Zenas BioPharma's shares dropped sharply on Monday after the company announced late-stage trial results for its investigational antibody, obexelimab, in IgG4-related disease. The Massachusetts-based biotech saw its stock fall 52% to $16.61 per share at market close, down from $34.50.
The Phase III INDIGO study enrolled 194 patients who received either a 250-mg dose of obexelimab or placebo subcutaneously every seven days for 52 weeks. According to Zenas, the treatment resulted in a statistically significant 56% reduction in disease flare-ups compared to placebo over the course of a year.
Despite this result, analysts at Truist Securities noted that obexelimab's efficacy was lower than that seen with Amgen’s B cell depleting agent Uplizna. In the Phase III MITIGATE study, Uplizna achieved an 87% placebo-adjusted reduction in disease flare-ups at 52 weeks and was approved by the FDA for IgG4-related disease in April last year.
Truist analysts described Zenas’ topline results as “positive though debatable,” adding: “We believe investors were disappointed by the efficacy comparison with Uplizna.”
However, Truist also highlighted that IgG4-related disease could represent a $3-billion market opportunity for Zenas, given there are about 20,000 diagnosed patients. The analysts said obexelimab may still have a “competitive profile” due to its subcutaneous administration—compared to Uplizna’s intravenous infusion—and what appears to be a better safety profile.
In the INDIGO study, upper respiratory tract infections occurred in 5% of patients treated with obexelimab versus an 11% rate reported in an open-label study of Uplizna.
Zenas stated it plans to submit a biologics license application for obexelimab in IgG4-related disease during the second quarter. The company is also expecting mid-stage data from trials in multiple sclerosis early this year and a Phase II readout in systemic lupus erythematosus by late 2026.
Obexelimab is designed as a self-administered bifunctional antibody targeting CD19 and FcγRIIb receptors on B cells. This approach suppresses autoimmune activity without depleting B cells themselves. In 2023, Bristol Myers Squibb paid $50 million for rights to develop and commercialize obexelimab across several Asia-Pacific markets including Japan and Australia.
