Zenas Biopharma has launched a Phase 2 clinical trial investigating obexelimab, a novel experimental therapy for relapsing forms of multiple sclerosis (MS) that offers a unique approach to targeting disease-causing B-cells. The trial marks a significant step forward in developing alternative treatment options for MS patients.
Novel Mechanism of Action
Unlike currently approved MS treatments such as Ocrevus, Briumvi, and Kesimpta that deplete B-cells by targeting CD20, obexelimab employs a distinctive dual-targeting mechanism. The drug targets both CD19 and FcgammaRIIb proteins on B-cells, aiming to reduce their activity without completely eliminating them. This approach could potentially affect a broader range of B-cells than existing therapies.
"This unique mechanism of action and self-administered, subcutaneous once-weekly injection regimen may broadly and effectively address the [disease-driving] role of B cell lineage in chronic autoimmune disease," according to Zenas Biopharma representatives.
MoonStone Trial Design and Objectives
The Phase 2 study, dubbed MoonStone (NCT06564311), is actively recruiting participants across more than 40 clinical sites throughout the United States, Europe, and China. The trial focuses on adults aged 18 to 60 diagnosed with either relapsing-remitting MS or active secondary progressive MS.
Eligible participants must meet specific criteria, including:
- At least one disease relapse in the past year, or
- Two relapses within the previous two years, or
- One actively inflamed lesion detected by MRI within six months before study entry
The study will randomize approximately 93 participants to receive either:
- 250 mg obexelimab weekly via subcutaneous injection
- Placebo injection weekly Both regimens will continue for 12 weeks during the initial controlled phase.
Extended Treatment Opportunities
Following the placebo-controlled phase, participants will have the opportunity to enter an open-label period where all patients receive obexelimab for at least three months. This will be followed by a one-year open-label extension, allowing researchers to gather long-term safety and efficacy data.
Primary Endpoints and Assessment
The trial's primary objective is to evaluate obexelimab's efficacy compared to placebo in reducing new actively inflamed lesions visible on MRI scans. Researchers will also assess various secondary endpoints, including other MRI outcomes and markers of nerve damage.
Lonnie Moulder, founder and CEO of Zenas, expressed optimism about the trial: "We enter 2025 with an opportunity to achieve major value-driving milestones with the anticipated results from our ongoing obexelimab Phase 2 and Phase 3 clinical trials. We are extremely proud of the accomplishments of our dedicated team."
Broader Therapeutic Potential
Beyond multiple sclerosis, Zenas is exploring obexelimab's potential in other conditions characterized by abnormal B-cell activity, including lupus. This broader development program underscores the potential versatility of the drug's novel mechanism of action in treating various autoimmune conditions.
Results from the MoonStone trial are expected in the third quarter of 2025, potentially offering new hope for MS patients seeking alternative treatment options.
