XXX,XXX, method-of-treatment claim directed to the psoriasis indication, filed August 2022). The coordination was conducted at the client's direction to ensure that the draft USPI language was consistent with the patent claims and that the Orange Book listing strategy was aligned with the sNDA submission timeline.

File Storage. All electronic files for this matter are stored on the Firm's secure document management system (Vireo Data Systems), organized within the matter workspace for 1018-00005, with appropriate access controls limited to the timekeepers identified in Section 3 above, the Firm's General Counsel, and authorized administrative personnel. Physical file materials, to the extent any exist (principally consisting of the executed original engagement letter and certain printed correspondence), are housed at the Firm's New York office, 1120 Avenue of the Americas, 32nd Floor, New York, New York 10036.

5. Key Matter Context for Future Reference

The following summary is provided to assist any future attorney reviewing this file upon reactivation of the matter. This section is intended as a reference overview and does not constitute legal advice or a comprehensive analysis of the regulatory issues involved. The memoranda and correspondence listed in Section 4 should be consulted for detailed analysis.

5.1 The Drug and Current Approval

VELONATIB® (velonatib hydrochloride) is a selective Janus kinase 1 ("JAK-1") inhibitor administered orally in tablet form, available in 5 mg and 10 mg dosage strengths. Velonatib is marketed by Penterra Pharmaceuticals Corp. under NDA No. 215-847, which was originally approved by the FDA on June 14, 2019. The currently approved indication is for the treatment of moderate-to-severe rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs ("DMARDs"). Velonatib is approved at doses of 5 mg and 10 mg once daily for the rheumatoid arthritis indication.

Penterra is the NDA holder and sole marketer of Velonatib in the United States. For fiscal year 2022, U.S. net sales for Velonatib were approximately $1.47 billion, representing approximately 67.4% of Penterra's total revenue of $2.18 billion. Velonatib is the company's principal commercial product and the primary revenue driver.

The current approved labeling for Velonatib includes a boxed Warning addressing risks of serious infections, malignancies (including lymphoma), major adverse cardiovascular events ("MACE"), and thrombosis (including pulmonary embolism and deep vein thrombosis). This boxed Warning was added in connection with the FDA's September 2021 class-wide JAK-inhibitor labeling update, which required boxed Warnings on all approved JAK inhibitors based on post-marketing safety data from the ORAL Surveillance trial (tofacitinib) and class-wide safety considerations. The boxed Warning and associated limitations on the approved patient population (restricting use to patients with inadequate response or intolerance to one or more TNF blockers in the rheumatoid arthritis indication) are significant factors in the regulatory strategy for the psoriasis sNDA and were discussed at length in the FDA Type B Pre-sNDA meeting.

5.2 The Proposed sNDA

The proposed regulatory submission is an Efficacy Supplement — Type 10 (new indication) under 21 C.F.R. § 314.70(b), to be submitted as a supplemental New Drug Application to the existing NDA No. 215-847. The proposed new indication is for the treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The proposed dose for the psoriasis indication is velonatib 10 mg once daily, which is the higher of the two approved doses for the rheumatoid arthritis indication.

The sNDA, if ultimately submitted and approved, would represent a significant label expansion for Velonatib and would position the product as a competitor to established JAK inhibitors and biologic therapies in the psoriasis market. The regulatory strategy memorandum (Item 2, dated August 12, 2022) provides a detailed analysis of the competitive landscape, regulatory pathway, and strategic considerations.

5.3 Clinical Program Summary

The clinical development program supporting the proposed psoriasis indication consists of three completed or partially completed studies and one planned redesigned study, summarized as follows:

CLARION-1 (Phase II dose-ranging study). Enrolled 287 patients with moderate-to-severe chronic plaque psoriasis. The study was completed in September 2020 and met its primary endpoint: PASI-75 response at Week 12 was achieved by 68.2% of patients in the velonatib 10 mg arm compared to 12.4% of patients in the placebo arm (p < 0.001). CLARION-1 supported dose selection (10 mg once daily) for the Phase III program and provided preliminary evidence of efficacy in the psoriasis population.

CLARION-2 (Phase III pivotal study #1). Enrolled 742 patients with moderate-to-severe chronic plaque psoriasis in a randomized, double-blind, placebo-controlled trial. The study was completed in April 2022 and met both co-primary endpoints: PASI-75 at Week 16 was achieved by 71.5% of patients receiving velonatib 10 mg compared to 9.1% of patients receiving placebo (p < 0.001); and static Physician Global Assessment ("sPGA") score of 0 or 1 at Week 16 was achieved by 58.3% of patients receiving velonatib compared to 5.7% of patients receiving placebo (p < 0.001). CLARION-2 constitutes the first of the two adequate and well-controlled Phase III trials required by the FDA for sNDA submission.

CLARION-3 (Phase III confirmatory study). Enrolled 698 patients with moderate-to-severe chronic plaque psoriasis in a randomized, double-blind, active comparator-controlled trial comparing velonatib 10 mg once daily to an adalimumab biosimilar (standard dosing). Top-line results were announced on November 17, 2022. The study failed to meet its co-primary endpoint of PASI-90 at Week 16: 43.9% of patients receiving velonatib achieved PASI-90 compared to 39.7% of patients receiving the adalimumab biosimilar (p = 0.174, not statistically significant). The secondary endpoint of PASI-75 at Week 16 was met: 69.8% of patients receiving velonatib achieved PASI-75 compared to 62.1% of patients receiving the adalimumab biosimilar (p = 0.012). The failure of CLARION-3 to meet the PASI-90 co-primary endpoint is the proximate cause of the sNDA filing delay and the resulting dormancy of this engagement. The Post-CLARION-3 Regulatory Path Analysis memorandum (Item 9, dated November 28, 2022) provides a detailed assessment of the implications of these results.

CLARION-3R (Phase III redesigned confirmatory study). In response to the CLARION-3 results, Penterra has designed a revised confirmatory study (CLARION-3R) with the following key parameters: target enrollment of approximately 950 patients (increased from 698 in CLARION-3 to improve statistical power); revised primary endpoint of PASI-75 at Week 16 (rather than PASI-90); PASI-90 at Week 16 as a key secondary endpoint (rather than co-primary); and retention of the active comparator design (adalimumab biosimilar). An IND amendment for CLARION-3R is projected to be submitted in March 2023, with study initiation projected for the third quarter of 2023 and top-line data availability projected for the second half of 2024. These projections were communicated by Lisa Moritani in her December 1, 2022 dormancy instruction email and are subject to revision.

