Nimacimab

Nimacimab Report

Name: Nimacimab Name (English): Nimacimab DrugBank ID: DB15115 Type: Biotech (Humanized monoclonal antibody) CAS Number: 2098636-09-8

Mechanism of Action: Nimacimab is a first-in-class humanized monoclonal antibody that acts as a negative allosteric modulator to inhibit CB1 signaling in the periphery. It binds to the CB1 receptor, a G-protein coupled receptor, and prevents its activation by endogenous cannabinoids. This peripheral inhibition of CB1 has shown potential in promoting energy expenditure, fat breakdown, improving leptin sensitivity, and modulating hunger and satiety. Unlike earlier CB1 inhibitors, nimacimab exhibits limited penetration into the central nervous system, potentially avoiding the neuropsychiatric side effects associated with central CB1 blockade.

Clinical Trials: Nimacimab is currently in Phase 2 clinical development for obesity.

• Phase 2a (CBeyond™): A randomized, double-blind, placebo-controlled study (NCT06577090) evaluating the efficacy and safety of nimacimab as a monotherapy and in combination with semaglutide (Wegovy®) in overweight or obese adults. The trial is fully enrolled, with interim data expected in late Q3/early Q4 2025. An open-label extension to 52 weeks has been approved.
• A Phase 2 study was also planned for diabetic gastroparesis, but no recent development has been reported, suggesting it may be discontinued.
• A previous Phase 1b study in patients with non-alcoholic fatty liver disease (NAFLD) and diabetes or prediabetes showed no serious adverse events and positive trends in some metabolic biomarkers.

Preclinical Studies: