Zenas BioPharma (ZBIO) Study update summary

Disease Overview and Unmet Need

• IgG4-related disease (IgG4-RD) is a chronic, progressive, multi-organ fibroinflammatory disorder with high relapse rates, significant risk of irreversible organ damage, increased mortality, and substantial economic impact.

• Diagnosis is challenging due to subclinical progression, lack of specific biomarkers or definitive tests, and overlap with other conditions, leading to under-recognition and delayed treatment.

• Current treatments, mainly glucocorticoids and B-cell depleting agents, are effective but associated with significant toxicity, infection risk, and inconvenience for chronic management.

• There is a substantial unmet need for safer, more convenient, and effective long-term therapies, improved early recognition, better diagnostic biomarkers, and long-term data to guide management.

INDIGO Study Design and Population

• INDIGO was a global, double-blind, randomized, placebo-controlled phase III trial enrolling 194 patients with active IgG4-RD across 15 countries and 114 sites, the largest trial in this disease to date.

• Patients were randomized 1:1 to receive weekly subcutaneous obexelimab or placebo for 52 weeks, with primary endpoint being time to first disease flare requiring rescue therapy and comprehensive flare assessment.

• Baseline demographics were balanced, with a mean age of ~59 years, majority male, and most patients having multi-organ involvement, commonly affecting salivary, lacrimal glands, pancreas, and lymph nodes.

Efficacy Results

• Obexelimab significantly reduced the risk of IgG4-RD flares versus placebo (hazard ratio 0.443, P=0.0005), with 73.2% of patients flare-free at 52 weeks.

• All key secondary endpoints were met: lower annualized flare rate, higher complete remission rate (37.1% vs 19.6%), and reduced cumulative glucocorticoid rescue use.

• Obexelimab was associated with less accumulated glucocorticoid toxicity, as measured by the Glucocorticoid Toxicity Index.

• Sustained reductions in serum IgG4 levels were observed, while B-cell counts remained above the lower limit of normal, differentiating it from depleting therapies.