Skye Bioscience's Obesity Drug Fails to Impress in Phase 2 Study, Casting Shadow on CB1 Inhibitor Class

Skye Bioscience's experimental obesity treatment, nimacimab, has fallen short of expectations in a phase 2 clinical trial, dealing another blow to the troubled CB1 inhibitor class of drugs. The study results, released on October 6, 2025, have sent shockwaves through the pharmaceutical industry and caused Skye's stock to plummet by over 60% in early premarket trading.

Disappointing Monotherapy Results

The 136-patient study evaluated a 200-mg weekly subcutaneous dose of nimacimab as a monotherapy and in combination with semaglutide, the active ingredient in Novo Nordisk's blockbuster weight loss drug Wegovy. As a standalone treatment, nimacimab demonstrated a meager 1.52% weight loss, barely surpassing the placebo group's 0.26% reduction and falling far short of semaglutide's impressive 10.25% weight loss.

Skye's Chief Medical Officer, Puneet Arora, M.D., attributed the underwhelming performance to "lower-than-expected drug exposure" from the 200-mg dose, suggesting that this "may have limited the observed effect."

Combination Therapy Shows Promise

Despite the monotherapy setback, Skye highlighted a potential silver lining in the study results. Patients receiving a combination of nimacimab and semaglutide achieved an average weight loss of 13.2%, outperforming semaglutide alone.

"The combination of nimacimab with semaglutide produced a clinically meaningful additional weight loss that exceeded semaglutide alone, with a favorable tolerability profile even in patients who achieved the highest exposure levels," Dr. Arora stated in the company's press release.

Safety Profile and Future Prospects

Importantly, Skye emphasized that "no neuropsychiatric concerns were observed" in the phase 2 study, a crucial point given the historical safety issues associated with CB1 inhibitors. The company reported a "clean" safety profile for nimacimab, with no increased gastrointestinal adverse events commonly seen with some weight loss medications.

Despite the setback, Skye remains optimistic about nimacimab's potential. The company is considering evaluating higher doses in future clinical trials, citing "multiple factors" that justify this approach. Dr. Arora noted, "With our preclinical data, toxicology safety margins, and PK modeling, we believe we have a path to support higher dosing, and we are evaluating the next stage of development to optimize dosing in potential future clinical trials."