Skye Bioscience, Inc. · NASDAQ:SKYE
Skye Bioscience — Investor Presentation (February 2026)
48 slides from Skye Bioscience's investor presentation, Feb 2, 2026
Slide 1: Developing Innovative Medicines to Treat Obesity and Other Metabolic Diseases
Developing Innovative Medicines to Treat Obesity and Other Metabolic Diseases February 2026 Nasdaq: SKYE
Slide 2: Cautionary Language Regarding Forward-Looking Statements
© 2 02 6 Sk ye B io sc ie nc e, In c. 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
Slide 3: Executive Summary
© 2 02 6 Sk ye B io sc ie nc e, In c. Executive Summary Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 3 Nimacimab Semaglutid e Additive Weight Loss Favorable Tolerability Profile CBeyond data established potential path for combination strategy with existing
Slide 4: Nimacimab: complementary, not competitive – potential scalable add-on to incretin therapy
© 2 02 6 Sk ye B io sc ie nc e, In c. Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 4 Nimacimab: complementary, not competitive – potential scalable add-on to enhance incretin therapy • Additive efficacy on top of GLP-1s: 13% weight-loss at 26 weeks, which
Slide 5: Nimacimab Target Product Profile
© 2 02 6 Sk ye B io sc ie nc e, In c. Opportunity across multiple treatment settings that adds clinically meaningful weight loss on top of GLP-1 therapy without adding tolerability burden and designed for chronic use. Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro
Slide 6: Presentation Overview
© 2 02 6 Sk ye B io sc ie nc e, In c. Presentation Overview 1.0 Nimacimab Overview – A Highly Peripherally-restricted CB1-inhibiting Antibody 2.0 CBeyond Extension Data Review – 52-week Combination Data 2.1 CBeyond – What We Learned 3.0 CBeyond2 – Phase 2b Adaptive Design Dose Ranging Study 3.1 Regu
Slide 7: Nimacimab: Highly Peripherally-restricted CB1-inhibiting Antibody
Nimacimab A Highly Peripherally-restricted CB1-inhibiting Antibody that Stands Apart from Small– molecule CB1 Inhibitors 1.0
Slide 8: Peripheral CB1 Signaling: Metabolic-focused Targets
© 2 02 6 Sk ye B io sc ie nc e, In c. Metabolic Disorders/ Obesity Adipose Tissue CB1 Triglyceride accumulation Lipolysis Kidneys Inflammation Fibrosis Metabolic Disorders/ Diabetes Liver & Pancreas De novo lipogenesis Insulin signaling Metabolic Disorders/ Diabetes + MASH Digestive System GI motili
Slide 9: Nimacimab: Peripherally-restricted CB1-inhibiting Antibody
© 2 02 6 Sk ye B io sc ie nc e, In c. Long Half-life Potential Safe & Effective Drug Exclusion from Brain • Stable antibody with half-life of 18-21 days (potential Q2W or monthly dosing) • Single mutation in the hinge region that prevents antibody Fab exchange • Multiple NHP studies: background leve
Slide 10: Nimacimab's Potential Differentiation from Small Molecule CB1 Inhibitors
© 2 02 6 Sk ye B io sc ie nc e, In c. 2-AG or AEA Negative Allosteric Modulator Significantly less brain penetration than small molecules currently in development Unlike small molecules currently in development, nimacimab retains potency even in the presence of competition Peripheral Restriction Al
Slide 11: Four Mechanistic Pillars of Nimacimab
© 2 02 6 Sk ye B io sc ie nc e, In c. Peripheral Modulation of Appetite Regulating Hormones GLP-1 Improvement and Restoration of Glycemic Control Reduced fasting insulin and improved glucose control Enhanced Lipid Metabolism Decreased steatosis and serum cholesterol Reduction of Obesity- Induced Inf
