Summary of Skye Bioscience Conference Call on Phase IIa Clinical Trial Results Company Overview - **Company**: Skye Bioscience (NasdaqGM:SKYE) - **Focus**: Development of Nimasumab for obesity treatment Key Industry Insights - **Clinical Trial**: Phase IIa CBON clinical trial results for Nimasumab - **Primary Endpoint**: Weight loss compared to placebo Core Findings 1. **Monotherapy Results**: - The 200 mg monotherapy arm did not meet the primary endpoint compared to placebo - Weight loss: -1.5% for Nimasumab vs -0.3% for placebo in the modified intent to treat population [8][34] - Lower than expected drug exposure was identified as a reason for this outcome [8][9] 2. **Combination Therapy Results**: - Combination of Nimasumab and Semaglutide showed a clinically meaningful weight loss of approximately -14.3% at 26 weeks compared to -10.8% for Semaglutide alone [13][35] - 100% of participants in the combination arm achieved at least 5% weight loss, and two-thirds achieved at least 10% [14][35] 3. **Safety Profile**: - Nimasumab demonstrated a favorable safety and tolerability profile, with adverse events similar to placebo [16][52] - No neuropsychiatric adverse events were reported, which is a significant differentiator from previous CB1 approaches [17][19] 4. **Pharmacokinetics (PK) Insights**: - Preliminary PK analysis indicated that many participants had lower than predicted drug exposure [41][43] - Higher dosing is suggested as a logical next step to improve efficacy [11][12] 5. **Future Directions**: - Plans to test higher doses (600 mg to 1000 mg) in future trials to explore efficacy further [72][73] - Ongoing extension study evaluating a 300 mg dose to gather additional PK and efficacy data [62][64] Additional Considerations - **Mechanistic Insights**: The combination of Nimasumab and Semaglutide works through complementary mechanisms, enhancing weight loss without increasing gastrointestinal side effects [15][60] - **Body Composition**: The combination therapy showed a favorable lean to fat mass ratio improvement compared to Semaglutide alone [39][61] - **Market Positioning**: Nimasumab is positioned as a complementary treatment in the obesity landscape, particularly against GLP-1s, which have GI burden challenges [21][60] Conclusion - The results from the Phase IIa trial provide valuable insights into the efficacy and safety of Nimasumab, highlighting the need for further exploration of dosing strategies to optimize therapeutic outcomes in obesity treatment. The combination therapy shows promise in enhancing weight loss while maintaining a favorable safety profile.

Clinical Trial Results - Nimacimab monotherapy (200 mg QW) did not meet the primary endpoint, with a placebo-adjusted weight loss of -126% (p=02699, mITT) and -133% (p=02878, PP) at 26 weeks[98] - Combination therapy with Semaglutide achieved a clinically meaningful placebo-adjusted weight loss compared to Semaglutide alone (-129% vs -999%, p=00372, mITT and -143% vs -108%, p=00178, PP)[98] - The combination arm showed an improved lean to fat mass ratio (026 vs 013, p = 00126)[98] Safety and Tolerability - The trial demonstrated a clean safety profile with no neuropsychiatric adverse events observed[98] - The combination of Nimacimab and Semaglutide did not add to the gastrointestinal (GI) burden compared to Semaglutide alone[98] Exposure and Dosing - The monotherapy effect was limited at the 200 mg dose, but exposure modeling and preclinical data suggest potential efficacy at higher doses[98] - A preliminary average AUC at 26 weeks for the 200 mg SC QW clinical dose was 243013 h*ug/mL, while DIO studies demonstrate a wide and effective dose range[73] Next Steps - The company will evaluate exposure/response data to determine next steps, including potential future clinical studies to confirm optimal exposure and regimen[98] - The company will focus on the combination strategy while continuing to evaluate higher-dose monotherapy[98] - The company is assessing a path for a monotherapy maintenance setting[98]

Core Insights - Skye Bioscience's experimental obesity drug failed to meet the primary endpoint in a mid-stage clinical trial [1] Company Summary - The company announced the results of its mid-stage study on Monday, indicating that the obesity drug did not achieve its main goal [1]

Core Insights - Skye Bioscience announced topline data from its 26-week Phase 2a CBeyond™ study of nimacimab, a CB1 inhibitor antibody targeting obesity and metabolic disorders [1][2] Study Results - The nimacimab monotherapy did not meet the primary endpoint for weight loss, showing a placebo-subtracted weight loss of -1.26% at week 26 [6][7] - In the combination cohort, nimacimab 200 mg plus semaglutide resulted in a significant weight loss of -13.2% compared to -10.25% with semaglutide alone, with a p-value of 0.0372 [3][12] - The combination therapy did not show a plateau in weight loss through Week 26, indicating potential for continued efficacy [3][12] Safety Profile - Nimacimab demonstrated a favorable safety profile, with tolerability similar to placebo and no increase in gastrointestinal adverse events when combined with semaglutide [4][9] - No neuropsychiatric adverse events were reported with nimacimab, indicating a clean safety profile [4][13] Pharmacokinetics and Dosing Insights - Preliminary pharmacokinetic analysis indicated that the 200 mg weekly dose of nimacimab was suboptimal as a monotherapy, suggesting the need for higher dosing [2][5] - The company is considering higher dosing strategies based on preclinical data and safety margins observed in the study [5][18] Future Directions - Skye plans to evaluate the next stage of development for nimacimab, including potential follow-on Phase 2 studies to optimize dosing [5][18] - Detailed results from the 26-week treatment period will be presented at ObesityWeek in November [19]

