Skye Bioscience, Inc. · NASDAQ:SKYE
Skye Bioscience — Investor Presentation (January 2024)
44 slides from Skye Bioscience's investor presentation, January 2024
Slide 1: Unlocking the Pharmaceutical Potential of the Endocannabinoid System
Unlocking the Pharmaceutical Potential of the Endocannabinoid System January 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 Pharmaceutical Company
Skye is Building an Endocannabinoid 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 treatment alternat
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, GSK other dedicated life science investors in Bird Rock Bio (a
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 Deborah Charych, PhD Keith Ward, PhD CEO & Chair of BOD Chief Development Offic
Slide 6: CB1: High-potential Target for Physiological Regulation
CB1: High-potential Target for Physiological Regulation CB1 is involved in many disease processes • CB1 (cannabinoid receptor 1) 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: Endocannabinoids: A Renewed Drug Development Frontier
Endocannabinoids: A Renewed Drug Development Frontier ECS (endocannabinoid system) receptors help modulate and maintain homeostasis of physiological functions. Over- or under-activation of these receptors is involved in an array of diseases Notable ECS Transactions Company Acquirer Deal Value Lead A
Slide 8: 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 end of 2024 2024 2025 Activity Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 NIMACIMAB Obesity Phase 2 Ph. 2 Ph. 2 interim data topline data SBI-100 OE Glaucoma1 Phase 2a (US) Phase 2b (US) Ph. 2a Ph. 2a Ph
Slide 9: 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 10: SBI-100 Ophthalmic Emulsion
SBI-100 Ophthalmic Emulsion Improving CB1-targeting drug design for glaucoma MOA Disease R&D Phase 1 Phase 2 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 intraocu
Slide 11: Broad Metabolic Potential With Clinically Validated Mechanism of Action
Nimacimab Broad Metabolic Potential With Clinically Validated Mechanism of Action 11
Slide 12: 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 13: 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 14: 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 15: 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 16: 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 17: 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 18: 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 19: Preclinical Strategy to Evaluate Key Opportunities
Preclinical Strategy to Evaluate Key Opportunities Skye’s human CB1 transgenic mouse: critical tool to model obesity and nephropathy Human CB1 knockin mice (C57BL/6) Obese Mice HFD: 8-10 weeks STZ: 8-10 weeks Diabetic Mice Q: Can peripheral CB1 blockade mediate weight loss comparable Q: Can peripher
Slide 20: Nimacimab: Phase 1 Clinical Data and Phase 2 Update
Nimacimab: Development Plan for Obesity Phase 1 Clinical Data and Phase 2 Update
Slide 21: 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 3 mg/kg IV q1w BLQ <0.02% <0.02% the brain High levels of nimacimab found Level in CSF determined Cyno 9 hours using quan
Slide 22: Nimacimab Toxicology – NOAEL > 75 mg/kg
Nimacimab Toxicology – NOAEL > 75 mg/kg Safe with significant safety window established • IND-enabling toxicology study completed with up to 75 mg/kg nimacimab administered weekly IV for 4 weeks. • No nimacimab-related observations in toxicology assessments performed including neurological observati
Slide 23: Nimacimab Phase 1 Data
Nimacimab Phase 1 Data Demonstrated encouraging tolerability, pharmacokinetics and encouraging evidence of efficacy Phase 1 SAD in Healthy Volunteers and MAD in NAFLD (diabetic/pre-diabetic) • SAD • 24 subjects enrolled (18 subjects used as PK population) • 0.6 mg/kg, 1.2 mg/kg and 2.5 mg/kg adminis
Slide 24: 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 25: 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 26: 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 baseline • Safety and tolerability • Overweight: BMI ≥ 27 with at least one at week 26 • Change in waist circumference
Slide 27: 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 28: 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 29: 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 30: 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 31: 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 32: 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 33: 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 34: 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 35: 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 36: SBI-100 OE Demonstrates Significantly Less Hyperaemia Compared to Other Therapies
SBI-100 OE Demonstrates Significantly Less Hyperaemia Compared to Other Therapies Hyperaemia has notable impact on patient adherence to drug regimen Incidence of hyperaemia in currently approved drugs vs. SBI-100 OE Latanoprost 16.5% Travoprost 33% Rhopressa SBI-100 OE Bimatoprost 53% <10% 40% 10% 2
Slide 37: 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 38: 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 39: Subgroup Analysis 1 – "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
Slide 40: 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 41: 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 Key Inclusion Criteria 4 Weeks 14 Days 21mmHg ≥ IOP < 34mmHg Screening Dosing Safety Follow-up No prior surgical interventions for Double-masked, POAG or OHT placebo-controlled Cohort 1 0.5 % BID P
Slide 42: Summary
Summary
Slide 43: 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 • Selectively evaluate business development opportunities to advance product pipeline • Uplist from OTCQB following suc
Slide 44: Thank you
Thank you Learn more, please contact: [email protected], +1 (858) 410-0266
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