速递｜Skye一年减重22.3%！CB1+GLP-1路线逼近“天花板”

Core Viewpoint - The article discusses the competitive landscape of weight loss drugs in the U.S., highlighting Skye Bioscience's promising clinical results for its combination therapy of nimacimab and semaglutide, which achieved an average weight loss of 22.3% over 52 weeks without reaching a plateau [4][6]. Group 1: Clinical Results - Skye's combination therapy resulted in a 14.4% weight loss in the first 26 weeks, followed by an additional 7.9% in the subsequent 26 weeks, totaling 22.3% weight loss [6]. - Notably, there was no observed plateau in weight loss at the 52-week mark, which is significant given the common trend of diminishing returns in current GLP-1 drugs [6][7]. - During a 13-week follow-up after stopping the treatment, the combination group only regained 17.8% of the lost weight, compared to a 37.3% rebound in the semaglutide-only group, indicating better weight maintenance with nimacimab [7]. Group 2: Mechanism and Safety - Nimacimab is designed as a peripheral CB1 receptor monoclonal antibody, aiming to avoid central nervous system entry and thus mitigate the psychiatric side effects associated with earlier CB1 inhibitors [8]. - Throughout the 52-week study, no serious adverse events were reported, reinforcing the safety profile of nimacimab [8]. Group 3: Commercial Viability and Future Outlook - The study had a limited sample size of 19 participants in the extended treatment phase, with only 7 completing the full 52 weeks in each group, indicating the need for larger studies to validate the findings [9]. - Skye is currently not profitable and is experiencing rapid cash burn, but its balance sheet shows cash reserves exceeding debts, suggesting short-term liquidity is manageable [9]. - The company plans to release complete top-line data from the CBeyond 2a study, including results for nimacimab as a monotherapy, by Q3 2026 [9]. Group 4: Strategic Collaborations - Skye has partnered with Halozyme Therapeutics to develop a high-dose subcutaneous formulation of nimacimab using the ENHANZE delivery technology, which could enhance dosing frequency and efficacy [10]. - In animal models, the combination of nimacimab with incretin-based drugs showed weight loss of up to 46%, although this result requires further validation in human trials [10].