SCHEDULE E
DEVELOPMENT PLAN
Schedule E to the Exclusive License Agreement
This Development Plan ("Schedule E" or "Development Plan") is attached to and forms an integral part of that certain Exclusive License Agreement (the "Agreement"), dated as of October 2, 2023, by and between Penterra Pharmaceuticals Corp., a Delaware corporation with its principal offices at 400 Innovation Drive, Suite 800, Cambridge, Massachusetts 02142 ("Licensor" or "Penterra"), and Meridian Bio Therapeutics Limited, a company incorporated under the laws of Hong Kong with its registered office at 28/F, Two International Finance Centre, 8 Finance Street, Central, Hong Kong ("Licensee" or "Meridian").
Effective Date: October 20, 2023
Compound: PPC-4187 (Penteracitinib), a selective Janus kinase 1 (JAK1) inhibitor.
Indication: Moderate-to-severe atopic dermatitis in adults.
Formulation: 25 mg and 50 mg film-coated oral tablets for once-daily oral administration.
Capitalized terms used but not defined herein shall have the meanings ascribed to them in the Agreement.
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1. BACKGROUND AND PURPOSE
1.1 Purpose. The purpose of this Schedule E is to set forth the Phase III clinical development plan for PPC-4187 (Penteracitinib) in the Licensed Territory (as defined below and as further described in Schedule D to the Agreement). This Development Plan describes in detail the anticipated clinical program, including trial design, enrollment targets, regulatory submission strategy, clinical supply arrangements, development governance, and development milestone trigger events as referenced in Article 5 of the Agreement. This Development Plan is intended to provide both parties with a comprehensive, good-faith roadmap for the clinical development of the Licensed Product in the Licensed Territory, and to establish the framework by which progress toward marketing authorization will be assessed, reported, and governed through the Joint Steering Committee.
1.2 Summary of Prior Development
PPC-4187 (Penteracitinib) is a novel, orally administered, selective JAK1 inhibitor discovered and initially developed by Penterra. Prior to the execution of the Agreement, Penterra completed a Phase IIb clinical trial (Study PPC-4187-201) in patients with moderate-to-severe atopic dermatitis in the United States and the European Union. The Phase IIb study enrolled a total of 420 patients across approximately 65 clinical sites in North America and Western Europe. Topline results from Study PPC-4187-201 were reported in June 2023 and demonstrated a statistically significant improvement compared to placebo (p<0.001) on the primary endpoint of the proportion of patients achieving at least a 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75) at Week 16. Secondary endpoints, including Investigator Global Assessment (IGA) 0/1 response and improvement in pruritus Numerical Rating Scale (NRS), also showed clinically meaningful and statistically significant results in both the 25 mg and 50 mg dose arms. The safety profile observed in Study PPC-4187-201 was generally consistent with the known class effects of selective JAK1 inhibitors, with no unexpected safety signals identified. The totality of Phase IIb data provides a strong scientific and clinical foundation upon which the Phase III development program described in this Schedule E will be designed and conducted.
1.3 Retained Rights of Licensor
The Licensor retains all development and commercialization rights for PPC-4187 and all Licensed Products outside the Licensed Territory, including without limitation the United States of America, Canada, the European Union and European Economic Area, the United Kingdom, Latin America, the Middle East, Africa, and all other countries and territories not specifically included in the Licensed Territory as defined in Section 2 of this Schedule E and Schedule D of the Agreement.
1.4 Licensee Responsibilities
The Licensee shall be responsible for all Phase III clinical development activities and all associated costs within the Licensed Territory, subject to oversight by the Joint Steering Committee ("JSC") as described in Article 3 of the Agreement. The Licensee shall conduct such activities in accordance with all applicable laws, regulations, and guidelines, including but not limited to ICH-GCP, local GCP requirements, and the specific regulatory requirements of each regulatory authority within the Licensed Territory. All clinical development activities shall be conducted in a manner consistent with the global development strategy for PPC-4187, as coordinated through the JSC.
2. LICENSED TERRITORY
2.1 Cross-Reference to Schedule D
The Licensed Territory is defined in and subject to the terms set forth in Schedule D to the Agreement. For convenience and clarity, the full list of countries and jurisdictions comprising the Licensed Territory is reproduced below.
