Skye Bioscience, Inc. · NASDAQ:SKYE
Skye Bioscience — Investor Presentation (April 2024)
44 slides from Skye Bioscience's investor presentation, Apr 12, 2024
Slide 1: Unlocking the Pharmaceutical Potential of the Endocannabinoid System
Nasdaq: SKYE Unlocking the Pharmaceutical Potential of the Endocannabinoid System April 2024
Slide 2: Disclaimer and Important Information for Investors
Disclaimer and Important Information for Investors This investor 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”). This Presentation is for informational purposes o
Slide 3: Skye is Building an Endocannabinoid System-targeting Pharmaceutical Company
Skye is Building an Endocannabinoid System-targeting Pharmaceutical Company Our Mission To pioneer and lead the development of new medicines that unlock the pharmaceutical potential of the endocannabinoid system, initially through modulation of the CB1 receptor, to advance the standard of care and t
Slide 4: Convergence of Right Space, Technology and Team
Convergence of Right Space, Technology and Team Endocannabinoid system is a renewed area of interest. ENDOCANNABINOIDS Two Phase 2 differentiated, endocannabinoid-system-targeting drugs in development. Supported by 5AM Ventures, Versant, Perceptive, GSK, Ally Bridge, Sphera, TOP TIER INVESTORS Altiu
Slide 5: Leadership
Leadership Contributed to commercialization of 47+ drugs/diagnostics, led high-value strategic transactions and co-founded multiple companies Executive Management Board of Directors Punit Dhillon Tu Diep, MSc Andy Schwab Annalisa Jenkins, MBBS FRCP Deborah Charych, PhD Keith Ward, PhD CEO & Chair of
Slide 6: CB1: High-potential Target for Physiological Regulation
CB1: High-potential Target for Physiological Regulation CB1 is involved in many disease processes • Cannabinoid receptor 1 (CB1) is a renewed target of Inflammatory interest for drug discovery. • Modulation of CB1 signaling can impact key biological processes including: − Inflammatory, metabolic, fi
Slide 7: Key Milestones Position Skye for Near Term Value Generation
Key Milestones Position Skye for Near Term Value Generation Multiple data catalysts across two key programs through early 2025 2024 2025 Activity Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 NIMACIMAB Obesity Phase 2 Ph. 2 interim data SBI-100 OE Glaucoma1 Phase 2a (US) Phase 2b (US) References are to calendar years. Al
Slide 8: Nimacimab
Nimacimab Novel CB1-targeting mAb therapeutic for cardiometabolic conditions: peripheral CB1 inhibitor MOA Disease R&D Phase 1 Phase 2 CB1 Receptor Inhibitor NIMACIMAB Obesity Sub-cutaneous Phase 2-ready molecule with open IND for obesity/weight loss. Best–in-class Monoclonal Only CB1 negative allos
Slide 9: SBI-100 Ophthalmic Emulsion
SBI-100 Ophthalmic Emulsion Improving CB1-targeting drug design for glaucoma MOA Disease R&D Phase 1 Phase 2a CB1 Receptor Agonist SBI-100 OE Glaucoma Topical Best–in-class Molecule First/only prodrug of THC developed and currently in the clinic for glaucoma. Clear Clinical Endpoint Lowering intraoc
Slide 10: Broad Metabolic Potential With Clinically Validated Mechanism of Action
Nimacimab Broad Metabolic Potential With Clinically Validated Mechanism of Action 10
Slide 11: Nimacimab: Differentiated Therapeutic in Obesity
Nimacimab: Differentiated Therapeutic in Obesity Upregulation of CB1 signaling is involved in multiple inflammatory, fibrotic and metabolic diseases in various organs with significant prevalence and unmet needs CB1 Nimacimab Key Differentiators 1 Target clinically validated Adipose Tissue Kidneys Li
Slide 12: The Promise of CB1 Inhibition
