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SCHEDULE B

LICENSED KNOW-HOW

Schedule B to the Exclusive License Agreement (the "Agreement") dated October 2, 2023, effective October 20, 2023 (the "Effective Date"), by and between Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware, having its principal place of business at 900 Innovation Drive, Suite 400, Cambridge, Massachusetts 02142 ("Licensor"), and Meridian Bio Therapeutics Limited, a company incorporated under the laws of Hong Kong, having its registered office at 18/F, Blossom Tower, 88 Queen's Road Central, Hong Kong SAR ("Licensee").

This Schedule B sets forth the Licensed Know-How as defined in Section 1.47 of the Agreement. All capitalized terms used but not defined herein shall have the meanings ascribed to them in the Agreement. The Licensed Know-How described in this Schedule B is licensed to Licensee on an exclusive basis within the Territory (as defined in Schedule D to the Agreement) for the development, manufacture, and commercialization of Licensed Products containing compound PPC-4187 (Penteracitinib), a selective Janus kinase 1 (JAK1) inhibitor, in accordance with and subject to the terms and conditions of the Agreement. For the avoidance of doubt, references to "Licensed Know-How" in this Schedule B include all data, information, results, reports, documents, methods, processes, techniques, formulations, compositions, specifications, protocols, and other proprietary know-how described herein, in each case to the extent owned or controlled by Licensor as of the Effective Date or generated or obtained by Licensor during the term of the Agreement in accordance with Section 11 below.

The Licensed Know-How is organized into the following categories, each of which is described in detail in the sections that follow.

1. Pre-Clinical Data Packages

The Licensed Know-How includes the following pre-clinical data packages generated by or on behalf of Licensor in connection with the research and development of PPC-4187 (Penteracitinib).

1.1 In Vitro Pharmacology Data

The Licensed Know-How includes all in vitro pharmacology data generated for PPC-4187, comprising the following:

(a) Selective JAK1 inhibitor activity assays, including half-maximal inhibitory concentration (IC50) and half-maximal effective concentration (EC50) data, together with full selectivity panels comparing inhibitory activity of PPC-4187 against JAK1 relative to JAK2, JAK3, and TYK2, including data from biochemical kinase assays, cellular signaling assays (STAT phosphorylation), and whole blood cytokine stimulation assays;

(b) Mechanism of action studies for PPC-4187, including binding kinetics data (kon, koff, KD), ATP-competitive binding analyses, co-crystallography data (if any), and functional selectivity assessments demonstrating the preferential inhibition of JAK1-dependent signaling pathways relevant to atopic dermatitis pathobiology;

(c) In vitro absorption, distribution, metabolism, and excretion (ADME) data, including without limitation: (i) metabolic stability data in hepatic microsomes and hepatocytes across relevant species (human, rat, dog, monkey); (ii) cytochrome P450 (CYP450) inhibition profiles (reversible and time-dependent) against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5; (iii) CYP450 induction profiles (CYP1A2, CYP2B6, CYP3A4); (iv) plasma protein binding data across species, including equilibrium dialysis and ultrafiltration data; (v) blood-to-plasma concentration ratios; and (vi) permeability assessments, including Caco-2 cell monolayer transport studies and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate and inhibitor evaluations.

1.2 In Vivo Pharmacology Data

The Licensed Know-How includes all in vivo pharmacology data generated for PPC-4187, comprising the following:

(a) Preclinical efficacy studies conducted in validated atopic dermatitis animal models, including, without limitation, oxazolone-induced dermatitis models in BALB/c mice, MC903 (calcipotriol)-induced atopic dermatitis models in mice, and NC/Nga mouse spontaneous dermatitis models, together with all study protocols, raw data, histopathological assessments, immunohistochemistry results, cytokine profiling data, and final study reports;

(b) Pharmacokinetic (PK) studies characterizing the oral bioavailability, elimination half-life (t½), volume of distribution (Vd), systemic clearance (CL), maximum plasma concentration (Cmax), time to maximum concentration (Tmax), and area under the plasma concentration-time curve (AUC) of PPC-4187 across multiple species, including rat, dog, and cynomolgus monkey, following single-dose and multi-dose oral and intravenous administration;

(c) Dose-response and dose-ranging study reports establishing the pharmacological dose-response relationship for PPC-4187 in the relevant animal models, including determination of minimum effective dose (MED), maximum tolerated dose (MTD), and no-observed-adverse-effect level (NOAEL) from pharmacology studies.

1.3 Toxicology Data

The Licensed Know-How includes all toxicology data generated for PPC-4187, comprising the following:

(a) Single-dose (acute) toxicology study reports conducted in at least two mammalian species (rat and dog) in compliance with Good Laboratory Practice (GLP) regulations (21 C.F.R. Part 58; OECD Principles of GLP), including determination of approximate lethal dose, target organ identification, and full histopathological evaluations;

(b) Repeat-dose (subacute and chronic) toxicology study reports, including 14-day, 28-day, 90-day, and 6-month repeat-dose oral toxicity studies in rat and dog, conducted in compliance with GLP, including NOAEL and lowest-observed-adverse-effect level (LOAEL) determinations, hematology, clinical chemistry, urinalysis, organ weight data, and complete histopathological evaluations of all major organ systems;

(c) Genotoxicity study reports, including: (i) bacterial reverse mutation assay (Ames test) using Salmonella typhimurium and Escherichia coli strains; (ii) in vitro chromosomal aberration assay in human peripheral blood lymphocytes or Chinese hamster ovary (CHO) cells; and (iii) in vivo micronucleus assay in rodent bone marrow or peripheral blood, each conducted in compliance with GLP and applicable ICH S2(R1) guidelines;

(d) Reproductive and developmental toxicology study reports, including: (i) fertility and early embryonic development studies (Segment I) in rats; (ii) embryo-fetal development studies (Segment II) in rats and rabbits; and (iii) pre- and postnatal development studies (Segment III) in rats, all conducted in accordance with ICH S5(R3) and GLP;

(e) Carcinogenicity study data, to the extent available as of the Effective Date, including any completed or ongoing 2-year rodent carcinogenicity bioassays, 6-month rasH2 transgenic mouse carcinogenicity studies, and any carcinogenicity risk assessments prepared in accordance with ICH S1A, S1B(R1), and S1C(R2);

(f) Safety pharmacology study reports, including: (i) cardiovascular safety pharmacology studies (hERG channel inhibition assay, telemetrized dog cardiovascular study evaluating blood pressure, heart rate, and electrocardiographic parameters including QTc interval); (ii) respiratory safety pharmacology studies (whole-body plethysmography in rats evaluating respiratory rate, tidal volume, and minute ventilation); and (iii) central nervous system (CNS) safety pharmacology studies (modified Irwin test or functional observational battery in rats);

(g) Toxicokinetic (TK) data collected as part of the GLP toxicology studies described above, including systemic exposure (AUC, Cmax) at each dose level, exposure multiples relative to the projected or observed human therapeutic exposure, assessment of accumulation upon repeat dosing, and any sex-based differences in exposure.

1.4 Pharmacology and Toxicology Summary Reports

The Licensed Know-How includes the following summary and compilation documents relating to PPC-4187 pharmacology and toxicology:

(a) The current edition of the Investigator's Brochure for PPC-4187 as of the Effective Date (Edition 4, dated July 15, 2023), including all appendices, addenda, and safety updates issued through the Effective Date;

(b) Non-clinical overview and non-clinical summary documents prepared by or on behalf of Licensor for Investigational New Drug (IND) application filings with the United States Food and Drug Administration (FDA) and Clinical Trial Application (CTA) filings with applicable regulatory authorities, including the Integrated Summary of Safety (ISS) and Integrated Summary of Efficacy (ISE) components to the extent relating to non-clinical data.

2. Clinical Data Packages

The Licensed Know-How includes the following clinical data packages generated by or on behalf of Licensor from clinical trials conducted with PPC-4187 (Penteracitinib) in human subjects.

2.1 Phase I Clinical Data

(a) Phase I single ascending dose (SAD) study report (Study PPC-4187-101): a first-in-human, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics of single oral doses of PPC-4187 (ranging from 1 mg to 200 mg) in healthy adult volunteers, including the complete clinical study report (CSR), all appendices, individual patient-level data, and statistical analyses;

(b) Phase I multiple ascending dose (MAD) study report (Study PPC-4187-102): a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics of multiple ascending oral doses of PPC-4187 (ranging from 10 mg to 100 mg once daily for 14 consecutive days) in healthy adult volunteers, including the complete CSR, all appendices, individual patient-level data, and statistical analyses;

(c) Phase I food-effect study report (Study PPC-4187-103): an open-label, randomized, two-period crossover study evaluating the effect of a high-fat meal on the pharmacokinetics of a single 50 mg oral dose of PPC-4187 in healthy adult volunteers, including the complete CSR and bioequivalence assessments;

(d) Phase I drug-drug interaction (DDI) study reports (Studies PPC-4187-104 and PPC-4187-105): open-label, fixed-sequence studies evaluating the effect of PPC-4187 on the pharmacokinetics of probe substrates for major CYP enzymes (e.g., midazolam for CYP3A4, caffeine for CYP1A2) and the effect of a strong CYP3A4 inhibitor (itraconazole) on PPC-4187 pharmacokinetics, including complete CSRs and clinical pharmacology assessments;

(e) Phase I PK/PD data, including plasma concentration-time profiles, individual and population pharmacokinetic model analyses (NONMEM or equivalent), exposure-response analyses for safety biomarkers (including lymphocyte counts and lipid parameters), and PK/PD modeling reports prepared by Licensor's quantitative clinical pharmacology group.

2.2 Phase IIa Clinical Data

(a) Phase IIa proof-of-concept study report (Study PPC-4187-200): a randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of PPC-4187 administered orally at 25 mg and 50 mg once daily for 12 weeks in approximately 120 adult patients with moderate-to-severe atopic dermatitis, including the complete CSR, all appendices, and individual patient-level datasets;

(b) Preliminary efficacy data from the Phase IIa study, including Eczema Area and Severity Index (EASI) scores, Investigator's Global Assessment (IGA) responses, pruritus Numerical Rating Scale (NRS) data, and Dermatology Life Quality Index (DLQI) assessments, together with preliminary safety data including adverse event listings, serious adverse event narratives, and laboratory parameter analyses.

