Skye Bioscience (SKYE) Guggenheim Global Healthcare Conference summary

Strategic focus and development pipeline

• Focused on metabolic diseases with a lead program targeting CB1 inhibition using nimacimab, a first-in-class antibody currently in phase II for obesity.

• Acquisition of nimacimab from Bird Rock Bio in August 2023, supported by Versant and 5AM Ventures, enabled a broader franchise strategy in metabolic disease.

• Cash runway extends until Q3 2027, supporting ongoing and future clinical programs.

• Recent preclinical evidence supports efficacy and safety, de-risking the program and positioning it attractively among obesity peers.

• 2025 is anticipated as a pivotal year for clinical and strategic milestones.

Clinical program design and differentiation

• Phase II-A study is a 26-week, randomized, placebo-controlled trial with monotherapy and combination arms.

• Monotherapy arm evaluates nimacimab’s effect on weight loss, body composition, and metabolic markers, aiming to minimize lean mass loss compared to GLP-1s.

• Combination arm tests nimacimab plus Wegovy versus Wegovy alone, exploring additive effects.

• Interim analysis planned at 50% patient completion, with a 13-week follow-up for long-term data.

• Exploratory endpoints include leptin and insulin sensitivity, and sleep quality improvements.

Mechanism of action and safety profile

• Nimacimab is a peripherally restricted CB1 antibody, designed to avoid neuropsychiatric side effects seen with earlier CB1 antagonists like rimonabant.

• Preclinical and PK modeling show a 600-fold lower CNS exposure compared to small molecules, supporting a wide therapeutic window.

• Peripheral CB1 inhibition is validated as sufficient for weight loss and metabolic benefits, with central effects mediated indirectly via improved leptin signaling.

• Phase I data showed zero neuropsychiatric adverse events; safety remains the top priority in phase II.

• Potential for monthly dosing due to long antibody half-life is under exploration.