The Promise of CB1 Inhibition Clinically validated MOA Rimonabant RIO-lipids Phase 3 study placebo (n=342); 5 mg rimonabant (n=345); \20 mg rimonabant (n=346) Rimonabant (Accomplia) developed by Sanofi and approved for weight loss in 2006 in EU Demonstrated up to 10% weight loss over 1 year Improvem
Slide 13: Rimonabant in the Periphery: Metabolic Benefits Beyond Caloric Restriction
Rimonabant in the Periphery: Metabolic Benefits Beyond Caloric Restriction Study highlights impact of peripheral CB1 inhibition Central Inhibition Only Global Inhibition 6/7 6/7 Using a DIO model with a specific vehicle arm to control for the anorexigenic effect (hashed bars = vehicle-pf) by matchin
Slide 14: 2nd Generation Peripherally Restricted CB1 Inhibitors Remain Efficacious
2nd Generation Peripherally Restricted CB1 Inhibitors Remain Efficacious Peripherally restricted CB1 inhibitors reduce food intake and body weight (DIO model) comparable to non-restricted CB1 inhibitors Peripheral CB1 inhibitors mediate reduction in fat mass but not lean mass Insulin Sensitivity Lep
Slide 15: Peripheral CB1 Receptors and Fat Metabolism
Peripheral CB1 Receptors and Fat Metabolism Blocking CB1 potentially triggers metabolic reprogramming in adipose tissues, mediating conversion of white adipose tissue to beige adipose tissue CB1R WAT • The ECS is deeply involved in controlling energy metabolism. x • CB1 is highly expressed in adipos
Slide 16: Targeting Obesity Comes in Different Flavors
Targeting Obesity Comes in Different Flavors CB1 impacts key metabolic pathways that complement existing products & strategies KEY TARGETS / MECHANISMS Key Targets Characteristics GLP-1 GIP Glucagon CB1 Decreases Appetite / Increases Satiety ✓ ? (limited) x ✓ Opportunities for Nimacimab Delays Gastr
Slide 17: Preclinical Rationale for Combination of CB1 and GLP-1
Preclinical Rationale for Combination of CB1 and GLP-1 Complementary pathways may provide additive therapeutic effects for GLP-1 agonists CB1 and GLP-1-dependent caloric restriction Increased insulin sensitivity with Significant weight loss with combination +/- Rimonabant CB1 inhibition CB1 KO mice
Slide 18: Phase 1 Clinical Data and Phase 2 Update
Nimacimab: Development Plan for Obesity Phase 1 Clinical Data and Phase 2 Update
Slide 19: Nimacimab Biodistribution
Nimacimab Biodistribution Little to no accumulation in the brain Day 1 Day 8 Day 15 Cyno (post 1st dose) (post 2nd dose) (post 3rd dose) Little to no nimacimab found in CSF/Serum the brain BLQ <0.02% <0.02% 3 mg/kg IV q1w High levels of nimacimab found Cyno 9 hours Level in CSF determined in the pla
Slide 20: Nimacimab Toxicology – NOAEL > 75 mg/kg
Nimacimab Toxicology – NOAEL > 75 mg/kg IND-enabling toxicology studies: safe with significant safety window established • 4-week study in cynomologus monkeys completed with up to 75 mg/kg nimacimab administered weekly IV • No nimacimab-related observations in toxicology assessments performed includ
Slide 21: Nimacimab Phase 1 Data
Nimacimab Phase 1 Data Demonstrated encouraging tolerability, pharmacokinetics and encouraging evidence of efficacy • SAD • 24 healthy volunteers enrolled (18 subjects used as PK population) • 0.6 mg/kg, 1.2 mg/kg and 2.5 mg/kg administered IV over 30 minutes • MAD • 82 patients enrolled with NAFLD
Slide 22: Rimonabant – A Closer Look at Safety
Rimonabant – A Closer Look at Safety Beyond psychiatric adverse events, rimonabant safety compares favorably to GLP-1RAs Rimonabant was generally well-tolerated, especially as it relates to gastrointestinal adverse events compared to GLP-1RAs. Rimonabant1 Semaglutide2 Gastrointestinal disorders 30.4
Slide 23: Why Did Weight Not Change in Phase 1 NAFLD Study?