2.3 Phase IIb Clinical Data — Study PPC-4187-201

The Licensed Know-How includes the complete data package from the pivotal Phase IIb clinical trial conducted by Licensor, Study PPC-4187-201, as described in detail below:

(a) Complete Clinical Study Report (CSR): The full CSR for Penterra-sponsored Study PPC-4187-201 (Protocol No. PPC-4187-201, Version 4.0, dated January 8, 2022), including all appendices (16.1 through 16.4), in-text tables and figures, individual patient data listings, and all amendments to the study protocol;

(b) Study Design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study conducted at 62 investigational sites across the United States, Canada, Germany, France, and the United Kingdom, evaluating PPC-4187 in adult patients (≥18 years of age) with moderate-to-severe atopic dermatitis (defined as EASI ≥16, IGA ≥3, and body surface area involvement ≥10%);

(c) Study Size: A total of 420 patients enrolled and randomized in a 1:1:1 ratio to receive PPC-4187 25 mg once daily (n=140), PPC-4187 50 mg once daily (n=140), or matching placebo once daily (n=140) for a treatment period of 16 weeks, followed by a 4-week safety follow-up period;

(d) Dosage Strengths Evaluated: 25 mg and 50 mg film-coated tablets of PPC-4187 (Penteracitinib), administered once daily by oral route. Matching placebo tablets were manufactured to be identical in appearance, size, and weight to the active tablets;

(e) Primary Endpoint: The proportion of patients achieving EASI-75 (i.e., ≥75% improvement from baseline in the Eczema Area and Severity Index) at Week 16;

(f) Topline Results (June 2023): The study met its primary endpoint with statistically significant improvement versus placebo for EASI-75 response rate at Week 16 in both the 25 mg and 50 mg dose groups. Specifically, EASI-75 response rates at Week 16 were 46.4% for PPC-4187 50 mg (p<0.001 vs. placebo), 33.6% for PPC-4187 25 mg (p<0.001 vs. placebo), and 12.9% for placebo. Key secondary endpoints, including IGA 0/1 response, change from baseline in pruritus NRS, and EASI-90, were also statistically significant for both active dose groups versus placebo after multiplicity adjustment;

(g) Individual Patient-Level Datasets: Complete individual patient-level datasets in SAS transport file format, including Study Data Tabulation Model (SDTM) datasets, Analysis Data Model (ADaM) datasets, and corresponding define.xml files, all prepared in accordance with the Clinical Data Interchange Standards Consortium (CDISC) standards;

(h) Statistical Analysis Plan (SAP) and Statistical Outputs: The final, approved SAP (Version 2.0, dated March 15, 2023), together with all statistical output tables, figures, and listings (TFLs) generated in support of the CSR, annotated case report forms (aCRFs), and the randomization scheme and code;

(i) Safety Database: The complete safety database for Study PPC-4187-201, including all adverse event data (coded using MedDRA Version 26.0), serious adverse event data and narratives, laboratory data (hematology, chemistry, lipids, liver function tests, lymphocyte subsets), vital signs, 12-lead electrocardiogram (ECG) data, and physical examination findings;

(j) Data Monitoring Committee (DMC) Reports and Meeting Minutes: All reports prepared for and minutes of meetings of the independent Data Monitoring Committee (chaired by Professor Ian R. Whitfield, M.D., University of Edinburgh) convened in connection with Study PPC-4187-201, including safety reports, interim analysis reports, and the DMC's recommendations regarding study continuation;

(k) Site-Level Data, Investigator Lists, and Informed Consent Templates: Complete site-level enrollment and data quality metrics, the list of all principal investigators and sub-investigators at each study site, model informed consent forms and institutional review board / ethics committee (IRB/EC) approval letters to the extent in Licensor's possession.

2.4 Regulatory Submissions and Correspondence

(a) All Investigational New Drug (IND) application filings submitted by Licensor to the United States Food and Drug Administration (FDA) in connection with PPC-4187 (IND No. 147823), including the original IND submission, all IND amendments and supplements, and all FDA correspondence, including acknowledgment letters, clinical hold notifications (if any), information requests, and Licensor's responses thereto;

(b) All Clinical Trial Application (CTA) filings submitted by Licensor to EU Member State regulatory authorities and the European Medicines Agency (EMA), as applicable, including initial CTA submissions, substantial amendments, and all regulatory authority correspondence, notifications, and responses relating thereto;

(c) Annual IND safety reports submitted to the FDA and corresponding annual safety update reports submitted to EU regulatory authorities for PPC-4187;

(d) Minutes and correspondence from all formal regulatory authority meetings relating to PPC-4187, including pre-IND meeting(s), end-of-Phase II meeting(s), and any Type A, Type B, or Type C meeting(s) with the FDA, as well as any Scientific Advice or Protocol Assistance meetings with the EMA or National Competent Authorities, in each case to the extent relating to PPC-4187 and in the possession or control of Licensor.

2.5 Clinical Supply Records

(a) Complete clinical supply chain documentation for PPC-4187 clinical trial material, including records of manufacture (batch production records and certificates of analysis), quality release documentation, distribution records (chain of custody logs, shipping records, temperature monitoring data), returns and destruction records, and drug accountability reconciliation reports for clinical trial material used in the Phase I, Phase IIa, and Phase IIb studies referenced in Sections 2.1 through 2.3 above;

(b) Certificates of analysis for all clinical trial material batches, specifications applied to clinical trial material, and any deviations, out-of-specification (OOS) investigations, or corrective and preventive actions (CAPAs) relating to clinical supply of PPC-4187.

3. Proprietary Manufacturing Process

The Licensed Know-How includes the following proprietary manufacturing process information relating to the synthesis, formulation, and manufacture of PPC-4187 (Penteracitinib) active pharmaceutical ingredient and drug product.

3.1 Active Pharmaceutical Ingredient (API) Manufacturing Process

(a) The detailed synthetic route and process description for the manufacture of PPC-4187 API, including the complete sequence of chemical reactions, all synthetic intermediates (designated INT-1 through INT-7), starting materials (including structural characterization and sourcing information), reagents, catalysts, and solvents used at each synthetic step, together with reaction conditions (temperature, pressure, pH, reaction time, stoichiometry, and order of addition);

(b) Identification and characterization of all process parameters, critical process parameters (CPPs), and critical quality attributes (CQAs) for each step of the API synthetic process, as determined through quality-by-design (QbD) principles, design of experiments (DoE), and process characterization studies, including proven acceptable ranges (PARs) and normal operating ranges (NORs) for each CPP;

(c) Process validation reports for the PPC-4187 API manufacturing process as conducted at the facility of Alkerra Manufacturing Inc. (contract manufacturing organization), located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, United States, including prospective process validation data from a minimum of three consecutive commercial-scale batches, performance qualification reports, and continued process verification protocols and data;

(d) Executed batch records for representative commercial-scale API batches manufactured at Alkerra Manufacturing Inc., including all in-process testing data, yield calculations, and deviation reports;

(e) Specifications for all starting materials, synthetic intermediates, reagents, catalysts, and solvents used in the API manufacturing process, together with certificates of analysis from qualified suppliers and approved supplier qualification documentation;

(f) In-process control (IPC) testing procedures and acceptance criteria at each stage of the synthetic process, including identity testing, purity testing, moisture content, and other quality-relevant measurements performed during manufacturing;

(g) Complete impurity profiles for PPC-4187 API, including: (i) all identified and unidentified process-related impurities (with structures where elucidated), qualification and toxicological assessment data, and control strategies; (ii) degradation products identified through forced degradation studies; (iii) residual solvent levels (per ICH Q3C(R8)); and (iv) elemental impurity assessments (per ICH Q3D(R2));

(h) Scale-up and technology transfer documentation tracing the progression of the PPC-4187 API manufacturing process from laboratory scale (gram quantities) through pilot scale to commercial scale (kilogram quantities), including scale-up risk assessments, comparative batch analyses, and technology transfer protocols and reports.

3.2 Drug Product Manufacturing Process

(a) Formulation development reports for the 25 mg and 50 mg film-coated tablet dosage forms of PPC-4187, including pre-formulation studies, excipient compatibility studies, prototype formulation screening, formulation optimization studies, and final formulation composition (qualitative and quantitative);

(b) Detailed manufacturing process descriptions for the PPC-4187 25 mg and 50 mg film-coated tablet formulations, including the following unit operations: (i) dispensing and sieving of active ingredient and excipients; (ii) dry blending and lubrication; (iii) wet or dry granulation (as applicable); (iv) milling and screening of granulate; (v) final blending; (vi) tablet compression; and (vii) aqueous film-coating, together with process flow diagrams for each unit operation;

(c) Identification and characterization of all process parameters, CPPs, and CQAs for drug product manufacture at each unit operation, including blend uniformity targets, granulation endpoint parameters, compression force ranges, tablet weight and hardness specifications, film-coat weight gain targets, and associated proven acceptable ranges;

(d) Process validation reports for the 25 mg and 50 mg tablet strengths, including prospective process validation data from a minimum of three consecutive commercial-scale batches at each strength, media fill and environmental monitoring data for the manufacturing suite, and continued process verification protocols;

(e) Executed batch manufacturing records for representative drug product batches at each tablet strength, including all in-process testing data, deviation and investigation reports, and reconciliation records;

(f) Equipment specifications and tooling details for all major manufacturing equipment utilized in drug product manufacture, including blender specifications, granulator specifications, tablet press specifications (rotary press model, punch and die tooling dimensions), and coating pan specifications, sufficient to enable Licensee to replicate or source equivalent equipment for commercial manufacturing;

(g) Excipient specifications for all excipients used in the 25 mg and 50 mg film-coated tablet formulations, together with approved supplier lists, supplier qualification documentation, and certificates of analysis for excipient lots used in validation batches;

(h) Packaging and labeling specifications for primary and secondary packaging configurations, including: (i) PVC/PVDC-aluminum blister packaging (configurations of 7, 14, 28, and 30 tablets); (ii) high-density polyethylene (HDPE) bottles with child-resistant closure and desiccant (configurations of 30 and 90 tablets); and (iii) secondary carton and labeling specifications, including artwork files and packaging component specifications;

(i) Cleaning validation studies and equipment hold-time studies for all product-contact manufacturing equipment used in PPC-4187 drug product manufacture, including determination of maximum allowable carryover limits, cleaning agent specifications, and validated cleaning procedures.

3.3 Alkerra Manufacturing Inc. — CMO Documentation

(a) The current manufacturing site master file for Alkerra Manufacturing Inc., 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, as prepared in accordance with PIC/S and WHO guidelines, describing the facility layout, equipment, utilities, quality systems, and personnel qualifications relevant to the manufacture of PPC-4187 API;

(b) Quality system documentation applicable to PPC-4187 API manufacture at the Alkerra facility, including relevant standard operating procedures (SOPs), quality manual excerpts, change control records, deviation and CAPA records, annual product quality review (APQR) reports, and supplier qualification records, in each case to the extent relating to PPC-4187 and to the extent Licensor has the right to disclose such documentation under its contractual arrangements with Alkerra Manufacturing Inc.;

(c) Regulatory inspection history and correspondence for the Alkerra Manufacturing Inc. facility as it relates to PPC-4187, including FDA pre-approval inspection (PAI) observations (if any), FDA Form 483 observations and Alkerra responses, EU Qualified Person (QP) audit reports, and any Establishment Inspection Reports (EIRs) in Licensor's possession;

(d) Environmental, health, and safety (EHS) data pertinent to PPC-4187 API manufacturing processes, including material safety data sheets (SDS) for PPC-4187 API, intermediates, and hazardous reagents, occupational exposure limit (OEL) assessments and control banding evaluations for PPC-4187, and waste stream characterization and disposal protocols.