Core Insights - Skye Bioscience, Inc. (NASDAQ: SKYE) has experienced significant stock performance, with double-digit gains this month and a remarkable increase of 145% over the past six months [1]. Company Performance - The stock of Skye Bioscience has shown strong momentum, indicating positive market sentiment and potential investor interest [1]. Analyst Background - Gamu Dave Innocent Pasi, a financial professional with extensive experience in investment research, has contributed insights into the financial landscape, emphasizing the importance of analyzing financial statements and capital markets [1]. - Pasi holds a Postgraduate Executive Certificate in Investments and Portfolio Management and a Bachelor of Business Studies Honors degree in Banking and Finance, showcasing a strong educational background in finance [1]. Investment Philosophy - The focus on responsible investment and the integration of Environmental, Social, and Governance (ESG) principles in decision-making reflects a growing trend in the investment community towards sustainable and socially impactful investing [1].

Core Insights - Skye Bioscience, Inc. (NASDAQ: SKYE) has experienced significant stock performance, with double-digit gains this month and a remarkable increase of 145% over the past six months [1] Company Performance - The stock's recent gains may be supported by positive developments in the company's operations or market conditions [1] Analyst Background - Gamu Dave Innocent Pasi, a financial professional with extensive experience in investment research, emphasizes the importance of analyzing financial statements and capital markets [1] - Pasi has contributed to reputable publications and holds advanced qualifications in investments and portfolio management [1] - The analyst is focused on promoting responsible investment and integrating Environmental, Social, and Governance (ESG) principles into investment strategies [1]

Core Insights - Skye Bioscience, Inc. announced positive results from the Phase 1b study of nimacimab for metabolic-associated steatotic liver disease (MASLD) at the EASD Annual Meeting, highlighting its safety and tolerability profile [1][2][3] Study Results - The Phase 1b study showed nimacimab was safe, well-tolerated, and had predictable pharmacokinetics with low immunogenicity across multiple ascending dose cohorts [1] - No serious adverse events or discontinuations due to adverse events were reported, and gastrointestinal side effects were infrequent and mild [2] Market Position and Future Expectations - Skye's management anticipates placebo-adjusted weight loss of 5%-8% for nimacimab monotherapy, with additional weight loss when combined with Wegovy, and no neuropsychiatric events reported [5] - Investment firm William Blair expects topline data from the Phase 2a CBeyond obesity study by the end of the month or early next quarter [4] Competitive Landscape - The obesity treatment market is competitive, particularly due to the success of GLP-1 receptor drugs like Novo Nordisk's Ozempic and Eli Lilly's Zepbound [8] - Despite competition, nimacimab's focus on tolerability and its potential clinical success could provide significant upside for investors [8] Analyst Insights - Analyst Andy Hsieh notes that CB1 receptor inverse agonism/antagonism could serve as an alternative or combination therapy for GLP-1 receptor agonists, with nimacimab showing promise in inducing weight loss with fewer gastrointestinal side effects [6][7] - The initial Phase 1 data and preclinical experiments support the hypothesis that nimacimab preferentially targets peripheral CB1 receptors, mitigating previous concerns related to psychiatric adverse events [7] Stock Performance - Following the announcement, SKYE stock increased by 0.76% to $3.97 [9]

Core Insights - Skye Bioscience, Inc. presented results from a Phase 1b study of nimacimab for metabolic-associated steatotic liver disease (MASLD) at the EASD Annual Meeting, highlighting its safety and tolerability profile [1][2][3] Company Overview - Skye Bioscience is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [1][5] - The company aims to create first-in-class therapeutics by leveraging biologic targets with substantial human proof of mechanism [5] Study Results - The Phase 1b study demonstrated that nimacimab was safe and well-tolerated, with no serious adverse events or discontinuations due to adverse events [2][3] - Gastrointestinal side effects were infrequent and mild, indicating a differentiated tolerability profile for nimacimab [2] - The study was previously conducted by Bird Rock Bio, Inc., which was acquired by Skye in 2023 [3] Future Focus - Skye's immediate focus is on the upcoming topline readout from the CBeyond™ Phase 2a obesity study, which is assessing nimacimab's efficacy [3][5] - The Phase 2a clinical trial is also evaluating the combination of nimacimab with a GLP-1R agonist (Wegovy®) [5]

Core Points - The presentation is led by Frank Tang, a Managing Director at Morgan Stanley, indicating a formal setting for discussing investment opportunities [1] - The event features a fireside chat with Skye Bioscience, highlighting the company's engagement with stakeholders and potential investors [2] Company Overview - Skye Bioscience is represented by its CEO, Punit Dhillon, suggesting a focus on leadership and strategic direction within the company [2]

Core Points - The presentation is led by Frank Tang, a Managing Director at Morgan Stanley, indicating a formal engagement with stakeholders [1] - The event features a fireside chat with Skye Bioscience, highlighting the company's leadership presence with CEO Punit Dhillon [2] Company Overview - Skye Bioscience is positioned for discussion, suggesting a focus on its strategic initiatives and market positioning [2] Industry Context - The involvement of a major investment bank like Morgan Stanley suggests significant interest in the biotechnology sector, particularly in companies like Skye Bioscience [1][2]