Skye Bioscience, Inc. · NASDAQ:SKYE
Skye Bioscience — Investor Day (October 2023)
90 slides from Skye Bioscience's investor day presentation, Oct 25, 2023
Slide 1: Skye Bioscience Investor Day
Skye Bioscience Investor Day CB1 Axis: Unlocking the Potential of the Endocannabinoid System October 25, 2023
Slide 2: Speakers
Speakers Skye Executive Management Punit Dhillon Tu Diep, MSc Chris Twitty, PhD Kaitlyn Arsenault, CPA CEO & Chairman Chief Development Officer Chief Scientific Officer Chief Financial Officer KOLs Sameh Mosaed, MD Brian Levy, OD Glenwood Gum, Ph.D. 2
Slide 3: Investor Day Agenda
Investor Day Agenda Presenter Corporate Strategy & Clinical Path forward Punit Dhillon | CEO Historical Perspectives of Cannabis/THC in Preclinical Research: Past Glenwood Gum, Ph.D. Challenges and Why it May Work Now SBI-100 OE Nonclinical Data and Biomarker Program Overview Pipeline & Research Upd
Slide 4: Safe Harbor and Forward-looking Statements
Safe Harbor and Forward-looking Statements Any discussion of the potential use or expected success of our product candidates is subject to our product candidates being approved by regulatory authorities. In addition, any discussion of clinical trial results for SBI-100 Ophthalmic Emulsion relates to
Slide 5: Corporate Strategy and Clinical Path Forward
Punit Dhillon, CEO & Chairman Corporate Strategy and Clinical Path Forward
Slide 6: 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 7: Highly Productive Clinical Development Strategy Optimized for Speed, Probability of Success
Highly Productive Clinical Development Strategy Optimized for Speed, Probability of Success Pipeline focused on CB1 axis and potential best-in-class molecules 1 In Three Years, Skye Bioscience… DERISKING Identify unmet need in validated • SBI-100 OE – Clinical formulation, IND, clinical targets deli
Slide 8: Strong Execution Track Record and Clear Clinical Path Forward
Strong Execution Track Record and Clear Clinical Path Forward 2021 2022 2023 2024 2025 Execution and advisory Australian Ethics Ph. 2a clinical trial protocol SBI-100 OE Ph. 2a interim Ph. 2 final readout for team buildout and Committee approval for approved from central readout glaucoma nimacimab c
Slide 9: CB1: High-potential Target for Physiological Regulation
CB1: High-potential Target for Physiological Regulation CB1 involved in many disease processes • CB1 (cannabinoid receptor 1) a renewed target of Inflammatory interest for drug discovery. • Modulation of CB1 signaling can impact key biological processes including: − Inflammatory, metabolic, fibrotic
Slide 10: 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 2023 2024 OPEX $16M1 $25M2 Activity Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 NIMACIMAB Nimacimab Ph. 2 ready asset acquired Cardio-Metabolic Indication Phase 2 through Bird Rock Bio acquisi
Slide 11: Nimacimab
Investor Day Q1 2024 Nimacimab Novel CB1-targeting mAb therapeutic MOA Disease R&D Phase 1 Phase 2 NIMACIMAB CB1 Receptor Inhibitor Cardio-Metabolic Sub-cutaneous Indication Phase 2 ready molecule with three open INDs. Best–in-class and Only CB1 negative allosteric modulating humanized monoclonal an
Slide 12: SBI-100 Ophthalmic Emulsion
Investor Day Q4 2023 SBI-100 Ophthalmic Emulsion Improving CB1-targeting drug design for glaucoma MOA Disease R&D Phase 1 Phase 2 SBI-100 OE CB1 Receptor Agonist Glaucoma Topical Best–in-class and First/only prodrug of THC developed and currently in the clinic for glaucoma. Only-in-class Molecules L
