Skye Bioscience, Inc. · NASDAQ:SKYE
Skye Bioscience — Technical Presentation (July 2024)
86 slides from Skye Bioscience's technical presentation, Jul 24, 2024
Slide 1: Metabolic Rewiring with CB1 Inhibition Virtual KOL Event
Metabolic Rewiring with CB1 Inhibition Virtual KOL Event Nasdaq: SKYE
Slide 2: Disclaimer and Important Information for Investors
A new Generation of CB1 inhibitors 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”). This Presentation is fo
Slide 3: Chapter 01: Welcome & Introduction
Chapter 01 | Punit Dhillon Welcome & Introduction
Slide 4: Event Agenda and Objectives
A new Generation of CB1 inhibitors Event Agenda and Objectives Welcome and Introduction (5 min) 1 Speaker: Punit Dhillon Why Treat Obesity in the Healthcare System? (10 min) 2 Speaker: Lee M. Kaplan, M.D. Ph.D. Intro to Nimacimab & Scientific Rationale for Peripheral CB1 Inhibition (20 min) 3 Speake
Slide 5: Mission, Who We Are
A new Generation of CB1 inhibitors Mission, Who We Are Mission Approach Program Harness the power of groundbreaking Nimacimab, a new and distinct To develop innovative medicines to research and technology to develop class of CB1 inhibitor, has the treat obesity and metabolic diseases medicines that
Slide 6: Skye Leadership and Key Opinion Leader Panel
A new Generation of CB1 inhibitors Skye Leadership and Key Opinion Leader Panel Skye Executive Management Key Opinion Leader Panel Punit Dhillon Tu Diep, M.Sc. Louis Aronne, M.D. Marcus Goncalves, M.D., Ph.D. CEO & Chair of BOD Chief Development Officer Former President, Obesity Society Associate Pr
Slide 7: We are Well-Positioned to Successfully Become a Fully Integrated Metabolic Company
A new Generation of CB1 inhibitors We are Well-Positioned to Successfully Become a Fully Integrated Metabolic Company Our team has the building Robust IP and Development Strategy 1 blocks to bring Nimacimab Planned Nimacimab EOP2 by 2027 and IP/composition of matter protection through 2037 through c
Slide 8: Strategic Roadmap | Vision through 2027 and Beyond
A new Generation of CB1 inhibitors Strategic Roadmap I Vision through 2027 and Beyond Clinical development strategy 2027+ 2026 Complete Phase 2 2025 Initiate Phase 2b meeting with FDA and 2024 obesity clinical trial Phase 3 planning Interim and topline Initiate Phase 2 (CBeyondTM 2) (CBeyondTM 3 & 4
Slide 9: Nimacimab: The Future of Metabolic Therapeutics
A new Generation of CB1 inhibitors Nimacimab: The Future of Metabolic Therapeutics Innovative scientific strategy to shape the optimal metabolic product profile Improved Safety New Product Meaningful Weight Loss No neuropsychiatric adverse events in Benchmark CB1 inhibition has demonstrated Nimacima
Slide 10: Nimacimab May Promote Sustainable and Healthy Weight-Loss
A new Generation of CB1 inhibitors Nimacimab May Promote Sustainable and Healthy Weight-Loss Opportunities in the current AOM landscape to address heterogeneity in patients with obesity Potential Monotherapy Benefits Weight Loss Impact - Illustrative • Effective weight loss GLP-RA • Sustainable resu
Slide 11: Nimacimab's History
A new Generation of CB1 inhibitors Nimacimab’s History We intend to advance Nimacimab into the clinic within 12 months of product acquisition September 2018 August 2023 January 2024 January & March 2024 August 2024 Skye Receives IND Skye Raises Completed Phase 1b Initiate Phase 2 Skye Acquires Clear
Slide 12: Phase 2 Success Catalyzes Growth of Metabolic Franchise
A new Generation of CB1 inhibitors Phase 2 Success Catalyzes Growth of Metabolic Franchise CB1 inhibitor with comprehensive therapeutic benefits for therapeutic pipeline MoA Disease R&D Phase 1 Phase 2 CB1 Receptor Inhibitor Obesity Nimacimab Sub-cutaneous Additional Metabolic Disorders Future First
Slide 13: Chapter 02: Why Treat Obesity in the Healthcare System?
