Skye Bioscience disclosed topline phase 2a data for Nimacimab, a peripherally restricted CB1 receptor inhibitor antibody targeting obesity. The monotherapy arm failed to meet its primary weight loss endpoint, showing only 1.5% loss versus placebo's 0.26%, leading to a greater-than 60% share price drop. However, combination treatment with semaglutide yielded a 13.2% average weight reduction without neuropsychiatric side effects. The company attributes the failure to lower-than-expected drug exposure at the 200 mg dose and is evaluating higher doses and combination regimens for future trials. This marks a setback for CB1-based obesity therapies, with a history of safety concerns halting prior approvals. Nonetheless, Skye remains optimistic about the potential for Nimacimab to complement existing incretin treatments.