Skye Bioscience faced a major setback when its CB1 receptor-blocking antibody nimacimab failed to achieve significant weight loss as monotherapy in a 26-week Phase 2a trial. Despite this, combination treatment with semaglutide showed encouraging additional weight loss. The company is exploring higher dosing regimens informed by exposure data and has plans to continue clinical development. This outcome echoes ongoing challenges for CB1-targeting drugs amid safety and efficacy concerns.