Chapter 02 | Lee M. Kaplan, M.D., Ph.D. Why Treat Obesity in the Healthcare System?
Slide 14: What is Obesity?
A new Generation of CB1 inhibitors What is Obesity? World Health Organization1: A disease characterized by abnormal abnormallyorplaced excessive fat that presents or excessive a risk to health fat that presents a risk to health Widely accepted description: A complex, chronic, possibly progressive di
Slide 15: The Fundamental Question
A new Generation of CB1 inhibitors The Fundamental Question Is obesity a disorder that is best treated within the healthcare system… Obesity … or in a commercial environment? Kaplan LM, 2024 Copyright © 2024 The Obesity and Metabolism Institute. All rights reserved. All drugs are investigational and
Slide 16: The Purpose of Health Care
A new Generation of CB1 inhibitors The Purpose of Health Care To relieve suffering arising from disturbances in the human body … … from symptoms … from disability … from fear … of complications … of dying … of developing a disability … of not being able to participate in the world Obesity causes suf
Slide 17: Body Fat Mass is Physiologically Regulated
A new Generation of CB1 inhibitors Body Fat Mass is Physiologically Regulated Body fat mass and distribution vary predictably across the lifecycle Loss of baby fat Fat changes with puberty Fat changes with aging and menopause Fat changes during and after pregnancy and lactation At any given time, fa
Slide 18: The Body Vigorously Defends its Desired Fat Mass
A new Generation of CB1 inhibitors The Body Vigorously Defends its Desired Fat Mass through a Protective Physiological Response that Limits the Effectiveness of Voluntary Calorie Restriction This response is called ‘metabolic adaptation’5-6 It includes increased appetite and decreased energy expendi
Slide 19: In Obesity, the Target Fat Mass is Dysregulated
A new Generation of CB1 inhibitors In Obesity, the Target Fat Mass is Dysregulated (Elevated) from Environmental Influences on Biologically Susceptible Individuals Altered nutrient Muscle Chronic Sleep Circadian Obesogenic composition dysfunction stress deprivation rhythm medications (e.g. ultra pro
Slide 20: Effective Obesity Treatments Normalize Fat Mass Regulation
A new Generation of CB1 inhibitors Effective Obesity Treatments Normalize Fat Mass Regulation Leading to Decreased Weight Without Activating Metabolic Adaptation Effective anti-obesity therapies Altered nutrient Muscle Chronic Sleep Circadian Obesogenic composition dysfunction stress deprivation rhy
Slide 21: Goals of Obesity Treatment
A new Generation of CB1 inhibitors Goals of Obesity Treatment Weight loss Improvement in obesity symptoms Ingestion-related Physical Dysphoric Improvement in existing obesity complications Metabolic Structural Inflammatory and autoimmune Cognitive and psychosocial Neoplastic Prevention of future obe
Slide 22: Obesity Stimulates a Multi-System Metabolic and Inflammatory Syndrome
A new Generation of CB1 inhibitors Obesity also Stimulates a Multi-System Metabolic and Inflammatory Syndrome Obesity Metabolic stress Ectopic fat accumulation, systemic inflammation, cell injury, and fibrosis Vascular Heart Liver Pancreas Kidney (HTN, CVD, CAD, PVD) (HFpEF) (MASLD) (T2D) (CKD) The
Slide 23: Growing List of Diseases that Benefit from Treating Obesity
A new Generation of CB1 inhibitors There is a Growing List of Diseases that Have Now Been Demonstrated to Benefit from Effective Treatment of the Underlying Obesity • Type 2 diabetes (T2D) – 2014 • Atherosclerotic cardiovascular disease (ASCVD) – 2023 • Heart failure with preserved ejection fraction
Slide 24: Given the Size of the Problem, If We Overcome These Barriers
A new Generation of CB1 inhibitors Given the Size of the Problem, IF We are Successful in Overcoming These Barriers… We should see an impact on obesity at a population level First, a reduction in the severity of the existing obesity Later, a reduction in the rate of obesity, as effective treatments
Slide 25: Chapter 03: Introduction to Nimacimab Peripheral CB1 Inhibition
Chapter 03 | Christopher Twitty, Ph.D.; Introduction to Nimacimab Peripheral CB1 Inhibition Marcus Goncalves, M.D., Ph.D.
