Obexelimab Reduces Number of New GdE T1 Lesions in Relapsing MS

Treatment with obexelimab (Zenas BioPharma), a novel bifunctional monoclonal antibody targeting CD19 and Fcγ receptor IIb (FcγRIIb), led to a near-complete suppression of new gadolinium-enhancing (GdE) T1 lesions by 12 weeks on treatment in patients with relapsing-remitting MS (RRMS), according to results from the phase 2 MoonStone clinical trial (NCT06564311).¹ The data were presented at the 2026 Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS), held February 5-7 in San Diego, California.

In the multicenter, randomized, double-blind, placebo-controlled study, a total of 116 patients across 34 international sites were randomized 2:1 to receive weekly subcutaneous obexelimab 250 mg or placebo for 12 weeks. Patients who received obexelimab showed a 95% relative reduction in the cumulative number of new gadolinium-enhancing T1-weighted hyperintense lesions (GdE T1 lesions) over weeks 8 and 12 compared with those treated with placebo. As such, the study met its primary end point.

According to the ACTRIMS abstract, the adjusted mean number of new lesions per scan was 0.01 (95% CI, 0.00–0.06) in the obexelimab group versus 0.23 (95% CI, 0.11–0.51) in the placebo group (P = .0009). It was noted that near-complete suppression of new GdE T1 lesions was seen as early as week 8 and maintained through week 12. In addition to its effects on GdE T1 lesions, obexelimab also significantly reduced the cumulative number of new and/or enlarging T2-weighted hyperintense lesions compared with placebo over the same time period. The safety profile of obexelimab was consistent with earlier completed studies, with reported adverse events including infections and hypersensitivity reactions, most commonly constituting mild injection site reactions.

MoonStone enrolled adults aged 18 to 55 years with RRMS and active secondary progressive MS (SPMS). According to the abstract, the reported findings provide the first clinical evidence for obexelimab activitiy in RMS, and data from an open-label extension study are expected to provide additional information about the efficacy, durability, and safety of obexelimab.

“We are very pleased that the MoonStone study was selected as a late-breaker oral presentation at ACTRIMS Forum 2026,” Lonnie Moulder, the founder and chief executive officer of Zenas, said in a statement.¹ “Further, we are excited to share today that through week 24 of the MoonStone trial, obexelimab demonstrated robust and durable activity, including near complete elimination of GdE T1 hyperintense lesions. The MoonStone 12-week primary end point results and 24-week data provide additional strong validation of obexelimab and the potential of B-cell inhibition to offer meaningful clinical activity in a wide range of autoimmune diseases. With its unique mechanism of action, compelling safety and tolerability profile, and at-home subcutaneous self-administration, obexelimab has the potential to become a franchise molecule and meaningfully impact the lives of patients living with autoimmune diseases. We look forward to reporting on additional progress this year, including the submission of marketing applications for Immunoglobulin G4-Related Disease to the United States FDA and the European Medicines Agency and topline results from our Phase 2 SunStone trial for Systemic Lupus Erythematosus.”

Formerly known as XmAb5871, obexelimab contains a dual engagement mechanism of action, binding to CD19 on B-cells while simultaneously engaging the inhibitory FcγRIIb via an Fc-engineered domain with high affinity.³ Obexelimab may be different from other marketed antiCD20 B-cell depleters in that it aims to modulate/inhibit B-cell activity without depleting the pool, potentially preserving immunoglobulin levels and vaccine responses relative to chronic depletion.

"The observed clinical activity in the MoonStone trial, combined with obexelimab’s unique inhibitory mechanism of action, subcutaneous self-administration and tolerability profile, position obexelimab as a potential option to broadly address the pathogenic role of B cells in autoimmune diseases,” Lisa von Moltke, MD, the head of research and development and chief medical officer at Zenas, said in an October 2025 press release announcing earlier data from MoonStone.³

Click here for more ACTRIMS 2026 coverage.

REFERENCES
1. Okuda DT, Melanson M, Ciarlone S, et al. LB1. Week 12 results from MoonStone, a phase 2 study of obexelimab in relapsing multiple sclerosis. Presented at: 2026 ACTRIMS Forum; Feb 5-7; San Diego, CA.
2. Week 12 results from MoonStone, a phase 2 study of obexelimab in relapsing multiple sclerosis. News release. Zenas BioPharma, Inc. February 9, 2026. Accessed February 12, 2026. https://investors.zenasbio.com/news-releases/news-release-details/zenas-biopharma-announces-late-breaking-platform-presentation
3. Zenas BioPharma announces positive results from phase 2 MoonStone trial of obexelimab in relapsing multiple sclerosis. News release. Zenas Biopharma. October 27, 2025. Accessed October 29, 2025. https://finance.yahoo.com/news/zenas-biopharma-announces-positive-results-110500218.html