Core Insights - Orelabrutinib is the first BTK inhibitor to show significant clinical activity in a Phase 2 clinical trial for Systemic Lupus Erythematosus (SLE) [1] - Zenas BioPharma has acquired exclusive rights to develop, manufacture, and commercialize orelabrutinib for Multiple Sclerosis (MS) globally, and for non-oncology fields outside Greater China and Southeast Asia [1][5] Clinical Trial Results - In the Phase 2b study, 187 patients were randomized into three groups: orelabrutinib 75 mg once-daily, orelabrutinib 50 mg once-daily, and placebo [2] - The primary endpoint, SLE Response Index-4 (SRI-4) response rate at week 48, was met with the 75 mg group showing a response rate of 57.1% compared to 34.4% for placebo (p < 0.05) [2] - Secondary endpoints, including SRI-6 and British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response rates, were also significantly higher in the 75 mg group compared to placebo (p < 0.05) [3] Safety and Tolerability - Orelabrutinib was well tolerated, exhibiting a safety profile consistent with BTK inhibition and the disease biology of SLE [3] Development Pipeline - Zenas is advancing orelabrutinib into a Phase 3 trial for Primary Progressive MS (PPMS) and plans to initiate a Phase 3 trial for Secondary Progressive MS (SPMS) in Q1 2026 [6] - Orelabrutinib is already approved for B cell malignancies in mainland China and Singapore, marketed by InnoCare [6] Company Overview - Zenas BioPharma is a clinical-stage global biopharmaceutical company focused on developing transformative therapies for autoimmune diseases [7] - The company is advancing two late-stage molecules: obexelimab and orelabrutinib, with obexelimab being a bifunctional monoclonal antibody targeting CD19 and FcγRIIb [7][8]

Summary of Zenas BioPharma Conference Call - October 08, 2025 Company Overview - **Company**: Zenas BioPharma (NasdaqGS: ZBIO) - **Industry**: Biopharmaceuticals, focusing on autoimmune diseases and multiple sclerosis Key Points Collaboration with Innocare Pharma - Zenas BioPharma announced a transformational global collaboration with Innocare Pharma, a fully integrated biopharmaceutical company [6][8] - The collaboration includes an upfront payment of $35 million in cash and 5 million shares of Zenas common stock [6] - Additional payments of $25 million and 2 million shares will be made upon the first patient treated in the Phase III study for secondary progressive multiple sclerosis (SPMS) [7] Pipeline and Product Candidates - Zenas has a differentiated pipeline with potential best-in-class molecules targeting autoimmune diseases, including relabrutinib for multiple sclerosis [6][8] - The company aims to launch three best-in-class franchise molecules across five indications in three therapeutic areas by 2031 [55] - The pipeline includes: - **Arelobrutinib**: A BTK inhibitor in Phase III trials for primary progressive multiple sclerosis (PPMS) and SPMS [10][25] - **Abexolumab**: Focused on IgG4-related disease, with Phase III results expected by year-end [33][55] - **ZB021**: An oral IL-17 targeting small molecule expected to enter clinical trials in 2026 [31] - **ZB022**: A brain-penetrant TYK2 inhibitor also anticipated to enter clinical trials in 2026 [31] Market Opportunity - The market for progressive multiple sclerosis is estimated at approximately $12 billion in potential peak sales in the U.S. alone [27][29] - The global multiple sclerosis market is projected to exceed $30 billion by 2030, with progressive forms representing over 40% of that market [29] Clinical Data and Efficacy - Arelobrutinib has shown promise in addressing disability progression in progressive MS patients, with a unique mechanism of action targeting both peripheral and central nervous system inflammation [12][28] - The Phase II trial for arelobrutinib demonstrated a greater than 90% reduction in new lesions compared to placebo [21] - The safety profile of arelobrutinib is consistent with other BTK inhibitors, with treatment emergent adverse events observed in 53% of the population [23] Regulatory Path and Future Trials - Phase III protocols for both PPMS and SPMS have been cleared by the FDA and EMA, with the first site for the PPMS study initiated in the U.S. [25][29] - The company is focused on regulatory alignment and is prepared to adapt to evolving regulatory endpoints for relapsing MS [90] Financial Position and Strategy - Zenas BioPharma has completed major financings and significantly advanced its pipeline, positioning itself as a fully integrated commercial-stage biopharmaceutical company [55] - The company emphasizes its strong financial position and global development capabilities to execute its vision [55] Conclusion - Zenas BioPharma is poised for significant growth with its strategic collaboration, robust pipeline, and focus on addressing unmet needs in autoimmune diseases, particularly in multiple sclerosis [55]

InnoCare Collaboration - Zenas BioPharma has a collaboration agreement with InnoCare Pharma, a biopharmaceutical company with a market cap exceeding $4.5 billion USD, two marketed products, and over 10 candidates in clinical development[9] - InnoCare will receive global rights to Orelabrutinib and ZB022, and global rights to ZB021 excluding China and Southeast Asia, while retaining global rights to Orelabrutinib in oncology indications[11] - Zenas will receive $35 million USD in cash and 5 million shares of Zenas common stock upfront from InnoCare[11] - Zenas is eligible for up to an additional 2 million shares of Zenas stock and up to $240 million USD in development and regulatory milestone payments for Orelabrutinib, as well as commercial sales milestone payments and tiered royalties on net sales[11] Orelabrutinib (BTKi) Program - A Phase 3 PPMS registration-directed trial has been initiated in the U S for Orelabrutinib, with a Phase 3 SPMS registration-directed trial expected to initiate in Q1 2026[11] - Orelabrutinib treatment in a Phase 2 RRMS trial resulted in a significant reduction in new GdE+ T1 lesions, with a >90% reduction observed at the 80mg QD dose at week 12 (P=0 0018)[48] - The global MS market is expected to exceed $30 billion USD, with SPMS and PPMS representing >$12 billion USD[61] Pipeline Programs - IND clearance and enrollment of the first patient for ZB021, an oral IL-17AA/AF inhibitor, and ZB022, a brain penetrant TYK2 inhibitor, are expected in 2026[11] - The anti-IL-17 biologics market is currently a $10 billion USD global market with ~50% average annual growth since first approval[74] Obexelimab Program - Phase 3 INDIGO trial for IgG4-RD is fully enrolled with topline results expected around year-end 2025[83] - Phase 2 MoonStone trial for RMS is fully enrolled with (12-week) data expected early Q4 2025[83] - Phase 2 SunStone trial for SLE is enrolling with (24-week) data expected mid-2026[83] - Obexelimab represents a compelling $1 billion+ USD commercial revenue opportunity in the U S alone for IgG4-RD[120]