Slide 26: Obesity and CB1 Introduction
A new Generation of CB1 inhibitors Obesity and CB1 Introduction Upregulation of CB1 signaling is involved in metabolic diseases, including obesity; inhibition of CB1 addresses fundamental drivers of obesity Obesity • Obesity can be defined as excessive fat deposition that impairs health, simplistica
Slide 27: Nimacimab is a First-in-Class, Peripherally Restricted CB1-Inhibiting Antibody
A new Generation of CB1 inhibitors Nimacimab is a First-in-Class, Peripherally Restricted Cannabinoid Receptor 1 (CB1)- Inhibiting Antibody Stable antibody with a half-life of 18-21 days (potential for bi-weekly or monthly dosing) Engineered IgG4 Single mutation in the hinge region that prevents ant
Slide 28: Nimacimab's Unique Inhibition of CB1: Negative Allosteric Modulation
A new Generation of CB1 inhibitors Nimacimab’s Unique Inhibition of CB1: Negative Allosteric Modulation Small molecule inverse agonists competes with endocannabinoid for CB1 binding; NAM antibody blocks CB1 signaling independent of endocannabinoid binding Productive CB1 Signaling Inhibition of CB1 S
Slide 29: Key MoA for Peripheral CB1 Inhibition in Obesity
A new Generation of CB1 inhibitors Key MoA for Peripheral CB1 Inhibition in Obesity Summary of key MoAs that make CB1 inhibition a promising approach in treating obesity Appetite Peripheral modulation of appetite regulating hormones (CCK/ghrelin/leptin/GLP1) can safely Hormones promote hypophagia. F
Slide 30: Chapter 03.1: Scientific Rationale for Peripheral CB1 Inhibition
Chapter 03.1 |Marcus Goncalves, M.D., Ph.D. Scientific Rationale for Peripheral CB1 Inhibition
Slide 31: Scientific Rationale for Peripheral CB1 Inhibition
A new Generation of CB1 inhibitors Scientific Rationale for Peripheral CB1 Inhibition Overview of key mechanisms behind CB1 inhibition in obesity treatment Fundamentals of Body Body weight regulation and obesity treatments; physiological features of weight loss Weight Regulation Human endocannabinoi
Slide 32: Body Weight Regulation and Treatments
A new Generation of CB1 inhibitors Body Weight Regulation and Treatments CB1 Inhibition Calorie restriction Incretin mimetics Energy Food Intake MC4R agonist Opioid antagonist Expenditure Sympathomimetics MC4R agonist Lipase inhibitors Nutrient Nutrient SGLT2 inhibitors Glucosidase inhibitors Absorp
Slide 33: Physiologic Features of Weight Loss
A new Generation of CB1 inhibitors Physiologic Features of Weight Loss Low T3 Atrophy Low Core Temp Hunger High Ghrelin Low Energy Expenditure CB1 Reward Low Insulin CB1 High Glucagon Hypothalamus Ketones Glucose Catecholamines Glucocorticoids Atrophy Fatty Acids CB1 High Cortisol Low Leptin CB1 CB1
Slide 34: CB1 Inverse Agonist Reduces Food Intake and Increases Energy Expenditure
A new Generation of CB1 inhibitors CB1 Inverse Agonist Reduces Food Intake and Increases Energy Expenditure Rimonabant Pair feeding Chow only Candy diet CNS adverse events limit utility9,10 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 34
Slide 35: CB1 Increases Food Intake via Peripheral Sensory Neurons
A new Generation of CB1 inhibitors CB1 Increases Food Intake via Peripheral Sensory Neurons Figure 111 Figure 211 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 35
Slide 36: Central vs Peripheral Effects
A new Generation of CB1 inhibitors Central vs Peripheral Effects Brain sparing peripheral agent CB1 CB1 Systemic agent Hypothalamus CB1 CB1 CB1 CB1 CB1 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 36
Slide 37: Separating Central vs Peripheral Effects
A new Generation of CB1 inhibitors Separating Central vs Peripheral Effects Central: Hypomotility12 Peripheral: GI Transit13 Sy Pe Pe ste rip rip m he h er ic ra al l All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 37
Slide 38: Peripheral CB1 Inv Agonist Reduces Food Intake and Increases Energy Expenditure
A new Generation of CB1 inhibitors Peripheral CB1 Inv Agonist Reduces Food Intake and Increases Energy Expenditure Figure 112 Figure 213 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 38