Slide 13: Historical Perspectives of Cannabis/THC in Preclinical Research
Historical Perspectives of Cannabis/THC in Preclinical Research: Past Challenges and Why it May Work Now
Slide 14: Cannabinoids for Glaucoma
Cannabinoids for Glaucoma October 25, 2023 Dr. Glenwood Gum, MS, PhD Ophthalmology Department: Pharmaron (US Lab) Services, San Diego
Slide 15: Early Studies with Cannabinoids
Early Studies with Cannabinoids ○ Early systemic studies with cannabinoids assumed the decrease in IOP effects was centrally derived1 ○ Mid 1970s studies in rabbits noted an increase in aqueous outflow through the Trabecular Meshwork2,3 ○ Different cannabinoid derivatives were tested for their abili
Slide 16: Cannabinoids in the Normotensive and Glaucomatous Beagles
Cannabinoids in the Normotensive and Glaucomatous Beagles University of Florida College of Veterinary Medicine • Dr.s Kirk N. Gelatt and Glenwood G. Gum tested a ∆ 9- tetrahydrocannabinol (THC) compound in the glaucoma dog model Formulation (supplied from Federal agency) 2% ∆ 9- tetrahydrocannabinol
Slide 17: Glaucomatous Beagle Results Similar to Other Canine Studies
Glaucomatous Beagle Results Similar to Other Canine Studies Scatterplot showing the percentage change from baseline (pretreatment) values in evening (5:00 pm) IOPs following topical administration of a 2% THC ophthalmic solution in 16 clinically normal adult dogs. Each diamond represents the value f
Slide 18: Possible Reasons why Δ9-THC was not Successful in Glaucomatous Beagles
Possible Reasons why ∆ 9- THC was not Successful in the Glaucomatous Beagles Problems with the formulation was the largest concern • Being an oily formulation, pipetting was more difficult than other glaucoma compounds • Light sensitivity with ∆ 9- THC formulation, required amber vials for protectio
Slide 19: Other Glaucoma Drug Development at the Time
Other Glaucoma Drug Development at the Time All of the following glaucoma drugs, including older marketed drugs, were effective in the glaucomatous beagle model • Beta blockers (Timolol) • Topical carbonic anhydrase inhibitors (Tom Maren, University of Florida, Depart. Pharmacology) • Alpha adrenerg
Slide 20: PGF2α Effects in the Normotensive and Glaucomatous Beagles
PGF2α Effects in the Normotensive and Glaucomatous Beagles Bito LZ, Camras CB, Gum GG, Resul B. The ocular hypotensive effects and side effects of prostaglandins on the eyes of experimental animals. The ocular effects of prostaglandins and other eicosanoids, Alan R. Liss, Inc., NT 1989, 349-368 20
Slide 21: New Role of Cannabinoids as Neuroprotection in Glaucoma
New Role of Cannabinoids as Neuroprotection in Glaucoma Rapino C, Tortolani D, Scipioni L, Maccarrone M. Neuroprotection by (Endo) Cannabinoids in Glaucoma and Retinal Neurodegenerative 21 Diseases. Curr NeurophRMacology 2018,16, 959-970.
Slide 22: In Vivo Ocular Modalities
In Vivo Ocular Modalities New imaging modalities added are Heidelberg Anterion and HRT3 RCM, Zeiss CLARUS fundus camera, and available OcuMetrics 22 Fluorotron. The Pharmaron Ophthalmology team has many decades of experience in glaucoma research and develpoment.
Slide 23: Microbeads Model can be Used to Test Cannabinoid Neuroprotection
Microbeads Model can be Used to Test Cannabinoid Neuroprotection 23
Slide 24: Thank you!
