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 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][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% [17] Market Data and Key Metrics Changes - The company aims to position 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 expanding the CBeyond study to include new intravenous cohorts to rapidly generate safety and pharmacokinetic data at higher exposures [13][14] - A collaboration with Halozyme is underway to develop a co-formulation of nimacimab using their ENHANZE technology, aiming for high-volume subcutaneous injections [15][16] - The company is focused on refining the Phase 2b clinical trial design based on FDA feedback, particularly for combination therapy development with GLP-1s [16][30] Management's Comments on Operating Environment and Future Outlook - Management believes nimacimab can fill an important void in the anti-obesity medicine landscape, emphasizing the need for clinical data to support its potential [13][19] - The company is not attempting to compete directly with first-line incretin therapies but rather to address unmet needs in patients who require additional support [21][30] Other Important Information - The company has identified four distinct mechanistic pillars through which nimacimab modulates metabolic pathways, providing confidence in its differentiated profile [23] - Early data from the antibody peptide conjugate program shows promising results, indicating potential for combination-like efficacy with simplified dosing [26][28] 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 exposure and expects updates by Q4 2026 [36][38] Question: Concerns about dose levels in the expansion study - Management believes the selected doses are sufficient for achieving the desired peripheral exposure and is open to evaluating higher doses in the future [46][47] Question: Profile and goals for the new program - The new program is seen as long-term optionality, with nimacimab remaining the core value driver while the antibody peptide conjugate data supports broader combination platforms [51][52] Question: Importance of peripheral tissues for nimacimab's effect - Adipose tissue and liver are critical for nimacimab's clinical effect, with different profiles expected for monotherapy versus combination therapy [58][60] Question: Use of IV in the Part C study - IV is being used for the fastest generation of high exposure PK and safety data, with plans to transition to subcutaneous delivery in Phase IIb [64][65]

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. reported financial results for Q4 and full year 2025, highlighting advancements in its clinical programs targeting obesity and related conditions [1][14]. Financial Performance - As of December 31, 2025, cash, cash equivalents, and short-term investments totaled $25.7 million, expected to fund operations through Q4 2026 [14]. - R&D expenses for Q4 2025 were $11.5 million, up from $7.8 million in Q4 2024, primarily due to manufacturing costs for the anticipated Phase 2b trial [15]. - For the full year 2025, R&D expenses reached $42.4 million, compared to $18.7 million in 2024, driven by clinical study and manufacturing costs [16]. - G&A expenses for Q4 2025 were $3.4 million, down from $4.6 million in Q4 2024, mainly due to reduced stock-based compensation and professional services [17]. - The net loss for Q4 2025 was $14.4 million, compared to $9.7 million in Q4 2024, with a full-year net loss of $55.9 million, significantly higher than the $26.6 million loss in 2024 [20][21]. Clinical Developments - The CBeyond Expansion Study initiated higher-dose evaluations of nimacimab, with cohorts receiving 400 mg and 600 mg IV doses, aiming to generate safety and pharmacokinetic data [6][7]. - Interim results from the Phase 2a trial showed a 22.3% mean weight loss at 52 weeks for the nimacimab plus semaglutide combination, with no plateau observed [12]. - The combination therapy demonstrated a statistically significant improvement in lean-to-fat mass ratio and waist circumference, with a lower weight regain during the follow-up period compared to semaglutide alone [12]. Upcoming Milestones - Skye plans to present preclinical data in Q2 2026 and finalize the Phase 2b study design by Q4 2026, with topline results from the CBeyond Expansion Study expected in the same quarter [13][18]. Research and Development Highlights - Skye is advancing its antibody-peptide conjugate (APC) program, which combines nimacimab's mechanism with a GLP-1 receptor agonist for enhanced therapeutic effects [12]. - The company is also working on optimizing manufacturing processes to support the anticipated Phase 2b trial and improve cost efficiency [11]. Company Overview - Skye Bioscience focuses on developing next-generation molecules targeting G-protein-coupled receptors for metabolic health, with nimacimab being a key candidate in its pipeline [23].

