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]

Summary of Skye Bioscience FY Conference Call Company Overview - **Company**: Skye Bioscience (NasdaqGM:SKYE) - **Focus**: Development of innovative therapeutics targeting obesity through a CB1 antibody approach Key Points and Arguments Pipeline and Development - Skye is in **Phase 2a** development for an obesity treatment using a **CB1 antibody**, which is a non-incretin target, contrasting with the dominant incretin class (GLP-1) in the market [2][3] - The clinical readout for the lead program is expected in **late Q3 to early Q4 2025** [2] - The company is also focused on **lifecycle management** of lead assets and improving the **target product profile (TPP)**, including exploring less frequent dosing options [3][32] Market Insights - The obesity treatment market is described as **heterogeneous**, indicating that a one-size-fits-all approach is ineffective [4] - Approximately **70% of patients** discontinue current obesity drugs within the first year, primarily due to tolerability issues [6] - Skye aims to address the **maintenance population** and those who discontinue other treatments due to side effects [5] Competitive Positioning - NEMAZENMEB is positioned to target patients who discontinue drugs like **Zepbound** or **Wegovy**, with a focus on **combination therapies** that could enhance weight loss outcomes [8][17] - The company anticipates achieving **5% to 8% weight loss** at 26 weeks in its proof of concept study, with a goal of demonstrating a clear separation from placebo [14][15] Mechanism of Action - NEMAZENMEB operates through a **peripheral-driven mechanism**, focusing on metabolic functions outside the brain, which is expected to regulate appetite and improve glucose metabolism [9][10] - Evidence suggests that NEMAZENMEB can positively influence **lipid metabolism** and reduce inflammation, which are critical factors in obesity management [11][12] Safety and Efficacy - Skye emphasizes the importance of **neuropsychiatric safety**, especially given past issues with similar drugs like rimonabant [19][20] - The company has established a robust safety profile with no reported neuropsychiatric adverse events in early trials [20][21] Financial Position - As of June 30, Skye reported a cash balance of **$48 million**, which is expected to fund operations until **Q1 2027** [31] - The company is committed to maintaining low general and administrative costs while focusing on development [33] Future Milestones - Key upcoming milestones include the **top-line data release** in late Q3 to early Q4 2025 and decisions regarding the **Phase 2b study** [37][38] - The company is also exploring broader applications of its CB1 pathway research, potentially addressing various comorbidities associated with obesity [27][28] Additional Important Insights - Skye is open to exploring **combination therapies** with existing GLP-1 drugs, aiming for a product that could be administered less frequently while maintaining efficacy [29] - The company recognizes the competitive landscape of obesity treatments and aims to differentiate itself through unique mechanisms and improved patient outcomes [25][26]

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.

Skye shares new preclinical DIO data at virtual KOL eventNimacimab + tirzepatide demonstrates over 40% weight loss in multiple preclinical DIO studies Nimacimab demonstrates durable post-treatment weight loss compared to tirzepatideNimacimab reduced rebound weight gain following treatment with tirzepatide or nimacimab + tirzepatideNimacimab outperformed monlunabant head-to-head, and is uniquely positioned as a well-tolerated therapeutic to potentially induce healthier and sustained weight loss, both as a mo ...

Core Insights - Skye Bioscience, Inc. has completed the treatment phase for the last patient in its Phase 2a CBeyond™ clinical trial evaluating nimacimab for obesity, with topline data expected in late Q3/early Q4 of 2025 [1][3] Group 1: Clinical Trial Details - The CBeyond™ Phase 2a trial is a randomized, double-blind, placebo-controlled study focusing on weight loss, safety, tolerability, and metabolic biomarkers in adults with obesity and overweight [2] - The primary endpoint of the trial is to compare weight change from baseline to 26 weeks between nimacimab and placebo [2] - An exploratory arm of the trial is assessing the combination of semaglutide (Wegovy®) with nimacimab versus semaglutide with placebo [2] Group 2: Study Progress and Future Plans - Skye has completed enrollment for a 26-week extension of the Phase 2a trial, which aims to provide data on 52 weeks of treatment with nimacimab, either as monotherapy or in combination with semaglutide [5] - Patients who completed the initial 26 weeks were eligible for the extension, potentially leading to a total treatment duration of 52 weeks followed by a 12-week follow-up [5] - Data from the extension study is expected to be reported in Q1 2026 [5] Group 3: Company Strategy and Market Context - Skye is focused on developing new therapeutic pathways for metabolic health, particularly through the modulation of G-protein coupled receptors [6] - The company believes that peripheral CB1 inhibition via an antibody presents a promising alternative to existing GLP-1 weight loss drugs, which may not meet all patients' needs [4] - Skye aims to advance nimacimab as a potential new therapeutic option for obesity and overweight, addressing limitations of current treatments [4]

