Core Insights - Zenas BioPharma's phase III INDIGO study for obexelimab in treating IgG4-related disease has met its primary endpoint, showing a significant reduction in flare risk [1][2][7] Study Results - Obexelimab demonstrated a 56% reduction in the risk of IgG4-RD flare compared to placebo over a 52-week period, achieving the primary endpoint of the INDIGO study [2][7] - The treatment also showed significant efficacy across four key secondary endpoints, including reductions in investigator-assessed flares and the number of flares requiring rescue therapy [3][7] Market Reaction - Despite the positive study results, Zenas BioPharma's shares fell by 51.9% on January 5, indicating that the efficacy data may not have met investor expectations [4][7] Future Plans - The company plans to submit a biologics license application to the FDA for obexelimab in Q2 2026 and a marketing authorization application to the European Medicines Agency in the second half of 2026 [5][7] Ongoing Development - Zenas BioPharma is also exploring obexelimab for other autoimmune diseases, with ongoing studies for systemic lupus erythematosus and multiple sclerosis [8][9] - The company is focused on the successful development of obexelimab and other pipeline candidates, as it currently lacks a marketed product [10] Stock Performance - Over the past six months, Zenas BioPharma's shares have increased by 69.7%, outperforming the industry average rise of 21.5% [6]

Summary of Zenas BioPharma Conference Call Company Overview - **Company**: Zenas BioPharma (NasdaqGS: ZBIO) - **Focus**: Development of obexelimab for the treatment of immunoglobulin G4-related disease (IgG4-RD) Key Industry Insights - **Disease Prevalence**: Estimated diagnosed prevalence of IgG4-RD in the U.S. is around 20,000 patients, with total prevalence (including undiagnosed) potentially reaching 40,000. Similar global prevalence is suggested [doc id='9'] - **Market Opportunity**: The market opportunity for IgG4-RD treatment is approximately $3 billion in the U.S. and $2 billion in Europe, with over half of diagnosed patients experiencing frequent flares [doc id='17'] Core Findings from INDIGO Trial - **Trial Results**: The INDIGO trial met its primary endpoint, showing a 56% reduction in the risk of IgG4-RD flare compared to placebo, with a hazard ratio of 0.443 and a p-value of 0.0005 [doc id='12'] - **Secondary Endpoints**: All four key secondary endpoints were met, including time to first flare and the proportion of patients achieving complete remission [doc id='13'] - **Safety Profile**: Obexelimab demonstrated a compelling safety and tolerability profile, with lower incidences of serious adverse events and infections compared to placebo [doc id='15] Treatment Advantages - **Mechanism of Action**: Obexelimab's unique inhibitory mechanism targets B-cells without depleting them, which may provide advantages over existing therapies like Uplizna [doc id='16'] - **Administration**: The drug is administered subcutaneously at home, aligning with patient preferences and reducing the need for infusion center visits [doc id='16'] - **Cost-Effectiveness**: The at-home administration model may lead to lower out-of-pocket costs for patients compared to high-priced infused therapies [doc id='17'] Future Plans - **Regulatory Submissions**: Plans to submit a Biologics License Application (BLA) to the U.S. FDA in Q2 and a marketing authorization application to the European Medicines Agency in the second half of the year [doc id='6'] - **Pipeline Expansion**: Zenas is advancing multiple candidates, including orelabrutinib and ZBO21, into clinical trials, aiming to establish a strong portfolio in autoimmune diseases [doc id='19'] Market Dynamics - **Underdiagnosis**: IgG4-RD is currently underdiagnosed, and the approval of obexelimab could enhance disease recognition and treatment [doc id='18'] - **Competitive Landscape**: The efficacy and safety profile of obexelimab positions it as a potential first-line therapy, especially for older patients who may not tolerate B-cell depletion [doc id='24'] Additional Insights - **KOL Feedback**: Key opinion leaders expressed enthusiasm for obexelimab's efficacy and safety, viewing it as a strong candidate for first-line treatment [doc id='23'] - **Payer Discussions**: Preliminary conversations with payers indicate a favorable view of obexelimab's risk-benefit profile, especially in comparison to existing therapies [doc id='49'] Conclusion - **Transformational Year**: 2025 was highlighted as a transformational year for Zenas, with the INDIGO results expected to drive momentum into 2026 and beyond [doc id='18']

