Summary of Skye Bioscience FY Conference Call Company Overview - **Company**: Skye Bioscience (NasdaqGM:SKYE) - **Focus**: Metabolic therapeutics, specifically developing a peripherally restricted CB1 antibody named Nemesumab - **Current Development Stage**: Phase 2 development with initial data reported from a 26-week trial Key Points and Arguments Clinical Data and Efficacy - The initial 26-week data from the phase 2 trial indicated that a 200-milligram dose of Nemesumab showed limited efficacy, establishing a floor for weight loss response [3][4] - A combination therapy with Semaglutide resulted in a 30% increase in weight loss compared to Semaglutide alone, with patients losing approximately 13% of their body weight over 26 weeks [3][11] - The company aims to achieve a weight loss trajectory of around 20% at the 52-week mark, positioning Nemesumab competitively against other therapies like CagriSema and tirzepatide [4][26] Mechanism of Action - The large molecule approach of Nemesumab is designed to avoid crossing the blood-brain barrier, reducing neuropsychiatric side effects associated with small molecules [5][6] - The combination of GLP-1 mechanism (caloric restriction) and CB1 inhibition (fat storage modulation) is believed to create a synergistic effect, enhancing weight loss [11][12] Safety and Dosing Strategy - The safety profile of Nemesumab is considered favorable, allowing for higher dosing without significant adverse effects [6][10] - Future dosing strategies may involve increasing the dose significantly beyond the current 200-milligram level, with estimates suggesting a range of 600 to 1,000 milligrams may be optimal based on preclinical data [21][23] Future Development Plans - The company is prioritizing the combination therapy while keeping options open for monotherapy, especially if it can achieve a weight loss target of 5%-8% [25][30] - An extension study is set to report data in Q1, which will inform the design of a potential phase 2B trial [30] Additional Important Insights - The company is exploring formulation and delivery technologies to facilitate at-home administration of higher volume injections [24] - There is a nuanced approach to interpreting data from patients who may have treatment gaps, particularly in the monotherapy group [28][29] - The competitive landscape is acknowledged, with a focus on demonstrating superior efficacy and safety profiles compared to existing therapies [26][30]