Core Viewpoint - Skye Bioscience, Inc. is set to discuss its second quarter 2025 financial results and business updates in a conference call scheduled for August 7, 2025 [1][2] Company Overview - Skye Bioscience is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [3] - The company is working on next-generation molecules that modulate G-protein coupled receptors, aiming to create first-in-class therapeutics with clinical and commercial differentiation [3] Clinical Trials - Skye is conducting a Phase 2 clinical trial for nimacimab, a negative allosteric modulating antibody that inhibits CB1, specifically targeting obesity [3] - The trial is also evaluating the combination of nimacimab with a GLP-1R agonist (Wegovy®) [3]

Core Insights - Skye Bioscience, Inc. is focused on developing nimacimab, an anti-obesity drug that targets peripheral CB1 receptors, aiming to address unmet needs in obesity treatment [1][2][3] - The company has launched a video series titled "Anatomy of Progress" to provide updates on nimacimab's development and its advantages over traditional treatments [1][2] Group 1: Product Development - Nimacimab is a peripherally-restricted CB1 antibody that aims to provide weight loss benefits without the neuropsychiatric side effects associated with small molecule CB1 inhibitors [4][3] - The video series discusses the mechanistic advantages of nimacimab, emphasizing its potential to revolutionize obesity treatment by addressing biological resistance to traditional therapies [3][4] Group 2: Clinical Insights - Skye's management participated in a panel discussing the clinical and preclinical experiences with nimacimab, highlighting its peripheral blockade of the CB1 pathway [5] - Presentations at the American Diabetes Association's 85th Scientific Sessions included data on nimacimab's effectiveness in promoting weight loss and reducing obesity-induced inflammation [6][8] Group 3: Market Positioning - The company is positioning nimacimab as a differentiated therapeutic option in the obesity market, particularly as a non-GLP1 alternative, based on feedback from obesity physicians [7] - The market opportunity for nimacimab is framed by its unique target product profile, which is expected to complement existing incretin-based therapies [7][9] Group 4: Research Findings - Preclinical studies demonstrated that nimacimab promotes metabolic homeostasis and improves hormonal regulation in diet-induced obesity models [8] - New biomarker data presented indicates significant reductions in obesity-related inflammation and liver steatosis, supporting nimacimab's potential as a standalone and combination therapy [6][8]

Core Insights - Skye Bioscience, Inc. is set to present new data on nimacimab at the American Diabetes Association's 85th Scientific Sessions, highlighting its focus on obesity and metabolic health disorders [1][2] Presentation Details - Skye's CEO, CMO, and CSO will participate in an invitation-only panel at the Evercore event during the ADA conference [3] - A symposium presentation titled "Mechanistic Insights into Weight Loss and Metabolic Regulation of Obese Mice Treated with Nimacimab" will be held on June 22, 2025, showcasing the therapeutic potential of nimacimab [4] - A poster presentation will discuss how nimacimab promotes metabolic homeostasis in a diet-induced obesity mouse model, emphasizing weight loss and hormonal regulation [5] Company Overview - Skye Bioscience is dedicated to developing next-generation therapeutics targeting G-protein coupled receptors, with a focus on obesity and metabolic health [6][7] - The company is conducting a Phase 2 clinical trial for nimacimab, assessing its effects both alone and in combination with a GLP-1R agonist [7]