Question: where do cannabinoids fit in the crowded market of glaucoma drugs? Thank you ! 24
Slide 25: Nonclinical Data and Biomarker Program Overview
SBI-100 OE: Pipeline and Research Update Nonclinical Data and Biomarker Program Overview
Slide 26: 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 CB1 is expressed in key ocular tissues and its engagement1: relevant mechanisms to support the use of can
Slide 27: 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 Tetrahydrocannabinol (THC) soluble and has poor bioavailability. Improves solubility,
Slide 28: Prodrug Strategy Enhances Ocular Biodistribution of THC
Prodrug Strategy Enhances Ocular Biodistribution of THC THC amino dicarboxylic acid prodrugs further enhance bioavailability • Different prodrug strategies were functionally evaluated in vitro and in vivo • Solubility, stability and bioavailability were associated with control of IOP Increased perme
Slide 29: SBI-100 OE Demonstrates Superior IOP Lowering
SBI-100 OE Demonstrates Superior IOP Lowering Nonclinical studies highlight favorable comparison with standard of care drugs 20 Timolol 25 Latanoprost SBI-100 18 IOP (mmHg) IOP (mmHg) 20 16 Latanoprost SBI-100 Rhopressa 14 SBI-100 + Rhopressa 15 0 3 6 9 0 3 6 9 12 15 18 21 24 Hours Hours SBI-100 dem
Slide 30: Human Trabecular Meshwork Model Highlights Key Mechanism of Action
Human Trabecular Meshwork Model Highlights Key Mechanism of Action Measuring outflow facility via trabecular Reduced markers of inflammation & fibrosis meshwork • Significant reduction in fibrotic and inflammatory • Both human 3D models demonstrated a significant proteins after 6 days of treatment i
Slide 31: Potential Neuroprotective Benefits with SBI-100
Potential Neuroprotective Benefits with SBI-100 Additional complementary therapeutic mechanism to address associated neuropathy Biodistribution studies demonstrated Glaucoma: Without Introduction of THC the presence of SBI-100 OE in the back of the eye Glutamate release Vasoconstriction Inflammation
Slide 32: Clinical Biomarker Program to Support SBI-100 OE
Clinical Biomarker Program to Support SBI-100 OE Analyses of immunological and neuroprotective markers in tear and blood components Serum/Tear Analyses • Multiplex proteomics Unlike a typical biomarker • Olink - target 96 inflammation/neurology panels program, our rationale is not to • Cytokine anal
Slide 33: Near-term R&D Efforts Support Pipeline Development
Near-term R&D Efforts Support Pipeline Development Glaucoma • Biomarker program: analysis of bio-samples from Ph2 glaucoma clinical trial • Preclinical studies to further SBI-100 development • Combination studies with 1L/2L glaucoma drugs in normotensive and glaucomatous models • Mechanistic studies
Slide 34: Phase 1 Clinical Data and Phase 2 Update
SBI-100 OE: Development Plan for Glaucoma and Ocular Hypertension Phase 1 Clinical Data and Phase 2 Update
Slide 35: Overview
Overview Phase 1 Study Design, Purpose and Rationale Inclusion/Exclusion Criteria Safety Assessments SAD/MAD Safety Data PK Data Intraocular Pressure Analysis Phase 2a Study and Next Steps 35
Slide 36: History and Safety of THC/Cannabis
History and Safety of THC/Cannabis Dronabinol/THC • Marinol (dronabinol) approved in 1985 for use Common Side Effects Potential Serious Adverse Effects anorexia associated weight loss in patients with Nausea and vomiting Seizures AIDS and nausea and vomiting associated with Anxiety Fainting chemothe
Slide 37: History of Cannabis in Glaucoma
LEGEND Inhalation studies History of Cannabis in Glaucoma Oral studies Eye drop studies Since 2021 Skye has rapidly progressed SBI-100 OE into the clinic Skye and new management Oral THC derivative First report that smoking cannabis SBI-100 reduces IOP by up to can reduce intraocular pressure discov