Core Insights - Zenas BioPharma announced positive results from the Phase 3 INDIGO trial of obexelimab, showing a 56% reduction in the risk of IgG4-RD flare compared to placebo, with a Hazard Ratio of 0.44 and p=0.0005 [1][2] - Obexelimab demonstrated statistically significant activity on all four key secondary efficacy endpoints, including reduction in flares requiring rescue therapy and the proportion of patients achieving complete remission [1][2] - The company plans to submit a Biologics License Application (BLA) to the FDA in Q2 2026 and a Marketing Authorization Application (MAA) to the EMA in H2 2026 [1][2] Company Overview - Zenas BioPharma is a clinical-stage global biopharmaceutical company focused on developing therapies for autoimmune diseases [15] - The company is advancing two late-stage product candidates: obexelimab and orelabrutinib, with obexelimab being the lead candidate targeting IgG4-RD [15] - Zenas aims to address the unmet medical needs of patients with autoimmune diseases through innovative therapies [15] Clinical Trial Details - The Phase 3 INDIGO trial enrolled 194 patients and was designed to evaluate the safety and efficacy of obexelimab over a 52-week period [10] - The primary endpoint was the time to first IgG4-RD flare requiring rescue therapy, with key secondary endpoints including the number of flares and the cumulative use of rescue therapy [11][12] - Obexelimab was well tolerated, with lower rates of infections and similar incidence of injection site reactions compared to placebo [1][2] Future Developments - Zenas expects to report topline results from the Phase 2 SunStone trial in Systemic Lupus Erythematosus (SLE) in Q4 2026 [4] - The company is also studying orelabrutinib in a global Phase 3 trial for Primary Progressive Multiple Sclerosis (PPMS) and plans to initiate a trial for non-active Secondary Progressive Multiple Sclerosis (naSPMS) in Q1 2026 [4] - Zenas is preparing to initiate Phase 1 clinical development for two additional product candidates, ZB021 and ZB022, in 2026 [4]

Core Insights - InnoCare Pharma presented over 20 studies on its BTK inhibitor orelabrutinib at the 67th Annual Meeting of the American Society of Hematology (ASH) [1] Efficacy and Safety - Orelabrutinib has shown significant efficacy and safety across multiple lymphoma types, including marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), primary central nervous system lymphoma (PCNSL), and diffuse large B-cell lymphoma (DLBCL) [2] - In a study involving newly diagnosed PCNSL, the combination of orelabrutinib, rituximab, and high-dose methotrexate achieved an objective response rate (ORR) of 89.5% and a complete response (CR) rate of 78.9% [4] - The orelabrutinib and obinutuzumab combination demonstrated an ORR of 96.0% in treatment-naïve MZL patients, with no severe toxicities reported [6][5] - Orelabrutinib combined with rituximab showed an ORR of 81.8% and a CR rate of 72.7% in treatment-naïve MZL patients who were unsuitable for local therapy [7][8] - The orelabrutinib plus bendamustine-rituximab regimen showed promising tumor response and survival outcomes in transplant-ineligible, intermediate- to high-risk MCL patients [9] Real-World Studies - A large-scale real-world study in China indicated that R-CHOP plus orelabrutinib achieved a CR rate of 81.4% in MCD-like DLBCL patients, supporting subtype-directed therapy [11] - Preliminary results from a phase II study suggest that the PRO-Pola regimen is a potential treatment option for elderly, unfit, or frail DLBCL patients, with a CRR of 77.8% and an ORR of 100% among those completing three cycles [12][13] - A retrospective real-world study indicated that orelabrutinib monotherapy achieved an ORR and disease control rate (DCR) of 100% in CLL patients [14] Future Directions - Additional studies on orelabrutinib have been selected for poster presentation and publication at the 2025 ASH Annual Meeting, indicating ongoing research and development efforts [15]