2.2 Countries and Jurisdictions
The Licensed Territory comprises the following countries and jurisdictions:
1. People's Republic of China (including Hong Kong Special Administrative Region and Macau Special Administrative Region)
2. Japan
3. Republic of Korea (South Korea)
4. Australia
5. New Zealand
6. Singapore
7. Thailand
8. Malaysia
9. Indonesia
10. Philippines
11. Vietnam
12. Taiwan
2.3 Primary Regulatory Jurisdictions
The primary regulatory jurisdictions targeted for Phase III clinical development and NDA/BLA submissions under this Development Plan are as follows:
• China: National Medical Products Administration ("NMPA")
• Japan: Pharmaceuticals and Medical Devices Agency ("PMDA")
• South Korea: Ministry of Food and Drug Safety ("MFDS")
• Australia: Therapeutic Goods Administration ("TGA")
Regulatory submissions in the remaining jurisdictions within the Licensed Territory (Singapore, Thailand, Malaysia, Indonesia, Philippines, Vietnam, Taiwan, and New Zealand) will be pursued following initial approvals in the primary regulatory jurisdictions, utilizing reference country approval mechanisms and applicable local regulatory pathways as further described in Section 7 of this Development Plan.
2.4 Regional Subsidiaries
Meridian's regional subsidiaries responsible for the execution of clinical development activities within the Licensed Territory are as follows:
• People's Republic of China: Meridian Pharma (Shanghai) Co., Ltd., a wholly foreign-owned enterprise organized under the laws of the People's Republic of China, with its registered office at Unit 3801, Tower A, Lujiazui Century Financial Plaza, 1568 Century Avenue, Pudong New Area, Shanghai 200122, PRC.
• Japan: Meridian Japan K.K., a kabushiki kaisha organized under the laws of Japan, with its registered office at 15F Toranomon Hills Mori Tower, 1-23-1 Toranomon, Minato-ku, Tokyo 105-6415, Japan.
• South Korea: Meridian Korea Inc., a corporation organized under the laws of the Republic of Korea, with its registered office at 10F, ASEM Tower, 517 Yeongdong-daero, Gangnam-gu, Seoul 06164, Republic of Korea.
• Australia: Meridian Bio Australia Pty Ltd, a proprietary limited company organized under the laws of Australia, with its registered office at Level 22, 101 Collins Street, Melbourne, Victoria 3000, Australia.
Each regional subsidiary shall act as the local regulatory sponsor and operational entity responsible for the conduct of clinical trial activities, regulatory filings, and interactions with local regulatory authorities within its respective jurisdiction, under the overall direction and control of Meridian Bio Therapeutics Limited.
3. PHASE III CLINICAL DEVELOPMENT PROGRAM
3.1 Overview of Phase III Strategy
Meridian shall design and conduct one or more pivotal Phase III clinical trials sufficient to support New Drug Application (NDA) or Biologics License Application (BLA) submissions, or their regulatory equivalents, in each of the primary regulatory jurisdictions within the Licensed Territory. The Phase III program shall be designed to build upon and leverage the efficacy and safety data generated in Study PPC-4187-201 (Phase IIb), while addressing the specific regulatory requirements and evidentiary standards applicable in each jurisdiction.
The anticipated Phase III program consists of one multi-regional, pivotal Phase III clinical trial (Study PPC-4187-301) to be conducted across clinical sites in China, Japan, South Korea, and Australia, with the potential for country-specific supplemental studies as required or recommended by local regulatory authorities. In particular, Meridian acknowledges that the PMDA may require or recommend a supplemental pharmacokinetic/pharmacodynamic (PK/PD) bridging study in Japanese patients, and Meridian shall be prepared to conduct such a study concurrently with or as a pre-specified sub-study within Study PPC-4187-301, as further described in Section 3.3 below.
Meridian's Chief Medical Officer, Dr. Kenji Morimoto, M.D., Ph.D., shall serve as the overall clinical program lead for the Phase III development of PPC-4187 in the Licensed Territory. Dr. Morimoto shall be responsible for oversight of clinical trial design, conduct, and reporting, and shall serve as the primary point of contact for clinical development matters with the JSC.
Meridian shall engage Nakamura & Takeda Law Offices (Tokyo, Japan) to provide regulatory legal counsel and to manage regulatory submissions to the PMDA in Japan, including IND/CTA filings, pre-NDA meetings, and NDA submissions.
Clinical trial insurance and product liability coverage for all Phase III development activities in the Licensed Territory shall be provided by Jade Dragon Insurance Limited (Hong Kong), in accordance with the minimum coverage requirements specified in Section 12.4 of the Agreement and applicable local regulatory requirements in each jurisdiction.