Slide 12: Review of Interim Extension Study: 52-Week Combination Data
2.0 Review of Interim Extension Study: 52-Week Combination Data
Slide 13: CBeyond Phase 2a Clinical Trial Design for Proof of Concept
© 2 02 6 Sk ye B io sc ie nc e, In c. SubQ Nimacimab 200 mg QW Treatment 26 weeks Follow-up 13 weeks End of Main Study Week 38 Interim Analysis Placebo QW Wegovy® + Placebo QW Wegovy® + Sub Q Nimacimab 200 mg QW Extension Study 26 weeks Follow-up 12 weeks Wegovy® + SubQ Nimacimab 200 mg QW Sub Q Nim
Slide 14: Nimacimab + Semaglutide Performed Better Than Semaglutide Alone
© 2 02 6 Sk ye B io sc ie nc e, In c. • Combination of nimacimab + semaglutide resulted in a 30% increase compared to semaglutide alone in CBeyond at 26 weeks. • Semaglutide alone and combination groups in CBeyond outperformed historical semaglutide data (STEP-1). Nimacimab + Semaglutide Performed B
Slide 15: Combination Subjects Similar between Extension and Follow-up Groups
© 2 02 6 Sk ye B io sc ie nc e, In c. • 10 subjects on active combination (nimacimab + semaglutide) rolled over to extension • 11 subjects on the nimacimab + semaglutide combination therapy went into off therapy follow up • There was minimal difference between the two groups in weight loss achieved
Slide 16: Combination Group Demonstrated 22.3% Weight Loss at 52-Weeks
© 2 02 6 Sk ye B io sc ie nc e, In c. • Following an additional 26-weeks of dosing of nimacimab + semaglutide, a further 7.9% weight loss was achieved • This represents 35% of total weight loss over 52-weeks. • The total weight loss after 52 weeks of treatment was 22.3% • No plateau in weight loss s
Slide 17: Semaglutide Subjects Were Different Between Extension and Follow-Up
© 2 02 6 Sk ye B io sc ie nc e, In c. • 9 subjects in the semaglutide alone (with placebo) arm enrolled in the extension study. • 11 subjects in the semaglutide arm went into off therapy follow • There was a marked difference in weight loss between these two groups at week 26 (85% greater weigh loss
Slide 18: Semaglutide Group Demonstrated a 19.7% Weight Loss at 52-Weeks
© 2 02 6 Sk ye B io sc ie nc e, In c. • Following an additional 26-weeks of dosing of semaglutide + placebo, a further 5.8% weight loss was achieved. • The additional 5.8% represents 29.4% of total weight loss over 52-weeks. • The total weight loss after 52 weeks of treatment was 19.7%. • This “Supe
Slide 19: Nimacimab Converts Patients to Super Responders
© 2 02 6 Sk ye B io sc ie nc e, In c. • Unusually high frequency of sema ‘super-responders’ makes it challenging to differentiate the combo effect • Sema discontinuation group closely mirrors the STEP-1 trajectory • Both combination cohorts closely track with the more active efficacy curves • Thus i
Slide 20: Nimacimab Reduces Weight Regain Off-Therapy
© 2 02 6 Sk ye B io sc ie nc e, In c. Nimacimab Reduces Weight Regain Off-Therapy follow up for 13 weeks after the last dose Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. Inclusion criteria: patients must have completed at least 75% of treatment and have at
Slide 21: Typical Semaglutide Rebound Profile
© 2 02 6 Sk ye B io sc ie nc e, In c. Typical Semaglutide Rebound Profile Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 21 Wilding et al., 2022. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension
Slide 22: Lean to Fat Mass Ratio and Waist Circumference Improve with Combination