Slide 39: Peripheral CB1 Inhibitor Reverse Leptin Resistance
A new Generation of CB1 inhibitors Peripheral CB1 Inhibitor Reverse Leptin Resistance Brain-sparing inverse agonist Figure 114 Figure 214 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 39
Slide 40: Central vs Peripheral Effects
A new Generation of CB1 inhibitors Central vs Peripheral Effects CB1 CB1 Hypothalamus Tissue-specific CB1R KO CB1 CB1 Systemic agent CB1 CB1 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 40
Slide 41: CB1 Loss in Adipose Protects Against Obesity
A new Generation of CB1 inhibitors CB1 Loss in Adipose Protects Against Obesity D Figure 115 Figure 215 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 41
Slide 42: CB1 Loss in Adipose Reduces Food Intake and Increases Energy Expenditure
A new Generation of CB1 inhibitors CB1 Loss in Adipose Reduces Food Intake and Increases Energy Expenditure Enhanced sympathetic innervation15 All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 42
Slide 43: Coordinated Effects of Peripheral CB1 Inhibition
A new Generation of CB1 inhibitors Coordinated Effects of Peripheral CB1 Inhibition Adipose Tissue Liver GI Tract Muscle Tissue CB1 CB1 CB1 CB1 Low food intake15 High insulin sensitivity16 High food intake yet same weight18 Less preference High energy expenditure for fatty food Less steatosis despit
Slide 44: Peripheral CB1 Inhibition is an Important Therapeutic Modality
A new Generation of CB1 inhibitors Peripheral CB1 Inhibition is an Important Therapeutic Modality Mechanisms address key metabolic drivers of obesity • Blockade of CB1 in peripheral tissues, including adipose tissue, GI tract, muscle, and liver promotes insulin and leptin sensitivity, reduces adipos
Slide 45: Chapter 03.2: Biodistribution and Preclinical Toxicology
Chapter 03.2 | Chris Twitty, Ph.D. Biodistribution and Preclinical Toxicology
Slide 46: Superior Exclusion of CB1 Inhibitor from Brain & No Neuropsychiatric Side Effects
A new Generation of CB1 inhibitors Superior Exclusion of CB1 Inhibitor from Brain & No Neuropsychiatric Side Effects High preclinical dosing concentration highlights Nimacimab’s lack of CNS accumulation Day 1 Day 8 Day 15 Cyno (post 1st dose) (post 2nd dose) (post 3rd dose) Phase 1 data showed absen
Slide 47: Nimacimab Toxicology – NOAEL > 75 mg/kg
A new Generation of CB1 inhibitors 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 performe
Slide 48: Chapter 04: Clinical Experience and Endpoints
Chapter 04 | Louis Aronne, M.D. Clinical Experience and Endpoints
Slide 49: Overview of Current AOM Landscape
A new Generation of CB1 inhibitors Overview of Current AOM Landscape GLP-1 receptor agonists are the preferred treatment option for patients with obesity Obesity Pharmacologic Treatment Paradigm19-30 US Efficacy Safety Product Class ROA More Common Less Common Approval % Losing ≥5% / Mean % Weight M
Slide 50: Complementary, Not Competitive
A new Generation of CB1 inhibitors Complementary, Not Competitive CB1 impacts key metabolic pathways that complement existing products & strategies KEY TARGETS / MECHANISMS Opportunities for Nimacimab Key Targets Characteristics GLP-131 GIP31 Glucagon31 Amylin32-34 Myostatin35-37 CB138-39 Decreases
Slide 51: Overview of Clinical Experience with CB1 Inhibition as an AOM
A new Generation of CB1 inhibitors Overview of Clinical Experience with CB1 Inhibition as an AOM CB1 inhibition is a clinically validated MoA; peripherally-directed CB1 inhibitors such as Nimacimab avoid neuropsychiatric adverse events Clinical Validation – 1st Generation CB1 Inhibitors Competitive
Slide 52: Nimacimab Phase 1 Data
A new Generation of CB1 inhibitors Nimacimab Phase 1 Data Demonstrated positive tolerability, pharmacokinetics, and encouraging evidence of efficacy Single Ascending Dose Multiple Ascending Dose • 24 healthy volunteers (18 subjects used as PK • 82 patients enrolled with NAFLD (diabetic/pre- populati
Slide 53: Why Did Weight Not Change in Phase 1 NAFLD Study?