5.4 Key FDA Interactions

The principal FDA interaction relevant to this matter was a Type B Pre-sNDA meeting held on May 4, 2022, under Meeting ID FDA-2022-M-1743. The meeting was attended by representatives of Penterra (including Dr. Karen Hessler and Dr. Priya Sundaram of Callendar Baines Group LLC) and the FDA's Division of Dermatology and Dentistry (CDER). Although the meeting occurred prior to the formal commencement of the Calderwood & Harkness engagement, the Firm reviewed and annotated the meeting minutes and incorporated the FDA's positions into the regulatory strategy memorandum (Item 2). The key outcomes of the Type B Pre-sNDA meeting were as follows:

• The FDA confirmed its requirement for two adequate and well-controlled Phase III trials supporting the psoriasis indication, consistent with the general statutory and regulatory framework for efficacy supplements.

• The FDA required that the confirmatory Phase III trial (CLARION-3) employ an active comparator design, citing the availability of approved biologic therapies for moderate-to-severe plaque psoriasis and the need to contextualize the benefit-risk profile of velonatib relative to existing treatments, particularly in light of the class-wide JAK-inhibitor safety concerns.

• The FDA specified PASI-90 as a co-primary endpoint in the confirmatory trial, reflecting evolving standards in psoriasis drug development and the Agency's view that PASI-90 provides a more clinically meaningful measure of treatment response than PASI-75 alone.

• The FDA required a minimum of 12 months of safety data in the psoriasis population as a condition of sNDA acceptance for filing.

• The FDA indicated that enhanced hepatotoxicity monitoring language would be required in the approved labeling for the psoriasis indication, based on signal detection from the CLARION-1 and CLARION-2 data (elevated ALT/AST observed in approximately 4.2% of velonatib-treated patients, compared to 1.1% of placebo-treated patients).

• The FDA required that a REMS assessment be included with the sNDA filing. Velonatib is not currently subject to a REMS under the rheumatoid arthritis approval, but the FDA indicated that the psoriasis indication — which could significantly expand the treated patient population — warrants a formal assessment of whether a REMS is necessary to ensure the benefits of the drug outweigh its risks in the broader population.

• The FDA issued a Pediatric Written Request under PREA and granted a deferral for the pediatric psoriasis study (see Section 5.5 below).

5.5 Pediatric Deferral

The FDA issued a Written Request dated June 3, 2022, for a pediatric study of velonatib in patients aged 12 to 17 years with moderate-to-severe chronic plaque psoriasis. A deferral of the pediatric study was granted on July 28, 2022, based on Penterra's request and the FDA's agreement that it was appropriate to complete and evaluate the adult clinical program before initiating pediatric studies. Under the terms of the deferral, pediatric study results are due no later than 18 months after approval of the adult psoriasis indication.

Annual progress reports on the status of the pediatric study are due by September 26 of each year during the deferral period. The first annual progress report was due September 26, 2023. Penterra's Regulatory Affairs department (Dr. Karen Hessler) is responsible for the preparation and submission of these annual progress reports. Calderwood & Harkness offered to review draft annual progress reports prior to submission, but this review was not included in the scope of the engagement letter and would constitute additional work to be billed separately if requested by the client. The pediatric deferral analysis memorandum (Item 3, dated September 8, 2022) provides a detailed assessment of the Written Request, deferral terms, and reporting obligations.

Note for future review: Any attorney reviewing this file upon reactivation should confirm with the client the status of pediatric deferral annual progress reports and whether any FDA communications regarding the pediatric study were received during the dormancy period.

5.6 Coordination with Other Advisors

The following third-party advisors have been involved in matters related to the Velonatib psoriasis sNDA, and coordination with one or more of these advisors may be required upon reactivation of the engagement:

Whitfield & Grange LLP — Outside intellectual property and patent counsel to Penterra, with offices in Washington, D.C. Primary contacts: Dr. Eleanor Cassidy (Lead Partner) and Brian Takata (Senior Associate). Whitfield & Grange handles the Orange Book listing strategy for Velonatib, including analysis of patents eligible for listing in connection with the sNDA submission, and is prosecuting the provisional patent application for the psoriasis method-of-treatment claim (U.S. Provisional Application No. 63/XXX,XXX, filed August 2022). Coordination with Whitfield & Grange was necessary during the active engagement period to ensure that draft USPI language (particularly the Clinical Studies and Indications and Usage sections) was consistent with the patent claims and did not inadvertently narrow or expand the scope of patent coverage. Upon reactivation, the status of the provisional patent application and any conversion to a non-provisional application should be confirmed with Whitfield & Grange.

Callendar Baines Group LLC — Regulatory and clinical strategy consultancy engaged by Penterra. Primary contacts: Dr. Priya Sundaram (Managing Director) and Dr. Neil Oxborough (Principal Consultant). Callendar Baines advised Penterra on clinical trial design for the CLARION program, prepared the FDA Type B Pre-sNDA meeting briefing document (in collaboration with Penterra's internal regulatory affairs team), and was expected to serve as the lead consultant for sNDA submission assembly. Callendar Baines' continued involvement in the CLARION-3R trial design and any future sNDA submission is expected, and coordination with their team will be necessary upon reactivation.

Thornfield Lewis LLP — Penterra's independent auditor, with engagement partner Richard Croydon, CPA. While Thornfield Lewis is not directly involved in the regulatory work underlying this engagement, their work is relevant to the extent that Penterra's 10-K and 10-Q disclosures reference the Velonatib sNDA pipeline, the status of the CLARION clinical program, and any contingent liabilities or asset impairment considerations arising from the CLARION-3 trial failure. Coordination with Thornfield Lewis is not anticipated to be necessary upon reactivation of this engagement, but is noted for completeness.

6. Reactivation Protocol

Upon receipt of written notice from the client — specifically from Lisa Moritani, Esq., General Counsel and Corporate Secretary of Penterra Pharmaceuticals Corp., or her successor or designee — to reactivate Matter No. 1018-00005, the following steps will be taken:

6.1 Staffing Confirmation

The responsible partner (Joel Strauss) will confirm staffing availability for the reactivated engagement. Specifically, the responsible partner will determine whether all previously assigned team members — including Sean Morrissey (Lead Associate) and Christopher Aiken (Working Associate) — remain with the Firm and are available to resume work on the matter without conflicts or capacity constraints. If any team member has departed the Firm or is otherwise unavailable (due to departure, leave of absence, reassignment, or other commitment), replacement staffing will be identified and communicated to the client promptly. Any replacement attorney will be brought up to speed on the matter through review of the file materials inventoried in Section 4 and the contextual summary provided in Section 5.

Any adjustments to billing rates — which may have changed during the dormancy period due to the Firm's annual rate adjustments — will be confirmed in writing to the client prior to commencement of any billable work. If the scope of services has changed materially from the original engagement (as is likely, given the need to incorporate CLARION-3R data and potentially revised sNDA strategy), updated engagement terms will be prepared and provided to the client for review and execution.