Why Did Weight Not Change in Phase 1 NAFLD Study? Body composition phenotypes are highly heterogeneous based on type of disease • Phase 1 study enrolled NAFLD patients who were both diabetic and pre- diabetic • 83% diabetic; 17% pre-diabetic • Novo studies using semaglutide in patients with diabetes
Slide 24: Nimacimab Bioavailability Study
Nimacimab Bioavailability Study Intravenous versus subcutaneous dosing Study Design: • Single 100 mg SC dose vs. single 100 mg IV dose of nimacimab • 10 subjects dosed SC vs. 10 subjects with IV Conclusions: • Absolute bioavailability approximately 60% after a single dose • No new trends in safety p
Slide 25: Proposed Phase 2 Clinical Trial Design: CB1/GLP1 Combo in Obesity
Proposed Phase 2 Clinical Trial Design: CB1/GLP1 Combo in Obesity Key Inclusion Criteria Primary Endpoint Secondary Endpoint • Obese: BMI ≥ 30 kg/m2 • Percent change in weight from • Safety and tolerability • Overweight: BMI ≥ 27 with at least baseline at week 26 • Change in waist circumference one
Slide 26: Challenges Associated with Long-Term Use of GLP-1 RA Treatment
Challenges Associated with Long-Term Use of GLP-1 RA Treatment Plateau and rebound effect Considerations of Long-term Treatment with GLP-1 Receptor Agonists STEP 5: Durability of Weight-loss Over 2 Years STEP 1 Trial Extension: Withdrawal of Semaglutide Garvey et al., Nat Med. 2022 Wilding et al., D
Slide 27: GLP-1 RA Effects on Muscle Wasting
GLP-1 RA Effects on Muscle Wasting Opportunities for improvement Clinical Data Ongoing Collaborations • As the FDA has not required body composition as a primary endpoint in weight loss • Lilly and Bioage Labs announced a collaboration (Oct 2023) studies, data surrounding GLP-1’s effect on lean body
Slide 28: Nimacimab Clinical Development Summary
Nimacimab Clinical Development Summary Broad metabolic potential • Nimacimab has significantly improved peripheral restriction than INV-202 • Potentially better safety • Nimacimab has potential to treat multiple metabolic indications • Rimonabant demonstrated clinical efficacy of CB1 inhibition in o
Slide 29: Significant Unmet Needs in Glaucoma with Opportunity for New Class of Medicine
SBI-100 OE Significant Unmet Needs in Glaucoma with Opportunity for New Class of Medicine
Slide 30: SBI-100 OE Phase 1 Safety Profile/Data Summary
SBI-100 OE Phase 1 Safety Profile/Data Summary Good Safety Profile: Generally safe and well-tolerated. No participants dropped out due to SBI-100 OE. Transient Discomfort: Main side effect is discomfort/pain upon drop instillation, but average duration of discomfort was less than 15 minutes. Lack of
Slide 31: SBI-100 OE Phase 2 Glaucoma Proof-of-Concept Study
SBI-100 OE Phase 2 Glaucoma Proof-of-Concept Study Primary open-angle glaucoma and ocular hypertension; dosed 56 patients, of 54 planned topline data Q2 Key Inclusion Criteria 4 Weeks 14 Days 21mmHg ≥ IOP < 34mmHg Screening Dosing Safety Follow-up No prior surgical interventions for POAG or OHT Coho
Slide 32: Summary
Summary
Slide 33: Capitalization
Capitalization Cap Table: December 31, 20231 Capital Common shares o/s2 12.3 M Cash & cash equivalents: Dec 31, 20231 $1.3 M Options and RSUs 1.3 M Gross proceeds from 2024 PIPE financings $90.0 M Warrants 3.3 M Restricted cash posted as appellate bond1 $9.1 M Convertible note (as-converted basis) 1
Slide 34: Skye Next Steps
Skye Next Steps • Advance nimacimab into clinical trials • Demonstrate IOP-reducing proof-of-concept for SBI-100 OE • Maintain focused operational and clinical development strategy Expected Clinical Development Milestones 2024 2025 SBI-100 OE Phase 2a completed enrollment – Q1 Nimacimab interim data