A new Generation of CB1 inhibitors 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-diabetic39 • Novo studies using sem
Slide 54: Future AOM Outlook
A new Generation of CB1 inhibitors Future AOM Outlook CB1 inhibitor has the potential to be the key player in the next wave of AOMs Unmet Needs Future AOM Outlook Key Winning Factors • Accessibility • Oral GLP-1 • More convenient dosing • Sustained weight loss • GLP-1/GIP/Glucagon combo • Improved t
Slide 55: Chapter 05: Ensuring Safety and Tolerability in Peripheral CB1 Inhibition
Chapter 05 | Beverly Tchang, M.D. Ensuring Safety and Tolerability in Peripheral CB1 Inhibition
Slide 56: Overview of CB1 AOM Safety Concerns
A new Generation of CB1 inhibitors Overview of CB1 AOM Safety Concerns CB1 AOM’s neuropsychiatric issues and challenges with getting new CB1 AOM approved Neuropsychiatric Challenges for CB1 Why Nimacimab? Concerns Inhibition • Prior brain-penetrated CB1 • Despite demonstrating clinical • Next-genera
Slide 57: Phase 1 MAD – Study Demographics and Baseline Characteristics
A new Generation of CB1 inhibitors Phase 1 MAD – Study Demographics and Baseline Characteristics Placebo 0.6 mg/kg 1.2 mg/kg 2.5 mg/kg Overall Treatment n=20 n=21 n=21 n=21 N=83 Sex, n (%) Female 11 (55.0) 10 (47.6) 11 (52.4) 9 (42.9) 41 (49.4) Male 9 (45.0) 11 (52.4) 10 (47.6) 12 (57.1) 42 (50.6) A
Slide 58: Phase 1 MAD – Demographics and Baseline Characteristics Cont'd
A new Generation of CB1 inhibitors Phase 1 MAD – Demographics and Baseline Characteristics Cont’d Placebo 0.6 mg/kg 1.2 mg/kg 2.5 mg/kg Overall Treatment n=20 n=21 n=21 n=21 N=84 Diabetes History, n (%) Diabetes 16 (80.0) 16 (76.2) 19 (90.5) 18 (85.7) 69 (83.1) Pre-diabetes 4 (20.0) 5 (23.8) 2 (9.5)
Slide 59: Phase 1 MAD – Treatment Emergent AEs by Preferred Term
A new Generation of CB1 inhibitors Phase 1 MAD – Treatment Emergent AEs by Preferred Term Placebo 0.6 mg/kg 1.2 mg/kg 2.5 mg/kg Active Overall Treatment n=20 n=22 n=21 n=21 N=63 AE Preferred Term in Descending Order of Frequency (Occurring in 2 or More Patients), n (%) Diarrhea* 8 (40.0) 7 (33.3) 13
Slide 60: Columbia-Suicide Severity Rating Scale (C-SSRS)
A new Generation of CB1 inhibitors Columbia-Suicide Severity Rating Scale (C-SSRS) Placebo 0.6 mg/kg 1.2 mg/kg 2.5 mg/kg Active Overall Treatment n=20 n=22 n=21 n=21 N=63 Baseline, n (%) Suicidal ideation 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Suicidal Behavior 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.
