We are recommending Skye Bioscience Inc. (SKYE) as our next investment opportunity in treating metabolic disease/obesity. Skye is developing a peripheral restricted CB1 antibody — nimacimab — to treat obesity by restoring leptin sensitivity and increasing fat metabolism, while avoiding the CB1-induced THC/neuro side effects, says John McCamant, editor of Medical Technology Stock Letter.
We believe this mechanism of action (MOA) is validated by Novo Nordisk’s (NVO) recent acquisition of privately-held Inversago for $1 billion. Nimacimab selectively targets the endocannabinoid system (ECS) to treat obesity/metabolic disorders. The primary role of the ECS is to introduce, accumulate, and store energy in the body enabled by activity of cannabinoidtype-1 receptor (CB1) in the brain and peripheral tissues.
SKYE started a Phase II study of nimacimab +/- semaglutide in obese patients in 2024 with preliminary data due in mid-2025. We believe the company’s unique approach to developing a selective, large-molecule antibody with muscle-sparing weight loss and no THC/neuro side effects has significant potential.
The key is that large molecules like antibodies are denied entry into the brain by the blood brain barrier (BBB), while CB1/THC small molecules easily access the brain and lead to significant impairment. The ongoing Phase II study is designed to demonstrate proof-of-concept for nimacimab’s unique MOA and to showcase a potentially differentiated safety and efficacy safety profile.
The Phase II obesity trial of nimacimab is currently enrolling 120 non-diabetic obese patients (BMI≥30) or overweight patients (BMI≥27). Forty patients each will be randomized to 200mg weekly subQ nimacimab, 2.4mg weekly subQ semaglutide, the combination, or placebo for 26 weeks with 12-week follow-up.
The primary endpoint is percent change in weight at week 26. Secondary endpoints include changes in waist circumference, body composition, fasting triglycerides, cholesterol, and A1c. Beyond weight loss, we anticipate that the nimacimab arms may show improved muscle preservation.
In preclinical studies, CB1 inhibition showed significant weight loss without loss of muscle mass over a 28-day period. We believe the company’s unique approach to developing a selective large-molecule antibody with muscle-sparing weight loss and no THC/neuro side effects has significant potential to treat metabolic disease/obesity.
In our view, the nimacimab Phase II obesity trial has potential to serve as proof of concept and positive data would be a huge catalyst for the stock. Positive Phase II data could result in a nimacimab partnership or even a SKYE acquisition by Big Pharma.
