Slide 1: Phase 2a Topline Clinical Data
All drugs are investigational and subject to regulatory approval. Phase 2a Topline Clinical Data 1 October 2025 Nasdaq: SKYE © 2025 Skye Bioscience, Inc.
Slide 2: Disclaimer and Important Information for Investors
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
Slide 3: Speakers
Speakers Skye Management Punit Dhillon Puneet Arora, MD Tu Diep, MSc Chris Twitty, PhD President & CEO Chief Medical Officer Chief Operating Officer Chief Scientific Officer All drugs are investigational and subject to regulatory approval. Expert Panel Dr. Sean Wharton Louis Aronne, M.D. Wharton Med
Slide 4: Agenda
Agenda 1 Introduction 2 Phase 2a Topline Data Overview 3 Safety and Tolerability 4 Summary and Path Forward 5 Questions & Answer Session
Slide 5: Phase 2a Trial Data Overview
5 All drugs are investigational and subject to regulatory approval. Overview Phase 2a Trial Data © 2025 Skye Bioscience, Inc.
Slide 6: CBeyond Phase 2a Study Design
CBeyond Phase 2a Study Design Patients with Overweight or Obesity Nimacimab 200 mg QW Nimacimab 300 mg QW Randomized Placebo QW 2:2:1:1 End of Main Study End of Ext Study Week 38 Week 76 Interim Analysis Final Analysis All drugs are investigational and subject to regulatory approval. Wegovy® + Place
Slide 7: PK Model / Rationale for mg Dosing
PK Model / Rationale for 200 mg Dosing Ctrough W16 = 83ug/mL All drugs are investigational and subject to regulatory approval. • 200 mg QW dose for CBeyond was selected based on modeling from nimacimab Phase 1 studies. • These models suggested significant peripheral exposure over 26 weeks with littl
Slide 8: Datasets for Analysis
Datasets for Analysis mITT (modified Intention to Treat) • All participants who were randomized and who received any amount of study medication (IP, active or placebo comparator), regardless of adherence to the treatment plan. For analyses, participants were included in the treatment group correspon
Slide 9: Primary Estimand for Analysis
Primary Estimand for Analysis Intercurrent events resulting in missing data were handled using a treatment policy strategy. All data collected was included in the analysis and observations were used without adjustment. The following are the possible intercurrent events: • Lost to follow-up prior to
Slide 10: CBeyond Phase 2a Topline Data Outcome
CBeyond Phase 2a Topline Data Outcome Endpoint Expectations to (Topline Read) support TPP 26-Week Results Primary endpoint not met: Nimacimab monotherapy did not achieve the primary endpoint of weight loss compared to placebo Efficacy: % Weight Loss Mono (-1.26%, p=0.2699, mITT and -1.33%, p=0.2878,
Slide 11: Subject Disposition & Demographics
Subject Disposition & Demographics Nimacimab Nimacimab Placebo Placebo 200 mg Overall 200 mg + Semaglutide + Semaglutide Participants Randomized 45 46 23 22 136 Primary Study Period Withdrawal 13 (28.9%) 14 (30.4%) 6 (26.1%) 4 (18.2%) 37 (27.2%) All drugs are investigational and subject to regulator
Slide 12: Primary Reason for Withdrawal from Primary Study Period
Primary Reason for Withdrawal from Primary Study Period Nimacimab Nimacimab Placebo Placebo 200 mg Overall 200 mg + Semaglutide + Semaglutide Participants Randomized 45 46 23 22 136 Lost to Follow-up 3 (6.7%) 2 (4.3%) 1 (4.3%) 1 (4.5%) 7 (5.1%) Protocol Deviation 1 (2.2%) 0 1 (4.4%) 0 2 (1.5%) All d
Slide 13: Percent Change in Body Weight from Baseline at Week 26 (mITT)
Percent Change in Body Weight from Baseline at Week 26 (mITT) Placebo Nimacimab 200 mg Placebo Nimacimab 200 mg + Semaglutide + Semaglutide n=44 n=40 n=24 n=28 Mean % Change from baseline 0.16 (5.394) -1.05 (4.855) -10.06 (6.216) 13.10 (7.108) (SD) All drugs are investigational and subject to regula
