Slide 1: 2025 Q4 Financial Results & Business Update
March 10, 2026 2025 Q4 Financial Results & Nasdaq: SKYE Business Update
Slide 2: Disclaimer and Important Information for Investors
© 2026 Skye Bioscience, Inc. Disclaimer and Important Information for Investors This presentation (“Presentation”) has been prepared solely for general information purposes Industry and Market Data, and Third-Party Reports by or on behalf of Skye Bioscience, Inc. (together with its subsidiaries and
Slide 3: Executive Summary
© 2026 Skye Bioscience, Inc. Executive Summary Accomplishments since Q3 2025 Update New Clinical Data Nimacimab Semaglutide CBeyond data established potential path for Additive Weight Improved Durability Favorable All drugs are investigational and subject to regulatory approval. combination strategy
Slide 4: What Has Objectively Changed in the CB1 Field
© 2026 Skye Bioscience, Inc. What Has Objectively Changed in the CB1 Field Since launching nimacimab in obesity, Skye has delivered a series of field-firsts for peripheral CB1 1 FIELD FIRST 2 CLINICAL FIRST 3 COMBINATION FIRST First-in-class modality First human obesity First CB1 + GLP-1 dataset pro
Slide 5: CBeyond: Three Primary Learnings
© 2026 Skye Bioscience, Inc. CBeyond: Three Primary Learnings Meaningful combo efficacy, clean safety, and a clear dosing path LEARNING 1 LEARNING 2 LEARNING 3 Meaningful combination signal Clean safety and tolerability Solvable development variable +3.0% 0 200 mg incremental weight loss vs nimacima
Slide 6: Dosing Rationale
Dosing Rationale es oo
Slide 7: Initial rationale for CBeyond dosing
© 2026 Skye Bioscience, Inc. Initial rationale for CBeyond dosing • Before pharmacodynamic data (clinical weight loss or DIO model), Skye developed clinical PK models (Phase 1 data) to understand dosing options • IC90 (serum) was used as a surrogate for target engagement • Similar IC90 at Cmax, ss w
Slide 8: Nimacimab biodistribution in lean and obese mice
© 2026 Skye Bioscience, Inc. Nimacimab biodistribution in lean and obese mice brain1 all tissues ng/mg with serum per tissue 4000 ✱✱✱✱ hypothalamus2 6000 ✱✱✱✱ CoD + saline Q3D sWAT 3 CoD + nima 75 mg/kg Q3D 3000 HFD + nima 75mg/kg Q3D BAT4 HFD + nima 240 mg/kg Q3D muscle5 4000 GI6 2000 All drugs are
Slide 9: Nimacimab tissue biodistribution in lean and obese mice
© 2026 Skye Bioscience, Inc. Nimacimab tissue biodistribution in lean and obese mice all tissues ng/mg 75mg/kg per tissue brain1 300 200 ✱ ✱✱✱✱ CoD + nima 75 mg/kg Q3D hypothalamus2 HFD + nima 75mg/kg Q3D sWAT 3 150 BAT4 200 muscle5 nimacimab ng/mg All drugs are investigational and subject to regula
Slide 10: Compartmental analysis: Efficacy requires CB1 inhibition in peripheral tissue
© 2026 Skye Bioscience, Inc. Compartmental analysis: Efficacy requires CB1 inhibition in peripheral tissue Blood Adipose Brain Dose Curves from Multiple DIO Studies Input dose nimacimab concentration (relative to IC90) All drugs are investigational and subject to regulatory approval. 200 mg 24 7.3x
Slide 11: CBeyond Expansion Study and Next Steps
CBeyond Expansion Study and Next Steps
Slide 12: CBeyond Expansion Study / Part C / IV Dosing
© 2026 Skye Bioscience, Inc. CBeyond Expansion Study / Part C / IV Dosing Cohort 2 Randomized 3:1 to either • Nimacimab 600 mg, QW, IV (n=6), equivalent to ~1000 mg SC • Matched placebo, QW, IV (n=2) Safe to Proceed to Cohort 2 following Cohort Review All drugs are investigational and subject to reg
Slide 13: Superior Exclusion of CB1 Inhibitor from Brain; No Neuropsychiatric Side Effects
© 2026 Skye Bioscience, Inc. Superior Exclusion of CB1 Inhibitor from Brain; No Neuropsychiatric Side Effects Day 1 Day 8 Day 15 Cyno (post 1st dose) (post 2nd dose) (post 3rd dose) CSF/Serum BLQ <0.02% <0.02% 3 mg/kg IV q1w All drugs are investigational and subject to regulatory approval. Cyno 9 ho