3.2 Pivotal Phase III Trial — Study Design
The following sets forth the key design parameters of the pivotal Phase III clinical trial to be conducted under this Development Plan:
Study Designation: PPC-4187-301 (or such other protocol number as Meridian may designate in accordance with its internal numbering conventions; in either case, "Study PPC-4187-301" or the "Pivotal Trial").
Study Design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter Phase III study.
Indication: Treatment of moderate-to-severe atopic dermatitis in adult patients (aged ≥18 years).
Dosage Arms: The study shall include three treatment arms:
(a) PPC-4187, 25 mg, administered orally once daily;
(b) PPC-4187, 50 mg, administered orally once daily; and
(c) Matching placebo, administered orally once daily.
Randomization shall be stratified by geographic region (China, Japan, South Korea, and Australia/New Zealand) and by baseline disease severity (moderate vs. severe, as determined by baseline EASI score).
Primary Endpoint: The proportion of patients achieving at least a 75% improvement from baseline in the Eczema Area and Severity Index (EASI-75 response) at Week 16, consistent with the primary endpoint used in the Phase IIb Study PPC-4187-201. Each active dose arm (25 mg and 50 mg) shall be compared separately to placebo, with multiplicity adjustment using a pre-specified gate-keeping procedure.
Key Secondary Endpoints:
(i) Proportion of patients achieving an Investigator Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-point improvement from baseline at Week 16;
(ii) Change from baseline in pruritus Numerical Rating Scale (NRS) score at Week 4;
(iii) Proportion of patients achieving at least a 90% improvement from baseline in the Eczema Area and Severity Index (EASI-90 response) at Week 16; and
(iv) Maintenance of EASI-75 response at Week 52 (assessed during the long-term extension period).
Additional exploratory endpoints may include changes from baseline in Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and SCORing Atopic Dermatitis (SCORAD) scores, as well as pharmacokinetic assessments, biomarker analyses (including serum JAK1-dependent cytokine levels), and immunogenicity assessments.
Treatment Duration: The study shall consist of two sequential periods:
(a) A 16-week randomized, double-blind, placebo-controlled treatment period (the "Double-Blind Period"); followed by
(b) A 36-week open-label, long-term extension period (the "Extension Period"), during which all patients (including those initially randomized to placebo) shall receive active treatment with PPC-4187 at the dose determined by the investigator.
The total study duration per patient shall be approximately 52 weeks of treatment, plus a 4-week post-treatment follow-up period.
Target Enrollment: The study shall target enrollment of approximately 800 patients across all sites and all treatment arms. The sample size has been calculated to provide at least 90% statistical power to detect a clinically meaningful treatment difference between each active dose arm and placebo on the primary endpoint, based on the effect size observed in Study PPC-4187-201, at a two-sided significance level of alpha = 0.05, with appropriate adjustment for multiplicity.
Enrollment Allocation by Region:
The regional enrollment targets are designed to ensure adequate representation of Asian patient populations and to satisfy the regulatory requirements of each primary regulatory jurisdiction, including the NMPA's requirements for Chinese patient data and the PMDA's requirements for Japanese patient data.
Number of Clinical Sites: Approximately 80 to 100 investigational sites across the Licensed Territory, including academic medical centers, hospital-based clinics, and community dermatology practices with demonstrated capability in the conduct of atopic dermatitis clinical trials.
Comparator: Placebo (matching in appearance to the active study drug). Rescue medication provisions shall be incorporated into the study protocol to permit patients with disease flares during the Double-Blind Period to receive standardized rescue therapy (e.g., medium-potency topical corticosteroids) in accordance with a pre-specified rescue algorithm. Patients requiring rescue therapy shall continue in the study and shall be analyzed in accordance with the pre-specified statistical analysis plan.
Statistical Powering: The study is powered at ≥90% to detect a treatment difference on the primary endpoint at a two-sided alpha level of 0.05, based on the effect size observed in the Phase IIb Study PPC-4187-201. The statistical analysis plan (SAP) shall be finalized prior to database lock and shall specify the primary analysis population (modified intent-to-treat), methods for handling missing data (including multiple imputation and tipping-point sensitivity analyses), and the multiplicity adjustment strategy.
3.3 Additional Country-Specific Studies
In addition to the Pivotal Trial, Meridian anticipates the potential need for one or more country-specific supplemental studies to satisfy the regulatory requirements of particular jurisdictions within the Licensed Territory. The following supplemental studies are currently anticipated:
3.3.1 Japan Bridging Study (if required by PMDA)
If required or recommended by the PMDA based on the outcome of pre-IND consultation meetings, Meridian shall conduct a supplemental PK/PD bridging study in Japanese patients to evaluate the pharmacokinetic and pharmacodynamic profile of PPC-4187 in the Japanese population and to assess the potential for intrinsic ethnic factors to affect the benefit-risk profile of the Licensed Product. The anticipated parameters of such a bridging study are as follows:
• Design: Open-label, single-arm or parallel-arm PK/PD study in Japanese patients with moderate-to-severe atopic dermatitis.