6.2 Conflicts Re-Run

A full conflicts check will be re-run through the Firm's conflicts management system to confirm that no new conflicts of interest have arisen during the dormancy period. This includes, but is not limited to, identification of any new client representations that may conflict with the Penterra engagement, any new matters involving competitors to Penterra in the JAK-inhibitor or psoriasis therapeutic space, any representations adverse to Penterra in any forum, and any personal conflicts that may have arisen for individual team members during the dormancy period. If a conflict is identified, it will be addressed in accordance with the Firm's conflicts resolution procedures and the applicable Rules of Professional Conduct, including determination of whether the conflict is consentable and, if so, obtaining appropriate waivers.

6.3 Regulatory Landscape Update Memorandum

Upon reactivation, the team will prepare a comprehensive status memorandum for the client identifying any regulatory developments that occurred during the dormancy period that may affect the sNDA filing strategy, labeling, or clinical development program. This memorandum will address, at a minimum, the following topics:

• New or revised FDA guidance documents relevant to JAK inhibitors, psoriasis drug development, or sNDA submissions, including any updates to the FDA's guidance on dermatologic drug development endpoints, patient-reported outcome measures, or active-comparator trial design.

• JAK-inhibitor class-wide labeling updates or safety communications issued by the FDA, including any modifications to the boxed Warning language, new post-marketing requirements, or safety-related label changes applicable to any member of the JAK-inhibitor class.

• Competitor developments in the psoriasis therapeutic space, including new drug approvals, label expansions, or market withdrawals, with particular attention to any new JAK-inhibitor approvals for dermatologic indications.

• Any changes to 21 C.F.R. Part 314 (Applications for FDA Approval to Market a New Drug) or Prescription Drug User Fee Act ("PDUFA") requirements that may affect the sNDA submission or review timeline.

• Advisory committee proceedings relevant to JAK inhibitors or psoriasis therapeutics, including meetings of the Dermatologic and Ophthalmic Drugs Advisory Committee or the Arthritis Advisory Committee that may have addressed JAK-inhibitor safety issues.

• Status of the pediatric Written Request and deferral reporting, including confirmation of whether Penterra submitted the required annual progress reports and whether any FDA correspondence was received regarding the pediatric study.

6.4 Work-Product Review

All prior work product — including memoranda, draft labeling documents, and correspondence — will be reviewed for continued accuracy and relevance in light of any regulatory, clinical, or competitive developments during the dormancy period. Draft USPI Rev. 3 (Item 6) and Draft Medication Guide Rev. 2 (Item 7) will be updated to incorporate CLARION-3R data (upon availability of top-line results and the clinical study report), any intervening changes to FDA labeling requirements or format specifications, any revisions to the boxed Warning or other safety-related labeling arising from post-marketing data, and any changes to the Velonatib rheumatoid arthritis labeling that occurred during the dormancy period and that must be reflected in the psoriasis sNDA labeling supplement.

6.5 Updated Engagement Terms

If the scope of services has materially changed from the original engagement — for example, if additional FDA meeting support is required (e.g., a new Type B or Type C meeting to discuss CLARION-3R results and revised sNDA filing strategy), if the sNDA strategy requires substantial revision, or if post-CLARION-3R labeling revisions are more extensive than originally anticipated — updated engagement terms will be confirmed in writing with the client. Any updated engagement letter or amendment will include a revised scope of services, a revised fee estimate reflecting the remaining work to be performed, confirmation of current billing rates, and any modifications to the staffing plan.

7. Annual Dormancy Review

Pursuant to the Firm's standard policy governing dormant matters (as set forth in the Calderwood & Harkness LLP Matter Management Policy, Section 8.4), dormant matters are reviewed annually to determine whether the matter should (a) remain on dormant status, (b) be reactivated, or (c) be formally closed. This annual review is the responsibility of the billing partner.

This matter will be reviewed on or before December 1, 2023, and annually thereafter for as long as the matter remains in dormant status.

At each annual review, the following steps will be taken:

• The billing partner (Miriam Calloway) will contact the client's designated representative (currently Lisa Moritani) to confirm the continued dormancy status and to inquire about any updates to the projected reactivation timeline.

• If no response is received from the client within thirty (30) days of the initial outreach, a formal follow-up letter will be sent by the billing partner via email and certified mail to the client's General Counsel at the address on file.

• If the matter remains dormant for more than twenty-four (24) months without any client contact or communication (i.e., beyond December 1, 2024), the Firm will initiate its standard file-closing procedures, including provision of written notice to the client, return or disposition of client files in accordance with the client's instructions and applicable retention obligations, and formal closure of the matter in the Firm's financial and administrative systems. File closure will be subject to client consent and any applicable document retention obligations, including those arising under the engagement letter, applicable Rules of Professional Conduct, and any preservation instructions received from the client.

Note regarding the December 2023 annual review: The projected reactivation timeline communicated by the client (second half of 2024, upon availability of CLARION-3R top-line data) falls within the standard annual review cycle. Accordingly, the December 2023 annual review should include a specific inquiry to the client regarding the status of CLARION-3R enrollment, any updates to the projected study completion and top-line data availability timeline, and any preliminary indications regarding whether the client anticipates reactivating the engagement in 2024. This information will inform the Firm's resource planning and ensure that appropriate staffing can be arranged in advance of reactivation.

8. Distribution and Filing

This memorandum is to be filed in the electronic matter file for 1018-00005 on the Firm's document management system. The memorandum should be filed under the "Administration" document category within the matter workspace and should be tagged with the keywords "dormancy," "file preservation," and "matter administration" to facilitate future retrieval.

Copies of this memorandum have been distributed to Joel Strauss (Responsible Partner), Sean Morrissey (Lead Associate), and Christopher Aiken (Working Associate) per the CC line of this memorandum.

No copy of this memorandum is to be sent to the client. This is an internal Firm administrative document intended solely for the Firm's matter management and file preservation purposes. The formal dormancy confirmation letter to the client — acknowledging receipt of the client's dormancy instruction, confirming the cessation of billable work, and summarizing the Firm's file preservation commitments — will be sent separately by Miriam Calloway under cover letter dated December 6, 2022. That letter constitutes the external client-facing communication regarding the dormancy of this matter.