Slide 61: Phase 1 MAD – Safety Summary
A new Generation of CB1 inhibitors Phase 1 MAD – Safety Summary Nimacimab appears to be safe and well-tolerated, with low rate of treatment Overall Safety emergent adverse events and no drug-related treatment discontinuation GI Tolerability Little to no gastrointestinal disorder associated adverse e
Slide 62: Overview of Nimacimab Safety History and Potential
A new Generation of CB1 inhibitors Overview of Nimacimab Safety History and Potential Nimacimab shows promise in establishing a differentiated safety profile for treating obesity No Neuropsychiatric Event Superior exclusion of CB1 inhibitor from brain in preclinical studies, and no neuropsychiatric
Slide 63: Chapter 06: CBeyond Phase 2 Study Design
Chapter 06 | Tu Diep, M.Sc. CBeyondTM: Phase 2 Study Design
Slide 64: Nimacimab – Target Product Profile
A new Generation of CB1 inhibitors Nimacimab – Target Product Profile Target Minimal Requirement Ideal Therapeutic Area Adults with BMI >30kg/m2 or >27 kg/m2 with co-morbidities Indications for Use For use as an adjunct to calorie diet and increased physical activity in chronic weight management. Do
Slide 65: Key Purposes of Nimacimab Phase 2 Clinical Trial Design
A new Generation of CB1 inhibitors Key Purposes of Nimacimab Phase 2 Clinical Trial Design Efficacy Proof of Concept • Demonstrate that “true” peripheral CB1R inhibition results in meaningful weight loss Combination Potential • Demonstrate that CB1R inhibitors, plus GLP-1R agonists, have additive/sy
Slide 66: CBeyond: A Phase 2 Study of Once Weekly Nimacimab
A new Generation of CB1 inhibitors CBeyond: A Phase 2 Study of Once Weekly Nimacimab Compared with Placebo and Once Weekly Nimacimab Co-administered with Semaglutide in Participants Who are Overweight or Obese Randomization Nimacimab 200 mg QW (N=40) 2:2:1:1 Placebo matching Nimacimab 200 mg QW (N=4
Slide 67: CBeyond Clinical Trial Objectives
A new Generation of CB1 inhibitors CBeyond Clinical Trial Objectives Overview of Phase 2 clinical trial objectives Primary Endpoint Secondary Endpoints Exploratory Endpoints • 40 subjects per arm between • Safety and tolerability • Evaluation of combination of Nimacimab and placebo is • Neuropsychia
Slide 68: Modeling Nimacimab Dosing for Phase 2 Study
A new Generation of CB1 inhibitors Modeling Nimacimab Dosing for Phase 2 Study PK modeling based on Nimacimab’s Phase 1 SC bioavailability study • Mean pharmacokinetic data from the 100 mg SC dose was simulated to predict concentrations that would achieve a target D dosing regimen beyond the IC90 •
Slide 69: Nimacimab Phase 2 Clinical Trial Design – Inclusion Criteria
A new Generation of CB1 inhibitors Nimacimab Phase 2 Clinical Trial Design – Inclusion Criteria Key Inclusion Criteria 1. Have Body Mass Index (BMI) of: a. ≥ 30 kg/m2 to ≤ 45 kg/m2 OR b. ≥ 27 kg/m2 and < 30 kg/m2 with clinically confirmed diagnosis of at least 1 of the following weight-related co-mo
Slide 70: Nimacimab Phase 2 Clinical Trial Design – Exclusion Criteria
A new Generation of CB1 inhibitors Nimacimab Phase 2 Clinical Trial Design – Exclusion Criteria Key Exclusion Criteria 1. Prior diagnosis of T1DM or T2DM, or rare forms of diabetes mellitus or laboratory value suggestive of diabetes during screening 2. Have a prior or planned surgical treatment for
Slide 71: Robust Plan to Evaluate Neuropsychiatric, Neurological Changes and Quality of Life
A new Generation of CB1 inhibitors Robust Plan to Evaluate Neuropsychiatric, Neurological Changes and Quality of Life Questionnaire/Test Purpose Columbia-Suicide Severity Rating Scale C-SSRS is a validated questionnaire that identifies whether someone is at risk for suicide, assess the (C-SSRS) seve
Slide 72: Secondary and Exploratory Endpoints
A new Generation of CB1 inhibitors Secondary and Exploratory Endpoints DEXA Scan for Body Composition Evaluation of OSA/Sleep Disturbance All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 72
