Zenas BioPharma (ZBIO) Study update summary

IgG4-RD burden and treatment need

• IgG4-RD is chronic, progressive and often multi-organ; active disease may be asymptomatic while causing irreversible fibrosis and organ damage, and relapses are common after treatment stops.

• Diagnosis is challenging because serum IgG4 can be normal in ~20% of patients; diagnosis integrates clinical, serological, histopathological and radiological features, and under-recognition contributes to delay.

• More than 85% of patients receive glucocorticoids; cited relapse rates were 30% within six months and ~90% by three years, underscoring the need for steroid-sparing maintenance options.

• Glucocorticoids and B-cell-depleting therapies have limitations including toxicity, prolonged B-cell depletion, declining IgG, cumulative infection risk and IV administration burden.

INDIGO Phase III design

• Global, double-blind, randomized, placebo-controlled trial enrolled 194 patients across 15 countries and 114 sites; 97 patients per arm, with nearly 90% completing 52 weeks in each arm.

• Patients received weekly subcutaneous obexelimab 250 mg or placebo for 52 weeks; both arms followed the same eight-week prednisone taper after starting at 20 mg.

• Primary endpoint was time to first IgG4-RD flare requiring rescue therapy, confirmed by blinded adjudication using organ-specific clinical, laboratory and imaging criteria.

• Most patients had multi-organ involvement; baseline demographics were balanced, with mean age ~59 years and a majority male.

Efficacy and safety

• 73.2% of obexelimab patients remained flare-free through week 52; hazard ratio for flare was 0.443 (95% CI 0.277–0.711; P=0.0005).

• All key secondary endpoints were met: complete remission at week 52 was 37.1% versus 19.6%, annualized flare rate was lower, and cumulative glucocorticoid rescue use was reduced versus placebo.

• Obexelimab was associated with less accumulated glucocorticoid toxicity; sustained serum IgG4 reductions were observed while B-cell counts remained above the lower limit of normal.

• Grade 3 or higher adverse events occurred in 11% with obexelimab versus 24% with placebo; serious and grade ≥3 events were less frequent with obexelimab, with no new safety signals.

• Three malignancies in the obexelimab arm were deemed unrelated by investigators.