Slide 38: Clinical Trial Design– SAD/MAD Randomized Placebo-Controlled
Clinical Trial Design– SAD/MAD Randomized Placebo-Controlled • 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 Emulsion relati
Slide 39: Dose Escalation Scheme
Dose Escalation Scheme Number of Participants Cohort Dose Level & Frequency (N) A1 (SAD) 1 single dose (1 drop) in right eye of 5.0 mg/mL (0.5%) 8 A2 (SAD) 1 single dose (1 drop) in right eye of 10.0 mg/mL (1.0%) 8 A3 (SAD) 1 single dose (1 drop) in right eye of 20.0 mg/mL (2.0%) 8 B1 (MAD) 5 days x
Slide 40: Pharmacokinetics – Dosing and PK Sampling Plan
Pharmacokinetics – Dosing and PK Sampling Plan Plasma samples analyzed for SBI-100, THC and 11-OH-THC 5 min 30 min 1 hr SAD PK 4 hr 24 hr Anytime Sampling Pre-dose 15 min 8 hr 12 hr Schedule Day 1 Day 2 EOS Dose 2 hr 6 hr SAME AS SAME AS 24 hours from DAY 1 SAD DAY 1 Dose 10 12 hours from 36 hours f
Slide 41: Key Inclusion Criteria
Key Inclusion Criteria 1. Male or female, 18 to 60 years of age at screening. 2. IOP as measured by iCare tonometer in each eye of ≥ 10 to ≤ 21 mmHg with a difference of ≤ 3 mmHg between each eye at screening and Day -1 (pre-dose). 3. Central corneal thickness in each eye ≥ 500 µm and ≤ 600 µm as me
Slide 42: Key Exclusion Criteria
Key Exclusion Criteria 1. Unable to discontinue contact lens use during study visits including confinement at the study site. 2. Previous ocular surgery: glaucoma surgery, glaucoma laser procedures, cataract or refractive surgery (e.g., radial keratotomy, photorefractive keratectomy, or laser in sit
Slide 43: Ocular Assessments – Slit Lamp
Ocular Assessments – Slit Lamp Evaluation of anterior segment of the eye: • Lids • Cornea • Conjunctiva • Anterior chamber • Iris • Lens • Posterior capsule For investor audiences only. 43
Slide 44: Ocular Assessments – Conjunctival Hyperaemia
Ocular Assessments – Conjunctival Hyperaemia Conjunctival hyperaemia was assessed using the Efron grading scale1. Efron Grading Scales for Contact Lens Complications Hyperaemia is one of the main reasons that patients stop treatment. Hyperaemia results in increased overall costs for patients, almost
Slide 45: Ocular Assessments – IOP, Visual Acuity, Visual Field, Pupil Diameter and OCT
Ocular Assessments – IOP, Visual Acuity, Visual Field, Pupil Diameter and Oct Optical Coherence Visual Acuity Visual Field Intraocular Pressure Pupil Diameter Tomography (OCT) For investor audiences only. 45
Slide 46: Clinical Trial Partners
Clinical Trial Partners Partner Role Ophthalmology assessments IP management/pharmacy – Royal Adelaide Hospital Pharmacy Local laboratory Pharmacokinetic analysis Shipping and courier services Data management and biostats Contract research organization Phase 1 clinical research unit For investor aud
Slide 47: Patient Demographics - SAD
Patient Demographics - SAD SBI-100 Ophthalmic Emulsion Single Ascending Dose (SAD) SBI-100 0.5% SBI-100 1% SBI-100 2% SAD Placebo SAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Sex Male 0 4 (66.7%) 1 (16.7%) 4 (66.7%) 9 (37.5%) Female 6 (100%) 2 (33.3%) 5 (83.3%) 2 (33.3%) 15 (62.5%) Age Mean (SD) 32.5
Slide 48: Treatment Emergent Adverse Events – by System Organ Class SAD
Treatment Emergent Adverse Events – by System Organ Class SAD Non-Ocular TEAEs by MedDRA Ocular TEAEs by MedDRA System System Organ Class and Preferred Organ Class and Preferred Term Term SYSTEM ORGAN CLASS SAD Placebo SAD Overall SYSTEM ORGAN CLASS SAD Placebo SAD Overall PREFERRED TERM (N=6) (N=24
Slide 49: Patient Demographics - MAD
Patient Demographics - MAD SBI-100 Ophthalmic Emulsion Multiple Ascending Dose (MAD) SBI-100 0.5% SBI-100 1% SBI-100 2% MAD Placebo MAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Sex Male 4 (66.7%) 3 (50.0%) 5 (83.3%) 5 (83.3%) 17 (70.8%) Female 2 (33.3%) 3 (50.0%) 1 (16.7%) 1 (16.7%) 7 (29.2%) Age Mean
