Financial Data and Key Metrics Changes - The company ended 2025 with $25.7 million in cash equivalents and short-term investments, managing its operating plan to extend its runway through Q4 2026 [29][30]. Business Line Data and Key Metrics Changes - The CBeyond program has shown promising results, with a combination of nimacimab and semaglutide achieving a clinically meaningful 3% improvement in weight loss over semaglutide alone at 26 weeks, and a mean weight loss of 22.3% over 52 weeks in the combination arm [6][17]. - Participants on semaglutide alone regained 38.7% of weight over 13 weeks after stopping therapy, while those on the combination of nimacimab plus semaglutide only regained 17.8% [18]. Market Data and Key Metrics Changes - The company positions nimacimab as a complementary therapy to GLP-1s, targeting second-line add-on settings for patients who have not achieved their weight loss goals with first-line therapies [19][20]. Company Strategy and Development Direction - The company is focusing on expanding the CBeyond study to include new intravenous cohorts to rapidly generate safety and pharmacokinetic data at higher exposures [13][16]. - The collaboration with Halozyme aims to develop a co-formulation of nimacimab for high-volume subcutaneous injections, enhancing convenience for patients [15][39]. Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of generating clinical data to support nimacimab's potential in the anti-obesity market, particularly in addressing unmet needs for patients who require additional weight loss solutions [13][18]. - The company is refining its Phase IIb clinical trial design based on FDA feedback, focusing on dose, duration, and endpoints [16][30]. Other Important Information - The company has identified four mechanistic pillars through which nimacimab modulates metabolic pathways, including blunting obesity-related inflammation and enhancing lipid metabolism [23]. - The first-generation antibody peptide conjugate program is seen as a long-term optionality, with potential for broader combination therapies beyond GLP-1s [22][52]. Q&A Session Summary Question: Plans to share data from higher dose cohorts - The company is expanding into the Part C expansion study to generate data on higher exposures and expects to provide updates by Q4 2026 [37][38]. Question: Status of formulation work using Halozyme technology - The co-formulation work with Halozyme is ongoing and expected to be ready for the Phase IIb study, utilizing a mix-and-deliver approach [39][40]. Question: Concerns about dose levels in the expansion study - Management believes the selected doses are sufficient based on current data, but they continue to evaluate the potential for higher dosing [46][47]. Question: Profile and goals for the new program - The new program is treated as long-term optionality, with nimacimab remaining the core value driver for the near term [52][53]. Question: Importance of peripheral tissues for nimacimab's clinical effect - Adipose tissue and liver are critical for nimacimab's efficacy, with different profiles expected for monotherapy versus combination therapy [60][62]. Question: Reason for using IV in the Part C phase - IV is used for the fastest generation of high exposure PK and safety data, with plans to transition to subcutaneous delivery in Phase IIb [64][65]. Question: Clarification on dosing equivalence for IV and subcutaneous - The company based the equivalence on a previous bioavailability study, indicating that subcutaneous dosing has about 56% relative bioavailability compared to IV [70][71]. Question: Bar for success from the expanded study - The focus is on PK and safety data rather than efficacy, with expectations that higher exposure will validate the dosing model [77][78].

Financial Data and Key Metrics Changes - The company ended 2025 with $25.7 million in cash equivalents and short-term investments, managing its operating plan to extend its runway through Q4 2026 [30] Business Line Data and Key Metrics Changes - The CBeyond program has shown a clinically meaningful 3% improvement in weight loss over semaglutide alone at 26 weeks, with a 22.3% mean weight loss in the combination arm over 52 weeks [6][18] - Participants on semaglutide alone regained 38.7% of weight over 13 weeks after stopping therapy, while those on the combination of nimacimab plus semaglutide only regained 17.8% [18] Market Data and Key Metrics Changes - The company is positioning nimacimab as a complementary therapy to GLP-1s, targeting second-line add-on settings for patients who have not achieved their weight loss goals with first-line therapies [20][21] Company Strategy and Development Direction - The company is expanding the CBeyond study to include new intravenous cohorts to rapidly generate safety and pharmacokinetic data at higher exposures [14] - The focus is on developing a co-formulation of nimacimab using Halozyme's ENHANZE technology to facilitate high-volume subcutaneous injections [16] - The company aims to determine the exposure and duration of peripheral CB1 engagement required to produce clinically meaningful efficacy [34] Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of generating clinical data to support nimacimab's potential in the anti-obesity medicine landscape, particularly in combination with GLP-1s [14][19] - The feedback from the FDA has helped refine the Phase 2b protocol, particularly regarding combination therapy development [17] Other Important Information - The company is advancing its first antibody peptide conjugate program, which aims to combine nimacimab's mechanism of action with a GLP-1 receptor agonist [25][28] Q&A Session Summary Question: Plans to share data from higher dose cohorts and status of formulation work - The company is expanding into the Part C expansion study to generate data on higher exposures and expects updates by Q4 2026 [38][39] - The formulation work with Halozyme is ongoing and expected to be ready for the Phase 2b study [40][41] Question: Concerns about dose levels in the expansion study - Management believes the selected doses are sufficient for the Phase 2b selection, but they are continuing to evaluate higher dosing [48] Question: Profile and goals for the new program - The new program is seen as long-term optionality, with nimacimab remaining the core value driver [52] Question: Importance of peripheral tissues for nimacimab's clinical effect - Adipose tissue and liver are critical for nimacimab's effects, with different profiles expected for monotherapy versus combination therapy [61] Question: Use of IV in the Part C phase of the study - IV is being used for the fastest generation of high exposure PK and safety information, with plans for subcutaneous delivery in Phase IIb [65]

March 10, 2026 2025 Q4 Financial Results & Business Update Nasdaq: SKYE © 2026 Skye Bioscience, Inc. Disclaimer and Important Information for Investors This presentation ("Presentation") has been prepared solely for general information purposes by or on behalf of Skye Bioscience, Inc. (together with its subsidiaries and affiliates, "Skye"). Any discussion of the potential use or expected success of our product candidates is subject to our product candidates being approved by regulatory authorities. Cautiona ...

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 - 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]