4. Analytical Methods

The Licensed Know-How includes the following validated analytical methods, method validation reports, and reference standard documentation relating to PPC-4187 API and drug product.

4.1 API Analytical Methods

(a) Validated analytical methods for the following quality attributes of PPC-4187 API: (i) identity (by infrared spectroscopy (IR) and high-performance liquid chromatography (HPLC) retention time comparison); (ii) assay/potency (by HPLC with UV detection); (iii) purity and related substances (by gradient HPLC); (iv) chiral purity (by chiral HPLC or chiral supercritical fluid chromatography (SFC)); (v) residual solvents (by headspace gas chromatography (GC)); (vi) water content (by Karl Fischer titration); (vii) heavy metals and elemental impurities (by inductively coupled plasma mass spectrometry (ICP-MS), per ICH Q3D(R2)); and (viii) particle size distribution (by laser diffraction);

(b) Analytical method validation reports for each of the foregoing methods, demonstrating compliance with ICH Q2(R1) (Validation of Analytical Procedures: Text and Methodology) guidelines for the applicable validation characteristics, including specificity, linearity, range, accuracy, precision (repeatability and intermediate precision), detection limit, quantitation limit, and robustness, as applicable;

(c) Reference standard characterization and certificate of analysis for the PPC-4187 primary reference standard (Penterra Reference Standard Lot No. PRS-001, established March 2020), including characterization by mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy (¹H and ¹³C), elemental analysis, HPLC purity, chiral purity, water content, residual solvent content, and assigned potency value.

4.2 Drug Product Analytical Methods

(a) Validated analytical methods for the following quality attributes of PPC-4187 25 mg and 50 mg film-coated tablets: (i) identity (by HPLC retention time and UV spectrum comparison); (ii) assay (by HPLC with UV detection); (iii) content uniformity (by HPLC, in accordance with USP <905>); (iv) dissolution (by HPLC, using USP Apparatus II (paddle), 50 rpm, 900 mL 0.1N HCl, at 37°C ± 0.5°C); (v) related substances and degradation products (by gradient HPLC); (vi) moisture content (by Karl Fischer titration or loss on drying); (vii) hardness (by tablet hardness tester); (viii) friability (by USP <1216> friability testing); and (ix) film-coat integrity (by visual inspection and disintegration testing);

(b) Analytical method validation reports for each of the foregoing drug product analytical methods, demonstrating compliance with ICH Q2(R1) guidelines;

(c) Compendial test methods and specifications applicable to PPC-4187 drug product testing, including references to United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.), and Japanese Pharmacopoeia (JP) general chapters and monographs, as applicable to the dosage form and excipients.

4.3 Cleaning and Residual Method Validation

(a) Validated analytical methods for cleaning verification and validation at the drug product and API manufacturing facilities, including swab sampling methods and rinse sampling methods for PPC-4187 residue detection on product-contact equipment surfaces;

(b) Method validation reports for the cleaning verification/validation analytical methods, demonstrating specificity, linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), swab recovery factors, and rinse recovery factors, and confirming the methods' suitability to detect PPC-4187 at levels below the calculated maximum allowable carryover.

4.4 Bioanalytical Methods

(a) Validated bioanalytical methods for the quantitative determination of PPC-4187 and its primary metabolites (M1, M2, and M3) in human plasma, serum, and urine, utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with stable isotope-labeled internal standards (PPC-4187-d6);

(b) Bioanalytical method validation reports for each matrix, demonstrating compliance with applicable FDA Guidance for Industry on Bioanalytical Method Validation (May 2018) and EMA Guideline on Bioanalytical Method Validation (EMEA/CHMP/EWP/192217/2009 Rev. 1), including validation of selectivity, sensitivity (lower limit of quantitation), calibration curve linearity, accuracy, precision (within-run and between-run), matrix effect, recovery, carryover, dilution integrity, and stability (short-term, long-term, freeze-thaw, processed sample, and stock solution stability).

5. Stability Data

The Licensed Know-How includes the following stability data packages for PPC-4187 API and drug product.

5.1 API Stability Data

(a) Long-term stability data for PPC-4187 API stored at 25°C ± 2°C / 60% RH ± 5% RH, with data available through a minimum of 36 months as of the Effective Date, and accelerated stability data for PPC-4187 API stored at 40°C ± 2°C / 75% RH ± 5% RH, with data available through 6 months, generated in accordance with ICH Q1A(R2) guidelines;

(b) Stress and forced degradation study reports evaluating the degradation behavior of PPC-4187 API under the following conditions: (i) acidic hydrolysis (0.1N HCl, 60°C, 24 hours); (ii) basic hydrolysis (0.1N NaOH, 60°C, 24 hours); (iii) oxidative stress (3% H2O2, 25°C, 24 hours); (iv) thermal stress (80°C, solid state, 7 days); and (v) photolytic stress (ICH Q1B Option 2, exposure to 1.2 million lux hours and 200 watt hours per square meter of near-UV energy), including identification and characterization of degradation products and demonstration of mass balance;

(c) Stability-indicating analytical method validation demonstrating the ability of the HPLC purity method to resolve PPC-4187 from all known degradation products and process-related impurities under forced degradation conditions;

(d) Proposed retest period for PPC-4187 API of 36 months when stored in the approved container closure system (double polyethylene bags within a fiber drum with desiccant) at controlled room temperature (15°C to 25°C), as supported by the available stability data.

5.2 Drug Product Stability Data

(a) Long-term stability data for PPC-4187 25 mg and 50 mg film-coated tablets in proposed commercial packaging (PVC/PVDC-aluminum blisters and HDPE bottles) stored at 25°C ± 2°C / 60% RH ± 5% RH, with data available through a minimum of 24 months as of the Effective Date, and accelerated stability data stored at 40°C ± 2°C / 75% RH ± 5% RH, with data available through 6 months, generated in accordance with ICH Q1A(R2);

(b) Photostability study reports for PPC-4187 25 mg and 50 mg film-coated tablets conducted in accordance with ICH Q1B, including confirmatory testing of the drug product in the proposed commercial packaging and evaluation of any photolytic degradation;

(c) In-use stability data for PPC-4187 drug product in HDPE bottle packaging, simulating expected patient use conditions (repeated opening and closing of the bottle over a 30-day period at 25°C/60% RH);

(d) Proposed shelf-life of 24 months for PPC-4187 25 mg and 50 mg film-coated tablets when stored in the approved packaging configurations at controlled room temperature (store below 30°C; protect from moisture), as supported by the available stability data;

(e) Stability protocols for ongoing and future long-term, accelerated, and intermediate stability studies, including sample pull schedules, test parameters, acceptance criteria, and data trending methodology for continued monitoring of commercial batches.

6. Chemistry, Manufacturing, and Controls (CMC) Documentation

The Licensed Know-How includes the following CMC documentation prepared by or on behalf of Licensor for regulatory submissions relating to PPC-4187.

6.1 Drug Substance (API) CMC

(a) Module 3.2.S sections of the Common Technical Document (CTD) as filed with or prepared for filing with the FDA, EMA, and other regulatory authorities, including: Section 3.2.S.1 (General Information), Section 3.2.S.2 (Manufacture), Section 3.2.S.3 (Characterisation), Section 3.2.S.4 (Control of Drug Substance), Section 3.2.S.5 (Reference Standards), Section 3.2.S.6 (Container Closure System), and Section 3.2.S.7 (Stability);

(b) Drug substance specifications for PPC-4187 API, including justification of specifications in accordance with ICH Q6A, and setting forth acceptance criteria for identity, appearance, assay, impurities (specified, unspecified, and total), chiral purity, residual solvents, water content, elemental impurities, particle size distribution, and any other relevant quality attributes;

(c) Container closure system descriptions for API packaging and shipping, including specifications for the primary packaging components (double low-density polyethylene bags with heat-sealed closures) and the secondary packaging (fiber drum with desiccant), together with extractables and leachables assessments as applicable.

6.2 Drug Product CMC

(a) Module 3.2.P sections of the CTD as filed with or prepared for filing with the FDA, EMA, and other regulatory authorities, including: Section 3.2.P.1 (Description and Composition), Section 3.2.P.2 (Pharmaceutical Development), Section 3.2.P.3 (Manufacture), Section 3.2.P.4 (Control of Excipients), Section 3.2.P.5 (Control of Drug Product), Section 3.2.P.6 (Reference Standards), Section 3.2.P.7 (Container Closure System), and Section 3.2.P.8 (Stability);

(b) Drug product specifications for PPC-4187 25 mg and 50 mg film-coated tablets, including justification of specifications in accordance with ICH Q6A, and setting forth acceptance criteria for appearance, identity, assay, content uniformity, dissolution, related substances (specified degradation products, unspecified degradation products, and total degradation products), moisture content, hardness, friability, disintegration, and microbial limits;

(c) Container closure system descriptions for drug product packaging, including detailed specifications for: (i) PVC/PVDC-aluminum blister packaging, including film thickness, barrier properties (moisture vapor transmission rate and oxygen transmission rate), and sealing parameters; and (ii) HDPE bottles with induction-sealed, child-resistant polypropylene closures and silica gel desiccant, including dimensional specifications, extractables and leachables assessments, and child-resistance and senior-friendliness testing data;

(d) Dissolution method development reports, including the rationale for selection of dissolution apparatus, medium, volume, and agitation speed, together with biorelevant dissolution data (using FaSSIF and FeSSIF media) and any in vitro-in vivo correlation (IVIVC) assessments performed for PPC-4187 25 mg and 50 mg tablets.

6.3 Comparability and Bridging Studies

(a) Any comparability protocols and reports relating to manufacturing site changes, process changes (including changes to synthetic route, process parameters, or equipment), or scale-up for PPC-4187 API or drug product, demonstrating that such changes did not adversely affect the quality, safety, or efficacy of the API or drug product;

(b) Bridging study data between the clinical formulation(s) used in Phase I and Phase II clinical trials and the proposed commercial formulation of PPC-4187 25 mg and 50 mg film-coated tablets, including comparative dissolution data, relative bioavailability study data (if applicable), and any statistical analyses demonstrating bioequivalence or pharmaceutical equivalence between the clinical and commercial formulations.