• Target Enrollment: Approximately 60 patients.
• Conduct: To be conducted concurrently with, or as a pre-specified sub-study embedded within, Study PPC-4187-301, at clinical sites in Japan operated under the supervision of Meridian Japan K.K.
• Regulatory Coordination: Meridian Japan K.K. shall coordinate directly with the PMDA regarding the design, scope, and acceptability of the bridging study, with regulatory legal support provided by Nakamura & Takeda Law Offices.
The decision to conduct a standalone bridging study or to integrate bridging endpoints into the Pivotal Trial will be made following pre-IND consultation with the PMDA, anticipated in Q4 2023 or Q1 2024.
3.3.2 China Ethnic Sensitivity Evaluation
In accordance with NMPA guidance documents concerning the acceptance of overseas clinical trial data for drug registration in China, Meridian shall ensure that Study PPC-4187-301 enrolls a sufficient number of Chinese patients to enable a robust ethnic sensitivity analysis. The target enrollment of approximately 350 Chinese patients within the Pivotal Trial is designed to satisfy NMPA requirements and to provide a dataset of sufficient size for pre-specified subgroup analyses of efficacy and safety in the Chinese patient population. The results of the ethnic sensitivity analysis shall be included in the NDA submission package to the NMPA. If, based on regulatory interactions with the NMPA, additional China-specific studies or data are required, Meridian shall discuss such requirements with the JSC and amend this Development Plan accordingly.
3.3.3 ASEAN Markets
Regulatory submissions for the Licensed Product in the ASEAN member states within the Licensed Territory — namely Singapore, Thailand, Malaysia, Indonesia, the Philippines, and Vietnam — shall rely primarily on the clinical data generated from Study PPC-4187-301, supplemented by applicable reference country approvals. Meridian anticipates that regulatory submissions in these jurisdictions will be made following the receipt of marketing authorization from the NMPA (China) or the TGA (Australia), utilizing the ASEAN Common Technical Dossier (ACTD) format where applicable, and leveraging reference country approval pathways available in each jurisdiction. Country-specific clinical data requirements, if any, shall be addressed on a jurisdiction-by-jurisdiction basis in consultation with local regulatory advisors.
Regulatory submissions in Taiwan shall similarly rely on the clinical data from Study PPC-4187-301 and shall be pursued following initial approvals in the primary regulatory jurisdictions, in accordance with the regulatory requirements of the Taiwan Food and Drug Administration (TFDA).
4. CLINICAL SUPPLY
4.1 Active Pharmaceutical Ingredient Supply
Penterra shall supply the active pharmaceutical ingredient (PPC-4187 API) and all necessary reference standards for all Phase III clinical trial activities conducted under this Development Plan, pursuant to and in accordance with the terms and conditions of the Supply Agreement between the parties (the "Supply Agreement"). The API shall be manufactured and supplied in compliance with current Good Manufacturing Practice (cGMP) requirements applicable in the relevant jurisdictions.
4.2 API Supply Pricing
API supply pricing under the Supply Agreement shall be set at Penterra's fully burdened manufacturing cost plus a markup of fifteen percent (15%) for the initial three (3)-year term following the Effective Date of this Schedule E (i.e., through October 20, 2026). Pricing for API supplied after the expiration of the initial three-year term shall be as agreed by the parties in accordance with the pricing provisions of the Supply Agreement.
4.3 Contract Manufacturer
PPC-4187 API for clinical supply shall be manufactured by Alkerra Manufacturing Inc., Penterra's designated contract manufacturer, located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, United States. Alkerra Manufacturing Inc. shall be responsible for the manufacture, testing, and release of API in accordance with the specifications and quality standards set forth in the Quality Agreement described in Section 4.5 below.
4.4 Finished Dosage Form Manufacturing
Manufacturing, packaging, and labeling of the finished dosage form (25 mg and 50 mg film-coated tablets) for use in clinical trials conducted within the Licensed Territory shall be the sole responsibility of Meridian. Meridian shall engage a cGMP-compliant contract manufacturing organization within the Asia-Pacific region or such other location as Meridian deems appropriate, subject to the quality standards and oversight provisions of the Quality Agreement. All finished dosage form manufacturing shall comply with the applicable regulatory requirements of the jurisdictions in which the clinical trials are conducted.