Core Viewpoint - Skye Bioscience, Inc. is set to discuss its 2025 fourth quarter and full-year financial results and business updates during a conference call on March 10, 2026 [1] 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 2a clinical trial for nimacimab, a negative allosteric modulating antibody that inhibits CB1, in the context of obesity [3] - The trial is also evaluating the combination of nimacimab with a GLP-1R agonist (Wegovy®) [3]

Core Viewpoint - The article discusses the competitive landscape of weight loss drugs in the U.S., highlighting Skye Bioscience's promising clinical results for its combination therapy of nimacimab and semaglutide, which achieved an average weight loss of 22.3% over 52 weeks without reaching a plateau [4][6]. Group 1: Clinical Results - Skye's combination therapy resulted in a 14.4% weight loss in the first 26 weeks, followed by an additional 7.9% in the subsequent 26 weeks, totaling 22.3% weight loss [6]. - Notably, there was no observed plateau in weight loss at the 52-week mark, which is significant given the common trend of diminishing returns in current GLP-1 drugs [6][7]. - During a 13-week follow-up after stopping the treatment, the combination group only regained 17.8% of the lost weight, compared to a 37.3% rebound in the semaglutide-only group, indicating better weight maintenance with nimacimab [7]. Group 2: Mechanism and Safety - Nimacimab is designed as a peripheral CB1 receptor monoclonal antibody, aiming to avoid central nervous system entry and thus mitigate the psychiatric side effects associated with earlier CB1 inhibitors [8]. - Throughout the 52-week study, no serious adverse events were reported, reinforcing the safety profile of nimacimab [8]. Group 3: Commercial Viability and Future Outlook - The study had a limited sample size of 19 participants in the extended treatment phase, with only 7 completing the full 52 weeks in each group, indicating the need for larger studies to validate the findings [9]. - Skye is currently not profitable and is experiencing rapid cash burn, but its balance sheet shows cash reserves exceeding debts, suggesting short-term liquidity is manageable [9]. - The company plans to release complete top-line data from the CBeyond 2a study, including results for nimacimab as a monotherapy, by Q3 2026 [9]. Group 4: Strategic Collaborations - Skye has partnered with Halozyme Therapeutics to develop a high-dose subcutaneous formulation of nimacimab using the ENHANZE delivery technology, which could enhance dosing frequency and efficacy [10]. - In animal models, the combination of nimacimab with incretin-based drugs showed weight loss of up to 46%, although this result requires further validation in human trials [10].

Core Insights - Skye Bioscience, Inc. has shared interim data from the Phase 2a CBeyond study of nimacimab, a negative allosteric modulating antibody targeting obesity, in combination with a GLP-1R agonist, semaglutide [1][2] Interim Data Summary - The extension phase of the CBeyond study for combination cohorts began in May 2025, with participants receiving either nimacimab plus semaglutide or placebo plus semaglutide [2] - In the nimacimab plus semaglutide arm, participants experienced a mean weight loss of 14.4% at 26 weeks [2] - Seven participants in the nimacimab plus semaglutide arm completed an additional 26 weeks, achieving a total mean weight loss of 22.3% after 52 weeks, with no weight loss plateau observed [3] Safety and Tolerability - The combination therapy of nimacimab and semaglutide demonstrated safety and was well-tolerated, with no serious adverse events reported during the extension period [3] Placebo Group Results - In the placebo plus semaglutide arm, participants had a mean weight loss of 13.9% at 26 weeks, and those who completed the additional 26 weeks lost an additional 5.8%, resulting in a total mean weight loss of 19.7% after 52 weeks [4] Comparison of Treatment Efficacy - Top-line data indicated that the combination of nimacimab and semaglutide achieved a clinically meaningful weight loss of -13.2% compared to -10.25% for semaglutide alone, with no plateau observed [5] - The nimacimab monotherapy did not meet the primary endpoint, showing a weight loss of -1.52% compared to -0.26% for placebo [5] Weight Regain Analysis - Participants treated with nimacimab + semaglutide regained only 17.8% of their weight loss at 26 weeks during a 13-week off-therapy follow-up, indicating a potential durable response [6] - In contrast, those on semaglutide alone experienced a weight regain of 37.3% from the weight lost at 26 weeks [6] Future Expectations - Topline data from the CBeyond Phase 2a extension, including monotherapy data and follow-up results, is anticipated in the third quarter of 2026 [7] Analyst Perspective - Analysts from William Blair noted that with a cash runway extending into the fourth quarter of 2026, further analysis of the Phase 2a study could attract investor interest, contingent on supportive data regarding the exposure/weight loss relationship [8] - At the time of publication, Skye Bioscience shares were down 5.53% to $0.95 [8]