Slide 14: Achieving Large Volume Dose Administration with ENHANZE
Achieving Large Volume Dose Administration © 2026 Skye Bioscience, Inc. with ENHANZE® • Skye has established a global collaboration and Large volume injection up licensing agreement with Halozyme Therapeutics to evaluate the co-formulation of nimacimab with to 10-12 mL ENHANZE® (rHuPH20). Reduced ad
Slide 15: Nimacimab Lifecycle Management
© 2026 Skye Bioscience, Inc. Nimacimab Lifecycle Management High Concentration Development Half-Life Extension Concentration Injection Volume (600 mg QW dose) Current Current 100 mg/mL 6 mL Concentration All drugs are investigational and subject to regulatory approval. Formulation 125 mg/mL 5 mL 150
Slide 16: Nimacimab Reduces Weight Regain
© 2026 Skye Bioscience, Inc. Nimacimab Reduces Weight Regain Off-Therapy follow up for 13 weeks after the last dose DIO Study rebound combos n=11: rebound combos 5 n=23 Change in body weight from baseline (%) n=26 0.52 0 n=11 All drugs are investigational and subject to regulatory approval. -4.75 -5
Slide 17: Differentiated Body Composition Through 13-Week Follow-up
© 2026 Skye Bioscience, Inc. Differentiated Body Composition Through 13-Week Follow-up Combo Group Combo Group Gains Lean to Fat Mass Maintains Fat Mass Lean Mass During Ratio Improves During Follow-Up Follow-Up Period Compared to Sema Change in Fat mass (%) Jan29 rebound Period Change in Lean mass
Slide 18: Crowded 1L Space with Significant Price Compression
© 2026 Skye Bioscience, Inc. Crowded 1L Space with Significant Price Compression • NuSH drugs will dominate the 1L setting, but it will become increasingly competitive with less room for profit margin. • The 2L setting has significant opportunity with few non-NuSH drugs available, or being developed
Slide 19: Nimacimab Complimentary, Not Competitive to GLP-1s
© 2026 Skye Bioscience, Inc. Nimacimab Complimentary, Not Competitive to GLP-1s Maintenance rationale for late comer GLP1s is to protect the patient base; nimacimab improves persistence and durability of 1L GLP1s WHY THEY DO IT WHY IT IS HARD FOR INCRETINS WHY NIMACIMAB WINS Maintenance is a rationa
Slide 20: Antibody Peptide Conjugation (APC) Program
Antibody Peptide Conjugation (APC) Program
Slide 21: Testing Efficacy of Nima-GLP-1RA in a DIO model
© 2026 Skye Bioscience, Inc. Study Design: Testing Efficacy of Nima-GLP-1RA (Antibody-Peptide-Conjugate) in a DIO model 8 weeks Tissue Days -7 0 22 Serum male hCB1 MRI Vehicle N=8 All drugs are investigational and subject to regulatory approval. Nimacimab 75 mg/kg Q3D HFD 16 weeks Nima-conjugate 75
Slide 22: APC demonstrates similar efficacy of combination dosing
© 2026 Skye Bioscience, Inc. APC demonstrates similar efficacy of combination dosing 0 Change in body weight from baseline (%) -5 -10 -13.8% Nimacimab -15 All drugs are investigational and subject to regulatory approval. -20 -20.9% Semaglutide -23.4% SBI-403 (GLP1RA) -25 -30 control DIO -33.6% Antib
Slide 23: Closing Remarks
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Slide 24: Key Takeaways
© 2026 Skye Bioscience, Inc. Key Takeaways Why Is This Important? This study will generate safety and PK data at higher CBeyond Expansion Study exposures, which we intend to take forward in future clinical Initiated trials. Body composition data demonstrates that fat mass loss is All drugs are inves
Slide 25: Anticipated Catalysts Through 2026
Anticipated Catalysts Through 2026 © 2026 Skye Bioscience, Inc. Q1 2026 Q2 2026 Q4 2026 ü CBeyond Interim Extension q Expansion Study Cohort 2 q Topline Clinical Data from Data initiates enrollment Expansion Study ü FDA Type C Meeting Minutes q Expansion Study Enrollment q Phase 2b Final Study Desig
Slide 26: Q&A
Q&A es oo
Slide 27: Thank You
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