Slide 50: Treatment Emergent Adverse Events – by System Organ Class MAD
Treatment Emergent Adverse Events – by System Organ Class MAD Non-Ocular TEAEs by MedDRA Ocular TEAEs by MedDRA System System Organ Class and Preferred Organ Class and Preferred Term Term SYSTEM ORGAN CLASS MAD Placebo MAD Overall SYSTEM ORGAN CLASS MAD Placebo MAD Overall PREFERRED TERM (N=6) (N=24
Slide 51: SBI-100 OE Demonstrates Significantly Less Hyperaemia Compared to Other Therapies
SBI-100 OE Demonstrates Significantly Less Hyperaemia Compared to Other Therapies Incidence of Hyperaemia in Currently Approved Drugs vs. SBI-100 OE Latanoprost 16.5% Travoprost 33% Rhopressa SBI-100 OE 53% <10% Bimatoprost 40% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% For investor audiences only. Ho
Slide 52: MAD 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 None Discomfort Score 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 Post-
Slide 53: 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 54: 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 55: 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
Slide 56: SBI-100 OE: Phase 1 Safety Clinical Data Summary
SBI-100 OE: Phase 1 Safety Clinical 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 o
Slide 57: SBI-100 OE Phase 2A Glaucoma Proof-of-Concept Study
SBI-100 OE Phase 2A 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 Double-masked, for POAG or OHT placebo- Cohort 1 controlled 0.5 % BID
Slide 58: SBI-100 OE – Target Product Profile
SBI-100 OE – Target Product Profile POPULATION MECHANISM OF ACTION DOSING & ADMINISTRATION Treatment to lower IOP in patients with ocular hypertension and primary open-angle CB-1 receptor agonist Single topical drop once per day glaucoma following recurrence or failure with first-line therapy PIVOTA
Slide 59: SBI-100 OE Next Steps – Roadmap to Commercialization
SBI-100 OE Next Steps – Roadmap to Commercialization 2024 Phase 2a 3-month Manufacturing Phase 2b Proof-of-concept and Toxicology Study Optimization and 3-month Dose Optimization Dose Ranging Study Scale-up Study Against Active Control (Once per day dosing) End of 2025 Manufacturing 6-month Phase 2
Slide 60: Physician's Commercial Perspective
SBI-100 OE: Treatment Paradigm and Clinical Data Physician’s Commercial Perspective
Slide 61: Challenges in Treating Glaucoma
Challenges in Treating Glaucoma Treatments Current State Key Unmet Needs in Glaucoma KOLs view current treatments as satisfactory; overall compliance is Patient Adherence: Patient adherence/compliance is a significant hurdle facing a problem regardless of IOP effective chronic treatment; greater adh
Slide 62: Key Opportunities for SBI-100 OE
Key Opportunities for SBI-100 OE 1. Targets the tissue of disease PGA Market Non-PGA Market • Current medications either: – Inhibit aqueous production from the ciliary body: beta- blockers and carbonic anhydrase inhibitors – Increase uveosceral outflow (secondary physiological outflow): prostaglandi
Slide 63: Challenges in Treating Patients with Glaucoma
Challenges in Treating Patients with Glaucoma Achieving and maintaining effective IOP lowering (20-30%) from baseline with existing medications: • Magnitude of IOP reduction is often titrated by disease severity and benefit/risk of desired treatment. • The more severe the disease the more aggressive
Slide 64: SBI-100 – Encouraging Phase 1 Results
SBI-100 – Encouraging Phase 1 Results • Directed at primary site of pathology • Trabecular meshwork • Early signs of beneficial safety profile over currently Trabecular meshwork available therapies blocked • Low incidence of hyperemia • No systemic side effects • Encouraging IOP lowering effects fro
Slide 65: Current Treatment Paradigm
