Zenas BioPharma (NASDAQ:ZBIO) reported top-line results from its registrational phase III INDIGO trial evaluating obexelimab for immunoglobulin G4-related disease (IgG4-RD), saying the study met its primary endpoint and all four key secondary endpoints with “high statistical significance.” Company executives also highlighted a safety profile they described as consistent with prior obexelimab studies and favorable versus placebo in several infection-related measures.
Phase III INDIGO design and patient population
Head of R&D and Chief Medical Officer Lisa von Moltke said INDIGO was designed in alignment with regulatory authorities worldwide and represents “the largest IgG4-RD clinical trial ever conducted.” Patients entered the study during an IgG4-RD flare, with diagnosis and flare status confirmed by a central committee. Patients received steroids to induce remission and, once remission was centrally confirmed, were randomized 1:1 to obexelimab or placebo.
Management also summarized baseline characteristics, noting a mean age of 59 and a male predominance. The company said 66.5% of patients had recurrent disease and 33.5% were newly diagnosed, while 93% had two or more organs involved. Enrollment was global: 21% North America, 24% Europe, 28% Japan, 23% other Asian countries, and 4% Latin America. Von Moltke said baseline characteristics were well-balanced across both arms.
Primary endpoint: time to first flare requiring rescue therapy
The primary endpoint was time to first IgG4-RD flare requiring initiation of rescue therapy, as determined by investigators and an adjudication committee, from randomization through week 52. Von Moltke said INDIGO met this endpoint, with obexelimab reducing the risk of flare by 56% versus placebo.
- Risk reduction: 56%
- Hazard ratio: 0.443
- p-value: 0.0005
- Flare rates: 27% (obexelimab) vs. 55% (placebo)
Von Moltke added that more than 70% of patients in the obexelimab arm were “protected from flare” through week 52.
Secondary endpoints and disclosure plans
Management said obexelimab achieved all four key secondary endpoints through week 52 versus placebo. The company listed the key secondary measures as:
- Time to first investigator-determined flare requiring initiation of rescue therapy
- Number of investigator-determined flares requiring initiation of rescue therapy
- Proportion of patients achieving complete remission
- Cumulative use of IgG4-RD glucocorticoid rescue therapy
However, executives said they were not providing additional detail on the key secondary endpoints at this time to preserve the ability to publish the full dataset and to respect investigators’ authorship expectations. CEO Lonnie Moulder later said the slide deck included p-values for the secondary endpoints, calling the p-value for cumulative glucocorticoid rescue therapy “highly, highly significant,” and noted the company plans further analysis of the Glucocorticoid Toxicity Index as an additional secondary endpoint.
During Q&A, Moulder also discussed “complete remission,” describing it as flare-free status plus no disease activity beyond flare criteria. He said complete remission is “highly correlated” to the flare outcome and suggested investors should not expect a “big upside surprise” on that metric relative to the observed flare reduction.
Safety and tolerability: infections numerically lower vs. placebo
Von Moltke said obexelimab was well tolerated and had a safety profile consistent with prior trials. She said serious adverse events were lower in the obexelimab arm than placebo, and overall infection rates were also lower. She further cited numerically lower rates of grade 3 infections, upper respiratory tract infections, COVID-19, and urinary tract infections in the obexelimab arm. Injection site reactions were described as similar between groups.
Asked about the relationship between B-cell counts and infection rates, Moulder said additional biomarker and assay analyses were still ongoing and that there was “no correlation to B-cell count at this point,” while reiterating that infection rates appeared numerically lower and “basically…about the same as placebo” when laid out in full detail.
Regulatory timing and commercialization positioning
Moulder said Zenas plans to submit a biologics license application (BLA) to the U.S. Food and Drug Administration in the second quarter and a marketing authorization application (MAA) to the European Medicines Agency in the second half of the year.
He emphasized what the company views as differentiation for obexelimab in IgG4-RD, including a “unique inhibitory mechanism” intended to avoid long-term B-cell depletion, at-home subcutaneous dosing, and potential cost and access advantages versus infused therapies. In the call, Moulder referenced KOL discussions following the data readout and said advisors were “very enthusiastic” about the 56% risk reduction, the proportion of patients protected from flare, and the safety profile, particularly given the non-depleting mechanism and convenience of at-home administration.
On market sizing, Moulder said Zenas estimates total prevalence of IgG4-RD at 30,000–40,000 in both the U.S. and Europe, and said roughly 20,000 patients are currently diagnosed and medically managed in the U.S. He added that over half of diagnosed patients experience frequent flares and could be candidates for maintenance therapy, describing the commercial opportunity as approximately $3 billion in the U.S. and $2 billion in Europe based on “current market pricing in this field.”
In Q&A, Moulder said payer discussions typically begin with medical review of efficacy and safety under confidentiality before moving to pricing and rebate conversations closer to launch. He also contrasted a competitor’s upfront infusion costs with a “monthly case pack” approach for self-administered therapy, arguing the economics and safety profile could support first-line use.
Moulder also addressed the company’s Royalty Pharma agreement, stating the transaction totaled $300 million, including $75 million upfront. He said Zenas is “currently not eligible” for a $75 million payment related to phase III data under the current agreement but that the parties are in “active discussions” about the milestone. He added Zenas remains eligible for a $75 million approval milestone for IgG4-RD and an additional approval milestone if approval is obtained in SLE.
Separately, Zenas said it expects additional clinical updates for obexelimab in other indications, including 24-week data from the MoonStone RMS trial this quarter and top-line results plus biomarker data from the phase II SunStone SLE trial in the fourth quarter.
About Zenas BioPharma (NASDAQ:ZBIO)
Zenas BioPharma, Inc is a clinical-stage biotechnology company focused on the discovery and development of novel therapies in oncology and infectious diseases. The company’s proprietary platform integrates structure-guided design, computational modeling and high-throughput screening to address challenging protein-protein interactions. Zenas BioPharma is advancing multiple preclinical and clinical-stage candidates aimed at providing new treatment options where current modalities may be limited by efficacy or safety concerns.
Founded in 2021 and headquartered in Cambridge, Massachusetts, Zenas BioPharma was built to streamline the drug discovery process from target identification through to IND-enabling studies.
