Inebilizumab-cdon

Zenas BioPharma released what it called "positive" Phase III data for its bifunctional monoclonal antibody obexelimab in IgG4-related disease, but investors weren't celebrating. The company's stock was down about 52% on Monday as investors seemed to be sizing up the data against Amgen's already-approved anti-CD19 drug Uplizna (inebilizumab-cdon).Uplizna was cleared by the FDA last April for adults with IgG4-RD, an immune-mediated inflammatory condition that can lead to fibrosis and permanent organ damage. The green light was based on the 135-patient Phase III MITIGATE trial showing it lowered the risk of IgG4-RD flares by 87% compared to placebo over a 52-week control period, a statistically significant result.On Monday, Zenas said its INDIGO trial, which enrolled 194 patients, showed obexelimab reduced the risk of IgG4-RD flares by a "highly statistically significant and clinically meaningful" 56% over 52 weeks versus placebo.The antibody also achieved significance across four key secondary measures, including investigator-assessed flares, rescue therapy use, complete remission rates and cumulative use of IgG4-RD rescue therapy. Zenas said safety results were clean as well, with infection rates including grade 3 cases lower than placebo and no new safety signals reported. Full data will be presented at a future medical meeting.Upcoming US, EU filings"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," said Lisa von Moltke, head of R&D at Zenas and the company's chief medical officer.The drug, which binds both CD19 and FcγRIIb, is designed to inhibit rather than deplete B cells, an approach the company says avoids compromising vaccination and infection responses. Uplizna, by contrast, depletes both immature and mature B cells.Despite Monday's negative market reaction, analysts at Wedbush Securities recently suggested obexelimab could offer a "less harsh mechanism of action," while pointing to its convenience and the ability to pause treatment as potential differentiators.Zenas plans to file for FDA approval of obexelimab in the second quarter, followed by a European submission in the latter half of this year. Meanwhile, CEO Lonnie Moulder is looking longer-term, saying IgG4-RD "represents a significant commercial opportunity" and that the INDIGO data support obexelimab as "a potential franchise molecule for rheumatic diseases."In October, Zenas reported results from the Phase II MoonStone trial in relapsing multiple sclerosis, where obexelimab demonstrated a 95% relative reduction in the cumulative number of new gadolinium-enhancing T1 hyperintense lesions versus placebo. Another mid-stage trial is ongoing in systemic lupus erythematosus, with topline results and biomarker data expected in the fourth quarter.

Dive Brief:Zenas BioPharma said Monday that its experimental drug obexelimab met the main goal of a trial in a rare inflammatory condition called IgG4 related-disease. But the effects appeared to fall short of what a standard one Wall Street analyst considered crucial for it to become a commercially viable drug.The trial tested obexelimab against placebo in people who are already on standard treatments for the condition, and found those given Zenas drug had a 56% reduced risk of disease flare-ups over the course of a year. Though cross-trial comparisons can be misleading, Amgens Uplizna, which was approved in April 2025 to treat the condition, reduced flare-ups by 87% in clinical testing.Zenas shares fell by more than 55% in morning trading Monday, erasing hundreds of millions of dollars in market value. Zenas recently reported promising data for obexelimab in multiple sclerosis, but a potential approval in that condition is likely years away.Dive Insight:IgG4-related disease is an autoimmune condition in which misfiring B cells attack organs and cause swelling, fibrosis and tumor-like masses. In the past, the disorder has typically been treated through steroids and off-label use of the older antibody drug Rituxan. But the clearance of Uplizna marked the first time a drug had specifically been approved for the disorder.Zenas has been hoping obexelimab will prove a viable alternative to Uplizna, with the Phase 3 trial result Monday serving as the main proof. The Massachusetts-based biotech enrolled 194 people in the trial, randomizing half to receive obexelimaband the other half to get a placebo in addition to standard steroid treatments. Obexelimabsmain objective was to lower patients chances of having a flare-up of inflammation that can worsen disease symptoms.Zenas said that, by that measure, the study was a success, as obexelimabs 56% risk reduction hit statistical significance. The company expects to file a U.S. approval application in the second quarter of 2026.However, in previewing the study readout, Jefferies analyst Roger Song wrote that obexelimabneeded to reduce the risk of flares by 65% to prove commercially viable. Song argued that obexelimab didnt necessarily need to match Upliznas effectiveness,because it has other differentiating features, such as the potential for in-home dosing and carrying less risk of opportunistic infections.Zenas had $297 million in cash, short-term investments and other current assets as of Sept. 30, 2025. It had expenses of more than $50 million per quarter through the first nine months of 2025.The company also recently raised money from Royalty Pharmaby selling a 5.5% royalty on future worldwide net sales of obexelimab. The deal, worth up to $300 million, consisted of a $75 million up front payment, and included additional payments of $75 million each on achievement of [the] defined success criteria in the Phase 3 trial and obexelimabs FDA approval. '