Miriam Calloway Partner, Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 1120 Avenue of the Americas, 32nd Floor New York, NY 10036

TO:	Matter File — 1018-00005
FROM:	Miriam Calloway, Billing Partner, Healthcare & Life Sciences Practice Group
CC:	Joel Strauss, Responsible Partner; Sean Morrissey, Lead Associate; Christopher Aiken, Working Associate
DATE:	December 5, 2022
RE:	Acknowledgment of Dormancy — Penterra Pharmaceuticals Corp. / Velonatib (NDA No. 215-847) sNDA Labeling Supplement for Chronic Plaque Psoriasis Indication
Matter No.:	1018-00005
Item	Amount
Total fees invoiced (July 7 – November 30, 2022)	$287,450.00
Total fees collected	$287,450.00
Outstanding accounts receivable (A/R)	$0.00
Unbilled work-in-progress (WIP)	$0.00
Write-offs	$0.00
Disbursements invoiced	$4,212.38
Disbursements collected	$4,212.38
Outstanding disbursements	$0.00
Timekeeper	Role	Billing Rate
Joel Strauss	Responsible Partner	$1,175/hr
Miriam Calloway	Billing Partner	$1,175/hr
Sean Morrissey	Lead Associate	$725/hr
Christopher Aiken	Working Associate	$725/hr
#	Document	Date	Author(s) / Preparer(s)	Status
1	Engagement Letter (executed, countersigned by Lisa Moritani)	July 7, 2022	Joel Strauss / Lisa Moritani	Final — Executed
2	Memorandum — Regulatory Strategy for Velonatib Psoriasis sNDA	August 12, 2022	Joel Strauss, Sean Morrissey	Final
3	Memorandum — Pediatric Study Deferral Analysis (PREA Written Request)	September 8, 2022	Sean Morrissey, Christopher Aiken	Final
4	Memorandum — Analysis of REMS Assessment Requirements	September 22, 2022	Joel Strauss, Sean Morrissey	Final

5	Email — Coordination with Whitfield & Grange LLP re: Draft USPI Language and Patent Considerations	October 3, 2022	Sean Morrissey (to Brian Takata, W&G)	Sent
6	Draft Prescribing Information (USPI) — Psoriasis Indication, Annotated (Rev. 3)	October 15, 2022	Sean Morrissey, Christopher Aiken; reviewed by Joel Strauss and Dr. Karen Hessler (PPC)	DRAFT — ON HOLD (hold effective November 22, 2022)
7	Draft Medication Guide Update — Psoriasis Indication (Rev. 2)	October 20, 2022	Christopher Aiken; reviewed by Sean Morrissey	DRAFT — ON HOLD (hold effective November 22, 2022)
8	Email — CLARION-3 Top-Line Results and Implications for sNDA Filing	November 18, 2022	Joel Strauss (to Lisa Moritani, Dr. Karen Hessler)	Sent
9	Memorandum — Post-CLARION-3 Regulatory Path Analysis	November 28, 2022	Joel Strauss, Sean Morrissey	Final
10	Email — Client Hold/Dormancy Notice from PPC General Counsel	December 1, 2022	Lisa Moritani (PPC) — received	Received
11	FDA Type B Pre-sNDA Meeting Briefing Document (C&H review comments)	April 18, 2022	C&H review/markup of PPC/CBG-prepared document	Final
12	FDA Type B Pre-sNDA Meeting Minutes (C&H annotated copy)	May 19, 2022	FDA-issued minutes; C&H annotations	Final