Summary of Skye Bioscience (SKYE) 2025 Conference Call Company Overview - **Company**: Skye Bioscience (SKYE) - **Focus**: Development of Nimazumab, a first-in-class CB1 blocking antibody targeting obesity Industry Context - **Market Opportunity**: The obesity treatment market is a multibillion-dollar opportunity with significant unmet needs, particularly as obesity rates in the U.S. are projected to reach 50% by 2035 [4][5] - **Current Treatments**: Existing GLP-1 drugs, such as Wegovy and Zepbound, have limitations including high discontinuation rates (over 30% within four weeks) and adverse gastrointestinal events [5][6] Core Points and Arguments - **Nimazumab's Unique Mechanism**: - Targets weight loss through a non-incretin pathway, specifically the peripheral CB1 receptor, which controls energy balance and metabolism without central nervous system risks [6][7] - Designed to provide better tolerability and a favorable body composition profile compared to existing therapies [5][6] - **Clinical Validation**: - Historical data shows that first-generation drugs achieved only 3% placebo-adjusted weight loss, while recent data from Novo reported 6% [8] - Nimazumab aims to maintain efficacy while avoiding CNS-related safety issues [8][9] - **Target Product Profile**: - Identified three core use cases: monotherapy, maintenance therapy, and combination therapy, each representing significant market segments [9] - **Antibody Characteristics**: - Engineered IgG4 antibody with a half-life of 18-21 days, allowing for less frequent dosing [10] - Demonstrated zero off-target GPCR binding and a wide safety window [10][11] - **Efficacy Data**: - Preclinical studies show dose-dependent weight loss in diet-induced obesity models, with a focus on fat loss and improved body composition [14][15] - Nimasumab has shown potential in improving glycemic control and reducing hepatic fat [16][18] - **Combination Therapy Potential**: - Early data from a combination study with tirzepatide showed a 31.5% weight loss, indicating additive effects [20] Important Developments - **Clinical Trials**: - Currently conducting a Phase II study called "See Beyond" with 120 patients, evaluating Nimazumab against placebo and in combination with GLP-1 [24] - Top-line data expected in late Q3 or early Q4 2025, with a follow-up study planned for 52 weeks [26] - **Financial Position**: - Raised approximately $107 million since August 2023, with sufficient cash to fund operations into Q1 2027 [27] - **Management Team**: - Experienced team with a strong track record in drug development and commercialization [28] Additional Insights - **Market Positioning**: - Nimazumab is positioned to complement existing incretin therapies rather than compete directly, addressing gaps in the current market [23] - **Regulatory Engagement**: - Plans to engage with regulators based on upcoming clinical data to inform the design of Phase 2b studies [26] This summary encapsulates the key points discussed during the conference call, highlighting Skye Bioscience's strategic focus, product development, and market positioning within the obesity treatment landscape.

Core Insights - Skye Bioscience, Inc. is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [1][2] - The company will participate in two upcoming healthcare conferences, including the Jefferies Global Healthcare Conference and the Sachs European BioPharma Obesity Innovation Forum [1] Company Overview - Skye is developing next-generation molecules that modulate G-protein coupled receptors, aiming for first-in-class therapeutics with clinical and commercial differentiation [2] - The company is conducting a Phase 2 clinical trial for nimacimab, a negative allosteric modulating antibody that inhibits CB1, and is also assessing its combination with a GLP-1R agonist (Wegovy®) [2]

Core Insights - Skye Bioscience is collaborating with Arecor Therapeutics to develop a higher concentration formulation of nimacimab, a CB1 inhibitor, utilizing Arecor's Arestat™ technology [1][2][3] - Nimacimab is currently being evaluated in a Phase 2a clinical trial for obesity, with initial data expected in late Q3 or early Q4 2025 [2][5] - The partnership allows Skye to fund Arecor's development activities and potentially license the new formulation and associated intellectual property [2][3] Company Overview - Skye Bioscience focuses on developing next-generation therapeutic pathways for metabolic health, particularly through G-protein coupled receptors [5] - The company is conducting a Phase 2a clinical trial for nimacimab, which is a negative allosteric modulating antibody that inhibits CB1 [5] - Arecor Therapeutics aims to enhance existing therapeutic products and has a proprietary technology platform, Arestat™, supported by a strong patent portfolio [4] Product Development - Nimacimab has a pharmacokinetic profile with a half-life of 18–21 days, which is significantly longer than GLP-1-based therapies, and is being evaluated for once-weekly dosing [3] - The collaboration aims to address issues related to tolerability and adherence seen in approved weight loss drugs, as well as concerns about neuropsychiatric toxicities associated with small molecule CB1 inhibitors [3]