7. Regulatory Dossier Components

The Licensed Know-How includes the following regulatory dossier components prepared by or on behalf of Licensor for PPC-4187:

(a) Common Technical Document (CTD) modules or sections prepared by or on behalf of Penterra Pharmaceuticals Corp. for PPC-4187, to the extent such modules or sections constitute Know-How within the meaning of the Agreement, specifically including Modules 2, 3, 4, and 5, and excluding Module 1 country-specific administrative and prescribing information outside the Territory;

(b) Quality Overall Summary (Module 2.3), providing a high-level summary and critical assessment of the CMC data for PPC-4187 API and drug product;

(c) Non-Clinical Overview (Module 2.4) and Non-Clinical Written and Tabulated Summaries (Module 2.6), providing an integrated assessment of the pharmacology, pharmacokinetics, and toxicology data for PPC-4187;

(d) Clinical Overview (Module 2.5) and Clinical Summary and Tabulated Summaries (Module 2.7), providing an integrated assessment of the clinical pharmacology, efficacy, and safety data from the PPC-4187 clinical development program.

For the avoidance of doubt, the regulatory dossier components described in this Section 7 are provided to facilitate Licensee's preparation of its own regulatory submissions in the Territory and do not constitute an assignment or transfer of any regulatory filings, marketing authorizations, or IND/CTA numbers held by Licensor.

8. Additional Know-How

8.1 Crystalline Form Information

The Licensed Know-How includes the following solid-state characterization data and crystalline form information for PPC-4187:

(a) Polymorphic form characterization data for PPC-4187, including identification, characterization, and physicochemical properties of the designated crystalline forms: Form A (the thermodynamically stable form selected for commercial development), Form B (a metastable polymorph), Form C (a hydrate form), and any other polymorphic, solvated, hydrated, or amorphous forms identified during polymorph screening studies;

(b) Solid-state characterization data for each identified form, including: (i) X-ray powder diffraction (XRPD) patterns and peak position tables; (ii) differential scanning calorimetry (DSC) thermograms, including melting points, enthalpies of fusion, and glass transition temperatures (for amorphous material); (iii) thermogravimetric analysis (TGA) data, including weight loss profiles; (iv) dynamic vapor sorption (DVS) isotherms; (v) Fourier transform infrared (FTIR) spectroscopy data; (vi) Raman spectroscopy data; and (vii) solid-state nuclear magnetic resonance (ssNMR) data, as available;

(c) Polymorph screening and selection reports, including the rationale for selection of Form A as the preferred crystalline form for commercial development, competitive slurry experiments, interconversion studies, and thermodynamic stability assessments;

(d) Documentation of the relationship between the crystalline Form A data and claims of U.S. Patent No. 11,345,678 (entitled "Crystalline Forms of Penteracitinib and Methods of Preparation Thereof," issued May 24, 2022, expiring November 3, 2038), which patent is listed on Schedule A (Licensed Patents) to the Agreement.

8.2 Competitive intelligence and Market Data

(a) Internal Penterra market assessments for PPC-4187 in the atopic dermatitis therapeutic area within the Territory, including market size and growth projections, patient population segmentation analyses, payer landscape assessments, and pricing and reimbursement benchmarking analyses;

(b) Competitive landscape analyses prepared by or on behalf of Licensor, including assessments of marketed and pipeline JAK inhibitors in atopic dermatitis (including but not limited to baricitinib, upadacitinib, and abrocitinib), comparative efficacy and safety profiling, and anticipated competitive positioning for PPC-4187;

(c) Clinical benchmarking data comparing PPC-4187 clinical results to published data for competing compounds in atopic dermatitis, in each case to the extent such information constitutes proprietary Know-How of Licensor and is not publicly available.

8.3 Invention Disclosures and Trade Secrets

(a) All unpublished invention disclosures relating to PPC-4187 formulation, manufacturing, or use that have been filed internally at Penterra Pharmaceuticals Corp. as of the Effective Date, including invention disclosures relating to: (i) novel formulation approaches for PPC-4187 (e.g., modified-release formulations, topical formulations, pediatric formulations); (ii) process improvements or alternative synthetic routes for PPC-4187 API; and (iii) new therapeutic uses or combination therapy approaches for PPC-4187, in each case to the extent not already captured in patent applications or issued patents listed on Schedule A;

(b) Trade secret documentation not otherwise captured in patent filings, including proprietary formulation rationale, process development notebooks, internal technical memoranda, and other confidential technical documentation relating to PPC-4187 that Licensor has maintained as trade secrets, subject to Licensor's obligation under the Agreement to use commercially reasonable efforts to compile and deliver such documentation.

9. Format and Delivery of Licensed Know-How

All Licensed Know-How described in this Schedule B shall be delivered to Licensee in electronic format via Licensor's secure file transfer platform (currently Citrix ShareFile, with AES-256 encryption) within thirty (30) calendar days of the Effective Date (i.e., no later than November 19, 2023), except as otherwise specified in the Technology Transfer Agreement referenced below. Electronic files shall be provided in their native format (e.g., PDF, Microsoft Word, Microsoft Excel, SAS transport files, and other standard file formats), organized in a logical folder structure corresponding to the sections of this Schedule B.

Hard-copy originals or certified copies of any Licensed Know-How documents shall be provided by Licensor upon Licensee's reasonable written request, at Licensee's expense for reproduction and shipping, within thirty (30) calendar days of such request.

All Licensed Know-How documents shall be provided in the English language. To the extent any original source documents constituting Licensed Know-How are in a language other than English, Licensor shall provide English translations of such documents at Licensor's expense, certified as accurate by a qualified translator where reasonably requested by Licensee.

All Licensed Know-How delivered in electronic format shall be transmitted to Licensee at the following address and to the attention of the following designated recipients:

Meridian Bio Therapeutics Limited 18/F, Blossom Tower 88 Queen's Road Central Hong Kong SAR

Attention: Dr. Kenji Morimoto, Chief Medical Officer

and David R. Cheung, General Counsel

Email: kmorimoto@meridianbio.com.hk; dcheung@meridianbio.com.hk

Hard-copy deliveries shall be addressed to the same physical address, marked "CONFIDENTIAL — Licensed Know-How," with tracking confirmation required.

The Parties acknowledge and agree that the detailed timeline, sequencing, and procedures for the transfer of manufacturing process know-how (including the know-how described in Section 3 of this Schedule B) shall be governed by the Technology Transfer Agreement entered into between Licensor and Licensee concurrently with the Agreement (the "Technology Transfer Agreement"), which provides for a twenty-four (24)-month completion deadline for the full transfer of all manufacturing process know-how (i.e., completion by no later than October 20, 2025). In the event of any conflict between this Schedule B and the Technology Transfer Agreement with respect to the timing or manner of delivery of manufacturing process know-how, the Technology Transfer Agreement shall control.

10. Confidentiality and Use Restrictions

All Licensed Know-How described in this Schedule B constitutes Confidential Information of Licensor and is subject to the confidentiality obligations set forth in Article 12 (Confidentiality) of the Agreement. Without limiting the generality of the foregoing:

(a) Licensee shall treat all Licensed Know-How as Confidential Information of Licensor and shall protect and safeguard such Licensed Know-How in accordance with the standards and procedures set forth in Section 12.1 of the Agreement, using no less than the same degree of care that Licensee uses to protect its own confidential information of a similar nature, but in no event less than reasonable care;

(b) Licensee's right to use the Licensed Know-How is limited exclusively to the development, manufacture, and commercialization of Licensed Products containing PPC-4187 (Penteracitinib) within the Territory, as defined in Schedule D to the Agreement, and solely as permitted under and in accordance with the terms and conditions of the Agreement;

(c) Licensee shall have no right to use the Licensed Know-How, in whole or in part, for any compound other than PPC-4187 (Penteracitinib), or for any indication other than the indications for which Licensee is authorized to develop, manufacture, and commercialize Licensed Products under the Agreement;

(d) Licensee may disclose Licensed Know-How to its Affiliates, sublicensees, subcontractors, and regulatory authorities only to the extent permitted under the Agreement and subject to appropriate confidentiality obligations consistent with those set forth in Article 12 of the Agreement.

11. Updates and Supplements

Licensor shall supplement this Schedule B with additional Know-How generated or obtained by Licensor during the term of the Agreement to the extent such additional Know-How relates to PPC-4187 (Penteracitinib) in the Territory, in accordance with the information-sharing obligations set forth in Section 4.6 of the Agreement. Such supplements shall be provided to Licensee in the format and manner described in Section 9 of this Schedule B, within forty-five (45) calendar days of generation or receipt of such additional Know-How by Licensor, unless a different timeline is mutually agreed upon by the Parties.

The Joint Steering Committee established pursuant to Section 3.1 of the Agreement, consisting of three (3) designated representatives from each Party, meeting on a quarterly basis (or more frequently as circumstances may require), shall oversee the exchange and supplementation of Licensed Know-How, including reviewing the completeness and adequacy of Know-How transfers, addressing any questions or issues raised by Licensee regarding the Licensed Know-How, and coordinating the resolution of any gaps or deficiencies identified during technology transfer.

The Joint Patent Committee established pursuant to Section 8.5 of the Agreement, consisting of two (2) designated representatives from each Party, shall coordinate on any new patentable inventions arising from or relating to the Licensed Know-How, including the evaluation and prosecution of patent applications, the allocation of patent filing and maintenance costs, and the ownership and licensing of any jointly developed intellectual property, all in accordance with Article 8 (Intellectual Property) of the Agreement.

Any updates or supplements to this Schedule B shall be deemed incorporated into and form part of this Schedule B upon delivery to Licensee, without the need for a formal amendment to the Agreement, unless the Parties otherwise agree in writing.

[Remainder of this page intentionally left blank. Signature page follows.]

SCHEDULE B — SIGNATURE PAGE

This Schedule B is incorporated into and forms part of the Exclusive License Agreement dated October 2, 2023, effective October 20, 2023, by and between Penterra Pharmaceuticals Corp. and Meridian Bio Therapeutics Limited. By executing this Schedule B below, each Party acknowledges that it has reviewed the contents hereof and confirms its agreement to the terms set forth herein.

LICENSOR:

PENTERRA PHARMACEUTICALS CORP.

