Skye Bioscience (SKYE) announced compelling preclinical results showing that its CB1-targeting antibody, nimacimab, produced more than 30% weight loss when combined with tirzepatide in a mouse model of diet-induced obesity (DIO). The update sent shares sharply higher, gaining around 67% on the day.
The study found that nimacimab alone resulted in a 23.5% reduction in body weight—on par with tirzepatide or monlunabant given as monotherapies. When used together, the combination achieved additive weight loss effects, surpassing the 30% threshold in 25 days.
Skye emphasized the differentiated mechanism of nimacimab, which acts via allosteric binding to the CB1 receptor—offering potential advantages over earlier CB1-targeting drugs like monlunabant that bind directly to the receptor’s active site and are associated with neuropsychiatric side effects. Notably, nimacimab is designed to remain peripherally restricted, reducing brain exposure and the risk of CNS-related adverse events.
In a related in vitro study, nimacimab’s potency remained stable even under high levels of CB1 receptor agonists, while monlunabant’s effectiveness dropped significantly. This suggests nimacimab may maintain therapeutic activity even in disease states characterized by elevated levels of endocannabinoids, such as obesity.
Skye is currently advancing nimacimab into clinical development with a Phase 2a obesity trial already underway. Top-line data from this study, which includes a combination arm with a GLP-1 receptor agonist, is expected in late Q3 or early Q4 2025.
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