CALDERWOOD & HARKNESS LLP
INTERNAL MEMORANDUM — FILE PRESERVATION AND MATTER ADMINISTRATION
1. Dormancy Status
Pursuant to instruction received from Lisa Moritani, Esq., General Counsel and Corporate Secretary of Penterra Pharmaceuticals Corp. ("Penterra" or "PPC"), by email dated December 1, 2022, Matter No. 1018-00005 is hereby placed on dormant status effective December 1, 2022.
The client in this matter is Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware, publicly traded on the New York Stock Exchange under the ticker symbol PTRC, and headquartered at 900 Commons Way, Suite 400, Dralvecen, New Jersey 08807.
The matter involves the Firm's engagement as outside regulatory counsel to Penterra for the preparation and submission of a supplemental New Drug Application ("sNDA") to the United States Food and Drug Administration ("FDA") seeking approval to add a new indication — moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy — to the approved labeling for VELONATIB® (velonatib hydrochloride) tablets, NDA No. 215-847. The engagement encompassed regulatory strategy development, coordination with the FDA, preparation of draft labeling materials (including the United States Prescribing Information and Medication Guide), analysis of pediatric study requirements under the Pediatric Research Equity Act ("PREA"), Risk Evaluation and Mitigation Strategy ("REMS") assessment analysis, and coordination with Penterra's other outside advisors, including intellectual property counsel and regulatory consultants.
The decision to place the matter on dormant status was triggered by the failure of the CLARION-3 confirmatory Phase III clinical trial to meet its co-primary endpoint of PASI-90 at Week 16. Top-line results from CLARION-3 were announced by Penterra on November 17, 2022. The trial did not achieve statistical significance on the PASI-90 co-primary endpoint, with 43.9% of patients receiving velonatib achieving PASI-90 at Week 16 compared to 39.7% of patients receiving an adalimumab biosimilar as the active comparator (p = 0.174). As a result of these trial results, Penterra determined that it could not proceed with sNDA submission based on the existing clinical data package and informed this Firm that all work on the sNDA should be suspended pending completion of a redesigned confirmatory trial.
Penterra has communicated its intention to pursue a redesigned confirmatory trial, designated CLARION-3R, and anticipates reactivating the engagement with this Firm upon availability of CLARION-3R top-line data. Based on current projections communicated by the client, CLARION-3R top-line data are expected in the second half of 2024, though this timeline is subject to change based on enrollment progress, clinical operations, and regulatory developments.
Effective immediately, no further billable work is to be performed on this matter without prior written authorization from the client. All timekeepers assigned to this matter should close their time entries as of November 30, 2022, and should not enter any additional time against matter number 1018-00005. Any inquiries from the client or from third parties regarding this matter should be directed to the undersigned or to Joel Strauss in the first instance.
For the record, the engagement letter governing the Firm's representation of Penterra in this matter was executed on July 7, 2022, by Joel Strauss on behalf of the Firm and countersigned by Lisa Moritani on behalf of Penterra. The engagement was active from July 7, 2022 through November 30, 2022, a period of approximately five months.
2. Financial Summary
The following table sets forth a comprehensive financial reconciliation for the engagement through the effective date of dormancy. All figures have been confirmed with the Firm's Finance Department as of the date of this memorandum and reflect all time entries, invoices, and payments processed through November 30, 2022.
The billing arrangement for this matter, as set forth in the engagement letter dated July 7, 2022, provides for blended hourly rates as follows: partners at $1,175 per hour and associates at $725 per hour. Disbursements are billed at cost. Invoices were submitted monthly and were payable within thirty (30) days of the invoice date, in accordance with Penterra's standard outside counsel payment terms.
The original estimated fee range for the full scope of the engagement (i.e., from regulatory strategy development through sNDA assembly, submission, and initial FDA correspondence related to filing review) was $475,000 to $625,000. The fees actually incurred during the active engagement period ($287,450.00) represent approximately 46% to 60% of the original budget estimate. This reflects the fact that the engagement progressed through the pre-submission phase — including strategy development, FDA meeting preparation and analysis, draft labeling preparation, pediatric deferral analysis, REMS assessment analysis, and coordination with co-counsel and consultants — but was halted prior to sNDA assembly and filing. The remaining budgeted work, including final sNDA document assembly, electronic Common Technical Document ("eCTD") review, pre-submission preparation, and post-submission support, was not performed.
No further invoices are to be submitted during the dormancy period unless specific services are requested by the client in writing. In the event the client requests limited advisory services during the dormancy period (e.g., review of a pediatric deferral annual progress report or analysis of a new FDA guidance), such work will be billed in accordance with the existing engagement terms and will be invoiced separately upon completion.
3. Staffing Record
The following timekeepers billed to Matter No. 1018-00005 during the active engagement period (July 7, 2022 through November 30, 2022):
No additional attorneys, of-counsel, paralegals, or other professional staff were assigned to this matter during the active engagement period. All substantive work was performed by the four timekeepers identified above. Joel Strauss served as the primary relationship partner and lead regulatory strategist; Miriam Calloway served as billing partner with periodic substantive involvement; Sean Morrissey served as lead associate responsible for day-to-day drafting, research, and client coordination; and Christopher Aiken served as working associate supporting research, drafting, and document preparation.
4. File Preservation — Inventory of Work Product
All physical and electronic files for Matter No. 1018-00005 are to be preserved in accordance with the Firm's document retention policy (most recently updated October 2021) and the client's specific preservation instruction, as communicated in the December 1, 2022 email from Lisa Moritani directing that all work product and correspondence be retained by the Firm pending potential reactivation of the engagement. No files are to be destroyed, archived to off-site storage, or purged from the Firm's document management system without express written authorization from both the billing partner and the client.
The following table provides a detailed inventory of all key work-product items currently on file for this matter:
The following additional notes apply to the inventory listed above:
Items 11 and 12 — FDA Type B Pre-sNDA Meeting Materials. The FDA Type B Pre-sNDA meeting (Meeting ID: FDA-2022-M-1743) was held on May 4, 2022, prior to the commencement of the Calderwood & Harkness engagement. However, the Firm received copies of both the briefing document and the official FDA meeting minutes during the engagement period. The briefing document (Item 11) was originally prepared by Penterra's internal regulatory affairs team and the Callendar Baines Group LLC, and was provided to the Firm for review and comment on April 18, 2022 (prior to engagement execution, at the request of the client, as part of the pre-engagement scoping process). The Firm's review comments were incorporated by the client team. The FDA meeting minutes (Item 12) were received from the FDA on or about May 19, 2022 and were provided to the Firm following engagement execution; the Firm prepared annotations to the minutes identifying key FDA positions and action items relevant to the sNDA filing strategy.
Items 6 and 7 — Draft USPI and Draft Medication Guide. Draft USPI Rev. 3 (Item 6) and Draft Medication Guide Rev. 2 (Item 7) were prepared by Sean Morrissey and Christopher Aiken in coordination with Dr. Karen Hessler, Senior Vice President, Regulatory Affairs, Penterra Pharmaceuticals Corp., and the Callendar Baines Group LLC (regulatory and clinical strategy consultancy), specifically Dr. Priya Sundaram (Managing Director) and Dr. Neil Oxborough (Principal Consultant). Both documents were placed on hold effective November 22, 2022, at the direction of Dr. Hessler following the announcement of the CLARION-3 top-line results, and remain in draft form pending future reactivation and updating.