© 2 02 6 Sk ye B io sc ie nc e, In c. Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 22 Lean to Fat Mass Ratio and Waist Circumference Improve with Nimacimab-Semaglutide Combination Nimacimab + semaglutide increases weight loss by ~30% & fat loss by 37% comp
Slide 23: Nimacimab + Semaglutide Better Than, Or Comparable To, Other Combinations
© 2 02 6 Sk ye B io sc ie nc e, In c. Nimacimab + Semaglutide Better Than, Or Comparable To, Other Combinations With No Plateau at 52 Weeks Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 23 0 10 20 30 40 50 60 70 -30 -25 -20 -15 -10 -5 0 Weeks W ei gh t L os
Slide 24: Summary and Conclusions
© 2 02 6 Sk ye B io sc ie nc e, In c. • We believe semaglutide-alone group self-selected for a “Super Responder” population which elected to continue enrollment in the 26-week extension study and showed continued weight loss beyond what is typically seen with semaglutide therapy alone. • Nimacimab h
Slide 25: What We Learned From Dosing Strategy and Rationale
2.1 What We Learned From Dosing Strategy and Rationale
Slide 26: What We Learned from CBeyond Regarding Dosing
© 2 02 6 Sk ye B io sc ie nc e, In c. Data from CBeyond, together with our preclinical models, suggests: 1. Concentration in the serum does not equal concentration in the tissues, and achieving a higher serum concentration and steady-state sooner through a loading dose can potentially improve respon
Slide 27: Initial Rationale for CBeyond Dosing
© 2 02 6 Sk ye B io sc ie nc e, In c. Initial rationale for CBeyond Dosing Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 27 • Before pharmacodynamic data (clinical weight loss or DIO model), Skye developed clinical PK models (Ph1 data) to understand dosing
Slide 28: Nimacimab Biodistribution in Lean and Obese Mice
© 2 02 6 Sk ye B io sc ie nc e, In c. Nimacimab biodistribution in lean and obese mice Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 28 2-way ANOVA followed by Tukey’s multiple comparison tests per tissue. Human IgG ELISA kit (Ray Biotech, catalog# ELH-IGG)
Slide 29: Nimacimab Tissue Biodistribution in Lean and Obese Mice
© 2 02 6 Sk ye B io sc ie nc e, In c. Nimacimab tissue biodistribution in lean and obese mice Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 29 A B C D 1 2 3 4 5 6 7 8 9 0 100 200 300 muscle heart GI liver brain nimacimab (ng/mg) hypothalamus BAT sWAT vWAT C
Slide 30: Beyond the Serum: CB1 Inhibition in Peripheral Tissues
© 2 02 6 Sk ye B io sc ie nc e, In c. Beyond the Serum: CB1 Inhibition in Peripheral Tissues Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 30 “S-MRI-1867 exhibited high exposure in most tissues, with concentrations ranging from 2 to 31 times greater than in
Slide 31: Compartmental Analysis: Activity Associated with CB1 Inhibition in Peripheral Tissue
© 2 02 6 Sk ye B io sc ie nc e, In c. Compartmental Analysis: Activity associated with CB1 inhibition in peripheral tissue Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 31 Blood Adipose Brain nimacimab concentration (relative to IC90) 6.4x 20x Nimacimab con
Slide 32: CBeyond Dosing Did Not Achieve Significant Concentrations in the Serum
© 2 02 6 Sk ye B io sc ie nc e, In c. • While 200 mg QW achieved median serum exposures of at least 7x over IC90; however, this dose proved to be sub- optimal. • Higher dosing strategies need to be evaluated to achieve median serum concentrations of at least 200 ug/mL • Based on our toxicity data, w
Slide 33: How Much Higher Can Nimacimab Be Safely Dosed?
