VYNE Therapeutics Inc. · NASDAQ:VYNE
VYNE Therapeutics — Investor Day (November 2023)
53 slides from VYNE Therapeutics's investor day presentation, Nov 9, 2023
Slide 1: R&D Day
%VYNE THERAPEUTICS R&D Day November 9, 2023 ROOTED IN INNOVATION
Slide 2: Forward Looking Statements and Important Notes
Forward Looking Statements and Important Notes This presentation by VYNE Therapeutics Inc. (“VYNE”) includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 including, but not limited to, statements regarding VYNE’s plans, regulatory filings and
Slide 3: Welcome
Welcome Topic Speaker Timing Intro David Domzalski, President and Chief Executive Officer 5 mins Vitiligo Background, Treatment Dr. Amit Pandya, former President of the Global Vitiligo Foundation Landscape & Unmet Need and Staff Dermatologist, Department of Dermatology, Palo Alto 15 mins Foundation
Slide 4: Investment Highlights
Investment Highlights (NASDAQ: VYNE) Advancing novel BET inhibitor platform to improve the lives of patients suffering from immuno-inflammatory conditions Innovative • BET inhibition represents a novel target for the treatment of autoimmune diseases: Addressing the complex signaling of immuno-inflam
Slide 5: VYNE's Drug Design Strategy
VYNE’s Drug Design Strategy Optimize benefit/risk profile of BET inhibitors to target autoimmune diseases VYN201 VYN202 Pan-BD BET Inhibitor BD2-Selective BET Inhibitor Maximize local effect & Improve efficacy and tolerability minimize systemic exposure through BD2-selectivity • Tissue targeted admi
Slide 6: VYN201: Vitiligo
VYN201: Vitiligo eV YNE’
Slide 7: Vitiligo Represents a Large and Growing Market Opportunity
Vitiligo Represents a Large and Growing Market Opportunity Addressable Market $ in millions Est. 0.3M to 0.45M patients seeking treatment • Market penetration: Opzelura is the 1.9M only product approved for treatment $725 of vitiligo • Patient activation represents large Annualized vitiligo net long
Slide 8: BET Inhibition – A Differentiated Treatment Strategy for Non-Segmental Vitiligo
BET Inhibition – A Differentiated Treatment Strategy for Non-Segmental Vitiligo Fully expressed BET Inhibition (VYN201) cytokine • BET proteins recognize (“read”) JAK-STAT acetylated lysine on the termini of Pathway histones that protrude from chromatin. NF-Κb complex signal transduction • BET inhib
Slide 9: VYN201: Preclinical Data
VYN201: Preclinical Data eV YNE’
Slide 10: Pathogenesis of Vitiligo is Primarily Linked to CD8+ T-Cell Proliferation and Hyperactivity
Pathogenesis of Vitiligo is Primarily Linked to CD8+ T-Cell Proliferation and Hyperactivity VYN201 has demonstrated marked inhibition of CD8+ t-cell expansion and activity at levels favorable to ruxolitinib CD8+ T-cell Proliferation CD8+ T-cell Activation Marker IFNγ CD8+ T-cell Viability 120 120 VY
Slide 11: VYN201: Human Tissue Model of Vitiligo
VYN201: Human Tissue Model of Vitiligo Demonstrated reduction in melanocyte loss and lowering of key inflammatory biomarkers VYN201 1% reduced the secretion of MMP9 relative VYN201 substantially prevents the loss of melanin to stimulated vehicle, and numerically superior to VYN201 affects a dose-dep
Slide 12: VYN201: Human Tissue Model of Vitiligo
VYN201: Human Tissue Model of Vitiligo VYN201 prevents melanocyte detachment, down regulates the expression of key cytokines and upregulates WNT pathway Stimulated and VYN201 1% treated Melanocyte detachment / migration Clear evidence of melanocyte Vehicle treated adhesion disruption, melanocyte det
Slide 13: VYN201: Phase 1 Proof-of-Concept
VYN201: Phase 1 Proof-of-Concept
Slide 14: VYN201: Phase 1b Study in Active Vitiligo Patients
VYN201: Phase 1b Study in Active Vitiligo Patients StudyStudy Design Design: Treatment on the face and target lesion on trunk of active vitiligo patients for up to 16 weeks of QD treatment • N = up to 30: 3 cohorts, evaluating 0.5%, 1.0% and 2.0% strengths • Safety assessments include TEAEs, pharmac