Item 5 — Patent Coordination Email. The patent coordination email (Item 5) involved communication with Whitfield & Grange LLP, outside intellectual property and patent counsel to Penterra. The primary contacts at Whitfield & Grange for purposes of this matter are Dr. Eleanor Cassidy (Lead Partner) and Brian Takata (Senior Associate). The coordination concerned Orange Book listing considerations for the following patents: U.S. Patent No. 10,412,XXX (compound patent, expiration February 2034) and U.S. Patent No. 10,891,XXX (formulation patent, expiration August 2036), as well as a provisional patent application (U.S. Provisional Application No. 63/XXX,XXX, method-of-treatment claim directed to the psoriasis indication, filed August 2022). The coordination was conducted at the client's direction to ensure that the draft USPI language was consistent with the patent claims and that the Orange Book listing strategy was aligned with the sNDA submission timeline.
File Storage. All electronic files for this matter are stored on the Firm's secure document management system (Vireo Data Systems), organized within the matter workspace for 1018-00005, with appropriate access controls limited to the timekeepers identified in Section 3 above, the Firm's General Counsel, and authorized administrative personnel. Physical file materials, to the extent any exist (principally consisting of the executed original engagement letter and certain printed correspondence), are housed at the Firm's New York office, 1120 Avenue of the Americas, 32nd Floor, New York, New York 10036.
5. Key Matter Context for Future Reference
The following summary is provided to assist any future attorney reviewing this file upon reactivation of the matter. This section is intended as a reference overview and does not constitute legal advice or a comprehensive analysis of the regulatory issues involved. The memoranda and correspondence listed in Section 4 should be consulted for detailed analysis.
5.1 The Drug and Current Approval
VELONATIB® (velonatib hydrochloride) is a selective Janus kinase 1 ("JAK-1") inhibitor administered orally in tablet form, available in 5 mg and 10 mg dosage strengths. Velonatib is marketed by Penterra Pharmaceuticals Corp. under NDA No. 215-847, which was originally approved by the FDA on June 14, 2019. The currently approved indication is for the treatment of moderate-to-severe rheumatoid arthritis in adults who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs ("DMARDs"). Velonatib is approved at doses of 5 mg and 10 mg once daily for the rheumatoid arthritis indication.
Penterra is the NDA holder and sole marketer of Velonatib in the United States. For fiscal year 2022, U.S. net sales for Velonatib were approximately $1.47 billion, representing approximately 67.4% of Penterra's total revenue of $2.18 billion. Velonatib is the company's principal commercial product and the primary revenue driver.
The current approved labeling for Velonatib includes a boxed Warning addressing risks of serious infections, malignancies (including lymphoma), major adverse cardiovascular events ("MACE"), and thrombosis (including pulmonary embolism and deep vein thrombosis). This boxed Warning was added in connection with the FDA's September 2021 class-wide JAK-inhibitor labeling update, which required boxed Warnings on all approved JAK inhibitors based on post-marketing safety data from the ORAL Surveillance trial (tofacitinib) and class-wide safety considerations. The boxed Warning and associated limitations on the approved patient population (restricting use to patients with inadequate response or intolerance to one or more TNF blockers in the rheumatoid arthritis indication) are significant factors in the regulatory strategy for the psoriasis sNDA and were discussed at length in the FDA Type B Pre-sNDA meeting.
5.2 The Proposed sNDA
The proposed regulatory submission is an Efficacy Supplement — Type 10 (new indication) under 21 C.F.R. § 314.70(b), to be submitted as a supplemental New Drug Application to the existing NDA No. 215-847. The proposed new indication is for the treatment of moderate-to-severe chronic plaque psoriasis in adults who are candidates for systemic therapy or phototherapy. The proposed dose for the psoriasis indication is velonatib 10 mg once daily, which is the higher of the two approved doses for the rheumatoid arthritis indication.
The sNDA, if ultimately submitted and approved, would represent a significant label expansion for Velonatib and would position the product as a competitor to established JAK inhibitors and biologic therapies in the psoriasis market. The regulatory strategy memorandum (Item 2, dated August 12, 2022) provides a detailed analysis of the competitive landscape, regulatory pathway, and strategic considerations.
5.3 Clinical Program Summary
The clinical development program supporting the proposed psoriasis indication consists of three completed or partially completed studies and one planned redesigned study, summarized as follows:
CLARION-1 (Phase II dose-ranging study). Enrolled 287 patients with moderate-to-severe chronic plaque psoriasis. The study was completed in September 2020 and met its primary endpoint: PASI-75 response at Week 12 was achieved by 68.2% of patients in the velonatib 10 mg arm compared to 12.4% of patients in the placebo arm (p < 0.001). CLARION-1 supported dose selection (10 mg once daily) for the Phase III program and provided preliminary evidence of efficacy in the psoriasis population.
CLARION-2 (Phase III pivotal study #1). Enrolled 742 patients with moderate-to-severe chronic plaque psoriasis in a randomized, double-blind, placebo-controlled trial. The study was completed in April 2022 and met both co-primary endpoints: PASI-75 at Week 16 was achieved by 71.5% of patients receiving velonatib 10 mg compared to 9.1% of patients receiving placebo (p < 0.001); and static Physician Global Assessment ("sPGA") score of 0 or 1 at Week 16 was achieved by 58.3% of patients receiving velonatib compared to 5.7% of patients receiving placebo (p < 0.001). CLARION-2 constitutes the first of the two adequate and well-controlled Phase III trials required by the FDA for sNDA submission.
CLARION-3 (Phase III confirmatory study). Enrolled 698 patients with moderate-to-severe chronic plaque psoriasis in a randomized, double-blind, active comparator-controlled trial comparing velonatib 10 mg once daily to an adalimumab biosimilar (standard dosing). Top-line results were announced on November 17, 2022. The study failed to meet its co-primary endpoint of PASI-90 at Week 16: 43.9% of patients receiving velonatib achieved PASI-90 compared to 39.7% of patients receiving the adalimumab biosimilar (p = 0.174, not statistically significant). The secondary endpoint of PASI-75 at Week 16 was met: 69.8% of patients receiving velonatib achieved PASI-75 compared to 62.1% of patients receiving the adalimumab biosimilar (p = 0.012). The failure of CLARION-3 to meet the PASI-90 co-primary endpoint is the proximate cause of the sNDA filing delay and the resulting dormancy of this engagement. The Post-CLARION-3 Regulatory Path Analysis memorandum (Item 9, dated November 28, 2022) provides a detailed assessment of the implications of these results.
CLARION-3R (Phase III redesigned confirmatory study). In response to the CLARION-3 results, Penterra has designed a revised confirmatory study (CLARION-3R) with the following key parameters: target enrollment of approximately 950 patients (increased from 698 in CLARION-3 to improve statistical power); revised primary endpoint of PASI-75 at Week 16 (rather than PASI-90); PASI-90 at Week 16 as a key secondary endpoint (rather than co-primary); and retention of the active comparator design (adalimumab biosimilar). An IND amendment for CLARION-3R is projected to be submitted in March 2023, with study initiation projected for the third quarter of 2023 and top-line data availability projected for the second half of 2024. These projections were communicated by Lisa Moritani in her December 1, 2022 dormancy instruction email and are subject to revision.
5.4 Key FDA Interactions
The principal FDA interaction relevant to this matter was a Type B Pre-sNDA meeting held on May 4, 2022, under Meeting ID FDA-2022-M-1743. The meeting was attended by representatives of Penterra (including Dr. Karen Hessler and Dr. Priya Sundaram of Callendar Baines Group LLC) and the FDA's Division of Dermatology and Dentistry (CDER). Although the meeting occurred prior to the formal commencement of the Calderwood & Harkness engagement, the Firm reviewed and annotated the meeting minutes and incorporated the FDA's positions into the regulatory strategy memorandum (Item 2). The key outcomes of the Type B Pre-sNDA meeting were as follows:
• The FDA confirmed its requirement for two adequate and well-controlled Phase III trials supporting the psoriasis indication, consistent with the general statutory and regulatory framework for efficacy supplements.
