Skye Bioscience Begins Phase 2 CBeyond Trial for Nimacimab in Obesity

Skye Bioscience, Inc., a clinical-stage biopharmaceutical company, has initiated patient screening for a Phase 2 clinical trial named CBeyond™. This trial aims to evaluate nimacimab, their innovative peripheral CB1 inhibitor, as a potential weight loss treatment. Nimacimab is a negative allosteric modulating antibody, and the study will examine its effectiveness and safety in reducing weight among obesity patients. Key parameters such as gastrointestinal tolerability and the retention of lean mass will also be assessed.

According to Punit Dhillon, CEO of Skye, there is a noticeable need for alternative weight loss mechanisms that can provide better health outcomes compared to current GLP-1 and GIP drugs. Peripheral CB1 inhibition, which nimacimab represents, may offer such benefits. The company plans to report interim data by Q2 of 2025 and final data by Q4 of the same year. Dhillon emphasized the potential of CB1 inhibition in promoting energy expenditure, fat breakdown, improving leptin sensitivity, and modulating hunger and satiety.

Tu Diep, Chief Development Officer of Skye, highlighted the importance of considering health outcomes beyond gastrointestinal tolerance and muscle loss. Diep pointed out that previous CB1 inhibitors like rimonabant, which affected the central nervous system, were associated with psychiatric side effects, including anxiety and depression. Second-generation CB1 inhibitors, while more peripherally restricted, still showed brain accumulation in preclinical models, posing potential safety concerns. In contrast, nimacimab, being a monoclonal antibody, is significantly more restricted from the brain and showed no psychiatric adverse events in preclinical and Phase 1 studies.

Dr. Harold Edward Bays, Medical Director of Louisville Metabolic and Atherosclerosis Research Center, expressed his excitement to participate in the study. He highlighted the innovative approach of targeting the CB1 receptor as a logical progression in obesity treatment options.

The Phase 2 clinical trial of nimacimab will focus on assessing its ability to reduce weight safely and effectively, with a special emphasis on long-term quality and sustainability of weight loss. The study will also preliminarily evaluate the combination of nimacimab with a GLP-1 drug for enhanced weight loss benefits.

Nimacimab is a pioneering monoclonal antibody that acts as a negative allosteric modulator to inhibit CB1 signaling in peripheral tissues. This inhibition has demonstrated various beneficial mechanisms like anti-fibrotic, anti-inflammatory, and metabolic effects, potentially addressing diseases like obesity, chronic kidney disease, and metabolic dysfunction-associated steatohepatitis (MASH).

In July 2024, Skye hosted an Obesity KOL event featuring key opinion leaders and company management to discuss the mechanisms of peripheral CB1 inhibition and nimacimab’s role in obesity treatment.

Skye Bioscience is dedicated to exploring new therapeutic pathways for metabolic health through developing next-generation molecules that modulate G-protein coupled receptors. Their strategy involves leveraging biologic targets with substantial human proof of mechanism to develop first-in-class therapeutics with clinical and commercial uniqueness. The ongoing Phase 2 clinical trial evaluates nimacimab as a monotherapy and in combination with a GLP-1 receptor agonist.

Skye Bioscience continues to push the boundaries of metabolic health treatments, aiming to provide innovative solutions for conditions like obesity.