Zenas Reports Positive Results from Phase 3 Study in IgG4-RD, But Stock Sinks

Rare Daily Staff

Zenas BioPharma reported positive results from its Phase 3 trial of obexelimab, an experimental therapy for the rare autoimmune condition immunoglobulin G4-related disease, which met its primary endpoint.

The company said obexelimab cut the risk of flare by 56 percent compared with a placebo over a yearlong period in the Phase 3 INDIGO trial, meeting the study’s primary endpoint with what it called “highly statistically significant” results.

Despite the positive findings, shares of Zenas fell more than 50 percent after the results were released because they fell short of investor expectations and did not outperform Amgen’s approved therapy Uplizna.

The treatment also showed benefits across all four key secondary measures, including the number of flares requiring additional therapy and the rate of complete remission. No new safety issues were reported, and overall infection rates were lower in patients treated with obexelimab than in those who received a placebo, the company said.

Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibroinflammatory condition that can affect nearly all organ systems, including the pancreas, biliary tract, salivary and lacrimal glands, lungs, and kidneys. Patients may present with involvement of a single organ but more often have multiple organs affected.

As the disease progresses, new or worsening symptoms may occur as lesions develop in additional organs. The cellular inflammation that characterizes early disease can evolve into a more fibrotic stage, leading to irreversible tissue damage and, ultimately, organ failure.

Obexelimab is a bifunctional monoclonal antibody designed to bind both CD19 and FcγRIIb, proteins broadly expressed across the B cell lineage, to inhibit the activity of immune cells implicated in many autoimmune diseases without depleting them. This unique inhibitory mechanism and its self-administered, subcutaneous injection regimen may enable more effective, long-term management of chronic autoimmune conditions.

Zenas said it plans to file for U.S. regulatory approval in the second quarter of 2026 and submit an application to European regulators later in the year.

“Given obexelimab’s significant clinical activity and compelling safety profile, we believe it may become a first-line therapy for long-term management of IgG4-RD,” said Lonnie Moulder, CEO of Zenas.

Photo: Lonnie Moulder, CEO of Zenas