By: ________

Name: Dr. Sarah E. Harrington

Title: President and Chief Executive Officer

Date: ________

LICENSEE:

MERIDIAN BIO THERAPEUTICS LIMITED

By: ________

Name: Michael T. Kwok

Title: Chief Executive Officer and Executive Director

Date: ________

SCHEDULE B
LICENSED KNOW-HOW
Schedule B to the Exclusive License Agreement (the "Agreement") dated October 2, 2023, effective October 20, 2023 (the "Effective Date"), by and between Penterra Pharmaceuticals Corp., a corporation organized and existing under the laws of the State of Delaware, having its principal place of business at 900 Innovation Drive, Suite 400, Cambridge, Massachusetts 02142 ("Licensor"), and Meridian Bio Therapeutics Limited, a company incorporated under the laws of Hong Kong, having its registered office at 18/F, Blossom Tower, 88 Queen's Road Central, Hong Kong SAR ("Licensee").
This Schedule B sets forth the Licensed Know-How as defined in Section 1.47 of the Agreement. All capitalized terms used but not defined herein shall have the meanings ascribed to them in the Agreement. The Licensed Know-How described in this Schedule B is licensed to Licensee on an exclusive basis within the Territory (as defined in Schedule D to the Agreement) for the development, manufacture, and commercialization of Licensed Products containing compound PPC-4187 (Penteracitinib), a selective Janus kinase 1 (JAK1) inhibitor, in accordance with and subject to the terms and conditions of the Agreement. For the avoidance of doubt, references to "Licensed Know-How" in this Schedule B include all data, information, results, reports, documents, methods, processes, techniques, formulations, compositions, specifications, protocols, and other proprietary know-how described herein, in each case to the extent owned or controlled by Licensor as of the Effective Date or generated or obtained by Licensor during the term of the Agreement in accordance with Section 11 below.
The Licensed Know-How is organized into the following categories, each of which is described in detail in the sections that follow.
1. Pre-Clinical Data Packages
The Licensed Know-How includes the following pre-clinical data packages generated by or on behalf of Licensor in connection with the research and development of PPC-4187 (Penteracitinib).
1.1 In Vitro Pharmacology Data
The Licensed Know-How includes all in vitro pharmacology data generated for PPC-4187, comprising the following:
(a) Selective JAK1 inhibitor activity assays, including half-maximal inhibitory concentration (IC50) and half-maximal effective concentration (EC50) data, together with full selectivity panels comparing inhibitory activity of PPC-4187 against JAK1 relative to JAK2, JAK3, and TYK2, including data from biochemical kinase assays, cellular signaling assays (STAT phosphorylation), and whole blood cytokine stimulation assays;
(b) Mechanism of action studies for PPC-4187, including binding kinetics data (kon, koff, KD), ATP-competitive binding analyses, co-crystallography data (if any), and functional selectivity assessments demonstrating the preferential inhibition of JAK1-dependent signaling pathways relevant to atopic dermatitis pathobiology;
(c) In vitro absorption, distribution, metabolism, and excretion (ADME) data, including without limitation: (i) metabolic stability data in hepatic microsomes and hepatocytes across relevant species (human, rat, dog, monkey); (ii) cytochrome P450 (CYP450) inhibition profiles (reversible and time-dependent) against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5; (iii) CYP450 induction profiles (CYP1A2, CYP2B6, CYP3A4); (iv) plasma protein binding data across species, including equilibrium dialysis and ultrafiltration data; (v) blood-to-plasma concentration ratios; and (vi) permeability assessments, including Caco-2 cell monolayer transport studies and P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrate and inhibitor evaluations.
1.2 In Vivo Pharmacology Data
The Licensed Know-How includes all in vivo pharmacology data generated for PPC-4187, comprising the following:
(a) Preclinical efficacy studies conducted in validated atopic dermatitis animal models, including, without limitation, oxazolone-induced dermatitis models in BALB/c mice, MC903 (calcipotriol)-induced atopic dermatitis models in mice, and NC/Nga mouse spontaneous dermatitis models, together with all study protocols, raw data, histopathological assessments, immunohistochemistry results, cytokine profiling data, and final study reports;
(b) Pharmacokinetic (PK) studies characterizing the oral bioavailability, elimination half-life (t½), volume of distribution (Vd), systemic clearance (CL), maximum plasma concentration (Cmax), time to maximum concentration (Tmax), and area under the plasma concentration-time curve (AUC) of PPC-4187 across multiple species, including rat, dog, and cynomolgus monkey, following single-dose and multi-dose oral and intravenous administration;
(c) Dose-response and dose-ranging study reports establishing the pharmacological dose-response relationship for PPC-4187 in the relevant animal models, including determination of minimum effective dose (MED), maximum tolerated dose (MTD), and no-observed-adverse-effect level (NOAEL) from pharmacology studies.
1.3 Toxicology Data
The Licensed Know-How includes all toxicology data generated for PPC-4187, comprising the following:
(a) Single-dose (acute) toxicology study reports conducted in at least two mammalian species (rat and dog) in compliance with Good Laboratory Practice (GLP) regulations (21 C.F.R. Part 58; OECD Principles of GLP), including determination of approximate lethal dose, target organ identification, and full histopathological evaluations;
(b) Repeat-dose (subacute and chronic) toxicology study reports, including 14-day, 28-day, 90-day, and 6-month repeat-dose oral toxicity studies in rat and dog, conducted in compliance with GLP, including NOAEL and lowest-observed-adverse-effect level (LOAEL) determinations, hematology, clinical chemistry, urinalysis, organ weight data, and complete histopathological evaluations of all major organ systems;
(c) Genotoxicity study reports, including: (i) bacterial reverse mutation assay (Ames test) using Salmonella typhimurium and Escherichia coli strains; (ii) in vitro chromosomal aberration assay in human peripheral blood lymphocytes or Chinese hamster ovary (CHO) cells; and (iii) in vivo micronucleus assay in rodent bone marrow or peripheral blood, each conducted in compliance with GLP and applicable ICH S2(R1) guidelines;
(d) Reproductive and developmental toxicology study reports, including: (i) fertility and early embryonic development studies (Segment I) in rats; (ii) embryo-fetal development studies (Segment II) in rats and rabbits; and (iii) pre- and postnatal development studies (Segment III) in rats, all conducted in accordance with ICH S5(R3) and GLP;
(e) Carcinogenicity study data, to the extent available as of the Effective Date, including any completed or ongoing 2-year rodent carcinogenicity bioassays, 6-month rasH2 transgenic mouse carcinogenicity studies, and any carcinogenicity risk assessments prepared in accordance with ICH S1A, S1B(R1), and S1C(R2);
(f) Safety pharmacology study reports, including: (i) cardiovascular safety pharmacology studies (hERG channel inhibition assay, telemetrized dog cardiovascular study evaluating blood pressure, heart rate, and electrocardiographic parameters including QTc interval); (ii) respiratory safety pharmacology studies (whole-body plethysmography in rats evaluating respiratory rate, tidal volume, and minute ventilation); and (iii) central nervous system (CNS) safety pharmacology studies (modified Irwin test or functional observational battery in rats);
(g) Toxicokinetic (TK) data collected as part of the GLP toxicology studies described above, including systemic exposure (AUC, Cmax) at each dose level, exposure multiples relative to the projected or observed human therapeutic exposure, assessment of accumulation upon repeat dosing, and any sex-based differences in exposure.
1.4 Pharmacology and Toxicology Summary Reports
The Licensed Know-How includes the following summary and compilation documents relating to PPC-4187 pharmacology and toxicology:
(a) The current edition of the Investigator's Brochure for PPC-4187 as of the Effective Date (Edition 4, dated July 15, 2023), including all appendices, addenda, and safety updates issued through the Effective Date;
(b) Non-clinical overview and non-clinical summary documents prepared by or on behalf of Licensor for Investigational New Drug (IND) application filings with the United States Food and Drug Administration (FDA) and Clinical Trial Application (CTA) filings with applicable regulatory authorities, including the Integrated Summary of Safety (ISS) and Integrated Summary of Efficacy (ISE) components to the extent relating to non-clinical data.
2. Clinical Data Packages
The Licensed Know-How includes the following clinical data packages generated by or on behalf of Licensor from clinical trials conducted with PPC-4187 (Penteracitinib) in human subjects.
2.1 Phase I Clinical Data
(a) Phase I single ascending dose (SAD) study report (Study PPC-4187-101): a first-in-human, randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics of single oral doses of PPC-4187 (ranging from 1 mg to 200 mg) in healthy adult volunteers, including the complete clinical study report (CSR), all appendices, individual patient-level data, and statistical analyses;
(b) Phase I multiple ascending dose (MAD) study report (Study PPC-4187-102): a randomized, double-blind, placebo-controlled study evaluating the safety, tolerability, and pharmacokinetics of multiple ascending oral doses of PPC-4187 (ranging from 10 mg to 100 mg once daily for 14 consecutive days) in healthy adult volunteers, including the complete CSR, all appendices, individual patient-level data, and statistical analyses;
(c) Phase I food-effect study report (Study PPC-4187-103): an open-label, randomized, two-period crossover study evaluating the effect of a high-fat meal on the pharmacokinetics of a single 50 mg oral dose of PPC-4187 in healthy adult volunteers, including the complete CSR and bioequivalence assessments;
(d) Phase I drug-drug interaction (DDI) study reports (Studies PPC-4187-104 and PPC-4187-105): open-label, fixed-sequence studies evaluating the effect of PPC-4187 on the pharmacokinetics of probe substrates for major CYP enzymes (e.g., midazolam for CYP3A4, caffeine for CYP1A2) and the effect of a strong CYP3A4 inhibitor (itraconazole) on PPC-4187 pharmacokinetics, including complete CSRs and clinical pharmacology assessments;
(e) Phase I PK/PD data, including plasma concentration-time profiles, individual and population pharmacokinetic model analyses (NONMEM or equivalent), exposure-response analyses for safety biomarkers (including lymphocyte counts and lipid parameters), and PK/PD modeling reports prepared by Licensor's quantitative clinical pharmacology group.
2.2 Phase IIa Clinical Data
(a) Phase IIa proof-of-concept study report (Study PPC-4187-200): a randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy, safety, and tolerability of PPC-4187 administered orally at 25 mg and 50 mg once daily for 12 weeks in approximately 120 adult patients with moderate-to-severe atopic dermatitis, including the complete CSR, all appendices, and individual patient-level datasets;
(b) Preliminary efficacy data from the Phase IIa study, including Eczema Area and Severity Index (EASI) scores, Investigator's Global Assessment (IGA) responses, pruritus Numerical Rating Scale (NRS) data, and Dermatology Life Quality Index (DLQI) assessments, together with preliminary safety data including adverse event listings, serious adverse event narratives, and laboratory parameter analyses.
2.3 Phase IIb Clinical Data — Study PPC-4187-201
The Licensed Know-How includes the complete data package from the pivotal Phase IIb clinical trial conducted by Licensor, Study PPC-4187-201, as described in detail below:
(a) Complete Clinical Study Report (CSR): The full CSR for Penterra-sponsored Study PPC-4187-201 (Protocol No. PPC-4187-201, Version 4.0, dated January 8, 2022), including all appendices (16.1 through 16.4), in-text tables and figures, individual patient data listings, and all amendments to the study protocol;