Current Treatment Paradigm Treatment Paradigm Prostaglandin Depending on data SBI-100 OE Selective Laser Analogue (PGA) could potentially be 1L therapy 1L Trabeculoplasty (SLT) (e.g. latanoprost) PGA + Added Agent Strong safety data and competitive (Added agents: beta blocker, carbonic anhydrase inh
Slide 66: Summary
Summary • SBI-100 OE is well positioned to become a favored option in patients with glaucoma and ocular hypertension. • Safety data from Phase 1 study shows that the drug is well-tolerated and currently does not present with either ocular or systemic side effects that would hinder future commercial
Slide 67: Market Opportunity and Positioning
SBI-100 OE: KOL Feedback for Glaucoma and Ocular Hypertension Market Opportunity and Positioning
Slide 68: Targeting Glaucoma (POAG & OH): Large Market, Unmet Needs
Targeting Glaucoma (POAG & OH): Large Market, Unmet Needs World’s leading cause of irreversible blindness $7B drug market worldwide MARKET LACKS INNOVATION predominantly using legacy classes of drugs and generic compounds. ~60M patients worldwide 1% ROCK Inhibitor 7% ~110M patients by 2026 Carbonic
Slide 69: Current Annual Price of Pharmacologic Products
Current Annual Price of Pharmacologic Products Marketed branded agents for the treatment of glaucoma are priced at <$3 K annually in the U.S. SBI-100 OE: Competitive product profile with significant market opportunity Travatan Z (travoprost) Lumigan (bimatoprost) Rocklatan Current Pricing Landscape
Slide 70: Pharmacologic Treatment Rate in POAG and OH
Pharmacologic Treatment Rate in POAG and OH Most patients, regardless of severity, are prescribed pharmacologic treatment to halt disease progression Pharmacologic Treatment Pharmacologic Treatment Rate* • Regardless of severity, pharmacologic treatment is commonplace (80 – 90%) in patients with POA
Slide 71: Current Treatment Paradigm for Glaucoma
Current Treatment Paradigm for Glaucoma Treatment Paradigm Once ocular hypertension progresses to the point of requiring treatment, PGA IOP-lowering monotherapy becomes the dominant 1L treatment option Prostaglandin Selective Laser Analogue (PGA) 1L Trabeculoplasty (SLT) First-line treatment can eit
Slide 72: 2L+ Pharmacologic Treatment in POAG and OH
2L+ Pharmacologic Treatment in POAG and OH In 2L+, KOLs report adding a pharmacologic treatment (e.g., beta blocker) to the existing PGA regimen Second Line and Beyond (2L+) Pharmacologic Treatment in POAG POAG 2L+ Pharmacologic Utilization by Class • The likelihood of progressing past 1L is directl
Slide 73: Potential Future Treatment Paradigm – SBI-100 OE
Potential Future Treatment Paradigm – SBI-100 OE KOLs expect patients will receive SBI-100 OE in 2L in monotherapy • SBI-100 OE has the potential to be used by some physicians as a first line SLT PGA treatment option, but payor access restrictions are expected to limit 1L use (e.g., 1L (sporadically
Slide 74: SBI-100 OE: Potential to Fulfill Clinical Unmet Needs
SBI-100 OE: Potential to Fulfill Clinical Unmet Needs Key Unmet Needs in Glaucoma Following initial approval of Patient Adherence: Patient adherence is a significant hurdle KOLs face when topical drug format, Skye would providing effective long-term care; greater adherence with current pharmacologic
Slide 75: Physician Feedback About SBI-100 OE
Physician Feedback About SBI-100 OE New drug with novel mechanism of action would be well-accepted by physicians “I have conducted extensive “Patients that are intolerant to Mechanism of research about [SBI-100’s] Market Opportunity “A lot of patients are going to be PGA therapy are subjected to Act
Slide 76: Market Analysis Summary
Market Analysis Summary Eye care providers: high level of excitement about CB1 agonist and class of drugs Glaucoma still facing significant unmet need UNMET NEED • Patient adherence, improved second-line therapies, novel mechanisms of action and neuroprotective benefits are seen as key unmet needs i
