Skye Bioscience (SKYE) 43rd Annual J.P. Morgan Healthcare Conference 2025 summary

Industry context and therapeutic landscape

• Obesity and metabolic diseases are now recognized as chronic conditions requiring drug intervention to address underlying causes, not just symptoms.

• Incretin-mimetic drugs (GLP-1s) have shown success but present significant GI side effects and high discontinuation rates, leaving unmet needs.

• CB1 inhibition, alongside incretin and amylin targets, is emerging as a validated and promising approach for obesity treatment.

• Approximately 20% of patients are non-responders to GLP-1s, highlighting the need for alternative mechanisms.

• Peripheral CB1 inhibition offers potential for improved safety and efficacy by avoiding CNS-related side effects.

Pipeline and scientific differentiation

• The lead program, nimacimab, is a peripherally restricted CB1 inhibitor antibody designed for sustainable weight loss and superior tolerability.

• Preclinical and Phase I data show no CNS accumulation and no neuropsychiatric adverse events, supporting a strong safety profile.

• Nimacimab acts as both an inverse agonist and antagonist, providing a broad therapeutic window and consistent CB1 inhibition.

• Animal studies demonstrate dose-dependent weight loss, fat mass reduction, lean mass preservation, and improved glucose tolerance.

• The antibody's 18–21 day half-life supports a favorable dosing profile.

Clinical development and milestones

• Phase II (CBeyond) trial includes four arms: nimacimab monotherapy, placebo, combination with semaglutide, and semaglutide alone.

• Primary endpoint is 8% mean weight loss difference at 26 weeks; secondary endpoints include safety, neuropsychiatric evaluation, and body composition.

• Interim data expected by end of Q2 2025, with top-line data by end of Q4 2025; full Phase II completion targeted for 2027.

• Enrollment is on track, with 50% of patients recruited as of November and completion expected soon.

• Robust dose-ranging studies and preparations for Phase II-B/III will follow based on these results.