Slide 14: Percent Change in Body Weight from Baseline at Week 26 (Per Protocol)
Percent Change in Body Weight from Baseline at Week 26 (Per Protocol) Placebo Nimacimab 200 mg Placebo Nimacimab 200 mg + Semaglutide + Semaglutide n=28 n=29 n=20 n=21 Mean % Change from baseline 0.53 (5.631) -0.44 (4.338) -10.38 (6.200) -13.65 (6.778) (SD) All drugs are investigational and subject
Slide 15: Weight Loss with Nimacimab Treatment
Weight Loss with Nimacimab Treatment 5 Data is plotted as mean ± SEM. Change in body weight from baseline (%) n=33 n=35 n=34 All drugs are investigational and subject to regulatory approval. n=37 n=38 0 n=44 n=42 n=39 0.16 mITT n=40 n=38 n=37 -1.05 mITT n=36 n=34 n=33 n=31 n=32 placebo nimacimab -5
Slide 16: Placebo-Adjusted Weight Loss with Nimacimab Treatment
Placebo-Adjusted Weight Loss with Nimacimab Treatment 5 Data is plotted as mean ± SEM. % body weight change (placebo adjusted) n=34 n=33 n=35 All drugs are investigational and subject to regulatory approval. n=38 n=37 n=42 n=39 n=44 0 n=40 n=37 n=38 n=36 n=34 -1.26% mITT n=33 n=31 n=32 placebo nimac
Slide 17: Weight Loss by Subject: Placebo v. Nimacimab
Weight Loss by Subject: Placebo v. Nimacimab Week 26 mITT Population, N=44 mITT Population, N=40 ≥5%WL = 7% ≥5%WL = 13% ≥10% WL = 2% ≥10% WL = 5% All drugs are investigational and subject to regulatory approval. Per Protocol Population, N=28 Per Protocol Population, N=29 ≥5%WL = 10% ≥5%WL = 7% ≥10%
Slide 18: Increased Weight Loss in Combination-Treated Patients
Increased Weight Loss in Combination-Treated Patients 5 Data is plotted as mean ± SEM. Change in body weight from baseline (%) n=34 n=33 n=35 n=37 0 n=44 n=24 n=42 n=39 n=38 0.16 mITT n=28 n=24 n=28 n=24 All drugs are investigational and subject to regulatory approval. n=23 -5 n=26 n=22 n=22 n=26 n=
Slide 19: Increased Weight Loss in Combination-Treated Patients (Placebo Adjusted)
Change in body weight from baseline ( n=35 n=32 n=39 n=38 n=37 Increased Weight 0 Loss in Combination-Treated Patients n=44 n=24 n=42 placebo adjusted n=24 n=28 change BW mITT placebo adjusted n=24 wk 26 no nima 5 -5 Data isn=28 plotted as mean ± SEM. n=23 Change in body weight from baseline (%) n=2
Slide 20: Semaglutide-Adjusted Weight Loss with Combo Treatment
Semaglutide-Adjusted Weight Loss with Combo Treatment 5 Data is plotted as mean ± SEM. % body weight change (semaglutide adjusted) n=22 n=21 n=22 All drugs are investigational and subject to regulatory approval. n=22 n=23 n=24 n=24 n=24 0 n=28 n=28 n=26 n=26 n=26 n=25 -2.95% mITT placebo + semagluti
Slide 21: Weight Loss by Subject: Semaglutide v. Combination
Weight Loss by Subject: Semaglutide v. Combination Week 26 All drugs are investigational and subject to regulatory approval. mITT Population, N=24 mITT Population, N=28 ≥5%WL = 71% ≥5%WL = 75% ≥10% WL = 42% ≥10% WL = 50% Per Protocol Population, N=20 Per Protocol Population, N=21 ≥5%WL = 85% ≥5%WL =
Slide 22: DEXA: Nimacimab Plus Semaglutide Improves Body Composition
DEXA: Nimacimab Plus Semaglutide Improves Body Composition Baseline vs Week 26 Change in Lean to Fat Mass Ratio Lean Mass vs. Fat Mass Loss with weight loss 0 Placebo Nimacimab 200 mg Fat Mass Loss + Semaglutide + Semaglutide -20 Lean Mass Loss n=20 n=25 Percent Change -24% All drugs are investigati
Slide 23: Association of Weight Loss and Exposure of Nimacimab
