Zenas BioPharma, Inc. recently announced positive results from the Phase 3 INDIGO trial of obexelimab in Immunoglobulin G4-Related Disease (IgG4-RD). 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, which were reduction in investigator assessed IgG4-RD flare, the number of flares requiring rescue therapy, the proportion of patients achieving complete remission and the cumulative use of IgG4-RD rescue therapy. Rates of infections, including Grade 3, were lower in the obexelimab arm compared to placebo, and the incidence of injection site reactions was similar across both study arms. The Company expects that full data from the INDIGO trial will be presented at a future medical meeting.

“Given obexelimab’s significant clinical activity and the compelling safety and tolerability profile observed in the INDIGO trial, we believe obexelimab may have an important role as a first line therapy in the long-term management of IgG4-RD,” said Lonnie Moulder, Founder and Chief Executive Officer of Zenas. “With its unique inhibitory mechanism, tolerability profile, at-home subcutaneous self-administration and potential to pause for vaccination or management of intercurrent illness, obexelimab has the potential to be a meaningful treatment option for patients. IgG4-RD represents a significant commercial opportunity for obexelimab and Zenas, and today’s data support obexelimab as a potential franchise molecule for rheumatic diseases. We look forward to submitting our Biologics License Application to the FDA in the second quarter of 2026 and our Marketing Authorization Application to the EMA in the second half of this year.”

“Patients living with IgG4-RD have faced limited treatment choices for far too long,” said John Stone, M.D., M.P.H., Professor of Medicine at Harvard Medical School and the Edward A. Fox Chair in Medicine at Massachusetts General Hospital. “The INDIGO study results suggest that obexelimab, with its intriguing mechanism of action – emphasizing B cell inhibition rather than B cell depletion – and self-administration by patients, may be an important new therapy for people living with IgG4-RD.”

“These INDIGO trial results build upon the highly positive results observed in our Phase 2 MoonStone trial in Relapsing Multiple Sclerosis and further validate obexelimab’s mechanism of action, optimized subcutaneous dosing and its potential to address the unmet medical needs of patients living with autoimmune diseases,” said Lisa von Moltke, M.D., Head of Research and Development and Chief Medical Officer of Zenas. “Without treatment, IgG4-RD meaningfully contributes to organ fibrosis, damage and failure. Obexelimab’s unique inhibitory mechanism, combined with its weekly subcutaneous dosing chosen for optimal pharmacokinetic and clinical activity, has the potential to sustain B cell inhibition and durably impact disease activity. The INDIGO trial results are supported by the largest body of clinical data ever reported in this indication and strengthen confidence in the ongoing Phase 2 SunStone trial in Systemic Lupus Erythematosus (SLE), which remains on track to report data later this year. On behalf of the Zenas team, I would like to thank the patients and healthcare professionals who took part in the INDIGO trial.”

Following these positive Phase 3 INDIGO results, Zenas anticipates submitting the obexelimab Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for the treatment of IgG4-RD in the second quarter of 2026. Zenas also intends to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the second half of 2026. Zenas’ partner Bristol Myers Squibb holds exclusive development and commercialization rights for obexelimab in Japan, South Korea, Taiwan, Hong Kong, Singapore and Australia.

Zenas also expects to report topline results, including a biomarker analysis, of the obexelimab Phase 2 SunStone trial in SLE in the fourth quarter of 2026. In addition, orelabrutinib, a potentially best-in-class, highly selective central nervous system (CNS)-penetrant, oral, small molecule Bruton’s Tyrosine Kinase (BTK) inhibitor, is being studied in a global Phase 3 clinical trial in patients with Primary Progressive Multiple Sclerosis (PPMS). A global Phase 3 trial of orelabrutinib in patients with non-active Secondary Progressive Multiple Sclerosis (naSPMS) is expected to initiate in the first quarter of 2026. Subject to Investigational New Drug (IND) clearance, Zenas expects to initiate Phase 1 clinical development for ZB021, a potentially best-in-class oral IL-17AA/AF inhibitor, in 2026. Pending Phase 1 data, Zenas expects to advance development of ZB021 for rheumatic and/or dermatologic diseases. In addition, subject to IND clearance, Zenas expects to initiate Phase 1 clinical development for ZB022, a potentially best-in-class brain penetrant TYK2 inhibitor, in 2026. Pending Phase 1 data, Zenas expects to advance development of ZB022 for neurologic diseases.

About Immunoglobulin G4-Related Disease

Immunoglobulin G4-Related Disease (IgG4-RD) is a chronic fibro-inflammatory disease that can affect virtually all organ systems, including the pancreas, biliary tract, salivary and lacrimal glands, lungs and kidneys. Patients with IgG4-RD may present with a single organ involved but more frequently present with multiple organ involvement.