Slide 77: SBI-100 OE: Phase 1 Safety Clinical Data Summary
SBI-100 OE: Phase 1 Safety Clinical 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 o
Slide 78: Skye Next Steps
Skye Next Steps • Advance nimacimab clinical trials with longer-term view toward franchise expansion • Achieve SBI-100 Ophthalmic Emulsion/glaucoma proof-of-concept milestone • Maintain focused operational and clinical development strategy • Selectively evaluate business development opportunities to
Slide 79: Q&A Session
skye’ Q&A Session
Slide 80: Convergence of Right Space, Technology and Team
Convergence of Right Space, Technology and Team Two clinical stage Phase 2 first- and only-in class pharmaceuticals in development, targeting the endocannabinoid system, ENDOCANNABINOIDS a renewed area of interest through next generation engineering. Lead asset acquired through transformational Bird
Slide 81: 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 Offi
Slide 82: Thank you to the patients, clinical trial investigators and operations staff
Thank you to the patients, clinical trial investigators and operations staff who participate in our research programs Learn more, please contact: ir@skyebioscience.com, +1 (858) 410-0266
Slide 83: Appendix
skye’ Appendix
Slide 84: Treatment Emergent Adverse Events (TEAE) – SAD Overall
Treatment Emergent Adverse Events (TEAE) – SAD Overall SBI-100 Ophthalmic Emulsion SAD Ascending Dose (SAD) SBI-100 0.5% SBI-100 1% SBI-100 2% SAD Placebo SAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Total Number of TEAEs 7 9 14 8 38 Total Number of TESAEs 0 0 0 0 0 Number (%) Participants Reporting a
Slide 85: Treatment Emergent Adverse Events – SAD Ocular
Treatment Emergent Adverse Events – SAD Ocular SBI-100 Ophthalmic Emulsion SAD Ascending Dose (SAD) SBI-100 0.5% SBI-100 1% SBI-100 2% SAD Placebo SAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Total Number of TEAEs 6 7 10 7 30 Total Number of TESAEs 0 0 0 0 0 Number (%) Participants Reporting at Least
Slide 86: Treatment Emergent Adverse Events – SAD Non-ocular
Treatment Emergent Adverse Events – SAD Non-ocular SBI-100 Ophthalmic Emulsion SAD Ascending Dose (SAD) SBI-100 0.5% SBI-100 1% SBI-100 2% SAD Placebo SAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Total Number of TEAEs 1 2 4 1 8 Total Number of TESAEs 0 0 0 0 0 Number (%) Participants Reporting at Leas
Slide 87: Treatment Emergent Adverse Events (TEAE) – MAD Overall
Treatment Emergent Adverse Events (TEAE) – MAD Overall SBI-100 Ophthalmic Emulsion MAD Ascending Dose (MAD) SBI-100 0.5% SBI-100 1% SBI-100 2% MAD Placebo MAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Total Number of TEAEs 28 53 68 19 168 Total Number of TESAEs 0 0 0 0 0 Number (%) Participants Reporti
Slide 88: Treatment Emergent Adverse Events – MAD Ocular
Treatment Emergent Adverse Events – MAD Ocular SBI-100 Ophthalmic Emulsion MAD Ascending Dose (MAD) SBI-100 0.5% SBI-100 1% SBI-100 2% MAD Placebo MAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Total Number of TEAEs 24 41 65 16 146 Total Number of TESAEs 0 0 0 0 0 Number (%) Participants Reporting at Le
Slide 89: Treatment Emergent Adverse Events – MAD Non-Ocular
Treatment Emergent Adverse Events – MAD Non-Ocular SBI-100 Ophthalmic Emulsion MAD Ascending Dose (MAD) SBI-100 0.5% SBI-100 1% SBI-100 2% MAD Placebo MAD Overall (N=6) (N=6) (N=6) (N=6) (N=24) Total Number of TEAEs 4 12 3 3 22 Total Number of TESAEs 0 0 0 0 0 Number (%) Participants Reporting at Le
Slide 90: Competitive Drug Pipeline
Competitive Drug Pipeline The clinical competitive pipeline is primarily made up of prostaglandin analogues and beta blockers Prostaglandins Phase 1 PolyActiva AGN-193408 60% of programs are Phase 2 prostaglandin analogs JeniVision AbbVie AGN-193408 JV-GL1 < 20% clinical stage Amneal programs are no