• The FDA required that the confirmatory Phase III trial (CLARION-3) employ an active comparator design, citing the availability of approved biologic therapies for moderate-to-severe plaque psoriasis and the need to contextualize the benefit-risk profile of velonatib relative to existing treatments, particularly in light of the class-wide JAK-inhibitor safety concerns.
• The FDA specified PASI-90 as a co-primary endpoint in the confirmatory trial, reflecting evolving standards in psoriasis drug development and the Agency's view that PASI-90 provides a more clinically meaningful measure of treatment response than PASI-75 alone.
• The FDA required a minimum of 12 months of safety data in the psoriasis population as a condition of sNDA acceptance for filing.
• The FDA indicated that enhanced hepatotoxicity monitoring language would be required in the approved labeling for the psoriasis indication, based on signal detection from the CLARION-1 and CLARION-2 data (elevated ALT/AST observed in approximately 4.2% of velonatib-treated patients, compared to 1.1% of placebo-treated patients).
• The FDA required that a REMS assessment be included with the sNDA filing. Velonatib is not currently subject to a REMS under the rheumatoid arthritis approval, but the FDA indicated that the psoriasis indication — which could significantly expand the treated patient population — warrants a formal assessment of whether a REMS is necessary to ensure the benefits of the drug outweigh its risks in the broader population.
• The FDA issued a Pediatric Written Request under PREA and granted a deferral for the pediatric psoriasis study (see Section 5.5 below).
5.5 Pediatric Deferral
The FDA issued a Written Request dated June 3, 2022, for a pediatric study of velonatib in patients aged 12 to 17 years with moderate-to-severe chronic plaque psoriasis. A deferral of the pediatric study was granted on July 28, 2022, based on Penterra's request and the FDA's agreement that it was appropriate to complete and evaluate the adult clinical program before initiating pediatric studies. Under the terms of the deferral, pediatric study results are due no later than 18 months after approval of the adult psoriasis indication.
Annual progress reports on the status of the pediatric study are due by September 26 of each year during the deferral period. The first annual progress report was due September 26, 2023. Penterra's Regulatory Affairs department (Dr. Karen Hessler) is responsible for the preparation and submission of these annual progress reports. Calderwood & Harkness offered to review draft annual progress reports prior to submission, but this review was not included in the scope of the engagement letter and would constitute additional work to be billed separately if requested by the client. The pediatric deferral analysis memorandum (Item 3, dated September 8, 2022) provides a detailed assessment of the Written Request, deferral terms, and reporting obligations.
Note for future review: Any attorney reviewing this file upon reactivation should confirm with the client the status of pediatric deferral annual progress reports and whether any FDA communications regarding the pediatric study were received during the dormancy period.
5.6 Coordination with Other Advisors
The following third-party advisors have been involved in matters related to the Velonatib psoriasis sNDA, and coordination with one or more of these advisors may be required upon reactivation of the engagement:
Whitfield & Grange LLP — Outside intellectual property and patent counsel to Penterra, with offices in Washington, D.C. Primary contacts: Dr. Eleanor Cassidy (Lead Partner) and Brian Takata (Senior Associate). Whitfield & Grange handles the Orange Book listing strategy for Velonatib, including analysis of patents eligible for listing in connection with the sNDA submission, and is prosecuting the provisional patent application for the psoriasis method-of-treatment claim (U.S. Provisional Application No. 63/XXX,XXX, filed August 2022). Coordination with Whitfield & Grange was necessary during the active engagement period to ensure that draft USPI language (particularly the Clinical Studies and Indications and Usage sections) was consistent with the patent claims and did not inadvertently narrow or expand the scope of patent coverage. Upon reactivation, the status of the provisional patent application and any conversion to a non-provisional application should be confirmed with Whitfield & Grange.
Callendar Baines Group LLC — Regulatory and clinical strategy consultancy engaged by Penterra. Primary contacts: Dr. Priya Sundaram (Managing Director) and Dr. Neil Oxborough (Principal Consultant). Callendar Baines advised Penterra on clinical trial design for the CLARION program, prepared the FDA Type B Pre-sNDA meeting briefing document (in collaboration with Penterra's internal regulatory affairs team), and was expected to serve as the lead consultant for sNDA submission assembly. Callendar Baines' continued involvement in the CLARION-3R trial design and any future sNDA submission is expected, and coordination with their team will be necessary upon reactivation.
Thornfield Lewis LLP — Penterra's independent auditor, with engagement partner Richard Croydon, CPA. While Thornfield Lewis is not directly involved in the regulatory work underlying this engagement, their work is relevant to the extent that Penterra's 10-K and 10-Q disclosures reference the Velonatib sNDA pipeline, the status of the CLARION clinical program, and any contingent liabilities or asset impairment considerations arising from the CLARION-3 trial failure. Coordination with Thornfield Lewis is not anticipated to be necessary upon reactivation of this engagement, but is noted for completeness.
6. Reactivation Protocol
Upon receipt of written notice from the client — specifically from Lisa Moritani, Esq., General Counsel and Corporate Secretary of Penterra Pharmaceuticals Corp., or her successor or designee — to reactivate Matter No. 1018-00005, the following steps will be taken:
6.1 Staffing Confirmation
The responsible partner (Joel Strauss) will confirm staffing availability for the reactivated engagement. Specifically, the responsible partner will determine whether all previously assigned team members — including Sean Morrissey (Lead Associate) and Christopher Aiken (Working Associate) — remain with the Firm and are available to resume work on the matter without conflicts or capacity constraints. If any team member has departed the Firm or is otherwise unavailable (due to departure, leave of absence, reassignment, or other commitment), replacement staffing will be identified and communicated to the client promptly. Any replacement attorney will be brought up to speed on the matter through review of the file materials inventoried in Section 4 and the contextual summary provided in Section 5.
Any adjustments to billing rates — which may have changed during the dormancy period due to the Firm's annual rate adjustments — will be confirmed in writing to the client prior to commencement of any billable work. If the scope of services has changed materially from the original engagement (as is likely, given the need to incorporate CLARION-3R data and potentially revised sNDA strategy), updated engagement terms will be prepared and provided to the client for review and execution.
6.2 Conflicts Re-Run
A full conflicts check will be re-run through the Firm's conflicts management system to confirm that no new conflicts of interest have arisen during the dormancy period. This includes, but is not limited to, identification of any new client representations that may conflict with the Penterra engagement, any new matters involving competitors to Penterra in the JAK-inhibitor or psoriasis therapeutic space, any representations adverse to Penterra in any forum, and any personal conflicts that may have arisen for individual team members during the dormancy period. If a conflict is identified, it will be addressed in accordance with the Firm's conflicts resolution procedures and the applicable Rules of Professional Conduct, including determination of whether the conflict is consentable and, if so, obtaining appropriate waivers.
6.3 Regulatory Landscape Update Memorandum
Upon reactivation, the team will prepare a comprehensive status memorandum for the client identifying any regulatory developments that occurred during the dormancy period that may affect the sNDA filing strategy, labeling, or clinical development program. This memorandum will address, at a minimum, the following topics:
• New or revised FDA guidance documents relevant to JAK inhibitors, psoriasis drug development, or sNDA submissions, including any updates to the FDA's guidance on dermatologic drug development endpoints, patient-reported outcome measures, or active-comparator trial design.
• JAK-inhibitor class-wide labeling updates or safety communications issued by the FDA, including any modifications to the boxed Warning language, new post-marketing requirements, or safety-related label changes applicable to any member of the JAK-inhibitor class.
