Skye to test cannabinoid antibody for obesity as GLP-1 alternative

As GLP-1 drugs increasingly become the standard treatment for obesity, Skye Bioscience is exploring an alternative approach. Historically, cannabinoid receptor 1 (CB1) inhibitors have shown promise in promoting weight loss, though their usage was halted due to neuropsychiatric side effects. Skye Bioscience has refined this approach by developing a monoclonal antibody (mAb) named nimacimab, which is designed to be active only in peripheral areas of the body.

Skye Bioscience is now progressing nimacimab into the Phase II CBeyond study. This clinical trial will evaluate the weight-loss efficacy of nimacimab both as a standalone treatment and in combination with Novo Nordisk's established obesity medication, Wegovy (semaglutide). The biotech firm hopes that nimacimab can avoid the gastrointestinal (GI) side effects often associated with GLP-1 receptor agonists, as well as the depressive symptoms linked to earlier CB1 inhibitors.

The CBeyond study will include 80 participants who are either obese or overweight and have a weight-related co-morbidity. These individuals will be randomized to receive weekly injections of either nimacimab or a placebo. Additionally, a separate cohort of 40 patients will receive nimacimab in combination with Wegovy, or Wegovy plus a placebo. The treatment duration is set for 26 weeks, followed by a 13-week evaluation period to assess the degree of weight loss in both groups. Interim data from the study are expected in the second quarter of 2025, with top-line results anticipated by the end of that year.

Sanofi's initial CB1 inhibitor, rimonabant, demonstrated consistent weight-loss effects but was discontinued due to its neuropsychiatric side effects. In contrast, nimacimab is restricted to peripheral action, which is believed to help the mAb target key receptors in the gastrointestinal tract, adipose tissue, kidneys, liver, and pancreas. These organs collectively contribute to inflammatory, fibrotic, and metabolic diseases. According to Skye Bioscience CEO Punit Dhillon, blocking CB1 with nimacimab has the potential to limit or even reverse disease pathologies related to these organs. Dhillon further noted that the mAb's unique mechanism of action could lead to sustainable weight loss with improved outcomes in terms of fat mass reduction and muscle preservation, along with better GI tolerability.

Rather than competing directly with established drugs, Dhillon suggests that nimacimab could work synergistically with Wegovy in the CBeyond study, potentially enhancing GI tolerability. This combination could drive additive or possibly synergistic effects due to their different mechanisms of action.

Skye Bioscience is not the only company exploring CB1 inhibitors for weight loss. Novo Nordisk is also investigating an oral CB1 inverse agonist named INV-202, which is currently in a Phase II trial. According to ClinicalTrials.gov, this study is expected to conclude in March. Novo Nordisk acquired the asset last year through its acquisition of Inversago, a deal that could be worth up to $1.1 billion if certain milestones are reached.

In summary, Skye Bioscience is making significant strides in the field of obesity treatment with its novel mAb nimacimab. The upcoming CBeyond study will provide crucial insights into its efficacy and safety, potentially positioning nimacimab as a valuable addition or alternative to current obesity therapies.