Core Viewpoint - InnoCare Pharma has presented over 20 studies on its BTK inhibitor orelabrutinib at the 67th Annual Meeting of the American Society of Hematology, highlighting its efficacy and safety in treating various lymphomas and chronic lymphocytic leukemia [1][2]. Group 1: Efficacy and Safety of Orelabrutinib - Orelabrutinib has shown significant efficacy in multiple lymphoma types, including marginal zone lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, primary central nervous system lymphoma, and diffuse large B-cell lymphoma [2]. - In a study involving newly diagnosed primary central nervous system lymphoma, the combination of orelabrutinib, rituximab, and high-dose methotrexate achieved an objective response rate (ORR) of 89.5% and a complete response (CR) rate of 78.9% [4]. - The orelabrutinib and obinutuzumab combination demonstrated an ORR of 96.0% in treatment-naïve marginal zone lymphoma patients, with no severe toxicities reported [5][6]. Group 2: Treatment Outcomes and Comparisons - The orelabrutinib plus bendamustine-rituximab regimen showed promising tumor response and survival outcomes compared to the standard bendamustine-rituximab regimen in transplant-ineligible, intermediate- to high-risk mantle cell lymphoma [9]. - In a large-scale real-world study of diffuse large B-cell lymphoma in China, the R-CHOP regimen combined with orelabrutinib achieved a CR rate of 81.4% in MCD-like patients, supporting subtype-directed therapy [11]. - A prospective phase II study indicated that the combination of pomalidomide, rituximab, and orelabrutinib is a potential treatment option for elderly, unfit, or frail patients with diffuse large B-cell lymphoma, achieving a CR rate of 77.8% among those who completed three cycles [12][13][14]. Group 3: Future Research and Development - Additional studies on orelabrutinib have been selected for poster presentation and publication at the 2025 ASH Annual Meeting, indicating ongoing research and development efforts [15]. - InnoCare is committed to discovering and commercializing innovative drugs for cancer and autoimmune diseases, with a focus on addressing unmet medical needs [17].

Core Insights - InnoCare Pharma presented three studies on its BCL2 inhibitor, Mesutoclax (ICP-248), at the 67th Annual Meeting of the American Society of Hematology, showcasing its efficacy and safety in treating various hematologic malignancies [1][2]. Group 1: Efficacy in Relapsed/Refractory Mantle Cell Lymphoma (MCL) - Mesutoclax monotherapy demonstrated an overall response rate (ORR) of 87.5% and a complete response rate (CRR) of 46.9% in MCL patients, with an ORR of 84.0% and CRR of 36.0% in BTK inhibitor-refractory patients [3][4]. - The drug was well tolerated across all dose levels (50-150 mg), with no dose-limiting toxicities (DLTs) observed, indicating a promising safety profile [4]. Group 2: Efficacy in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) - In CLL/SLL patients, both treatment-naive and relapsed/refractory, the ORR was 100% for those receiving 125 mg of mesutoclax, with a 65% undetectable minimal residual disease (uMRD) rate at week 36 when combined with orelabrutinib [5][6]. - Mesutoclax exhibited a tolerable safety profile, with no DLTs reported up to 150 mg QD [6]. Group 3: Efficacy in Acute Myeloid Leukemia (AML) - The combination of mesutoclax and azacitidine (AZA) achieved a composite complete response (CR+CRi) rate of 92% in treatment-naive AML patients, with 82.6% achieving undetectable minimal residual disease (uMR) [7][8]. - The combination therapy was well tolerated, with no DLTs or tumor lysis syndrome (TLS) events reported, and a 90-day mortality rate of 0% [8]. Group 4: Ongoing Clinical Trials - InnoCare is conducting two registrational clinical trials: one for the combination of mesutoclax and orelabrutinib for treatment-naive CLL/SLL, and another for MCL patients refractory to BTK inhibitors [9]. - The clinical study of mesutoclax as a first-line treatment for AML has entered the dose expansion phase globally, and a study for myelodysplastic syndrome (MDS) is being launched [9].