• Competitor developments in the psoriasis therapeutic space, including new drug approvals, label expansions, or market withdrawals, with particular attention to any new JAK-inhibitor approvals for dermatologic indications.
• Any changes to 21 C.F.R. Part 314 (Applications for FDA Approval to Market a New Drug) or Prescription Drug User Fee Act ("PDUFA") requirements that may affect the sNDA submission or review timeline.
• Advisory committee proceedings relevant to JAK inhibitors or psoriasis therapeutics, including meetings of the Dermatologic and Ophthalmic Drugs Advisory Committee or the Arthritis Advisory Committee that may have addressed JAK-inhibitor safety issues.
• Status of the pediatric Written Request and deferral reporting, including confirmation of whether Penterra submitted the required annual progress reports and whether any FDA correspondence was received regarding the pediatric study.
6.4 Work-Product Review
All prior work product — including memoranda, draft labeling documents, and correspondence — will be reviewed for continued accuracy and relevance in light of any regulatory, clinical, or competitive developments during the dormancy period. Draft USPI Rev. 3 (Item 6) and Draft Medication Guide Rev. 2 (Item 7) will be updated to incorporate CLARION-3R data (upon availability of top-line results and the clinical study report), any intervening changes to FDA labeling requirements or format specifications, any revisions to the boxed Warning or other safety-related labeling arising from post-marketing data, and any changes to the Velonatib rheumatoid arthritis labeling that occurred during the dormancy period and that must be reflected in the psoriasis sNDA labeling supplement.
6.5 Updated Engagement Terms
If the scope of services has materially changed from the original engagement — for example, if additional FDA meeting support is required (e.g., a new Type B or Type C meeting to discuss CLARION-3R results and revised sNDA filing strategy), if the sNDA strategy requires substantial revision, or if post-CLARION-3R labeling revisions are more extensive than originally anticipated — updated engagement terms will be confirmed in writing with the client. Any updated engagement letter or amendment will include a revised scope of services, a revised fee estimate reflecting the remaining work to be performed, confirmation of current billing rates, and any modifications to the staffing plan.
7. Annual Dormancy Review
Pursuant to the Firm's standard policy governing dormant matters (as set forth in the Calderwood & Harkness LLP Matter Management Policy, Section 8.4), dormant matters are reviewed annually to determine whether the matter should (a) remain on dormant status, (b) be reactivated, or (c) be formally closed. This annual review is the responsibility of the billing partner.
This matter will be reviewed on or before December 1, 2023, and annually thereafter for as long as the matter remains in dormant status.
At each annual review, the following steps will be taken:
• The billing partner (Miriam Calloway) will contact the client's designated representative (currently Lisa Moritani) to confirm the continued dormancy status and to inquire about any updates to the projected reactivation timeline.
• If no response is received from the client within thirty (30) days of the initial outreach, a formal follow-up letter will be sent by the billing partner via email and certified mail to the client's General Counsel at the address on file.
• If the matter remains dormant for more than twenty-four (24) months without any client contact or communication (i.e., beyond December 1, 2024), the Firm will initiate its standard file-closing procedures, including provision of written notice to the client, return or disposition of client files in accordance with the client's instructions and applicable retention obligations, and formal closure of the matter in the Firm's financial and administrative systems. File closure will be subject to client consent and any applicable document retention obligations, including those arising under the engagement letter, applicable Rules of Professional Conduct, and any preservation instructions received from the client.
Note regarding the December 2023 annual review: The projected reactivation timeline communicated by the client (second half of 2024, upon availability of CLARION-3R top-line data) falls within the standard annual review cycle. Accordingly, the December 2023 annual review should include a specific inquiry to the client regarding the status of CLARION-3R enrollment, any updates to the projected study completion and top-line data availability timeline, and any preliminary indications regarding whether the client anticipates reactivating the engagement in 2024. This information will inform the Firm's resource planning and ensure that appropriate staffing can be arranged in advance of reactivation.
8. Distribution and Filing
This memorandum is to be filed in the electronic matter file for 1018-00005 on the Firm's document management system. The memorandum should be filed under the "Administration" document category within the matter workspace and should be tagged with the keywords "dormancy," "file preservation," and "matter administration" to facilitate future retrieval.
Copies of this memorandum have been distributed to Joel Strauss (Responsible Partner), Sean Morrissey (Lead Associate), and Christopher Aiken (Working Associate) per the CC line of this memorandum.
No copy of this memorandum is to be sent to the client. This is an internal Firm administrative document intended solely for the Firm's matter management and file preservation purposes. The formal dormancy confirmation letter to the client — acknowledging receipt of the client's dormancy instruction, confirming the cessation of billable work, and summarizing the Firm's file preservation commitments — will be sent separately by Miriam Calloway under cover letter dated December 6, 2022. That letter constitutes the external client-facing communication regarding the dormancy of this matter.
Miriam Calloway Partner, Healthcare & Life Sciences Practice Group Calderwood & Harkness LLP 1120 Avenue of the Americas, 32nd Floor New York, NY 10036
TO: | Matter File — 1018-00005
FROM: | Miriam Calloway, Billing Partner, Healthcare & Life Sciences Practice Group
CC: | Joel Strauss, Responsible Partner; Sean Morrissey, Lead Associate; Christopher Aiken, Working Associate
DATE: | December 5, 2022
RE: | Acknowledgment of Dormancy — Penterra Pharmaceuticals Corp. / Velonatib (NDA No. 215-847) sNDA Labeling Supplement for Chronic Plaque Psoriasis Indication
Matter No.: | 1018-00005
Item | Amount
Total fees invoiced (July 7 – November 30, 2022) | $287,450.00
Total fees collected | $287,450.00
Outstanding accounts receivable (A/R) | $0.00
Unbilled work-in-progress (WIP) | $0.00
Write-offs | $0.00
Disbursements invoiced | $4,212.38
Disbursements collected | $4,212.38
Outstanding disbursements | $0.00
Timekeeper | Role | Billing Rate
Joel Strauss | Responsible Partner | $1,175/hr
Miriam Calloway | Billing Partner | $1,175/hr
Sean Morrissey | Lead Associate | $725/hr
Christopher Aiken | Working Associate | $725/hr
# | Document | Date | Author(s) / Preparer(s) | Status
1 | Engagement Letter (executed, countersigned by Lisa Moritani) | July 7, 2022 | Joel Strauss / Lisa Moritani | Final — Executed
2 | Memorandum — Regulatory Strategy for Velonatib Psoriasis sNDA | August 12, 2022 | Joel Strauss, Sean Morrissey | Final
3 | Memorandum — Pediatric Study Deferral Analysis (PREA Written Request) | September 8, 2022 | Sean Morrissey, Christopher Aiken | Final
4 | Memorandum — Analysis of REMS Assessment Requirements | September 22, 2022 | Joel Strauss, Sean Morrissey | Final
5 | Email — Coordination with Whitfield & Grange LLP re: Draft USPI Language and Patent Considerations | October 3, 2022 | Sean Morrissey (to Brian Takata, W&G) | Sent
6 | Draft Prescribing Information (USPI) — Psoriasis Indication, Annotated (Rev. 3) | October 15, 2022 | Sean Morrissey, Christopher Aiken; reviewed by Joel Strauss and Dr. Karen Hessler (PPC) | DRAFT — ON HOLD (hold effective November 22, 2022)
7 | Draft Medication Guide Update — Psoriasis Indication (Rev. 2) | October 20, 2022 | Christopher Aiken; reviewed by Sean Morrissey | DRAFT — ON HOLD (hold effective November 22, 2022)
8 | Email — CLARION-3 Top-Line Results and Implications for sNDA Filing | November 18, 2022 | Joel Strauss (to Lisa Moritani, Dr. Karen Hessler) | Sent
9 | Memorandum — Post-CLARION-3 Regulatory Path Analysis | November 28, 2022 | Joel Strauss, Sean Morrissey | Final
10 | Email — Client Hold/Dormancy Notice from PPC General Counsel | December 1, 2022 | Lisa Moritani (PPC) — received | Received
11 | FDA Type B Pre-sNDA Meeting Briefing Document (C&H review comments) | April 18, 2022 | C&H review/markup of PPC/CBG-prepared document | Final
12 | FDA Type B Pre-sNDA Meeting Minutes (C&H annotated copy) | May 19, 2022 | FDA-issued minutes; C&H annotations | Final

CALDERWOOD & HARKNESS LLP

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