Slide 15: Vitiligo Disease Activity within PoC Study Designs
Vitiligo Disease Activity within PoC Study Designs Patients with Active Disease Will Continue to Depigment Patient Population and Asset Development Status in Areas that Show High Activity without Therapy5 Disease Activity Status VYN201 P1b • PoC achieved • Active Only (VYNE) • Phase 1b completed • P
Slide 16: Baseline Demographic and Clinical Characteristics
Baseline Demographic and Clinical Characteristics 0.5% Cohort 1% Cohort 2% Cohort Total (N=10) (N=10) (N=9) (N=29) Age - year mean 49.2 53.2 56.8 52.9 Age group - no. / % 0 0% 0 0% 0 0% 0 0% 12-17 0 0% 0 0% 0 0% 0 0% 18-64 9 90% 8 80% 8 89% 25 86% >=65 1 10% 2 20% 1 11% 4 14% Female sex - no. / % 6
Slide 17: Promising Onset of Action and F-VASI Response
Promising Onset of Action and F-VASI Response VYN201 Phase 1b: QD Treatment in 100% active disease study population 0% 90% Individual Subject F-VASI Response Week 16 -5% 80% -7.5% F-VASI75 -10% 70% Mean % CFB in F-VASI -15% 60% (p = 0.0138 vs. VYN201 0.5%)* -20% F-VASI50 50% % CFB in F-VASI (Improve
Slide 18: Demonstrated Competitive Efficacy at 16 Weeks vs. JAK Class at 24 Weeks
Demonstrated Competitive Efficacy at 16 Weeks vs. JAK Class at 24 Weeks VYN201 Phase 1b: QD Treatment in 100% active disease study population 0.0% JAK Class (P2b) Week 24 data -5.0% -7.5% -10.0% Mean % CFB in F-VASI -15.0% Litfulo -18.5% -20.0% -25.0% -30.0% -30.2% Rinvoq Povorcitinib -35.6% -35.0%
Slide 19: Preclinical & Clinical Data Highlight Potential for Differentiated Product Profile
Preclinical & Clinical Data Highlight Potential for Differentiated Product Profile VYN201 Opzelura Litfulo Povorcitinib Characteristic (Ruxolitinib) (Ritlecitinib) 45mg2 1% 2% Cream 1.5% 50mg1 Novel MOA / JAK Class Alternative Targeted Dosing Posology QD BID QD QD Rapid Onset of Action Moderate Mode
Slide 20: Phase 1b Select Images
Phase 1b Select Images Subject with near-complete depigmentation (High FVASI) Baseline Week 16 (0.5% cohort, Fitzpatrick skin type: 5) 20
Slide 21: Phase 1b Select Images
Confidential Phase 1b Select Images Subject with significant repigmentation response Baseline Week 16 (2.0% cohort, Fitzpatrick skin type: 2) 21
Slide 22: Phase 1b Select Images
Confidential Phase 1b Select Images Subject examples with marked active disease Confetti-like depigmentation presentation Inflamed vitiligo presentation Baseline Baseline Week 16 Week 16 (1.0% cohort, Fitzpatrick skin type: 6) (2.0% cohort, Fitzpatrick skin type: 5) 22
Slide 23: Demonstrated Favorable Safety & Tolerability Profile
Demonstrated Favorable Safety & Tolerability Profile Adverse Events Local Skin Tolerability Mean Score No serious adverse events reported Assessment Range 0 (None) to 3 (Severe) Burning/Stinging 0.26 No treatment related discontinuations Scaling 0.15 Dryness 0.22 All treatment emergent adverse event
Slide 24: VYN201 Phase 1b: Low Systemic Exposure in Vitiligo Subjects
VYN201 Phase 1b: Low Systemic Exposure in Vitiligo Subjects Correlates with No Impact on Platelet Counts Available data for treatment up to 16 weeks supports “soft” drug approach for topical pan-BD BET inhibitor 500 1000 Free EC50 450 BD1 Log VYN201 plasma concentration (ng/ml) 100 ULN BRD4 400 (400
Slide 25: Key Takeaways from VYN201 Phase 1b Results
Key Takeaways from VYN201 Phase 1b Results • Significant clinical response shown with rapid onset of action • Clear evidence of dose response • Efficacy data suggest potential to be category leader • Favorable efficacy results and onset of action compared with the JAK competitive landscape in a more
Slide 26: VYN201 Phase 2b Study Design Summary
VYN201 Phase 2b Study Design Summary Randomized, double-blinded, vehicle-controlled Phase 2b trial with separate active treatment extension phase evaluating the efficacy, safety & pharmacokinetics of VYN201 in the treatment of non-segmental vitiligo Trial size: N=~150 to 200 patients with non-segmen
Slide 27: VYN202: BD2 selective BET inhibitor