Slide 35: Thank you
Thank you Learn more, please contact: ir@skyebioscience.com, +1 (858) 410-0266
Slide 36: CB1 Agonism as New Therapeutic Class to Treat Glaucoma
CB1 Agonism as New Therapeutic Class to Treat Glaucoma Reduced IOP and associated mechanisms suggest potential for a novel therapeutic • Research with THC and other CB1 agonists have highlighted relevant mechanisms CB1 is expressed in key ocular tissues and its engagement1: to support the use of can
Slide 37: SBI-100 Ophthalmic Emulsion: Synthetic THC-based Prodrug
SBI-100 Ophthalmic Emulsion: Synthetic THC-based Prodrug Prodrug technology and novel formulation addresses hurdles with THC therapeutics DESIGN FACTOR RATIONALE SBI-100 STRUCTURE Therapeutic backbone is not water soluble Tetrahydrocannabinol (THC) and has poor bioavailability. Improves solubility,
Slide 38: Targeting Glaucoma (POAG & OH): Large Market, Unmet Needs
Targeting Glaucoma (POAG & OH): Large Market, Unmet Needs A leading cause of irreversible blindness worldwide $7B Overall glaucoma drug market worldwide (2020) MARKET LACKS INNOVATION Predominantly using legacy classes of drugs and generic compounds. ~69M Patients POAG patients worldwide (2020) 1% R
Slide 39: Phase 1 Clinical Trial – SAD/MAD Randomized Placebo-Controlled: Completed
Phase 1 Clinical Trial – SAD/MAD Randomized Placebo-Controlled: Completed • Randomized, placebo-controlled study in up to 48 healthy volunteers across 6 treatment cohorts. • Primary objective: establish safety and tolerability of single ascending and multiple ascending doses of SBI-100 Ophthalmic Em
Slide 40: Pharmacokinetics – Little to no Exposure of THC in Plasma
Pharmacokinetics – Little to no Exposure of THC in Plasma MAD PK population 0.5% SBI-100 1.0% SBI-100 2.0% SBI-100 N=6 N=6 N=6 Day 1 PK Parameters, Mean (SD) AUC (h*ng/mL) SBI-100 0.9184 (0.4252) 0.8252 (0.2533) 2.131 (1.139) Cmax (ng/mL) SBI-100 0.2742 (0.07336) 0.2973 (0.1103) 0.7202 (0.3403) Day
Slide 41: SBI-100 OE Demonstrates Significantly Less Hyperaemia Compared to Other Therapies
SBI-100 OE Demonstrates Significantly Less Hyperaemia Compared to Other Therapies Hyperaemia (red eyes) has notable impact on patient adherence to drug regimen Incidence of hyperaemia in SBI-100 OE vs. currently approved drugs Latanoprost 16.5% Travoprost 33% Rhopressa SBI-100 OE Bimatoprost 53% <10
Slide 42: MAD Day 1 & 5 – Discomfort is Transient and Quickly Resolves
MAD Day 1 & 5 – Discomfort is Transient and Quickly Resolves Day 1 (am) Day 1 (pm) 100 100 Level of Discomfort Level of Discomfort None Discomfort Score None Discomfort Score Mild Mild Moderate 50 Moderate 50 Severe Severe 0 0 Post-Dose 15 min Post-Dose 15 min Post-Dose 15 min Post-Dose 15 min place
Slide 43: Intraocular Pressure Analysis – Full Population
Intraocular Pressure Analysis – Full Population Low baseline IOP across all subjects • Historically, glaucoma drugs do not significantly reduce IOP in healthy volunteers • Participants receiving placebo and active had similar reductions in IOP. • This is potentially due to the lower baseline IOP mea
Slide 44: Subgroup Analysis – High IOP
Subgroup Analysis1 – “High IOP” • Because of the relatively low mean baseline IOP in this healthy volunteer population, we did not see any significant reductions in IOP when evaluating active against placebo. • A subgroup analysis of participants with “high” baseline IOP was evaluated. • We evaluate