Skye Bioscience’s Nimacimab Shows Promise as Add-on Therapy for Obesity, Data Suggest

BOSTON, MA – November 10, 2025 – Skye Bioscience today announced positive topline results from its Phase 2a clinical trial evaluating nimacimab, a first-in-class peripherally-restricted CB1 modulator, in combination with semaglutide for the treatment of obesity. The data presented suggest a compelling new approach to weight management, potentially addressing the limitations of currently available therapies.

A Novel Mechanism for a Growing Problem

The global obesity epidemic continues to escalate, driving demand for effective and well-tolerated treatment options. While GLP-1 receptor agonists like semaglutide have demonstrated significant efficacy, challenges remain, including weight regain after treatment cessation and gastrointestinal side effects. Skye Bioscience’s nimacimab aims to address these limitations by targeting the CB1 receptor, a key regulator of metabolism and appetite, but with a crucial distinction: its design restricts it to the periphery, minimizing the risk of neuropsychiatric side effects associated with earlier CB1 inhibitors.

“The data suggest nimacimab could provide an additive benefit to existing therapies,” explains one industry analyst. “By targeting a different pathway, it could potentially overcome some of the limitations we've seen with GLP-1 agonists alone.”

Phase 2a Results: Efficacy and Safety

The Phase 2a trial involved participants with obesity. Results demonstrated that the combination of nimacimab and semaglutide resulted in a greater weight loss compared to semaglutide alone. Importantly, this additional weight loss was achieved without a significant increase in adverse events.

“One of the most encouraging findings was the favorable safety profile,” states a clinical advisor with Skye Bioscience. “We observed no increase in neuropsychiatric events, and the incidence of GI side effects was comparable to what we've seen with semaglutide alone.”

The trial also revealed a potential benefit in limiting weight regain. While long-term data are still needed, preliminary results suggest that nimacimab may help maintain weight loss after treatment cessation – a key challenge with many existing therapies.

Differentiation in a Crowded Market

The obesity drug market is becoming increasingly competitive, with Eli Lilly's Zepbound and Novo Nordisk’s Wegovy dominating the landscape. However, Skye Bioscience believes nimacimab’s unique mechanism of action and safety profile could carve out a niche.

“We’re not trying to compete head-to-head with GLP-1 agonists,” explains a Skye Bioscience spokesperson. “We see nimacimab as a complementary therapy, an add-on that could enhance efficacy and address unmet needs.”

Analysts agree that differentiation is key.

“The market is rapidly evolving, and there's room for innovation,” notes one industry observer. “Nimacimab’s peripherally-restricted approach could be a significant advantage, particularly if it can demonstrate durable weight loss without the neuropsychiatric side effects that plagued earlier CB1 inhibitors.”

Addressing the Challenges of CB1 Modulation

The history of CB1 modulation in obesity treatment is fraught with challenges. Rimonabant, a small-molecule CB1 inhibitor, was initially hailed as a breakthrough but was ultimately withdrawn from the market due to safety concerns, including an increased risk of depression and suicidal ideation. This led to skepticism about targeting the CB1 receptor.

Skye Bioscience’s nimacimab is designed to overcome these challenges by restricting its action to the periphery, preventing it from crossing the blood-brain barrier. Preclinical studies have confirmed that nimacimab does not accumulate in the brain, minimizing the risk of CNS-related side effects. The Phase 2a results further support this, demonstrating a clean neuropsychiatric safety profile.

What’s Next?

Skye Bioscience is currently enrolling participants in a 26-week extension study to assess the long-term safety and efficacy of nimacimab in combination with semaglutide. The company anticipates data from this study in the first quarter of 2026. They are also planning for initial manufacturing runs to support future clinical trials.

“We’re committed to advancing this program and bringing a new treatment option to patients who struggle with obesity,” says a Skye Bioscience representative. “We believe nimacimab has the potential to make a real difference in the lives of those affected by this chronic disease.”

Market Outlook
The global anti-obesity drug market is projected to reach over $60 billion by 2030, growing at a rapid rate. The demand for effective and well-tolerated treatments continues to rise as the prevalence of obesity increases worldwide. While GLP-1 agonists currently dominate the market, there is a growing need for innovative approaches that can address unmet needs and overcome the limitations of existing therapies. Nimacimab's unique mechanism of action and favorable safety profile could position it as a valuable addition to the obesity treatment landscape.

Disclaimer: This article is based on publicly available information and research findings. It is not intended as medical advice. Please consult with a healthcare professional for any health concerns or before making any decisions related to your health or treatment.