As the disease progresses and patients experience new or worsening symptoms (i.e., flares), lesions may develop in additional organs and the cellular inflammation characterizing early disease moves toward a more fibrotic stage, which can lead to major irreversible tissue damage and ultimately organ failure. We estimate that the currently diagnosed population of IgG4-RD patients in the U.S. is approximately 20,000, with comparable prevalence rates globally.

Despite the growing recognition of IgG4-RD and advances in the understanding of its pathophysiology, treatment options are limited. The pathogenesis of IgG4-RD suggests that B cell-targeted therapies may provide therapeutic benefit. One B cell depleting agent is currently approved to treat IgG4-RD in the U.S. and others (e.g., rituximab) are occasionally administered to patients with IgG4-RD. However, B cell depleting agents can compromise a patient’s ability to mount a response to vaccinations and can compromise response to infections including serious and opportunistic infections should they occur.

Glucocorticoids (GCs), while not approved for the treatment of IgG4-RD, are commonly used to treat disease flares. Although GC treatment is initially effective, long-term treatment can often result in various complications and co-morbidities. GCs do not address underlying disease activity that can meaningfully contribute to organ fibrosis, damage and failure. Most patients treated with GCs relapse within 12 months of discontinuing treatment, and maintenance therapy with GCs has not been shown to prevent recurrence of disease.

About the Phase 3 INDIGO Trial

The Phase 3 INDIGO trial, which enrolled 194 patients, is a global, registration-directed, double-blind, placebo-controlled trial, designed to evaluate the safety and efficacy of obexelimab in patients with IgG4-RD. After an initial screening period, patients were randomized 1:1 to 250 mg of obexelimab or placebo administered as a subcutaneous injection every seven days for 52 weeks, followed by an opportunity for eligible patients to continue in an open-label extension period where all patients will receive treatment with obexelimab.

The primary efficacy endpoint of INDIGO is the time to first IgG4-RD flare as determined per protocol, that requires initiation of rescue therapy as determined by the investigator and the adjudication committee (AC) from randomization to week 52. Key secondary endpoints included time to first IgG4-RD flare as determined per protocol, that requires initiation of rescue therapy as determined by the investigator from randomization to week 52; the number of investigator and AC-determined flares requiring initiation of rescue therapy from randomization to week 52; the proportion of patients achieving complete remission at week 52; and the cumulative dose of IgG4-RD rescue therapy from randomization to week 52.

More information on the INDIGO trial (NCT05662241) is available at clinicaltrials.gov.

About Obexelimab

Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb, 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. In October 2025, Zenas reported that the Phase 2 MoonStone trial for Relapsing Multiple Sclerosis met its 12-week primary endpoint demonstrating a highly statistically significant 95% relative reduction in the cumulative number of new gadolinium-enhancing T1 hyperintense lesions over week 8 and week 12 compared with placebo (p=0.0009). A randomized Phase 2 trial for Systemic Lupus Erythematosus is ongoing and Zenas expects to report topline results, including biomarker data from this trial in the fourth quarter of 2026.

About Zenas BioPharma, Inc.

Zenas is a clinical-stage global biopharmaceutical company committed to becoming a leader in the development and commercialization of transformative therapies for patients living with autoimmune diseases. Our core business strategy combines our experienced leadership team with a disciplined product candidate acquisition approach to identify, acquire and develop product candidates globally that we believe can provide meaningful clinical benefits to patients living with autoimmune diseases. Zenas is advancing two late-stage, potential franchise molecules, obexelimab and orelabrutinib. Obexelimab, Zenas’ lead product candidate, is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb, which are broadly present across B cell lineage, to inhibit the activity of cells that are implicated in many autoimmune diseases without depleting them. We believe that obexelimab’s unique inhibitory mechanism of action and self-administered, subcutaneous injection regimen may broadly and effectively address the pathogenic role of B cell lineage in chronic autoimmune disease. Orelabrutinib is a potentially best-in-class, highly selective central nervous system (CNS)-penetrant, oral, small molecule BTK inhibitor. Orelabrutinib’s mechanism of action targets pathogenic B cells not only in the periphery but also within the CNS. Additionally, it directly modulates macrophages and microglial cells in the CNS, with the potential to address compartmentalized inflammation and disease progression in Multiple Sclerosis (MS). Zenas’ earlier stage programs include ZB021, a preclinical, potentially best-in-class, oral, IL-17AA/AF inhibitor, and ZB022, a preclinical, potentially best-in-class, oral, brain-penetrant, TYK2 inhibitor. For more information about Zenas BioPharma, please visit https://zenasbio.com/ and follow us on LinkedIn.