Novel monoclonal antibody obexelimab demonstrates efficacy in phase 2 trial

Week 12 results from the phase 2 MoonStone trial provide the first clinical evidence supporting the efficacy of obexelimab, a novel humanised bifunctional monoclonal antibody, in patients with relapsing-remitting MS (RRMS). No new safety concerns arose from the study results.

Obexelimab is designed to inhibit B-cell activation and function by co-engaging cluster of differentiation 19 (CD19) and the inhibitory Fcγ receptor IIb (FcγRIIb). As explained by Prof. Amit Bar-Or (University of Pennsylvania, PA, USA), obexelimab “mimics the inhibitory signalling normally mediated by immune complexes.” He further noted: “It has been shown to potently inhibit B-cell antibody production, proliferation, cytokine secretion, and antigen presentation to T-cells” [1].

MoonStone (NCT06564311) is the first phase 2 trial evaluating this novel therapeutic mechanism in MS. This randomised, double-blind, placebo-controlled study enrolled 116 adults with RRMS and an Expanded Disability Status Scale (EDSS) score ≥5.5. Participants were randomised 2:1 to receive weekly subcutaneous obexelimab 250 mg (n=72) or placebo (n=38) for 12 weeks, after which the placebo group transitioned to active treatment. The primary endpoint was the cumulative number of new gadolinium-enhancing T1-weighted (Gd+) hyperintense lesions at weeks 8 and 12.

“Obexelimab met the primary endpoint, with a 95% relative reduction in the cumulative number of Gd+ T1 lesions after 8 and 12 weeks compared with placebo,” said Prof. Bar-Or. The mean number of new lesions per scan was 0.01 in the obexelimab group versus 0.23 in the placebo group (P=0.0009). The cumulative number of new lesions during this period was 2 among 72 patients receiving obexelimab, compared with 19 among 38 patients receiving placebo. Obexelimab was also associated with an 81% relative reduction in new and/or enlarging T2 lesions (P=0.0018), indicating near-complete suppression of inflammatory lesion activity over 12 weeks.

Prof. Bar-Or further noted that mean B-cell values decreased to approximately 37% at weeks 8 and 12 in the experimental group. Consistent with obexelimab’s inhibitory (rather than depleting) mechanism, these values remained within the normal range.

The safety profile was consistent with previous trials in other indications. The most common adverse events were mild injection site reactions (11.5%). Overall, these findings support continued clinical development of obexelimab in RRMS.

Okuda DT, et al. Week 12 results from MoonStone, a phase 2 study of obexelimab in relapsing multiple sclerosis. LB1.3, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.