Skye Bioscience's CB1 Blocker Fails to Reduce Weight in Phase 2 Obesity Study

Skye Bioscience's obesity candidate, nimacimab, has failed to demonstrate significant weight reduction in a phase 2 clinical trial, dealing another blow to the CB1 inhibitor class of drugs. The study results, released on October 6, 2025, have sent the company's shares plummeting by over 60% in early premarket trading.

Study Results and Implications

The phase 2 trial, which involved 136 patients who were overweight or obese, 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 drug Wegovy. The results showed that nimacimab alone achieved only a 1.52% weight loss, barely surpassing the placebo group's 0.26% reduction and falling far short of the 10.25% weight loss observed in the semaglutide cohort.

Despite the disappointing monotherapy results, Skye Bioscience highlighted a potential silver lining in the combination therapy arm. Patients receiving nimacimab in conjunction with semaglutide experienced an average weight loss of 13.2%, exceeding the effect of semaglutide alone.

Dr. Puneet Arora, Skye's Chief Medical Officer, attributed the underwhelming monotherapy results to "lower-than-expected drug exposure" from the 200-mg dose. The company is now considering higher dosing options for potential future clinical trials.

Safety Profile and Industry Context

Importantly, Skye reported that nimacimab demonstrated a "clean" safety profile with no observed neuropsychiatric concerns. This is particularly noteworthy given the historical challenges faced by CB1 blockers in the obesity treatment landscape.

The CB1 inhibitor class has a checkered past in obesity treatment. Sanofi's CB1 drug, initially approved in Europe, had its approval withdrawn in 2009 due to doubled risks of psychiatric disorders. More recently, Roche's $1.1 billion acquisition of Inversago Pharma in 2023 led to the development of CB1 drugs that were also associated with neuropsychiatric side effects.

While more than a quarter of patients across Skye's trial discontinued treatment, only 3.7% of discontinuations were attributed to adverse events. The company emphasized that nimacimab did not increase gastrointestinal adverse events, a common issue with some weight loss medications.

Future Prospects and Industry Implications

Despite the setback, Skye Bioscience remains optimistic about nimacimab's potential. The company is evaluating the next stage of development, focusing on optimizing dosing in future clinical trials. This persistence underscores the ongoing interest in CB1 inhibitors as a potential treatment for obesity, despite the challenges faced by the drug class.

The outcome of Skye's trial and its future development plans will likely be closely watched by the pharmaceutical industry, as companies continue to search for effective and safe treatments for obesity, a growing global health concern.