Skye Bioscience (NASDAQ: SKYE) Shares Plunge 62.74% on Disappointing Nimacimab Trial Data, Hit 10-Month Low

Shares of Skye Bioscience (NASDAQ: SKYE) plummeted nearly 62.74% intraday on October 6, 2025, marking a fresh 10-month low as investors reacted to underwhelming clinical trial data for its experimental weight loss drug, nimacimab. The stock’s collapse followed preliminary results from the CBeyond™ Phase 2a trial, where nimacimab monotherapy failed to demonstrate statistically significant weight loss compared to a placebo. Patients receiving the 200 mg weekly dose lost only 1.52% of their body weight versus 0.26% in the placebo group, falling far short of expectations for a CB1 receptor inhibitor targeting obesity.

While the monotherapy setback dominated the market’s attention, the trial revealed a modest but statistically significant benefit when nimacimab was combined with semaglutide (Wegovy). The combination therapy achieved a 13.2% weight loss compared to 10.25% with semaglutide alone—a 3 percentage point improvement Skye described as "clinically meaningful." The company highlighted nimacimab’s favorable safety profile, noting no increase in gastrointestinal side effects or neuropsychiatric risks, which had previously plagued CB1 inhibitors. However, the combination’s results fell below internal projections of a 5-8 percentage point enhancement, fueling skepticism about the drug’s standalone potential.

Management acknowledged the need to reevaluate nimacimab’s dosing strategy, citing preclinical data and pharmacokinetic modeling to justify higher-dose trials. Chief Medical Officer Puneet Arora attributed the monotherapy’s suboptimal performance to "lower-than-expected drug exposure" at the 200 mg level. The company now plans to explore elevated doses for monotherapy and expand combination studies, aligning with industry trends of multimodal obesity treatments. This pivot reflects broader challenges in translating preclinical promise into clinical success, as competitors like Novo Nordisk also grapple with CB1 inhibitor trials.

Investor sentiment was further dampened by Skye’s reliance on nimacimab as its lead candidate and the trial’s limited 26-week duration, which left long-term efficacy questions unanswered. The firm’s recent stock rally—driven by preclinical optimism and the obesity market’s growth—now faces headwinds as the trial’s mixed results highlight the high-risk nature of clinical-stage biotech ventures. With additional data anticipated in early 2026 from a 26-week extension study, Skye’s ability to optimize nimacimab’s development path will be critical in regaining market confidence and navigating the competitive obesity drug landscape.