Skye Bioscience (SKYE) Shares Plunge 12.63% on Disappointing Phase IIa Monotherapy Trial Results

Shares of Skye Bioscience (SKYE) plummeted 12.63% in intraday trading on October 7, 2025, marking a two-day decline of 65.05% and sending the stock to its lowest level since April 2025. The sharp sell-off followed the release of underwhelming Phase IIa clinical trial results for its lead candidate, nimacimab, as a monotherapy for obesity.

The CBeyond trial, which evaluated nimacimab’s efficacy in 136 adults, revealed that the 200 mg weekly dose achieved only a 1.52% weight loss over 26 weeks—well below the statistically significant threshold compared to the 0.26% loss in the placebo group. The company attributed the suboptimal outcome to "lower-than-expected drug exposure," despite the dose being deemed safe and well-tolerated. This failure to meet primary endpoints raised immediate concerns about nimacimab’s viability as a standalone treatment, a critical pillar of Skye’s development strategy.

However, the trial highlighted potential in combination therapy. When nimacimab was paired with Novo Nordisk’s Wegovy (semaglutide), the duo delivered a 13.2% weight loss over 26 weeks—3% higher than Wegovy alone. The combination also demonstrated a favorable safety profile, with no additional gastrointestinal or neuropsychiatric adverse events. These results suggested nimacimab could complement existing obesity treatments but did little to offset investor skepticism about its monotherapy limitations.

Market reaction remained bearish, with Skye’s shares having already underperformed the biotech sector this year. The stock’s 60% drop reflected broader doubts about the company’s ability to advance nimacimab beyond its current phase, particularly as Novo Nordisk dominates the obesity drug market with Wegovy. Skye plans to extend the CBeyond trial for another 26 weeks, testing higher doses in monotherapy and continuing combination therapy, but the path forward involves risks such as increased side effects or regulatory delays.

Investor sentiment was further weighed by the trial’s 27% discontinuation rate, with 3.7% of exits linked to adverse events. While Skye emphasized nimacimab’s safety margins, the high attrition rate underscored the practical challenges of maintaining patient adherence in obesity treatments. The company now faces the dual challenge of optimizing dosing strategies while navigating a competitive landscape where CB1 inhibitors have historically struggled to meet expectations.

With extended trial data expected in early 2026, Skye’s future hinges on demonstrating long-term efficacy and securing partnerships to differentiate its approach. For now, the stock’s collapse underscores the market’s intolerance for unmet clinical milestones in the high-stakes biotech sector.