© 2 02 6 Sk ye B io sc ie nc e, In c. Nimacimab NOAEL based on 26-week NHP study is 75mg/kg How Much Higher Can Nimacimab Be Safely Dosed? Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 33 Phase 2b Simulations: Limiting toxicity assessment Considering the hu
Slide 34: Modeling NHP Toxicity Study Provides Guidance for Dosing Regimens
© 2 02 6 Sk ye B io sc ie nc e, In c. • Skye has conducted two non-human primate toxicology studies both establishing 75mg/kg as NOAEL dose. 1. 26-Week Subcutaneous Dosing (N=9) 2. 4-Week IV Dosing (N=10) • Direct concentration comparisons (e.g. Cmax and AUC) in non-human primate PK is highly predic
Slide 35: Monlunabant's Dose Dependent Increase in Brain Exposure and Neuropsychiatric Adverse Events
© 2 02 6 Sk ye B io sc ie nc e, In c. Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. 35 • Monlunbant’s Phase 2a 16-week data demonstrated a dose dependent increase in neuropsychiatric side effects (Knop et al.). • Neuropsychiatric adverse events were identif
Slide 36: Nimacimab Has Wide Safety Margin in the Brain
© 2 02 6 Sk ye B io sc ie nc e, In c. Nimacimab Has Wide Safety Margin in the Brain References: Phase 1 biodistribution study – internal data; NHP biodistribution study – internal data; NHP toxicology study – internal data; Fjord-Larsen et al., 2021; Wang et al., 2018 Al l d ru gs a re in ve st ig a
Slide 37: Clinical Strategy: Phase 2b Adaptive Design Dose-Ranging Study
Clinical Strategy Phase 2 Adaptive Design Dose-Ranging Study 3.0
Slide 38: Path to the Potential Phase 3 Pivotal Studies
© 2 02 6 Sk ye B io sc ie nc e, In c. Phase 2b An adaptive study designed to optimize combination therapy doses + Define individual contributions of nimacimab and semaglutide Part A Monotherapy Dose Selection Evaluate 3 doses of nimacimab as a single agent against placebo Select 2 doses for combinat
Slide 39: Achieving Large Volume Dose Administration with ENHANZE
Al l d ru gs a re in ve st ig at io na l a nd s ub je ct to re gu la to ry a pp ro va l. © 2 02 6 Sk ye B io sc ie nc e, In c. Achieving Large Volume Dose Administration with ENHANZE® • Skye has established a global collaboration and licensing agreement with Halozyme Therapeutics to evaluate the co-
Slide 40: Mix-and-Deliver Approach – Ensuring Compliance
© 2 02 6 Sk ye B io sc ie nc e, In c. • In the potential Phase 2b study, all patients will be required to visit the site for their weekly injections. • These mandatory weekly visits are intended to ensure compliance, while also allowing for ENHANZE® and nimacimab to be co-formulated on-site prior to
Slide 41: Positive Part A Enables Broader Clinical Pipeline & Commercial Opportunity
© 2 02 6 Sk ye B io sc ie nc e, In c. Phase 2b An adaptive study designed to optimize combination therapy doses + Define individual contributions of nimacimab and semaglutide Part A Monotherapy Dose Selection Evaluate 3 doses of nimacimab as a single agent against placebo Part B Sema Combination Dos
Slide 42: Regulatory Strategy: Combination Approval, Monotherapy Opportunity
Regulatory Strategy Combination Approval, Monotherapy Opportunity 3.1
Slide 43: Combination Regulatory Strategy
© 2 02 6 Sk ye B io sc ie nc e, In c. • Phase 2b adaptive design is meant to satisfy the FDA’s requirement to evaluate contribution of parts between nimacimab and semaglutide. • If acceptable, we believe the pivotal Phase 3 design may only require a two-arm study comparing combination of nimacimab +
Slide 44: Monotherapy Opportunities
© 2 02 6 Sk ye B io sc ie nc e, In c. • We believe nimacimab has opportunity to fill gaps in the 2nd line therapy space after patients fail NuSH therapies (i.e. GLP1, GLP1/GIP, or amylin). • If nimacimab alone can demonstrate at least +8% pbo-adjusted weight loss then it could be an ideal 2nd line t
Slide 45: Financial Overview and Team
Financial Overview and Team 4.0
Slide 46: Selected Financial Figures & Metrics
© 2 02 6 Sk ye B io sc ie nc e, In c. • $107M in equity capital raised since August 2023 (no new equity financing issuances since March 2024 PIPE) • Supported by top-tier specialist life science investors • Cash runway into Q4 2026, excludes: the clinical cost of any potential Phase 2b study and the
Slide 47: Leadership
Deborah Charych, PhD Co-founder and ex-CTO, RayzeBio Contributed to commercialization of 40+ drugs/diagnostics, led high-value strategic transactions, and co-founded multiple companiesLeadership 47 Executive Management Board of Directors Tu Diep, MSc Chief Operating Officer Chris Twitty, PhD Chief S
Slide 48: Thank You
THANK YOU 11250 El Camino Real, Suite 100 San Diego, CA 92130 ir@skyebioscience.com Please learn more or contact us at: +1 (858) 410-0266 Spotlight
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