Nimacimab
Nimacimab, peripherally restricted CB1 antibody
An antibody that blocks the cannabinoid CB1 receptor outside the brain; alone it did little, but with semaglutide it reached 22.3% weight loss at 52 weeks and halved regain during a drug holiday.
Overview
Nimacimab (Skye Bioscience) is a negative allosteric modulator antibody that cannot cross into the brain, an attempt to keep the metabolic benefit of CB1 blockade without the psychiatric effects that sank rimonabant. In the CBeyond Phase 2a, monotherapy missed its endpoint, but nimacimab plus semaglutide produced 13.2% loss at 26 weeks versus 10.25% for semaglutide alone, and 22.3% at 52 weeks in the extension. During a 13-week drug holiday participants regained about half as much weight. A higher-dose study started in 2026.
Mechanism of action
Negative allosteric modulation of CB1 receptors in fat, liver and gut, reducing lipogenesis and improving insulin sensitivity without central nervous system exposure.
Key studies & citations
- Human2025
CBeyond: nimacimab alone and with semaglutide in obesity
Combination 13.2% versus 10.25% on semaglutide alone at 26 weeks.
ClinicalTrials.gov NCT06577090 - Human2026
Skye reports positive CBeyond extension results
22.3% loss at 52 weeks; 50% less regain during a 13-week drug holiday.
Skye Bioscience press release
Frequently asked questions
Is this related to rimonabant?
Same target, different approach. Rimonabant entered the brain and caused depression and anxiety; nimacimab is an antibody that stays in the periphery, and the Phase 2a did not show that psychiatric signal.