Association of Weight Loss and Exposure of Nimacimab Nimacimab vs %WL at Week 16 10 Predicted Ctrough Exposure r= -0.56 (%) 10 5 27.5 50 72.5 95 p=0.008 5 Change in body weight Weight Change 5 expected (%) All drugs are investigational and subject to regulatory approval. % baseline [nimacimab] 0 0 f
Slide 24: Preliminary PK Curves Highlight Inconsistent Exposure
Preliminary PK Curves Highlight Inconsistent Exposure Initial Anti-Drug Antibody (ADA) analysis suggests that ADA is not driving nimacimab clearance The majority of patients had PK curves below the predicted exposure through Week 16 Observed in both monotherapy and combination cohorts All drugs are
Slide 25: DIO Studies Demonstrate a Wide and Effective Dose Range
DIO Studies Demonstrate a Wide and Effective Dose Range Clinical translation of nimacimab exposure in the CBeyond trial highlights the potential for greater weight loss with a higher dose pAUC Weight Change (%) Relative Nimacimab Dose h*ug/mL 24-day mouse DIO Efficacy 7.5 mg/kg Q3D 103,278 - 2.3 CBe
Slide 26: Safety and Tolerability
CBeyond’ Safety and Tolerability
Slide 27: Reported TEAEs by Severity
Reported TEAEs by Severity Nimacimab Nimacimab 200 mg + Placebo Placebo + Semaglutide Overall 200 mg Semaglutide Max Severity n=40 n=44 n=28 n=24 n=136 Mild 20 (50.0%), 174 14 (31.8%), 109 11 (39.3%), 80 10 (41.7%), 113 55 (40.4%), 476 All drugs are investigational and subject to regulatory approval
Slide 28: TEAEs by System Organ Class
TEAEs by System Organ Class Nimacimab Nimacimab 200 mg + Placebo + Placebo Overall 200 mg Semaglutide Semaglutide System Organ Class n=40 n=44 n=28 n=24 n=136 General disorders and 16 (40.0%), 101 14 (31.8%), 33 7 (25.0%), 12 11 (45.8%), 39 48 (35.3%), 185 All drugs are investigational and subject t
Slide 29: Most Reported TEAEs by Preferred Term
Most Reported TEAEs by Preferred Term Nimacimab Nimacimab 200 mg + Placebo + Placebo Overall Preferred Term 200 mg Semaglutide Semaglutide n=40 n=44 n=28 n=24 n=136 Injection site erythema 7 (17.5%), 50 6 (13.6%), 12 2 (7.1%), 3 3 (12.5%) 15 18 (13.2%), 80 Nausea 5 (12.5%), 6 4 (9.1%), 4 9 (32.1%),
Slide 30: Gastrointestinal Disorders
Gastrointestinal Disorders Nimacimab Nimacimab 200 mg + Placebo Placebo + Semaglutide Overall Max Severity 200 mg Semaglutide n=40 n=44 n=28 n=24 n=136 Mild 8 (20.0%), 16 8 (18.2%), 15 11 (39.3%), 27 11 (45.8%), 32 38 (27.9%), 90 Moderate 3 (7.5%), 3 5 (11.4%), 5 5 (17.9%), 10 5 (20.8%), 5 18 (13.2%
Slide 31: Higher Nimacimab Concentration Was Not Associated with GI-AEs
Higher Nimacimab Concentration Was Not Associated with GI-AEs Mono GI-AE vs [Nimacimab] at W16 Combo GI-AE vs [Nimacimab] at W16 8 8 [nimacimab] ≥ [nimacimab] ≥ predicted levels predicted levels 6 6 Cumulative AEs cumulative AEs All drugs are investigational and subject to regulatory approval. 4 4 2
Slide 32: Psychiatric Disorders
Psychiatric Disorders Nimacimab Nimacimab 200 mg + Placebo Placebo + Semaglutide Overall Max Severity 200 mg Semaglutide n=40 n=44 n=28 n=24 n=136 Mild 1 (2.5%), 1 1 (2.3%), 1 0, 0 1 (4.2%), 2 3 (2.2%), 4 Moderate 0, 0 0.0 0, 0 1 (4.2%), 1 1 (0.7%), 1 Severe 0, 0 0, 0 0, 0 0, 0 0, 0 Missing 0, 0 0,
Slide 33: Summary and the Path Forward
Summary and the Path Forward © 2025 Skye Bioscience, Inc.
Slide 34: Summary and the Path Forward
Summary and the Path Forward Key Results • Monotherapy (200 mg QW): Did not meet primary endpoint; placebo-adjusted weight loss at 26 weeks was -1.26%, p=0.2699, mITT and -1.33%, p=0.2878, PP. • Combination with Semaglutide: Achieved a clinically meaningful placebo-adjusted weight loss vs semaglutid
Slide 35: Question & Answer Session
CBeyond Question & Answer Session