Skye Bioscience’s cannabinoid receptor 1 (CB1) antagonist, nimacimab, failed to achieve significant weight loss compared to placebo in a mid-stage clinical trial involving overweight and obese patients. While nimacimab induced a modest 1.5% weight loss over 26 weeks versus 0.3% with placebo, the effect was not statistically significant. However, combination treatment with semaglutide resulted in greater weight loss than semaglutide alone, suggesting potential synergy. The company cited lower-than-expected drug exposure at the tested 200 mg dose as a limitation and is evaluating higher doses in future trials. The setback reflects broader challenges faced by CB1 antagonists, which have encountered safety concerns and regulatory hurdles in obesity treatment.