Core Insights - Skye Bioscience announced interim 52-week data from the Phase 2a CBeyond study of nimacimab, a peripherally-restricted CB1 inhibitor antibody, showing promising weight loss results in combination with semaglutide [1][9] Study Design and Participant Details - The CBeyond extension study began in May 2025, involving participants who completed 26 weeks of treatment with either nimacimab plus semaglutide or placebo plus semaglutide [2] - A total of 19 participants from the combination cohorts entered the extension study, with 10 in the nimacimab plus semaglutide arm and 9 in the placebo plus semaglutide arm [2] Weight Loss Results - Participants in the nimacimab plus semaglutide arm experienced a mean weight loss of 14.4% at 26 weeks, with an additional 7.9% lost during the extension, totaling 22.3% after 52 weeks [3][8] - In the placebo plus semaglutide arm, mean weight loss was 13.9% at 26 weeks, with an additional 5.8% lost during the extension, resulting in a total of 19.7% after 52 weeks [4] Comparison with Previous Data - The combination of nimacimab and semaglutide achieved a clinically meaningful weight loss of -13.2% compared to semaglutide alone at 26 weeks [5] - The overall weight loss for all participants in the nimacimab plus semaglutide group was -13.6% at 26 weeks, with a follow-up weight regain of only 17.8% during a 13-week off-therapy period [6][10] Safety and Tolerability - The combination therapy demonstrated a strong safety profile, with no serious adverse events reported during the extension period [3][8] - The treatment was well tolerated at the tested doses, reinforcing the potential for nimacimab as a safe option in obesity treatment [9][11] Future Outlook - The company anticipates that further optimization of nimacimab dosing could lead to even greater weight loss and improved outcomes in future clinical trials [9][11] - Full topline reporting of the CBeyond Phase 2a extension data, including monotherapy data, is expected in Q3 2026 [11]

Core Insights - Skye Bioscience is presenting research on its CB1-inhibitor antibody, nimacimab, at an upcoming conference focused on obesity therapeutics [1] - The presentation will explore nimacimab's efficacy alone and in combination with tirzepatide, as well as its potential as a maintenance therapy after discontinuation of tirzepatide [1][4] Company Overview - Skye Bioscience is a clinical-stage biotechnology company dedicated to developing new therapeutic pathways for obesity and metabolic health disorders [3] - The company is focused on creating next-generation molecules that modulate G-protein coupled receptors, aiming for first-in-class therapeutics with clinical and commercial differentiation [3] Product Details - Nimacimab is a first-in-class, peripherally-restricted monoclonal antibody that inhibits the CB1 receptor without penetrating the central nervous system, potentially reducing neuropsychiatric side effects [2] - It acts independently of the GLP-1 pathway and has shown additive effects when combined with incretin-based therapies in both preclinical and clinical studies [2] Clinical Trials - Skye is conducting a Phase 2a clinical trial for nimacimab in obesity, which also assesses its combination with a GLP-1R agonist, Wegovy® [3] - The trial is registered under ClinicalTrials.gov with the identifier NCT06577090 [3]