4.5 Quality Agreement
Quality specifications for PPC-4187 API and finished dosage forms, including acceptance criteria, testing methods, stability requirements, release procedures, and deviation management, shall be governed by a Quality Agreement to be executed by the parties within sixty (60) days of the Effective Date (i.e., by no later than December 19, 2023). The Quality Agreement shall define the respective quality responsibilities of Penterra (and its contract manufacturer, Alkerra Manufacturing Inc.) and Meridian with respect to all clinical supply activities under this Development Plan.
4.6 Technology Transfer
Technology transfer of the manufacturing process for PPC-4187 finished dosage forms from Penterra (through Alkerra Manufacturing Inc.) to Meridian's designated Asia-Pacific contract manufacturer shall be completed within twenty-four (24) months of the Effective Date (i.e., by no later than October 20, 2025), in accordance with the terms and procedures set forth in the Technology Transfer Agreement between the parties (the "Technology Transfer Agreement"). The technology transfer shall encompass all information, data, know-how, and documentation reasonably necessary to enable Meridian's designated manufacturer to manufacture, test, and release PPC-4187 finished dosage forms in compliance with the applicable quality specifications and regulatory requirements.
5. ANTICIPATED DEVELOPMENT TIMELINE
5.1 Key Milestones and Timeline
The following table sets forth the key activities and anticipated dates or timeframes for the Phase III development of PPC-4187 in the Licensed Territory:
The foregoing timeline represents Meridian's current best estimate of the development trajectory for PPC-4187 in the Licensed Territory and is subject to the assumptions and qualifications set forth in Section 5.2 below.
5.2 Timeline Assumptions and Qualifications
All dates set forth in Section 5.1 are Meridian's good-faith estimates based on information available as of the Effective Date of this Schedule E, including the results and data from Study PPC-4187-201, Meridian's operational experience conducting multi-regional clinical trials in the Licensed Territory, and preliminary feedback received from regulatory authorities in anticipation of pre-IND consultation meetings. All dates are subject to change based on, among other things, regulatory authority feedback and requirements, the pace of clinical site activation and patient enrollment, clinical data outcomes, safety events, manufacturing and supply considerations, and other factors beyond Meridian's reasonable control.
Meridian shall use Commercially Reasonable Efforts (as defined in Section 1.15 of the Agreement) to achieve each milestone within the estimated timeframe set forth in the Development Plan. Meridian's obligation is one of diligence and good faith, not a guarantee of specific outcomes or dates.
Material delays or changes to the Development Plan shall be reported to and discussed with the JSC at the next regularly scheduled quarterly meeting or, if the delay exceeds six (6) months with respect to any milestone event set forth in Section 5.1, on an expedited basis (and in any event within thirty (30) days of the date on which Meridian becomes aware of such delay). In the event of a material delay, Meridian shall present to the JSC a remediation plan setting forth the steps Meridian intends to take to mitigate the impact of the delay and to bring the development program back on track to the extent commercially reasonable.
For the avoidance of doubt, Penterra retains a tie-breaking vote on JSC matters related to global intellectual property strategy, including but not limited to patent prosecution, patent enforcement, and patent licensing decisions that could affect the value or scope of the Licensed Patents globally. Meridian retains a tie-breaking vote on JSC matters related to Territory-specific commercialization and development matters, including but not limited to clinical trial design, site selection, and regulatory submission strategy within the Licensed Territory, in each case as further specified in Article 3 of the Agreement.
6. DEVELOPMENT MILESTONE PAYMENTS AND TRIGGER EVENTS
6.1 Development Milestone Payments
The following Development Milestone Payments shall be payable by Meridian to Penterra pursuant to Article 5 of the Agreement, upon the first occurrence of each milestone event set forth below:
6.2 Total Development Milestone Payments
The total aggregate Development Milestone Payments payable by Meridian to Penterra under this Section 6 shall not exceed Thirty-Two Million United States Dollars ($32,000,000), calculated as follows:
$6,000,000 (Milestone 1) + $8,000,000 (Milestone 2) + $10,000,000 (Milestone 3) + $8,000,000 (Milestone 4) = $32,000,000
6.3 One-Time Payments
Each Development Milestone Payment is payable only once, regardless of the number of Licensed Products, formulations, dosage strengths, indications, or countries in the Licensed Territory with respect to which the relevant milestone event is achieved. For illustration purposes, if Meridian achieves the Milestone 1 trigger by dosing the first patient in China, no additional Milestone 1 payment shall be owed upon the subsequent dosing of the first patient in Japan, South Korea, or Australia.
