Skye Bioscience Clinical Model Demonstrating Necessity of Peripheral CB1 Inhibition for Weight Loss Presented at European Congress on Obesity

• This model demonstrates that central inhibition of CB1 is not required for weight loss

• Anti-CB1 inhibiting antibody, nimacimab, showed greatest peripheral restriction compared with monlunabant and rimonabant, small molecule-based CB1 inhibitors, which both exhibited increasing dose-dependent brain penetration

• This model predicts nimacimab’s potentially superior therapeutic index, which is dependent on minimal brain exposure while maintaining sufficient peripheral inhibition

SAN DIEGO, May 13, 2025 (GLOBE NEWSWIRE) -- Skye Bioscience, Inc. (Nasdaq: SKYE) (“Skye”), a clinical-stage biotechnology company focused on unlocking new therapeutic pathways for obesity and other metabolic health disorders, presented a clinical pharmacokinetic (“PK”) and pharmacodynamic (“PD”) model that underscores the fundamental relationship between biodistribution and efficacy of CB1 inhibitors at the annual European Congress on Obesity meeting. This model demonstrated that achieving strong peripheral CB1 inhibition is sufficient to achieve efficacy, including weight loss. In contrast, blocking CB1 in the brain (central inhibition), which is associated with neuropsychiatric side effects, is not enough on its own to achieve weight loss.

Published clinical PK and potency data coupled with Phase 2 (“P2”) and Phase 3 efficacy data from Novo Nordisk’s monlunabant and Sanofi’s rimonabant, respectively, as well as Phase 1 data from nimacimab were used to develop a model to determine whether peripheral CB1 inhibition alone is sufficient for weight loss, or if central inhibition is also required for optimal efficacy. The results showed that central inhibition of CB1 alone was not sufficient for weight loss with P2 data for monlunabant, and demonstrated that increasing drug levels in the brain did not improve efficacy. Relatedly, monlunabant’s Ph2 dose range established that all doses achieved significant peripheral inhibition, resulting in significant but similar weight loss. The model also showed that a 5 mg dose of rimonabant that had significant levels in the brain but not peripherally was not effective, leading to only minimal weight loss.