Core Insights - Skye Bioscience, Inc. will host a virtual KOL event on September 4, 2025, to discuss the upcoming topline results from the Phase 2a CBeyond™ trial of nimacimab, a first-in-class peripheral CB1 antibody for obesity [1][2] - The event aims to provide clarity on what constitutes success in the proof-of-concept study, focusing on safety, tolerability, and new preclinical insights related to nimacimab [2][7] Company Overview - Skye Bioscience is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [1][8] - The company is conducting a Phase 2a clinical trial for nimacimab, which is designed to inhibit peripheral CB1 and is also assessing its combination with a GLP-1R agonist [8] KOL Event Highlights - The event will feature discussions with leading obesity experts, including Skye's CEO, Punit Dhillon, who will address the significance of safety and tolerability benchmarks in the obesity treatment landscape [2][7] - Key opinion leaders participating include Dr. Kevin Cannon, Dr. Sean Wharton, and Dr. Marcus Goncalves, who bring extensive experience in metabolic health and obesity research [3][4][6] Research Focus - The event will cover the mechanism and potential role of peripheral CB1 inhibition as a differentiated anti-obesity therapeutic pathway [7] - Newly generated preclinical data with nimacimab will be highlighted, contributing to the understanding of its potential advancement into Phase 2b development [2][7]

Core Insights - Skye Bioscience, Inc. is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [4] - The company is conducting a Phase 2a clinical trial for nimacimab, an antibody that inhibits CB1, and is also assessing its combination with a GLP-1R agonist [4] Investment Conferences - Skye will participate in several investment conferences, including: - Cantor Global Healthcare Conference on September 5, 2025 - H.C. Wainwright Global Investment Conference on September 8, 2025 - Morgan Stanley Global Healthcare Conference on September 10, 2025 [6] Medical/Scientific Conferences - Skye will also present at medical conferences, including: - Obesity Science & Innovation on September 16, 2025, with a keynote panel discussing pipeline priorities in obesity therapeutics - European Association for the Study of Diabetes Annual Meeting on September 19, 2025, presenting a study on the safety and tolerability of nimacimab in subjects with metabolic associated fatty liver disease [6]

Financial Data and Key Metrics Changes - The company ended the second quarter with cash and cash equivalents totaling $48.6 million, with guidance indicating that current capital is projected to fund operations through at least Q1 2027 [29] - Research and development expenses for the three months ended June 30, 2025, were $14.3 million, compared to $4.1 million for the same period in 2024, primarily due to increased clinical trial costs and contract manufacturing [30] - The net loss for the three months ended June 30, 2025, totaled $17.6 million, compared to $7.9 million for the same period in 2024 [31] Business Line Data and Key Metrics Changes - The phase two a CBEYOND trial is advancing as planned, with enrollment completed ahead of schedule, and the 26-week visit for the last patient projected to occur shortly [7] - Approximately 50% of patients from the original study are eligible for enrollment in the extension study, with optimism that a majority will choose to participate [7][56] Market Data and Key Metrics Changes - The company identifies three market opportunities for Nimasumab: as a monotherapy for patients who cannot tolerate incretin therapeutics, as a combination partner to amplify efficacy, and as a maintenance therapy to sustain weight loss [22] - The obesity treatment market is evolving beyond caloric restriction to address broader metabolic impacts, indicating a shift in treatment paradigms [26] Company Strategy and Development Direction - The company aims to position Nimasumab as a next-generation backbone candidate for durable and combinable obesity care, addressing the limitations of current therapies [25] - The focus is on expanding therapeutic options in obesity treatment, particularly for patients who discontinue existing therapies due to side effects [24] Management's Comments on Operating Environment and Future Outlook - Management emphasizes the importance of disciplined execution and operational rigor as the company enters a crucial execution period [32] - The upcoming top-line data from the CBEYOND trial is expected to provide insights into the efficacy and safety of Nimasumab, guiding future development [34] Other Important Information - The company plans to host a KOL event at Nasdaq on September 4, focusing on clinical data expectations and market positioning [33] - The phase one SADMAD MAFLD data will be presented at EASD on September 19, reinforcing hepatic and metabolic benefits [33] Q&A Session Summary Question: What accounted for the increase in R&D expenses? - The increase was primarily due to contract manufacturing costs related to the phase two a resupply and the supply for the phase two b trial [41] Question: What are the expectations for Nimasumab's weight loss efficacy at week 26? - The goal is to demonstrate a clinically meaningful weight loss separation from placebo, ideally in the range of 5% to 8% [46] Question: What is the expected discontinuation rate within 26 weeks? - The company expects a discontinuation rate similar to trends seen in other obesity studies, around 25% to 30% [50] Question: What is the protocol for the independent board overseeing trial safety? - The board meets quarterly and reviews all adverse events and serious adverse events reported during the study [73] Question: Will there be a follow-up period after the extension study to track durability of weight loss? - Yes, there will be a 13-week follow-up period after the extension study, with data expected in 2026 [82]

Clinical Progress - Top-line data from the CBeyond study is expected in late Q3/early Q4[15] - A KOL event is scheduled for September 2025 to discuss the mechanism, Phase 2a clinical data expectations, and market positioning[15, 49] Nimacimab's Differentiation and Mechanism - Nimacimab exhibits significantly less brain penetration compared to small molecule CB1 inhibitors[18] - Nimacimab retains potency even in the presence of competition, unlike small molecules[20] - Preclinical data suggests nimacimab enhances weight loss when combined with low-dose tirzepatide[26] - Preclinical data suggests nimacimab prevents weight rebound and shows potential as maintenance therapy, with tirzepatide rebound at 29.7% and nimacimab maintenance at 12.8% in Phase B[31, 33] Market Opportunity - Nearly two-thirds (66.67%) of patients discontinue GLP-1 RA therapy after one year, and over 80% discontinue after two years, highlighting a therapeutic gap[36] - The company believes nimacimab represents a potential multi-billion dollar opportunity in monotherapy, maintenance, and combination therapy for obesity[37]