6.4 Payment Terms
Each Development Milestone Payment shall be due and payable within forty-five (45) days of the date on which Meridian provides written notice to Penterra certifying that the applicable milestone event has been achieved, together with reasonable supporting documentation (e.g., copies of regulatory acknowledgment letters, enrollment reports, or DSMB communiqués, as applicable). All Development Milestone Payments shall be made in United States Dollars by wire transfer to the account designated by Penterra in accordance with Article 5 of the Agreement.
6.5 Relationship to Other Payments
For the avoidance of doubt, the Development Milestone Payments set forth in this Section 6 are in addition to, and shall not be credited against, the following payments due under the Agreement:
(a) The upfront license fee of Eighteen Million United States Dollars ($18,000,000), payable by Meridian to Penterra upon execution of the Agreement;
(b) The Regulatory Milestone Payments, in the aggregate amount of up to Twenty-Five Million United States Dollars ($25,000,000), payable upon the achievement of specified regulatory milestones as set forth in Article 5 of the Agreement;
(c) The Commercial Milestone Payments, in the aggregate amount of up to Forty-Five Million United States Dollars ($45,000,000), payable upon the achievement of specified annual Net Sales thresholds as set forth in Article 5 of the Agreement; and
(d) Tiered royalties on Net Sales of Licensed Products in the Licensed Territory, as set forth in Article 6 of the Agreement.
6.6 Total Deal Value
The total potential deal value under the Agreement is up to One Hundred Twenty Million United States Dollars ($120,000,000), comprising:
• $18,000,000 upfront payment;
• $32,000,000 in Development Milestone Payments;
• $25,000,000 in Regulatory Milestone Payments; and
• $45,000,000 in Commercial Milestone Payments;
plus tiered royalties on Net Sales as described in the Agreement.
7. REGULATORY STRATEGY
7.1 Regulatory Submissions
Meridian shall serve as the regulatory sponsor for all Investigational New Drug Applications (INDs), Clinical Trial Applications (CTAs), and their regulatory equivalents filed in the Licensed Territory, as well as for all New Drug Applications (NDAs), Biologics License Applications (BLAs), and their regulatory equivalents submitted to regulatory authorities in the Licensed Territory. All regulatory submissions shall be prepared and filed by Meridian (through its regional subsidiaries) at Meridian's sole cost and expense.
The primary regulatory submission targets under this Development Plan are as follows, in the anticipated order of submission:
(a) NMPA (China): NDA for PPC-4187 for the treatment of moderate-to-severe atopic dermatitis in adults. Submission anticipated Q1 2026.
(b) PMDA (Japan): NDA (新薬承認申請) for PPC-4187 for the treatment of moderate-to-severe atopic dermatitis in adults. Submission anticipated Q2 2026.
(c) MFDS (South Korea): NDA for PPC-4187 for the treatment of moderate-to-severe atopic dermatitis in adults. Submission anticipated Q2–Q3 2026.
(d) TGA (Australia): Application for registration of PPC-4187 on the Australian Register of Therapeutic Goods (ARTG) for the treatment of moderate-to-severe atopic dermatitis in adults. Submission anticipated Q3 2026.
Regulatory submissions in the remaining jurisdictions within the Licensed Territory — specifically Singapore, Thailand, Malaysia, Indonesia, the Philippines, Vietnam, and Taiwan — shall follow based on reference country approvals obtained from the NMPA, PMDA, or TGA, as applicable, and shall utilize applicable local regulatory pathways, including but not limited to the ASEAN harmonized regulatory procedures, verification and abridged evaluation routes, and the TFDA's New Drug Application pathway in Taiwan. The timing and sequencing of ASEAN and Taiwan submissions shall be determined by Meridian in its reasonable discretion, in consultation with the JSC.
Penterra shall provide reasonable support to Meridian in connection with regulatory submissions in the Licensed Territory, including access to the complete Phase IIb clinical data package from Study PPC-4187-201, Chemistry, Manufacturing, and Controls (CMC) documentation, non-clinical pharmacology and toxicology study reports, and all other information and documentation constituting Licensed Know-How as set forth in Schedule B to the Agreement. Such support shall be provided in a timely manner and at no additional charge to Meridian, except as otherwise provided in the Agreement with respect to out-of-pocket expenses exceeding agreed thresholds.