Slide 73: Zepbound Includes OSA in Labeling Language
A new Generation of CB1 inhibitors Zepbound (tirzepatide) includes OSA in Labeling Language, with the Potential for OSA to be More Broadly Recognized as an Indication for GLP-1s • Chronic weight management in • Cardiovascular risk management in • Chronic weight management in adults with obesity or o
Slide 74: Clear Development Path for Nimacimab in Obesity
A new Generation of CB1 inhibitors Clear Development Path for Nimacimab in Obesity Our key milestones position for value generation 2024 2025 2026 2027 2028 Activity Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Ph2 interim Ph2 topline data data P2 POC study Clinical Ph2b topline P3 In
Slide 75: Nimacimab Subcutaneous Injection – Future Developments
A new Generation of CB1 inhibitors Nimacimab Subcutaneous Injection – Future Developments Phase 2 Phase 2b Commercial Future Pre-filled Syringe with Pre-filled Syringe with Auto-Injector with Safe Injection Unit Auto-Injector Unit Smart Technology Plan for future ease-of-use and implementation of te
Slide 76: Key Takeaways
A new Generation of CB1 inhibitors Key Takeaways Description Goal • Includes exploratory Nimacimab + semaglutide treatment arm Improve upon GLP-1 product profile; Treatment Arms • Designed to demonstrate the efficacy of multiple Nimacimab Facilitate treatment flexibility by offering treatment approa
Slide 77: Chapter 07: Panel Session and Q&A
Chapter 07 | Panel and Punit Dhillon Panel Session and Q&A
Slide 78: FAQs
A new Generation of CB1 inhibitors FAQs Key Question Response Section / Speaker Ensuring Safety and Tolerability in Nimacimab is peripherally restricted and does not show neuropsychiatric How is Nimacimab different than rimonabant? Peripheral CB1 Inhibition side effects; first generation CB1 agonist
Slide 79: Obesity Pipeline Overview
A new Generation of CB1 inhibitors Obesity Pipeline Overview Obesity Clinical Pipeline53 Number of Assets by Phase CB1 Inhibitor Key Pipeline Insights 2 additional CB1 inhibitors are in preclinical development - INV-347 (Phase 1) - INV-202 (Phase 2) - Nimacimab (Phase 2) • Obesity pipeline is primar
Slide 80: Audience Q+A
A new Generation of CB1 inhibitors Audience Q+A All drugs are investigational and subject to regulatory approval . © 2024 Skye Bioscience, Inc. 80
Slide 81: Chapter 08: Closing Remarks and Next Steps
Chapter 08 | Punit Dhillon Closing Remarks and Next Steps
Slide 82: Event Summary
A new Generation of CB1 inhibitors Event Summary Key points of today’s KOL discussion • NAM antibody blocks CB1 signaling independent of endocannabinoid binding • Functions as an antagonist (in presence of CB1 agonist with B-arrestin endpoint) and as an inverse agonist (twice as potent as rimonabant
Slide 83: Obesity Program: Planned Next Steps and Upcoming Milestones
A new Generation of CB1 inhibitors Obesity Program: Planned Next Steps and Upcoming Milestones Nimacimab’s Phase 2 trial is expected to initiate in Q3 2024, with interim data expected by Q2 2025 2024 Nimacimab obesity IND clearance – Q1 GMP Manufacturing to support future clinical trials – Initiated
Slide 84: Obesity Program: Path to Success
A new Generation of CB1 inhibitors Obesity Program: Path to Success Current AOM landscape and aspirational targets for Nimacimab Future Market Considerations • GLP-1 market saturation and generic entrants • Incretin therapies as the “backbone” • CB1 blockade being a monotherapy and additive to incre
Slide 85: Thank You
Thank You Learn more, please contact: 11250 El Camino Real, Suite 100 [email protected] +1 (858) 410-0266 San Diego, CA 92130 © 2024 Skye Bioscience, Inc.
Slide 86: Reference
A new Generation of CB1 inhibitors Reference 1. World Health Organization, 2022. Obesity 28. Sunyer et al., NEJM. 2015 2. Kaplan LM, 2023 29. FDA. Wegovy Website 3. Kaplan LM, 2024 30. Jastreboff et al., NEJM. 2022 4. Kaplan LM, 2012 31. Guggenheim Obesity Report 5. Sumithran P et al. N Engl J Med.