Skye Bioscience (SKYE) Piper Sandler 36th Annual Healthcare Conference summary

Cannabinoid system and obesity

• CB1 receptor is central to energy homeostasis and metabolic regulation, making it a key target for obesity therapies.

• Historical drugs like rimonabant showed strong weight loss efficacy but were limited by neuropsychiatric side effects due to central CB1 inhibition.

• Peripheral CB1 inhibition is now recognized as a safer approach, avoiding central nervous system adverse events.

Differentiation of nimacimab

• Nimacimab is a peripherally restricted CB1 antibody, designed to avoid brain exposure and related neuropsychiatric risks.

• Preclinical data in humanized mouse models showed up to 16% dose-dependent weight loss with fat mass reduction and lean mass preservation.

• The antibody acts as a non-competitive, allosteric inverse agonist, offering mechanistic advantages over small molecules.

Competitive landscape and clinical strategy

• Recent competitor data (e.g., monlunabant, Corbus) validate the CB1 pathway but highlight safety concerns with small molecules due to central exposure.

• Nimacimab's large therapeutic window allows for dose optimization and potential monthly dosing, improving patient convenience.

• Combination studies with GLP-1s are planned to explore additive or synergistic effects on weight loss.