7.2 Regulatory Interactions
Meridian shall provide Penterra with advance written notice of all material regulatory submissions and material regulatory correspondence in the Licensed Territory, including but not limited to IND/CTA applications, pre-NDA meeting requests and briefing documents, NDA/BLA submissions, regulatory authority questions and deficiency letters, and responses thereto. Such notice shall be provided at least ten (10) business days prior to submission, or as soon as reasonably practicable in the case of time-sensitive regulatory interactions, and shall include copies of the relevant submissions or correspondence (in English or accompanied by an English-language summary if originally prepared in another language).
The JSC shall oversee the overall regulatory strategy for PPC-4187 in the Licensed Territory, including the design of the regulatory submission package, the sequencing of regulatory filings, and the approach to regulatory authority interactions. The Joint Patent Committee ("JPC"), established pursuant to Article 10 of the Agreement, shall coordinate all patent-related regulatory matters, including but not limited to applications for patent term extensions or supplementary protection certificates, patent linkage filings (e.g., filings under China's early resolution mechanism for drug patent disputes or Japan's patent linkage system), and responses to third-party patent challenges that arise in connection with regulatory filings.
Meridian shall use commercially reasonable efforts to evaluate whether a Technology Import/Export filing is required under the People's Republic of China's Technology Import and Export Administration Regulations (技术进出口管理条例) and related implementing rules in connection with the technology transfer and licensing arrangements contemplated by the Agreement, and shall take all steps necessary to obtain any required approvals, registrations, or filings. In addition, Meridian shall use commercially reasonable efforts to obtain all necessary PRC outbound remittance approvals and foreign exchange registrations required for the payment of Development Milestone Payments, Regulatory Milestone Payments, Commercial Milestone Payments, and royalties from Meridian Pharma (Shanghai) Co., Ltd. to Penterra, including any approvals required under the State Administration of Foreign Exchange (SAFE) regulations and applicable tax withholding and treaty benefit procedures.
8. DEVELOPMENT GOVERNANCE
8.1 Joint Steering Committee Oversight
All clinical development activities under this Development Plan shall be subject to oversight by the Joint Steering Committee (JSC), established pursuant to Article 3 of the Agreement. The JSC shall comprise three (3) representatives designated by each party, for a total of six (6) members, and shall meet on a quarterly basis (or more frequently as circumstances require) to review and discuss the progress of the Phase III development program, including enrollment status, clinical data, safety information, regulatory interactions, and any proposed amendments to this Development Plan.
8.2 JSC Representatives
Penterra's JSC representatives shall be designated by:
(a) Leland J. Cho, Senior Vice President, Business Development, Penterra Pharmaceuticals Corp.; and
(b) Dr. Priya Nandakumar, Ph.D., Vice President, intellectual Property, Penterra Pharmaceuticals Corp.
The third Penterra JSC representative shall be designated by Penterra in writing to Meridian prior to the first JSC meeting.
Meridian's JSC representatives shall be designated by:
(a) Angela C.Y. Fong, Chief Executive Officer, Meridian Bio Therapeutics Limited; and
(b) Dr. Kenji Morimoto, M.D., Ph.D., Chief Medical Officer, Meridian Bio Therapeutics Limited.
The third Meridian JSC representative shall be designated by Meridian in writing to Penterra prior to the first JSC meeting.
Either party may replace its designated JSC representatives at any time upon written notice to the other party.
8.3 Development Sub-Committee
The JSC may, at its discretion, establish a development sub-committee (the "Development Sub-Committee") to manage day-to-day clinical operations, data review, safety monitoring, and regulatory interactions related to the Phase III development program. The Development Sub-Committee shall report to and operate under the authority of the JSC, and shall comprise such members as the JSC may designate from time to time.
8.4 Quarterly Development Reports
Meridian shall provide quarterly written development progress reports to the JSC, delivered no later than fifteen (15) business days following the end of each calendar quarter. Each quarterly report shall include, at a minimum, the following information:
(a) Enrollment status, including the number of patients screened, enrolled, randomized, and discontinued, by clinical site and by country;
(b) Safety updates, including summaries of serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), and any safety signals identified by the DSMB or the clinical team;
(c) Timeline adherence, including a comparison of actual progress against the milestones and dates set forth in Section 5.1 of this Development Plan, together with an explanation of any material deviations and proposed remediation steps;
(d) Budget tracking, including a summary of development expenditures incurred during the quarter and cumulative expenditures to date, compared against the approved development budget; and
(e) Regulatory interaction updates, including summaries of any material correspondence or meetings with NMPA, PMDA, MFDS, TGA, or other regulatory authorities in the Licensed Territory.