Summary of Zenas BioPharma FY Conference Call Company Overview - **Company**: Zenas BioPharma (NasdaqGS: ZBIO) - **Date of Conference**: December 03, 2025 Key Accomplishments in 2025 - Completion of patient enrollment in the Phase III trial for obexelimab targeting IgG4-related disease, with last patient out in November [2][5] - Successful enrollment in a lupus study, with results expected in Q3 of the following year [3][5] - Significant results from the MOONSTONE Global Phase II study in relapsing multiple sclerosis (RMS), showing a 95% reduction in new T1 GAD-enhancing lesions compared to placebo [4][5] - Expansion of the pipeline with the acquisition of orelabrutinib, now in Phase III trials for progressive MS [4][5] - Partnership with Royalty Pharma for a potential $300 million financing related to obexelimab [5] Clinical Trials and Data Insights - The MOONSTONE study involved 116 patients and demonstrated a new benchmark for B-cell targeting agents in RMS [3][4] - Upcoming 24-week data from the MOONSTONE study will provide insights into various parameters, including T1 GAD-enhancing lesions and biomarkers [10][11] - Discussion on regulatory pathways for RMS trials, emphasizing the need for evolving endpoints beyond annualized relapse rates [14] Market Opportunities - Estimated 20,000 to 40,000 diagnosed patients in the U.S. for IgG4-related disease, with a potential market size based on competitive drug pricing exceeding $250,000 annually [23][24] - Observations on the competitive landscape, noting the successful launch of a competing drug with sales growth from mid-$20 million to over $40 million in the first two quarters [25] Future Expectations - Anticipation of Phase II SUNSTONE results for lupus, aiming for a significant difference from placebo [26][27] - Plans to integrate findings from the lupus study into the broader rheumatology franchise [27] Differentiation of Products - Obexelimab is positioned as a more flexible treatment option compared to continuous B-cell depleting therapies, with at-home auto-injector capabilities [20][21] - Orelabrutinib is highlighted as a best-in-class BTK inhibitor, with superior brain penetration and potency compared to competitors [28][29] Conclusion - Zenas BioPharma has made significant strides in 2025, with promising clinical trial results and strategic partnerships that position the company for future growth in the biopharmaceutical market. The focus on innovative treatment options and market opportunities in IgG4-related disease and lupus reflects a strong potential for success in upcoming years.

Core Insights - Zenas BioPharma reported significant advancements in its clinical trials, particularly with obexelimab, which showed promising results in treating autoimmune diseases [1][2][3] - The company has secured substantial funding to support its clinical development and commercialization efforts, including a $300 million agreement with Royalty Pharma [1][6] - Zenas is expanding its product pipeline with the acquisition of three new autoimmune product candidates, including orelabrutinib, which is in Phase 3 development for multiple sclerosis [1][3][10] Clinical Trial Updates - The Phase 3 INDIGO trial for obexelimab in Immunoglobulin G4-Related Disease (IgG4-RD) is set to report topline results around year-end 2025, marking it as the largest clinical trial for this condition to date [1][3] - The Phase 2 MoonStone trial for obexelimab in Relapsing Multiple Sclerosis (RMS) demonstrated a 95% relative reduction in new gadolinium-enhancing lesions compared to placebo, with a p-value of 0.0009 [3][4] - Zenas expects to report 24-week data from the MoonStone trial in the first quarter of 2026 [3] Financial Highlights - As of September 30, 2025, Zenas had cash, cash equivalents, and investments totaling $301.6 million, which, along with recent financing, is expected to fund operations into the fourth quarter of 2026 [7][18] - The company reported a net loss of $51.5 million for the third quarter of 2025, compared to a net loss of $38.6 million for the same period in 2024 [13][17] - Research and development expenses for the quarter were $34.4 million, while general and administrative expenses increased to $13.2 million from $7.5 million year-over-year [7][17] Pipeline Expansion - Zenas has entered into a license agreement for orelabrutinib, a BTK inhibitor, granting global development and commercialization rights outside Greater China and Southeast Asia [3][10] - The company is also advancing two additional product candidates, ZB021 and ZB022, both of which are expected to enter Phase 1 clinical development in 2026 [4][10] Company Overview - Zenas BioPharma is focused on developing transformative therapies for autoimmune diseases, with a strategy that includes acquiring and developing product candidates that offer superior clinical benefits [11] - The company aims to become a leader in the biopharmaceutical industry, leveraging its experienced leadership and disciplined approach to product development [11]

