Skye Bioscience (SKYE) Update / Briefing Transcript

Summary of Skye Bioscience (SKYE) Update / Briefing September 04, 2025 Company Overview - Company: Skye Bioscience (SKYE) - Focus: Development of Nimazumab, a monoclonal antibody targeting the CB1 receptor for obesity and metabolic disorders Key Industry Insights - Clinical Trials: Discussion centered around the CBEYOND Phase 2 trial, with a focus on the efficacy and safety of Nimazumab in treating obesity - Mechanism of Action: Nimazumab acts as a negative allosteric modulator of the CB1 receptor, designed for peripheral action, minimizing brain penetration and associated neuropsychiatric risks Core Points and Arguments 1. Clinical Data Presentation: New preclinical data was shared, indicating that Nimazumab reduces fat metabolism while preserving lean mass, improves glycemic control, and shows weight loss durability after treatment cessation [4][8][10] 2. Weight Loss Efficacy: In preclinical studies, Nimazumab demonstrated up to 24.2% weight loss in DIO mice, outperforming the small molecule monlunabant [26][27] 3. Rebound Weight Gain: Post-treatment weight regain was significantly lower with Nimazumab compared to monlunabant, indicating its potential for long-term weight maintenance [28][34] 4. Combination Therapy Potential: The combination of Nimazumab with tirzepatide showed promising results, achieving up to 44% weight loss, suggesting enhanced efficacy when used together [31][34] 5. Safety Profile: Emphasis on the reduced risk of neuropsychiatric side effects due to Nimazumab's limited brain penetration, a significant concern with previous CB1 antagonists [50][72] 6. Tolerability: The company aims for better gastrointestinal tolerability compared to existing GLP-1 therapies, which is crucial for patient adherence and long-term treatment success [49][52] Important but Overlooked Content 1. Market Need: There is a significant unmet need for more tolerable obesity treatments, as many patients discontinue current therapies due to side effects [18][82] 2. Patient Feedback: Surveys conducted with endocrinologists highlighted the demand for therapies that improve tolerability and support chronic use [17][18] 3. Future Expectations: The Phase 2 proof of concept readout is anticipated in late Q3 to early Q4 2025, with a focus on achieving 5-8% placebo-adjusted weight loss [11][45] 4. Long-term Data: The company is preparing for a 52-week data readout from the extension study, which will provide further insights into the long-term efficacy and safety of Nimazumab [43][44] Conclusion Skye Bioscience is positioning Nimazumab as a potentially groundbreaking treatment for obesity, with a focus on safety, tolerability, and efficacy. The upcoming clinical data will be critical in validating its therapeutic profile and addressing the significant market need for effective obesity treatments.