Core Insights - The model presented by Skye Bioscience indicates that central inhibition of CB1 is not necessary for weight loss, emphasizing the importance of peripheral CB1 inhibition for efficacy [1][3] - Nimacimab, an anti-CB1 inhibiting antibody, shows superior peripheral restriction compared to small molecule-based CB1 inhibitors like monlunabant and rimonabant, which penetrate the brain more [1][3] - The therapeutic index of nimacimab is potentially more favorable due to its minimal brain exposure while maintaining effective peripheral inhibition [1][3] Company Overview - Skye Bioscience is a clinical-stage biotechnology company focused on developing new therapeutic pathways for obesity and metabolic health disorders [5] - The company is conducting a Phase 2 clinical trial for nimacimab, which is a negative allosteric modulating antibody that inhibits CB1 peripherally [6] - Skye aims to differentiate its therapeutics through biologic targets with substantial human proof of mechanism [5] Clinical Findings - The model developed utilized published clinical pharmacokinetic and potency data from other CB1 inhibitors, demonstrating that central inhibition alone does not lead to significant weight loss [2][4] - Phase 2 data for monlunabant showed that all doses achieved significant peripheral inhibition, resulting in similar weight loss outcomes [2] - Nimacimab's Phase 2 dose achieves peripheral CB1 engagement at over seven times the inhibition threshold while remaining significantly below this threshold in the brain [4] Safety and Efficacy - The model provides insights into the therapeutic index of different CB1 inhibitors, indicating that increased central inhibition correlates with neuropsychiatric adverse events [3][4] - Nimacimab has been shown to be virtually undetectable in the brain, which is a challenge faced by small molecule CB1 inhibitors [3][4]

Financial Data and Key Metrics Changes - Cash and cash equivalents and short-term investments totaled $59.2 million as of March 31, 2025 [18] - Research and development expenses increased to $7.2 million for the three months ended March 31, 2025, compared to $1.9 million for the same period in 2024 [19] - General and administrative expenses rose to $4.6 million for the three months ended March 31, 2025, compared to $4.2 million for the same period in 2024 [19] - The net loss for the three months ended March 31, 2025, was $11.1 million, with non-cash share-based compensation expense of $2.2 million [20] Business Line Data and Key Metrics Changes - The company completed enrollment in its Phase IIa CBEYOND trial ahead of schedule and amended the study to extend to 52 weeks [5][6] - Compelling new preclinical data was generated that validates the potential of nirmasumab as a weight loss therapy [6][7] - The Data Safety Monitoring Committee completed three reviews with no safety concerns reported [8] Market Data and Key Metrics Changes - The evolving policy environment presents regulatory uncertainties, particularly regarding drug pricing policy [9] - The company believes its exposure to these regulatory changes is limited in the near term as it prioritizes clinical development milestones [9] Company Strategy and Development Direction - The company aims to address the chronic nature of obesity with sustainable long-term solutions through its differentiated approach to weight loss therapies [10] - The management team emphasizes the importance of clear differentiation from small molecule inhibitors and the potential for nirmasumab to provide durable weight loss with fewer safety concerns [6][10] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing clinical trials and the potential for nirmasumab to deliver significant weight loss [10] - The company is closely monitoring regulatory developments and has preserved flexibility in its supply chain and capital deployment planning [9][22] Other Important Information - The company anticipates that its current capital will fund operations and key clinical milestones through at least Q1 2027 [19] - The final drug substance is manufactured in Germany, with no expected impact from tariffs on raw materials or excipients [20][21] Q&A Session Summary Question: What can we expect to see at ADA and ECO? - Management deferred to the CSO for details on the presentations at ADA and ECO, highlighting the importance of differentiating their mechanism from small molecules [25][27] Question: How do you view the difference between nirmasumab and monlunabant? - Management believes investors are beginning to grasp the differences, emphasizing the additive effects of nirmasumab in combination with tirzepatide [26][28] Question: What is the incremental benefit of extending the CBION study to 52 weeks? - The extension allows for broader efficacy and safety data collection, which will inform the Phase IIb study [66][68] Question: What are the expectations for separation from placebo in monotherapy? - The primary endpoint is targeting an 8% separation from placebo at 26 weeks [60] Question: How are you managing discontinuations in the combination arm? - The company has minimized gaps in treatment to avoid extended periods off semaglutide, ensuring patients remain on effective doses [100] Question: What are the plans for regulatory interactions? - The company has submitted a protocol amendment to the FDA and expects to resolve minor clarifications without needing a formal meeting [93][94]

