Zenas BioPharma, Inc.(ZBIO) - 2025 Q4 - Annual Report

Clinical Trials and Efficacy - Obexelimab demonstrated a 56% reduction in the risk of IgG4-RD flare compared to placebo in the Phase 3 INDIGO trial, with a Hazard Ratio of 0.44 (p=0.0005) and met all key secondary endpoints [17]. - The Phase 2 MoonStone trial for relapsing multiple sclerosis (RMS) showed a 95% relative reduction in new gadolinium-enhancing lesions compared to placebo (p=0.0009) at the 12-week primary endpoint [18]. - Obexelimab has been evaluated in eight clinical trials with a total of 383 subjects, demonstrating a well-tolerated safety profile and clinical activity [29]. - In the IgG4-RD trial, 80% of patients showed a reduction in disease score, with 67% achieving complete remission [50]. - The Phase 2 trial of obexelimab in SLE showed a treatment difference of 17.3% in the ITT population (40.4% obexelimab vs. 23.1% placebo, p=0.06) [51]. - The Phase 2 trial of obexelimab for IgG4-RD included 20 patients, with 15 receiving 5 mg/kg IV every two weeks for 24 weeks [68]. - The Phase 2 trial showed that 21 out of 50 (42.0%) obexelimab-treated patients achieved the primary endpoint, although not statistically significant (p = 0.183) [100]. - Obexelimab demonstrated a 42.0% response rate in the EE population compared to 28.6% in the placebo group, with a treatment difference of 17.3% in the ITT analysis [100]. - The overall safety profile of obexelimab was favorable, with the majority of TEAEs being mild or moderate across multiple studies [107]. - The most common treatment-emergent adverse events included abdominal pain and nausea (20%), with no new safety signals observed at week 24 [76][79]. Product Development and Commercialization - The company plans to submit a Biologics License Application (BLA) for obexelimab to the FDA in Q2 2026 and a Marketing Authorization Application (MAA) to the EMA in the second half of 2026 [17]. - Each of the indications for obexelimab, including IgG4-RD, RMS, and systemic lupus erythematosus (SLE), represents a multi-billion-dollar commercial opportunity in the U.S. alone [16]. - The company has no product candidates approved for commercial sale and has not generated any revenue from product sales to date [25]. - The company plans to leverage initial successes to expand into broader I&I opportunities and evaluate strategic collaborations for commercialization [43]. - A recent licensing agreement secured rights to develop and commercialize orelabrutinib in MS worldwide, excluding greater China and Southeast Asia [43]. - The company plans to initiate a second Phase 3 trial for orelabrutinib in non-active SPMS in the first quarter of 2026, enrolling approximately 990 patients [140]. Intellectual Property and Licensing Agreements - The company owns or exclusively in-licenses 28 patent families covering various product candidates, with expiration dates ranging from 2027 to 2047 [194]. - The company has 14 patent families specifically covering obexelimab, with the first patent family expiring in May 2028 and others extending to October 2044 [197][198]. - The company entered into a License Agreement with InnoCare, making a one-time non-refundable upfront cash payment of $35.0 million and issuing 5,000,000 shares of common stock as partial consideration [185]. - The company received a one-time upfront payment of $50.0 million under the BMS Agreement, with potential milestone payments totaling up to $79.5 million for development and regulatory achievements, and up to $70.0 million for sales milestones [179]. - The last-to-expire patent under the BMS Agreement is set to expire on October 2, 2044, assuming all applications are allowed [180]. Future Developments and Pipeline - Orelabrutinib is being advanced in a Phase 3 trial for Primary Progressive Multiple Sclerosis (PPMS) and a second Phase 3 trial for non-active Secondary Progressive Multiple Sclerosis (SPMS) is expected to initiate in Q1 2026 [21]. - ZB021, an oral IL-17AA/AF inhibitor, is expected to initiate Phase 1 clinical studies in 2026, with initial data anticipated in 2027 [34]. - ZB022, a brain-penetrant TYK2-JH2 inhibitor, is in IND-enabling studies, with an IND application expected in 2026 [23]. - The company is also developing ZB014, an anti-CD-19 and FcγRIIb monoclonal antibody currently in pre-clinical studies [121]. Management and Strategy - The management team has extensive experience in biopharmaceuticals, having been responsible for numerous INDs and successful product launches [38]. - The strategy includes developing obexelimab for multiple I&I indications, with ongoing Phase 2 trials for RMS and SLE, and a Phase 3 trial for IgG4-RD [43].