(b) Study Design: Randomized, double-blind, placebo-controlled, parallel-group, multicenter study conducted at 62 investigational sites across the United States, Canada, Germany, France, and the United Kingdom, evaluating PPC-4187 in adult patients (≥18 years of age) with moderate-to-severe atopic dermatitis (defined as EASI ≥16, IGA ≥3, and body surface area involvement ≥10%);
(c) Study Size: A total of 420 patients enrolled and randomized in a 1:1:1 ratio to receive PPC-4187 25 mg once daily (n=140), PPC-4187 50 mg once daily (n=140), or matching placebo once daily (n=140) for a treatment period of 16 weeks, followed by a 4-week safety follow-up period;
(d) Dosage Strengths Evaluated: 25 mg and 50 mg film-coated tablets of PPC-4187 (Penteracitinib), administered once daily by oral route. Matching placebo tablets were manufactured to be identical in appearance, size, and weight to the active tablets;
(e) Primary Endpoint: The proportion of patients achieving EASI-75 (i.e., ≥75% improvement from baseline in the Eczema Area and Severity Index) at Week 16;
(f) Topline Results (June 2023): The study met its primary endpoint with statistically significant improvement versus placebo for EASI-75 response rate at Week 16 in both the 25 mg and 50 mg dose groups. Specifically, EASI-75 response rates at Week 16 were 46.4% for PPC-4187 50 mg (p<0.001 vs. placebo), 33.6% for PPC-4187 25 mg (p<0.001 vs. placebo), and 12.9% for placebo. Key secondary endpoints, including IGA 0/1 response, change from baseline in pruritus NRS, and EASI-90, were also statistically significant for both active dose groups versus placebo after multiplicity adjustment;
(g) Individual Patient-Level Datasets: Complete individual patient-level datasets in SAS transport file format, including Study Data Tabulation Model (SDTM) datasets, Analysis Data Model (ADaM) datasets, and corresponding define.xml files, all prepared in accordance with the Clinical Data Interchange Standards Consortium (CDISC) standards;
(h) Statistical Analysis Plan (SAP) and Statistical Outputs: The final, approved SAP (Version 2.0, dated March 15, 2023), together with all statistical output tables, figures, and listings (TFLs) generated in support of the CSR, annotated case report forms (aCRFs), and the randomization scheme and code;
(i) Safety Database: The complete safety database for Study PPC-4187-201, including all adverse event data (coded using MedDRA Version 26.0), serious adverse event data and narratives, laboratory data (hematology, chemistry, lipids, liver function tests, lymphocyte subsets), vital signs, 12-lead electrocardiogram (ECG) data, and physical examination findings;
(j) Data Monitoring Committee (DMC) Reports and Meeting Minutes: All reports prepared for and minutes of meetings of the independent Data Monitoring Committee (chaired by Professor Ian R. Whitfield, M.D., University of Edinburgh) convened in connection with Study PPC-4187-201, including safety reports, interim analysis reports, and the DMC's recommendations regarding study continuation;
(k) Site-Level Data, Investigator Lists, and Informed Consent Templates: Complete site-level enrollment and data quality metrics, the list of all principal investigators and sub-investigators at each study site, model informed consent forms and institutional review board / ethics committee (IRB/EC) approval letters to the extent in Licensor's possession.
2.4 Regulatory Submissions and Correspondence
(a) All Investigational New Drug (IND) application filings submitted by Licensor to the United States Food and Drug Administration (FDA) in connection with PPC-4187 (IND No. 147823), including the original IND submission, all IND amendments and supplements, and all FDA correspondence, including acknowledgment letters, clinical hold notifications (if any), information requests, and Licensor's responses thereto;
(b) All Clinical Trial Application (CTA) filings submitted by Licensor to EU Member State regulatory authorities and the European Medicines Agency (EMA), as applicable, including initial CTA submissions, substantial amendments, and all regulatory authority correspondence, notifications, and responses relating thereto;
(c) Annual IND safety reports submitted to the FDA and corresponding annual safety update reports submitted to EU regulatory authorities for PPC-4187;
(d) Minutes and correspondence from all formal regulatory authority meetings relating to PPC-4187, including pre-IND meeting(s), end-of-Phase II meeting(s), and any Type A, Type B, or Type C meeting(s) with the FDA, as well as any Scientific Advice or Protocol Assistance meetings with the EMA or National Competent Authorities, in each case to the extent relating to PPC-4187 and in the possession or control of Licensor.
2.5 Clinical Supply Records
(a) Complete clinical supply chain documentation for PPC-4187 clinical trial material, including records of manufacture (batch production records and certificates of analysis), quality release documentation, distribution records (chain of custody logs, shipping records, temperature monitoring data), returns and destruction records, and drug accountability reconciliation reports for clinical trial material used in the Phase I, Phase IIa, and Phase IIb studies referenced in Sections 2.1 through 2.3 above;
(b) Certificates of analysis for all clinical trial material batches, specifications applied to clinical trial material, and any deviations, out-of-specification (OOS) investigations, or corrective and preventive actions (CAPAs) relating to clinical supply of PPC-4187.
3. Proprietary Manufacturing Process
The Licensed Know-How includes the following proprietary manufacturing process information relating to the synthesis, formulation, and manufacture of PPC-4187 (Penteracitinib) active pharmaceutical ingredient and drug product.
3.1 Active Pharmaceutical Ingredient (API) Manufacturing Process
(a) The detailed synthetic route and process description for the manufacture of PPC-4187 API, including the complete sequence of chemical reactions, all synthetic intermediates (designated INT-1 through INT-7), starting materials (including structural characterization and sourcing information), reagents, catalysts, and solvents used at each synthetic step, together with reaction conditions (temperature, pressure, pH, reaction time, stoichiometry, and order of addition);
(b) Identification and characterization of all process parameters, critical process parameters (CPPs), and critical quality attributes (CQAs) for each step of the API synthetic process, as determined through quality-by-design (QbD) principles, design of experiments (DoE), and process characterization studies, including proven acceptable ranges (PARs) and normal operating ranges (NORs) for each CPP;
(c) Process validation reports for the PPC-4187 API manufacturing process as conducted at the facility of Alkerra Manufacturing Inc. (contract manufacturing organization), located at 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, United States, including prospective process validation data from a minimum of three consecutive commercial-scale batches, performance qualification reports, and continued process verification protocols and data;
(d) Executed batch records for representative commercial-scale API batches manufactured at Alkerra Manufacturing Inc., including all in-process testing data, yield calculations, and deviation reports;
(e) Specifications for all starting materials, synthetic intermediates, reagents, catalysts, and solvents used in the API manufacturing process, together with certificates of analysis from qualified suppliers and approved supplier qualification documentation;
(f) In-process control (IPC) testing procedures and acceptance criteria at each stage of the synthetic process, including identity testing, purity testing, moisture content, and other quality-relevant measurements performed during manufacturing;
(g) Complete impurity profiles for PPC-4187 API, including: (i) all identified and unidentified process-related impurities (with structures where elucidated), qualification and toxicological assessment data, and control strategies; (ii) degradation products identified through forced degradation studies; (iii) residual solvent levels (per ICH Q3C(R8)); and (iv) elemental impurity assessments (per ICH Q3D(R2));
(h) Scale-up and technology transfer documentation tracing the progression of the PPC-4187 API manufacturing process from laboratory scale (gram quantities) through pilot scale to commercial scale (kilogram quantities), including scale-up risk assessments, comparative batch analyses, and technology transfer protocols and reports.
3.2 Drug Product Manufacturing Process
(a) Formulation development reports for the 25 mg and 50 mg film-coated tablet dosage forms of PPC-4187, including pre-formulation studies, excipient compatibility studies, prototype formulation screening, formulation optimization studies, and final formulation composition (qualitative and quantitative);
(b) Detailed manufacturing process descriptions for the PPC-4187 25 mg and 50 mg film-coated tablet formulations, including the following unit operations: (i) dispensing and sieving of active ingredient and excipients; (ii) dry blending and lubrication; (iii) wet or dry granulation (as applicable); (iv) milling and screening of granulate; (v) final blending; (vi) tablet compression; and (vii) aqueous film-coating, together with process flow diagrams for each unit operation;
(c) Identification and characterization of all process parameters, CPPs, and CQAs for drug product manufacture at each unit operation, including blend uniformity targets, granulation endpoint parameters, compression force ranges, tablet weight and hardness specifications, film-coat weight gain targets, and associated proven acceptable ranges;
(d) Process validation reports for the 25 mg and 50 mg tablet strengths, including prospective process validation data from a minimum of three consecutive commercial-scale batches at each strength, media fill and environmental monitoring data for the manufacturing suite, and continued process verification protocols;
(e) Executed batch manufacturing records for representative drug product batches at each tablet strength, including all in-process testing data, deviation and investigation reports, and reconciliation records;
(f) Equipment specifications and tooling details for all major manufacturing equipment utilized in drug product manufacture, including blender specifications, granulator specifications, tablet press specifications (rotary press model, punch and die tooling dimensions), and coating pan specifications, sufficient to enable Licensee to replicate or source equivalent equipment for commercial manufacturing;
(g) Excipient specifications for all excipients used in the 25 mg and 50 mg film-coated tablet formulations, together with approved supplier lists, supplier qualification documentation, and certificates of analysis for excipient lots used in validation batches;
(h) Packaging and labeling specifications for primary and secondary packaging configurations, including: (i) PVC/PVDC-aluminum blister packaging (configurations of 7, 14, 28, and 30 tablets); (ii) high-density polyethylene (HDPE) bottles with child-resistant closure and desiccant (configurations of 30 and 90 tablets); and (iii) secondary carton and labeling specifications, including artwork files and packaging component specifications;
(i) Cleaning validation studies and equipment hold-time studies for all product-contact manufacturing equipment used in PPC-4187 drug product manufacture, including determination of maximum allowable carryover limits, cleaning agent specifications, and validated cleaning procedures.
3.3 Alkerra Manufacturing Inc. — CMO Documentation
(a) The current manufacturing site master file for Alkerra Manufacturing Inc., 5200 Meridian Parkway, Research Triangle Park, North Carolina 27713, as prepared in accordance with PIC/S and WHO guidelines, describing the facility layout, equipment, utilities, quality systems, and personnel qualifications relevant to the manufacture of PPC-4187 API;