Financial Data and Key Metrics Changes - Cash and cash equivalents and short-term investments totaled $59.2 million as of March 31, 2025 [17] - Research and development expenses increased to $7.2 million for the three months ended March 31, 2025, compared to $1.9 million for the same period in 2024 [18] - General and administrative expenses rose to $4.6 million for the three months ended March 31, 2025, compared to $4.2 million for the same period in 2024 [18] - The net loss for the three months ended March 31, 2025, was $11.1 million, with non-cash share-based compensation expense of $2.2 million [19] Business Line Data and Key Metrics Changes - The company completed enrollment in its Phase IIa CBEYOND trial ahead of schedule and amended the study to extend to 52 weeks [4][5] - New preclinical data validated the potential of nirmasumab as a weight loss therapy, showing significant weight loss comparable to less restricted small molecules [5][6] Market Data and Key Metrics Changes - The evolving policy environment presents regulatory uncertainties, particularly regarding drug pricing policy and FDA transitions [8][9] - The company believes its exposure to these uncertainties is limited in the near term as it prioritizes clinical development milestones [9] Company Strategy and Development Direction - The company aims to address the chronic nature of obesity with sustainable long-term solutions through its differentiated antibody approach [10] - The management is focused on disciplined execution while tracking developments in the regulatory landscape [9] Management Comments on Operating Environment and Future Outlook - Management expressed confidence in the clinical progress and the potential of nirmasumab to deliver durable weight loss with fewer safety concerns [6][10] - The company is preparing for key scientific and investor events to present additional data [6] Other Important Information - The company is closely monitoring potential tariff impacts on its manufacturing activities, with no expected immediate effects [19][21] - The independent Data Safety Monitoring Committee has completed three reviews with no safety concerns reported [7][58] Q&A Session Summary Question: What can be expected at ADA and ECO? - Management deferred details about ADA and ECO presentations to the CSO, who mentioned a cohesive model comparing different CB1 inhibitors will be presented at ECO [24][30] Question: How does management view the differentiation between nirmasumab and monlunabant? - Management believes investors are beginning to grasp the differences, emphasizing the additive effects of nirmasumab in combination with tirzepatide [25][27] Question: What is the plan for regulatory interactions? - The company plans to have discussions with the FDA regarding the Phase IIa data and potential Phase IIb study after data readouts [35][39] Question: How does nirmasumab preserve lean muscle mass? - The combination of nirmasumab with tirzepatide shows significant fat mass reduction while preserving lean mass, with the greatest effect observed in combination [42][46] Question: What are the expectations for the primary endpoint at 26 weeks? - The primary endpoint is targeting an 8% weight loss at 26 weeks, with expectations for separation from placebo [61] Question: What is the incremental benefit of extending the CBION study to 52 weeks? - The extension allows for broader efficacy and safety data collection, which will inform the Phase IIb study [68][70] Question: How is the trial powered based on preclinical studies? - The preclinical data has increased confidence in the expected outcomes, with robust inhibition of CB1 and significant weight loss observed [78][80]

