Skye Bioscience reported that its CB1 receptor inhibitor, nimacimab, did not achieve statistically significant weight loss in a mid-stage Phase 2a trial when used as monotherapy. The antibody induced an average 1.5% weight loss over 26 weeks, comparable to placebo, but combination treatment with semaglutide delivered a clinically meaningful additional weight reduction. Safety data were favorable, with no neuropsychiatric adverse events observed, prompting plans for further dose optimization studies. The results highlight challenges facing CB1-targeting obesity therapies and underscore the potential for combination regimens.