8.5 Amendments to Development Plan
Material amendments to this Development Plan shall require approval by the JSC. For purposes of this Section 8.5, a "material amendment" includes, without limitation, any change to the primary endpoint or pivotal study design of Study PPC-4187-301, any addition or elimination of a treatment arm, any significant change to the target enrollment or enrollment allocation by region, and any delay of more than six (6) months to any milestone event set forth in Section 5.1.
9. PHARMACOVIGILANCE AND SAFETY REPORTING
9.1 Pharmacovigilance Agreement
The exchange of safety data and the reporting of adverse events during Phase III development of PPC-4187 in the Licensed Territory shall be governed by the Pharmacovigilance Agreement to be executed between the parties (the "Pharmacovigilance Agreement"), which shall set forth in detail the respective responsibilities, procedures, timelines, and data formats for safety data exchange, adverse event reporting, and signal detection. The Pharmacovigilance Agreement shall be executed concurrently with or promptly following the execution of the Agreement and in any event prior to the dosing of the first patient in Study PPC-4187-301.
9.2 Local Safety Reporting
Meridian shall be responsible for all local safety reporting to regulatory authorities within the Licensed Territory, including but not limited to the NMPA, PMDA, MFDS, TGA, and the regulatory authorities of all other jurisdictions in the Licensed Territory in which clinical trials are conducted or marketing authorizations are obtained. All safety reports shall be submitted in compliance with applicable local regulations and in accordance with the ICH E2A, E2B(R3), E2C(R2), and E2D guidelines, as applicable.
9.3 Global Safety Database
Penterra shall maintain the global safety database for PPC-4187. Meridian shall report all serious adverse events (SAEs) occurring in clinical trials conducted under this Development Plan to Penterra within twenty-four (24) hours of Meridian becoming aware of such SAE, in accordance with the format and procedures specified in the Pharmacovigilance Agreement and consistent with ICH E2B(R3) and E2D standards. Penterra shall be responsible for the assessment and management of the aggregate global safety profile of PPC-4187, including the preparation and distribution of Development Safety Update Reports (DSURs) and Periodic Safety Update Reports (PSURs) or Periodic Benefit-Risk Evaluation Reports (PBRERs), as applicable.
9.4 Data Safety Monitoring Board
An independent Data Safety Monitoring Board (DSMB) shall be established for Study PPC-4187-301, composed of independent members with appropriate expertise in dermatology, biostatistics, and clinical trial safety monitoring. The DSMB shall operate under a written charter specifying its membership, meeting schedule, operating procedures, and decision-making criteria, including pre-specified rules for recommending study continuation, modification, or early termination based on safety and/or futility analyses. The DSMB charter shall be agreed upon by both parties through the JSC prior to the initiation of patient enrollment in the Pivotal Trial.
10. INTELLECTUAL PROPERTY CONSIDERATIONS DURING DEVELOPMENT
10.1 Licensed Patent Portfolio
The patent portfolio covering PPC-4187, as licensed to Meridian under the Agreement, is set forth in Schedule A to the Agreement (Licensed Patents). Meridian acknowledges that the Licensed Patents include, without limitation, the following key patents relevant to the development and commercialization of PPC-4187 in the Licensed Territory:
Composition-of-Matter Patents:
The foregoing expiration dates are stated before any patent term extension, supplementary protection certificate, or equivalent extension of patent term that may be available under applicable law.
Crystalline Form Patent:
Additional Licensed Patents, including patents and patent applications covering methods of use, formulations, and manufacturing processes, are set forth in full in Schedule A.
10.2 Joint Patent Committee
The Joint Patent Committee (JPC), established pursuant to Article 10 of the Agreement, shall oversee the prosecution, maintenance, and enforcement of the Licensed Patents in the Licensed Territory during the development period, including the filing and prosecution of divisional, continuation, and counterpart applications; the payment of maintenance and annuity fees; and the initiation and management of any enforcement actions against third-party infringers.
10.3 Improvement Patents and Joint Inventions
Any inventions, discoveries, or improvements arising from Phase III development activities conducted under this Development Plan shall be handled in accordance with the Agreement's provisions on improvement patents and joint inventions, as set forth in Article 10 of the Agreement. Meridian shall promptly disclose to Penterra and the JPC any patentable inventions arising from the Phase III program, and the parties shall cooperate in good faith to determine the appropriate ownership, prosecution, and licensing arrangements for such inventions.