(b) Quality system documentation applicable to PPC-4187 API manufacture at the Alkerra facility, including relevant standard operating procedures (SOPs), quality manual excerpts, change control records, deviation and CAPA records, annual product quality review (APQR) reports, and supplier qualification records, in each case to the extent relating to PPC-4187 and to the extent Licensor has the right to disclose such documentation under its contractual arrangements with Alkerra Manufacturing Inc.;
(c) Regulatory inspection history and correspondence for the Alkerra Manufacturing Inc. facility as it relates to PPC-4187, including FDA pre-approval inspection (PAI) observations (if any), FDA Form 483 observations and Alkerra responses, EU Qualified Person (QP) audit reports, and any Establishment Inspection Reports (EIRs) in Licensor's possession;
(d) Environmental, health, and safety (EHS) data pertinent to PPC-4187 API manufacturing processes, including material safety data sheets (SDS) for PPC-4187 API, intermediates, and hazardous reagents, occupational exposure limit (OEL) assessments and control banding evaluations for PPC-4187, and waste stream characterization and disposal protocols.
4. Analytical Methods
The Licensed Know-How includes the following validated analytical methods, method validation reports, and reference standard documentation relating to PPC-4187 API and drug product.
4.1 API Analytical Methods
(a) Validated analytical methods for the following quality attributes of PPC-4187 API: (i) identity (by infrared spectroscopy (IR) and high-performance liquid chromatography (HPLC) retention time comparison); (ii) assay/potency (by HPLC with UV detection); (iii) purity and related substances (by gradient HPLC); (iv) chiral purity (by chiral HPLC or chiral supercritical fluid chromatography (SFC)); (v) residual solvents (by headspace gas chromatography (GC)); (vi) water content (by Karl Fischer titration); (vii) heavy metals and elemental impurities (by inductively coupled plasma mass spectrometry (ICP-MS), per ICH Q3D(R2)); and (viii) particle size distribution (by laser diffraction);
(b) Analytical method validation reports for each of the foregoing methods, demonstrating compliance with ICH Q2(R1) (Validation of Analytical Procedures: Text and Methodology) guidelines for the applicable validation characteristics, including specificity, linearity, range, accuracy, precision (repeatability and intermediate precision), detection limit, quantitation limit, and robustness, as applicable;
(c) Reference standard characterization and certificate of analysis for the PPC-4187 primary reference standard (Penterra Reference Standard Lot No. PRS-001, established March 2020), including characterization by mass spectrometry, nuclear magnetic resonance (NMR) spectroscopy (¹H and ¹³C), elemental analysis, HPLC purity, chiral purity, water content, residual solvent content, and assigned potency value.
4.2 Drug Product Analytical Methods
(a) Validated analytical methods for the following quality attributes of PPC-4187 25 mg and 50 mg film-coated tablets: (i) identity (by HPLC retention time and UV spectrum comparison); (ii) assay (by HPLC with UV detection); (iii) content uniformity (by HPLC, in accordance with USP <905>); (iv) dissolution (by HPLC, using USP Apparatus II (paddle), 50 rpm, 900 mL 0.1N HCl, at 37°C ± 0.5°C); (v) related substances and degradation products (by gradient HPLC); (vi) moisture content (by Karl Fischer titration or loss on drying); (vii) hardness (by tablet hardness tester); (viii) friability (by USP <1216> friability testing); and (ix) film-coat integrity (by visual inspection and disintegration testing);
(b) Analytical method validation reports for each of the foregoing drug product analytical methods, demonstrating compliance with ICH Q2(R1) guidelines;
(c) Compendial test methods and specifications applicable to PPC-4187 drug product testing, including references to United States Pharmacopeia (USP), European Pharmacopoeia (Ph. Eur.), and Japanese Pharmacopoeia (JP) general chapters and monographs, as applicable to the dosage form and excipients.
4.3 Cleaning and Residual Method Validation
(a) Validated analytical methods for cleaning verification and validation at the drug product and API manufacturing facilities, including swab sampling methods and rinse sampling methods for PPC-4187 residue detection on product-contact equipment surfaces;
(b) Method validation reports for the cleaning verification/validation analytical methods, demonstrating specificity, linearity, accuracy, precision, limit of detection (LOD), limit of quantitation (LOQ), swab recovery factors, and rinse recovery factors, and confirming the methods' suitability to detect PPC-4187 at levels below the calculated maximum allowable carryover.
4.4 Bioanalytical Methods
(a) Validated bioanalytical methods for the quantitative determination of PPC-4187 and its primary metabolites (M1, M2, and M3) in human plasma, serum, and urine, utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with stable isotope-labeled internal standards (PPC-4187-d6);
(b) Bioanalytical method validation reports for each matrix, demonstrating compliance with applicable FDA Guidance for Industry on Bioanalytical Method Validation (May 2018) and EMA Guideline on Bioanalytical Method Validation (EMEA/CHMP/EWP/192217/2009 Rev. 1), including validation of selectivity, sensitivity (lower limit of quantitation), calibration curve linearity, accuracy, precision (within-run and between-run), matrix effect, recovery, carryover, dilution integrity, and stability (short-term, long-term, freeze-thaw, processed sample, and stock solution stability).
5. Stability Data
The Licensed Know-How includes the following stability data packages for PPC-4187 API and drug product.
5.1 API Stability Data
(a) Long-term stability data for PPC-4187 API stored at 25°C ± 2°C / 60% RH ± 5% RH, with data available through a minimum of 36 months as of the Effective Date, and accelerated stability data for PPC-4187 API stored at 40°C ± 2°C / 75% RH ± 5% RH, with data available through 6 months, generated in accordance with ICH Q1A(R2) guidelines;
(b) Stress and forced degradation study reports evaluating the degradation behavior of PPC-4187 API under the following conditions: (i) acidic hydrolysis (0.1N HCl, 60°C, 24 hours); (ii) basic hydrolysis (0.1N NaOH, 60°C, 24 hours); (iii) oxidative stress (3% H2O2, 25°C, 24 hours); (iv) thermal stress (80°C, solid state, 7 days); and (v) photolytic stress (ICH Q1B Option 2, exposure to 1.2 million lux hours and 200 watt hours per square meter of near-UV energy), including identification and characterization of degradation products and demonstration of mass balance;
(c) Stability-indicating analytical method validation demonstrating the ability of the HPLC purity method to resolve PPC-4187 from all known degradation products and process-related impurities under forced degradation conditions;
(d) Proposed retest period for PPC-4187 API of 36 months when stored in the approved container closure system (double polyethylene bags within a fiber drum with desiccant) at controlled room temperature (15°C to 25°C), as supported by the available stability data.
5.2 Drug Product Stability Data
(a) Long-term stability data for PPC-4187 25 mg and 50 mg film-coated tablets in proposed commercial packaging (PVC/PVDC-aluminum blisters and HDPE bottles) stored at 25°C ± 2°C / 60% RH ± 5% RH, with data available through a minimum of 24 months as of the Effective Date, and accelerated stability data stored at 40°C ± 2°C / 75% RH ± 5% RH, with data available through 6 months, generated in accordance with ICH Q1A(R2);
(b) Photostability study reports for PPC-4187 25 mg and 50 mg film-coated tablets conducted in accordance with ICH Q1B, including confirmatory testing of the drug product in the proposed commercial packaging and evaluation of any photolytic degradation;
(c) In-use stability data for PPC-4187 drug product in HDPE bottle packaging, simulating expected patient use conditions (repeated opening and closing of the bottle over a 30-day period at 25°C/60% RH);
(d) Proposed shelf-life of 24 months for PPC-4187 25 mg and 50 mg film-coated tablets when stored in the approved packaging configurations at controlled room temperature (store below 30°C; protect from moisture), as supported by the available stability data;
(e) Stability protocols for ongoing and future long-term, accelerated, and intermediate stability studies, including sample pull schedules, test parameters, acceptance criteria, and data trending methodology for continued monitoring of commercial batches.
6. Chemistry, Manufacturing, and Controls (CMC) Documentation
The Licensed Know-How includes the following CMC documentation prepared by or on behalf of Licensor for regulatory submissions relating to PPC-4187.
6.1 Drug Substance (API) CMC
(a) Module 3.2.S sections of the Common Technical Document (CTD) as filed with or prepared for filing with the FDA, EMA, and other regulatory authorities, including: Section 3.2.S.1 (General Information), Section 3.2.S.2 (Manufacture), Section 3.2.S.3 (Characterisation), Section 3.2.S.4 (Control of Drug Substance), Section 3.2.S.5 (Reference Standards), Section 3.2.S.6 (Container Closure System), and Section 3.2.S.7 (Stability);
(b) Drug substance specifications for PPC-4187 API, including justification of specifications in accordance with ICH Q6A, and setting forth acceptance criteria for identity, appearance, assay, impurities (specified, unspecified, and total), chiral purity, residual solvents, water content, elemental impurities, particle size distribution, and any other relevant quality attributes;
(c) Container closure system descriptions for API packaging and shipping, including specifications for the primary packaging components (double low-density polyethylene bags with heat-sealed closures) and the secondary packaging (fiber drum with desiccant), together with extractables and leachables assessments as applicable.
6.2 Drug Product CMC
(a) Module 3.2.P sections of the CTD as filed with or prepared for filing with the FDA, EMA, and other regulatory authorities, including: Section 3.2.P.1 (Description and Composition), Section 3.2.P.2 (Pharmaceutical Development), Section 3.2.P.3 (Manufacture), Section 3.2.P.4 (Control of Excipients), Section 3.2.P.5 (Control of Drug Product), Section 3.2.P.6 (Reference Standards), Section 3.2.P.7 (Container Closure System), and Section 3.2.P.8 (Stability);
(b) Drug product specifications for PPC-4187 25 mg and 50 mg film-coated tablets, including justification of specifications in accordance with ICH Q6A, and setting forth acceptance criteria for appearance, identity, assay, content uniformity, dissolution, related substances (specified degradation products, unspecified degradation products, and total degradation products), moisture content, hardness, friability, disintegration, and microbial limits;
(c) Container closure system descriptions for drug product packaging, including detailed specifications for: (i) PVC/PVDC-aluminum blister packaging, including film thickness, barrier properties (moisture vapor transmission rate and oxygen transmission rate), and sealing parameters; and (ii) HDPE bottles with induction-sealed, child-resistant polypropylene closures and silica gel desiccant, including dimensional specifications, extractables and leachables assessments, and child-resistance and senior-friendliness testing data;
(d) Dissolution method development reports, including the rationale for selection of dissolution apparatus, medium, volume, and agitation speed, together with biorelevant dissolution data (using FaSSIF and FeSSIF media) and any in vitro-in vivo correlation (IVIVC) assessments performed for PPC-4187 25 mg and 50 mg tablets.
6.3 Comparability and Bridging Studies
(a) Any comparability protocols and reports relating to manufacturing site changes, process changes (including changes to synthetic route, process parameters, or equipment), or scale-up for PPC-4187 API or drug product, demonstrating that such changes did not adversely affect the quality, safety, or efficacy of the API or drug product;
(b) Bridging study data between the clinical formulation(s) used in Phase I and Phase II clinical trials and the proposed commercial formulation of PPC-4187 25 mg and 50 mg film-coated tablets, including comparative dissolution data, relative bioavailability study data (if applicable), and any statistical analyses demonstrating bioequivalence or pharmaceutical equivalence between the clinical and commercial formulations.
