Skye Bioscience’s peripherally restricted CB1 receptor inhibitor nimacimab failed to meet the primary endpoint in a 26-week Phase 2a trial for weight loss monotherapy in overweight and obese patients, showing only 1.5% weight loss compared to placebo’s 0.3%. However, combination therapy of nimacimab with semaglutide resulted in 13.2% weight loss. The company is investigating higher doses and potential combination treatments to optimize efficacy. The results represent a setback for the CB1 class in obesity therapeutics.