Core Insights - Zenas BioPharma announced positive results from the Phase 2 MoonStone trial of obexelimab in Relapsing Multiple Sclerosis (RMS), achieving a 95% relative reduction in new gadolinium-enhancing T1 lesions compared to placebo [1][2][3] Company Overview - Zenas BioPharma is a clinical-stage global biopharmaceutical company focused on developing transformative therapies for autoimmune diseases [12] - The company is advancing two late-stage product candidates: obexelimab and orelabrutinib, with obexelimab being the lead candidate [12] Clinical Trial Results - The MoonStone trial enrolled 116 patients and demonstrated a near-complete suppression of new GdE T1 hyperintense lesions by 8 weeks, sustained through week 12 [3][9] - The adjusted mean number of new GdE T1 lesions per scan in the obexelimab group was 0.01 compared to 0.23 in the placebo group [3] - Obexelimab also significantly reduced the cumulative number of new and/or enlarging T2 weighted hyperintense lesions, indicating a reduction in disease burden [3] Future Developments - Zenas plans to report 24-week data from the MoonStone trial in Q1 2026, which will include additional secondary and exploratory endpoints [4] - The company expects to report topline results from the Phase 3 INDIGO trial in IgG4-RD by the end of 2025 and from the Phase 2 SunStone trial in Systemic Lupus Erythematosus by mid-2026 [4] Mechanism of Action - Obexelimab is a bifunctional monoclonal antibody designed to inhibit B cell activity without depleting them, targeting both CD19 and FcγRIIb [10][12] - This unique mechanism may effectively address the pathogenic role of B cells in chronic autoimmune diseases [10][12] Disease Context - Multiple Sclerosis (MS) is a chronic autoimmune disorder affecting approximately 2.9 million people globally, with RMS being the most common subtype [5][8] - Early intervention with effective therapies is crucial to manage the disease and prevent disability progression [7][8]

Group 1 - The Zenas deal reflects a trend of U.S. pharmaceutical companies seeking innovation from China, where biotechnology startups benefit from lower costs and regulatory flexibility [3] - Concerns are rising among U.S. biotech companies and investors about losing competitive edge due to the growing pipeline of drugs from China, prompting a bipartisan commission to warn about the situation [4] - The pace of licensing Chinese drugs has accelerated, with four deals announced in the previous month, despite calls from top pharmaceutical executives for government support to bolster the U.S. biotech industry [5] Group 2 - Zenas BioPharma is enhancing its pipeline by acquiring three experimental autoimmune medicines from InnoCare Pharma, including a multiple sclerosis treatment currently in Phase 3 testing [6][7] - InnoCare is set to receive up to $100 million in upfront and near-term cash payments, with the total deal potentially exceeding $2 billion, including royalties [7] - Zenas has also secured a private placement of stock worth approximately $120 million to ensure operational cash flow into late 2026 and possibly early 2027 [7]