[Skye Bioscience First Quarter 2025 Results and Corporate Highlights](index=1&type=section&id=Skye%20Bioscience%20Reports%20First%20Quarter%202025%20Results) [Clinical and Corporate Highlights](index=1&type=section&id=Clinical%20and%20Corporate%20Highlights) Skye Bioscience advanced its lead candidate nimacimab for obesity, emphasizing its peripherally restricted mechanism, with Phase 2a trial data expected in late Q3 or early Q4 2025 - CEO Punit Dhillon emphasized that nimacimab's peripherally restricted mechanism may differentiate it from GLP-1s and small-molecule CB1 inhibitors, potentially reshaping the obesity treatment landscape[3](index=3&type=chunk) - Top-line data from the CBeyond™ Phase 2a study of nimacimab is expected in late Q3 or early Q4 2025[5](index=5&type=chunk) - The clinical trial is progressing well: the Data Safety Monitoring Committee has completed three reviews with no safety concerns, and the IRB has approved a 52-week open-label study extension[6](index=6&type=chunk) [Research & Development Highlights](index=2&type=section&id=Research%20%26%20Development%20Highlights) Preclinical data demonstrated nimacimab's efficacy in weight loss, both as monotherapy and in combination, highlighting its peripherally restricted mechanism to avoid neuropsychiatric side effects - Nimacimab's highly-peripherally restricted mechanism is sufficient to drive weight loss, avoiding brain exposure and potential neuropsychiatric side effects seen in less-restricted CB1 inhibitors like monlunabant[12](index=12&type=chunk) - In a preclinical study, nimacimab combined with the dual GLP-1/GIP agonist tirzepatide achieved over **30% weight loss**[12](index=12&type=chunk) - As a monotherapy, nimacimab produced **23.5% weight loss**, which was comparable to both monlunabant and tirzepatide alone in the same study[12](index=12&type=chunk) - In vitro data highlighted nimacimab's superior potency compared to the small molecule CB1 inhibitor monlunabant, especially under elevated concentrations of CB1 agonist associated with obesity[5](index=5&type=chunk)[12](index=12&type=chunk) [First Quarter 2025 Financial Results](index=2&type=section&id=First%20Quarter%202025%20Financial%20Results) Skye Bioscience reported a net loss of **$11.1 million** for Q1 2025, with **$59.2 million** in cash expected to fund operations through Q1 2027, driven by increased operating expenses for the nimacimab Phase 2a study - As of March 31, 2025, cash, cash equivalents, and short-term investments totaled **$59.2 million** This capital is expected to fund operations through at least Q1 2027, covering the completion of the extended Phase 2a study for nimacimab[8](index=8&type=chunk) Q1 2025 vs. Q1 2024 Operating Results | Financial Metric | Q1 2025 | Q1 2024 | Change Driver | | :--- | :--- | :--- | :--- | | **R&D Expenses** | $7.2 million | $1.9 million | Increased contract manufacturing and clinical trial costs for nimacimab | | **G&A Expenses** | $4.6 million | $4.2 million | Increased investor relations, marketing, and consulting fees | | **Net Loss** | $11.1 million | $5.0 million | Higher operating expenses, particularly in R&D | [Consolidated Financial Statements](index=4&type=section&id=Consolidated%20Financial%20Statements) This section presents the unaudited consolidated financial statements for Skye Bioscience, including Statements of Operations for Q1 2025 and Balance Sheets as of March 31, 2025 [Consolidated Statements of Operations](index=4&type=section&id=CONSOLIDATED%20STATEMENTS%20OF%20OPERATIONS) Total operating expenses for Q1 2025 increased to **$11.8 million** from **$6.2 million** year-over-year, resulting in a net loss of **$11.1 million** or **$0.28 per share** Consolidated Statements of Operations (Unaudited, USD) | | Three Months Ended March 31, | | :--- | :---: | :---: | | | **2025** | **2024** | | **Operating expenses** | | | | Research and development | $7,197,257 | $1,946,450 | | General and administrative | $4,562,305 | $4,205,800 | | **Total operating expenses** | **$11,759,562** | **$6,152,250** | | **Operating loss** | **($11,759,562)** | **($6,152,250)** | | **Net loss** | **($11,103,319)** | **($5,019,531)** | | **Loss per common share (Basic & Diluted)** | **($0.28)** | **($0.18)** | | **Weighted average shares outstanding (Basic & Diluted)** | 39,651,888 | 27,999,901 | [Consolidated Balance Sheets](index=5&type=section&id=CONSOLIDATED%20BALANCE%20SHEETS) As of March 31, 2025, total assets were **$64.8 million**, a decrease from **$72.8 million** at year-end 2024, primarily due to cash used in operations, while total liabilities increased to **$5.5 million** Consolidated Balance Sheet Highlights (Unaudited, USD) | | **March 31, 2025** | **December 31, 2024** | | :--- | :--- | :--- | | **ASSETS** | | | | Cash and cash equivalents | $46,421,299 | $68,415,741 | | Total current assets | $63,027,781 | $70,827,247 | | **Total assets** | **$64,793,240** | **$72,763,773** | | **LIABILITIES & EQUITY** | | | | Total current liabilities | $5,319,460 | $4,338,887 | | **Total liabilities** | **$5,542,926** | **$4,612,049** | | **Total stockholders' equity** | **$59,250,314** | **$68,151,724** | | **Total liabilities and stockholders' equity** | **$64,793,240** | **$72,763,773** |