Skye Bioscience says nimacimab did not meet primary endpoint in CBeyond study

Skye Bioscience (SKYE) announced the topline data from its 26-week Phase 2a CBeyond proof-of-concept study of nimacimab, its peripherally-restricted CB1 inhibitor antibody. In CBeyond, the nimacimab monotherapy arm did not achieve the primary endpoint of weight loss compared to placebo. Preliminary pharmacokinetic analysis showed an association between exposure and response, suggesting that the 200 mg, subcutaneous weekly dose was suboptimal as a monotherapy. In the combination cohort, nimacimab 200 mg plus semaglutide demonstrated a clinically meaningful magnitude of weight loss compared to semaglutide alone, with no plateau being observed through Week 26. This finding supports potential further studies to evaluate combinations of nimacimab and incretin-based therapies. At the tested dose and exposure levels, nimacimab 200 mg demonstrated a favorable safety profile with placebo-like tolerability. In combination with semaglutide, there was no increase in gastrointestinal adverse events. Importantly, there were no increases in neuropsychiatric adverse events reported resulting from treatment with nimacimab. Monotherapy dosed at 200 mg demonstrated lower than expected drug exposure. In the monotherapy arm, nimacimab 200 mg did not achieve the primary endpoint, with placebo-subtracted weight loss of -1.26% at week 26. Preliminary pharmacokinetic analysis showed lower than expected drug exposure of nimacimab, supporting evaluation of higher dosing. Clinically meaningful add-on efficacy with semaglutide. -13.2% weight loss in the nimacimab plus semaglutide combination arm at Week 26 compared to -10.25% in the semaglutide-alone arm. Notably, no plateau was observed at 26 weeks, which indicates potential for future weight loss. High frequency of responders in the combination arm. In the per protocol analysis, 100% achieved greater than5% weight loss and 67% achieved greater than10% weight loss. Body composition. An improvement in lean mass to fat mass ratio was observed at Week 26 comparing the nimacimab plus semaglutide combination arm to the placebo arm, and the combination arm compared to semaglutide alone. Favorable tolerability results. Nimacimab 200 mg demonstrated a clean safety profile as a monotherapy with placebo-like tolerability. When combined with semaglutide, no increase in gastrointestinal adverse events were observed. In the safety analysis population, rates of GI adverse events were 27% with nimacimab alone versus 29.5% with placebo, and 57.1% in combination with semaglutide versus 66.7% with semaglutide alone. Neuropsychiatric safety. No neuropsychiatric concerns were observed, with no increase in anxiety, insomnia, or depression resulting from treatment with nimacimab 200 mg as a monotherapy or in combination with semaglutide. Patient discontinuation. The CBeyond study had an overall discontinuation rate of 27%; 3.7% discontinuations across the study were due to adverse events, with the placebo group contributing to 60% of these discontinuations. Skye believes multiple factors support evaluation of nimacimab at higher doses, including the combination of preclinical toxicology margins and modeling; preclinical data showing dose-dependent increases in weight loss with nimacimab monotherapy and GLP-1 combinations; and the notable safety profile in this Phase 2a study. Skye is continuing to evaluate the data to determine next steps, including a potential follow-on Phase 2 study beyond the ongoing Phase 2a extension study. The next set of detailed results from the 26-week treatment period of the CBeyondTM trial will be presented at ObesityWeek in November.