7. Regulatory Dossier Components
The Licensed Know-How includes the following regulatory dossier components prepared by or on behalf of Licensor for PPC-4187:
(a) Common Technical Document (CTD) modules or sections prepared by or on behalf of Penterra Pharmaceuticals Corp. for PPC-4187, to the extent such modules or sections constitute Know-How within the meaning of the Agreement, specifically including Modules 2, 3, 4, and 5, and excluding Module 1 country-specific administrative and prescribing information outside the Territory;
(b) Quality Overall Summary (Module 2.3), providing a high-level summary and critical assessment of the CMC data for PPC-4187 API and drug product;
(c) Non-Clinical Overview (Module 2.4) and Non-Clinical Written and Tabulated Summaries (Module 2.6), providing an integrated assessment of the pharmacology, pharmacokinetics, and toxicology data for PPC-4187;
(d) Clinical Overview (Module 2.5) and Clinical Summary and Tabulated Summaries (Module 2.7), providing an integrated assessment of the clinical pharmacology, efficacy, and safety data from the PPC-4187 clinical development program.
For the avoidance of doubt, the regulatory dossier components described in this Section 7 are provided to facilitate Licensee's preparation of its own regulatory submissions in the Territory and do not constitute an assignment or transfer of any regulatory filings, marketing authorizations, or IND/CTA numbers held by Licensor.
8. Additional Know-How
8.1 Crystalline Form Information
The Licensed Know-How includes the following solid-state characterization data and crystalline form information for PPC-4187:
(a) Polymorphic form characterization data for PPC-4187, including identification, characterization, and physicochemical properties of the designated crystalline forms: Form A (the thermodynamically stable form selected for commercial development), Form B (a metastable polymorph), Form C (a hydrate form), and any other polymorphic, solvated, hydrated, or amorphous forms identified during polymorph screening studies;
(b) Solid-state characterization data for each identified form, including: (i) X-ray powder diffraction (XRPD) patterns and peak position tables; (ii) differential scanning calorimetry (DSC) thermograms, including melting points, enthalpies of fusion, and glass transition temperatures (for amorphous material); (iii) thermogravimetric analysis (TGA) data, including weight loss profiles; (iv) dynamic vapor sorption (DVS) isotherms; (v) Fourier transform infrared (FTIR) spectroscopy data; (vi) Raman spectroscopy data; and (vii) solid-state nuclear magnetic resonance (ssNMR) data, as available;
(c) Polymorph screening and selection reports, including the rationale for selection of Form A as the preferred crystalline form for commercial development, competitive slurry experiments, interconversion studies, and thermodynamic stability assessments;
(d) Documentation of the relationship between the crystalline Form A data and claims of U.S. Patent No. 11,345,678 (entitled "Crystalline Forms of Penteracitinib and Methods of Preparation Thereof," issued May 24, 2022, expiring November 3, 2038), which patent is listed on Schedule A (Licensed Patents) to the Agreement.
8.2 Competitive intelligence and Market Data
(a) Internal Penterra market assessments for PPC-4187 in the atopic dermatitis therapeutic area within the Territory, including market size and growth projections, patient population segmentation analyses, payer landscape assessments, and pricing and reimbursement benchmarking analyses;
(b) Competitive landscape analyses prepared by or on behalf of Licensor, including assessments of marketed and pipeline JAK inhibitors in atopic dermatitis (including but not limited to baricitinib, upadacitinib, and abrocitinib), comparative efficacy and safety profiling, and anticipated competitive positioning for PPC-4187;
(c) Clinical benchmarking data comparing PPC-4187 clinical results to published data for competing compounds in atopic dermatitis, in each case to the extent such information constitutes proprietary Know-How of Licensor and is not publicly available.
8.3 Invention Disclosures and Trade Secrets
(a) All unpublished invention disclosures relating to PPC-4187 formulation, manufacturing, or use that have been filed internally at Penterra Pharmaceuticals Corp. as of the Effective Date, including invention disclosures relating to: (i) novel formulation approaches for PPC-4187 (e.g., modified-release formulations, topical formulations, pediatric formulations); (ii) process improvements or alternative synthetic routes for PPC-4187 API; and (iii) new therapeutic uses or combination therapy approaches for PPC-4187, in each case to the extent not already captured in patent applications or issued patents listed on Schedule A;
(b) Trade secret documentation not otherwise captured in patent filings, including proprietary formulation rationale, process development notebooks, internal technical memoranda, and other confidential technical documentation relating to PPC-4187 that Licensor has maintained as trade secrets, subject to Licensor's obligation under the Agreement to use commercially reasonable efforts to compile and deliver such documentation.
9. Format and Delivery of Licensed Know-How
All Licensed Know-How described in this Schedule B shall be delivered to Licensee in electronic format via Licensor's secure file transfer platform (currently Citrix ShareFile, with AES-256 encryption) within thirty (30) calendar days of the Effective Date (i.e., no later than November 19, 2023), except as otherwise specified in the Technology Transfer Agreement referenced below. Electronic files shall be provided in their native format (e.g., PDF, Microsoft Word, Microsoft Excel, SAS transport files, and other standard file formats), organized in a logical folder structure corresponding to the sections of this Schedule B.
Hard-copy originals or certified copies of any Licensed Know-How documents shall be provided by Licensor upon Licensee's reasonable written request, at Licensee's expense for reproduction and shipping, within thirty (30) calendar days of such request.
All Licensed Know-How documents shall be provided in the English language. To the extent any original source documents constituting Licensed Know-How are in a language other than English, Licensor shall provide English translations of such documents at Licensor's expense, certified as accurate by a qualified translator where reasonably requested by Licensee.
All Licensed Know-How delivered in electronic format shall be transmitted to Licensee at the following address and to the attention of the following designated recipients:
Meridian Bio Therapeutics Limited 18/F, Blossom Tower 88 Queen's Road Central Hong Kong SAR
Attention: Dr. Kenji Morimoto, Chief Medical Officer
and David R. Cheung, General Counsel
Email: kmorimoto@meridianbio.com.hk; dcheung@meridianbio.com.hk
Hard-copy deliveries shall be addressed to the same physical address, marked "CONFIDENTIAL — Licensed Know-How," with tracking confirmation required.
The Parties acknowledge and agree that the detailed timeline, sequencing, and procedures for the transfer of manufacturing process know-how (including the know-how described in Section 3 of this Schedule B) shall be governed by the Technology Transfer Agreement entered into between Licensor and Licensee concurrently with the Agreement (the "Technology Transfer Agreement"), which provides for a twenty-four (24)-month completion deadline for the full transfer of all manufacturing process know-how (i.e., completion by no later than October 20, 2025). In the event of any conflict between this Schedule B and the Technology Transfer Agreement with respect to the timing or manner of delivery of manufacturing process know-how, the Technology Transfer Agreement shall control.
10. Confidentiality and Use Restrictions
All Licensed Know-How described in this Schedule B constitutes Confidential Information of Licensor and is subject to the confidentiality obligations set forth in Article 12 (Confidentiality) of the Agreement. Without limiting the generality of the foregoing:
(a) Licensee shall treat all Licensed Know-How as Confidential Information of Licensor and shall protect and safeguard such Licensed Know-How in accordance with the standards and procedures set forth in Section 12.1 of the Agreement, using no less than the same degree of care that Licensee uses to protect its own confidential information of a similar nature, but in no event less than reasonable care;
(b) Licensee's right to use the Licensed Know-How is limited exclusively to the development, manufacture, and commercialization of Licensed Products containing PPC-4187 (Penteracitinib) within the Territory, as defined in Schedule D to the Agreement, and solely as permitted under and in accordance with the terms and conditions of the Agreement;
(c) Licensee shall have no right to use the Licensed Know-How, in whole or in part, for any compound other than PPC-4187 (Penteracitinib), or for any indication other than the indications for which Licensee is authorized to develop, manufacture, and commercialize Licensed Products under the Agreement;
(d) Licensee may disclose Licensed Know-How to its Affiliates, sublicensees, subcontractors, and regulatory authorities only to the extent permitted under the Agreement and subject to appropriate confidentiality obligations consistent with those set forth in Article 12 of the Agreement.
11. Updates and Supplements
Licensor shall supplement this Schedule B with additional Know-How generated or obtained by Licensor during the term of the Agreement to the extent such additional Know-How relates to PPC-4187 (Penteracitinib) in the Territory, in accordance with the information-sharing obligations set forth in Section 4.6 of the Agreement. Such supplements shall be provided to Licensee in the format and manner described in Section 9 of this Schedule B, within forty-five (45) calendar days of generation or receipt of such additional Know-How by Licensor, unless a different timeline is mutually agreed upon by the Parties.
The Joint Steering Committee established pursuant to Section 3.1 of the Agreement, consisting of three (3) designated representatives from each Party, meeting on a quarterly basis (or more frequently as circumstances may require), shall oversee the exchange and supplementation of Licensed Know-How, including reviewing the completeness and adequacy of Know-How transfers, addressing any questions or issues raised by Licensee regarding the Licensed Know-How, and coordinating the resolution of any gaps or deficiencies identified during technology transfer.
The Joint Patent Committee established pursuant to Section 8.5 of the Agreement, consisting of two (2) designated representatives from each Party, shall coordinate on any new patentable inventions arising from or relating to the Licensed Know-How, including the evaluation and prosecution of patent applications, the allocation of patent filing and maintenance costs, and the ownership and licensing of any jointly developed intellectual property, all in accordance with Article 8 (Intellectual Property) of the Agreement.
Any updates or supplements to this Schedule B shall be deemed incorporated into and form part of this Schedule B upon delivery to Licensee, without the need for a formal amendment to the Agreement, unless the Parties otherwise agree in writing.
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SCHEDULE B — SIGNATURE PAGE
This Schedule B is incorporated into and forms part of the Exclusive License Agreement dated October 2, 2023, effective October 20, 2023, by and between Penterra Pharmaceuticals Corp. and Meridian Bio Therapeutics Limited. By executing this Schedule B below, each Party acknowledges that it has reviewed the contents hereof and confirms its agreement to the terms set forth herein.
LICENSOR:
PENTERRA PHARMACEUTICALS CORP.
By: ________
Name: Dr. Sarah E. Harrington
Title: President and Chief Executive Officer
Date: ________
LICENSEE:
MERIDIAN BIO THERAPEUTICS LIMITED
By: ________
Name: Michael T. Kwok
Title: Chief Executive Officer and Executive Director
Date: ________

SCHEDULE B

LICENSED KNOW-HOW

LICENSOR:

PENTERRA PHARMACEUTICALS CORP.

LICENSEE:

MERIDIAN BIO THERAPEUTICS LIMITED

Record

Parties

Dates

Amounts