Announcement • Jun 03
Zenas Biopharma Presents Data from Registrational Phase 3 Indigo Trial of Obexelimab in Immunoglobulin G4-Related Disease Zenas BioPharma presented additional positive data from the Phase 3 INDIGO trial evaluating obexelimab in Immunoglobulin G4-Related Disease (IgG4-RD) at the European Alliance of Associations for Rheumatology 2026 Congress, held from June 3-6, 2026, in London, England and published online by the New England Journal of Medicine. Collectively, the results consistently demonstrated reductions in disease activity including flare burden as well as glucocorticoid use and toxicity across multiple endpoints. The safety profile of obexelimab was comparable to placebo. In INDIGO, 194 IgG4-RD patients with newly diagnosed or recurrent disease were randomized 1:1 to receive 250 mg of obexelimab or placebo subcutaneously weekly for 52 weeks. Patient demographics and clinical characteristics were generally balanced across arms at baseline. Obexelimab demonstrated a highly statistically significant and clinically meaningful 56% reduction in the risk of IgG4-RD flare compared to placebo (HR 0.44; 95% CI 0.277–0.711; p=0.0005) during the 52-week randomized controlled period. A majority of patients treated with obexelimab (73.2%) remained flare-free through Week 52, compared to fewer than half (45.4%) of placebo-treated patients. These findings indicate a sustained reduction in flare risk over time following glucocorticoid withdrawal. Time to first investigator-determined flare requiring rescue therapy was significantly longer with obexelimab and risk of investigator-determined disease flare requiring rescue therapy was reduced by 59% with obexelimab compared to placebo (HR 0.41; 95% CI 0.26-0.66; p=0.0001). The annualized adjudicated flare rate was 52% lower for obexelimab compared to placebo (HR 0.48; 95% CI 0.32-0.74; p=0.0008); 36 flares were observed in the obexelimab group compared with 72 in the placebo group. At Week 52, 37.1% of patients receiving obexelimab achieved complete remission compared to 19.6% of patients who received placebo, representing a 17.7% improvement (p=0.0049). Complete remission was defined as no AC-determined flare, no treatment for flare and an IgG4-RD Responder Index (RI) of 0 or investigator determination of no active disease. At Week 52, mean cumulative glucocorticoid rescue therapy use was 329.5 mg across all obexelimab-treated patients and 929.8 mg for placebo-treated patients, representing an approximate 600 mg difference (p=0.0042; 65% reduction with obexelimab). Glucocorticoid toxicity was assessed using the Glucocorticoid Toxicity Index (GTI) and included 8 domains: body mass index, glucose tolerance, blood pressure, lipid metabolism, infection, GC myopathy, skin toxicity, and neuropsychiatric effects. At Week 52, the proportion of patients exceeding predefined glucocorticoid toxicity worsening thresholds was significantly lower in the obexelimab group compared to placebo, with 42.2% vs. 61.2% of patients reaching a =20-point GTI-CWS increase (p=0.0135) and 28.9% vs. 49.4% reaching a =30-point increase (p=0.0090). After an initial decrease that remained above the lower limit of normal (LLN), mean B-cell levels in obexelimab-treated patients stabilized and consistently remained above the LLN. Treatment-emergent adverse events (TEAEs) occurred in 97.9% of obexelimab-treated patients compared to 95.9% of placebo-treated patients. The incidence of Grade =3 TEAEs was lower with obexelimab (11.3%) compared to placebo (23.7%), and the incidence of serious adverse events was also lower for obexelimab (10.3%) compared with placebo (18.6%). Infections occurred in 53.6% of obexelimab-treated patients compared to 62.9% of placebo-treated patients. 3.5% of obexelimab doses resulted in injection-site reactions compared to 2.3% of placebo doses. Grade 2 or higher hypersensitivity occurred in 16.5% of obexelimab-treated patients compared to 11.3% of placebo-treated patients. All were Grade 2 except one Grade 3 reaction in an obexelimab-treated patient. There were no deaths in the obexelimab group and one death (1.0%) in the placebo group. Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and Fc?RIIb, which are broadly present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. This unique inhibitory mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of the B cell lineage in chronic autoimmune disease. Obexelimab has been evaluated in eight clinical trials in a total of 383 subjects, including INDIGO. Obexelimab was well tolerated and demonstrated clinical activity across these clinical trials. The registrational Phase 3 INDIGO trial for Immunoglobulin G4-Related Disease met its primary endpoint and all four key secondary endpoints with high statistical significance. The trial continues to evaluate patients in the 3-year open label extension period which will further build upon the largest body of clinical data reported for IgG4-RD patients to date. Enrollment in a randomized Phase 2 trial for Systemic Lupus Erythematosus is completed. Zenas expects to report topline results, including biomarker data from this trial in the fourth quarter of 2026. A Biologics License Application (BLA) for obexelimab in IgG4-RD was submitted to the FDA in May. ZBIO
Live News • May 30
Zenas BioPharma Submits FDA Application for Obexelimab Targeting IgG4-Related Disease Zenas BioPharma has submitted a Biologics License Application (BLA) to the U.S. FDA for obexelimab as a treatment for Immunoglobulin G4-Related Disease (IgG4-RD).
The filing is supported by positive data from the Phase 3 INDIGO trial, where obexelimab reduced the risk of IgG4-RD flare compared with placebo.
The company states that obexelimab may play an important role as a first-line therapy option for long-term management of IgG4-RD.
This BLA submission moves obexelimab into the formal U.S. regulatory review process, which can be a key milestone for any clinical-stage company with a specialty drug candidate.
Investors may want to focus on future FDA review timelines, potential label scope if approved, and the competitive context in IgG4-RD to evaluate the potential importance of this asset within Zenas BioPharma’s portfolio. Announcement • May 28
Zenas BioPharma Submits Biologics License Application To U.S. FDA For Obexelimab In Immunoglobulin G4-Related Disease Zenas BioPharma, Inc. submitted its Biologics License Application (BLA) to the U.S. Food and Drug Administration for obexelimab in Immunoglobulin G4-Related Disease (IgG4-RD). IgG4-RD is a debilitating chronic fibro-inflammatory disease affecting multiple organ systems, often resulting in irreversible tissue damage and organ failure. Obexelimab, an investigational therapy, is a bifunctional monoclonal antibody designed to bind both CD19 and FcgRIIb to inhibit B cell function. The BLA submission is supported by the results of the Phase 3 INDIGO registrational trial of obexelimab for the treatment of IgG4-RD. In INDIGO, obexelimab met the primary endpoint, demonstrating a highly statistically significant and clinically meaningful 56% reduction in the risk of IgG4-RD flare compared to placebo (Hazard Ratio 0.44, p=0.0005) during the 52-week randomized placebo-controlled period. Obexelimab also met and demonstrated highly statistically significant activity compared to placebo on all four key secondary endpoints and was generally well tolerated. Data from the INDIGO trial will be presented during an oral session at the European Alliance of Associations for Rheumatology (EULAR) 2026 Congress in London, UK, on June 4, 2026. Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and FcgRIIb, which are broadly present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. This unique inhibitory mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of the B cell lineage in chronic autoimmune disease. Obexelimab has been evaluated in eight clinical trials in a total of 383 subjects, including INDIGO. Obexelimab was well tolerated and demonstrated clinical activity across these clinical trials. The registrational Phase 3 INDIGO trial for Immunoglobulin G4-Related Disease met its primary endpoint and all four key secondary endpoints with high statistical significance. The trial continues to evaluate patients in the 3-year open label extension period, which will further build upon the largest body of clinical data reported for IgG4-RD patients to date. Enrollment in a randomized Phase 2 trial for Systemic Lupus Erythematosus is completed and Zenas expects to report topline results, including biomarker data from this trial in the fourth quarter of 2026. 