VYN202: BD2 selective BET inhibitor
Slide 28: VYNE's Drug Design Strategy
VYNE’s Drug Design Strategy Optimize benefit/risk profile of BET inhibitors to target autoimmune diseases VYN201 VYN202 Pan-BD BET Inhibitor BD2-Selective BET Inhibitor Maximize local effect & Improve efficacy and tolerability minimize systemic exposure through BD2-selectivity • Tissue targeted admi
Slide 29: Maximizing On-target Potency vs. BD2 and Minimizing Affinity to BD1
Maximizing On-target Potency vs. BD2 and Minimizing Affinity to BD1 May Be The Key to Optimizing the Benefit/Risk Profile of BET Inhibitors for Autoimmune Diseases VYN202 is believed to be the most potent and BD2-selective BET Inhibitor in development1 which is designed to improve efficacy and toler
Slide 30: Strategies to Control Dysregulated TH17 Immune Cell Activity
Strategies to Control Dysregulated TH17 Immune Cell Activity Inhibitors of TH17 cell differentiation (risankizumab, tildrakizumab, guselkumab, ustekinumab) Existing strategies target: Naïve TH0 cell TH17 cell • Extracellular cytokines IL-6, TGF-β1, IL-1, IL-23 IL-21 IL-22 • Cytokine receptor inhibit
Slide 31: BET Inhibitors Disrupt Inflammatory Gene Transcription in T Cells
BET Inhibitors Disrupt Inflammatory Gene Transcription in T Cells to Directly Address the Complex Signaling of Immuno- & Fibro-inflammatory Diseases Fully expressed cytokine NF-Κb complex signal transduction Translation Transcription machinery ACTIVE gene BET INHIBITION 1 Clinical PoC of BET Transcr
Slide 32: Demonstrated Potency Against Th17 Cytokines
Demonstrated Potency Against Th17 Cytokines VYN202 Potency vs. IL-17A compares favorably to Secukinumab and DC-806 VYN202 Potency vs. IL-17A Therapeutic Agent IC50IL17A (nM) BA83_IL17 VYN202 (VYNE) 0.27 100 Secukinumab (Cosentyx - NVS): 0.37 80 Percent inhibition DC-806 (DICE/LLY) 5.7 60 40 20 0 -6
Slide 33: Minimal Inhibition on Key Innate Immune Chemokine Demonstrates Selectivity
Minimal Inhibition on Key Innate Immune Chemokine Demonstrates Selectivity of Cytokine Expression (IL-17A and IL-22 vs. CXCL10) Cytokine VYN202 IC50 (nM) Selectivity vs. CXCL10 • VYN202 significantly more potent against Th17 Cytokines vs. CXCL10 IL-17A 0.27 >13,000 • CXCL10 interacts with CXCR3 to a
Slide 34: Preclinical Safety Data
Preclinical Safety Data eV YNE’
Slide 35: Dog Toxicokinetics & Effect on Hematopoietic system
Dog Toxicokinetics & Effect on Hematopoietic system • VYN202 exposure significantly above free EC50BD2 BRD4 at 1,3 & 10mg/kg QD for 24 hours • No effect on platelet counts VYN202 Exposure after 14 Days of Treatment Effect of VYN202 on Platelet Counts at 1, 3 and 10mg/kg QD PO (Day 15) 100000 500 EC5
Slide 36: Effect on Gastrointestinal (GI) System
Effect on Gastrointestinal (GI) System Compared to pan-BD BET inhibitors Oral pan-BD BET inhibitors (like ABBV-075) are Treatment with BD2 selective VYN202 had no effect on GI villus morphology or goblet cell number known to negatively impact GI mucosa via goblet cell toxicity, leading to related ga
Slide 37: Preclinical Efficacy Models
Preclinical Efficacy Models
Slide 38: VYN202: Psoriasis Model
VYN202: Psoriasis Model eV YNE’
Slide 39: VYN202: Comparable Onset of Action and Efficacy to Deucravacitinib
VYN202: Comparable Onset of Action and Efficacy to Deucravacitinib1 at Equivalent Dosing in Preclinical in vivo Model of Psoriasis Dorsal depilated BALB-C mice were dosed for 14 days with topical imiquimod cream (Day 1-7: induction phase, Day 8-14: treatment phase). N=8 animals were assigned to each
Slide 40: VYN202 Reduced Key Cytokines Associated with Pathogenesis of Psoriasis
VYN202 Reduced Key Cytokines Associated with Pathogenesis of Psoriasis in Preclinical in vivo Model 15 80 70 >93% lower expression of IL-17 for VYN202 vs. Placebo IMI/Placebo IMI/Placebo 60 10 IMI/VYN202 IMI/VYN202 50 (1mg/kg) (1mg/kg) Pg/ml Pg/ml IMI/VYN202 IMI/VYN202 40 (3mg/kg) (3mg/kg) IMI/VYN20
Slide 41: VYN202: Marked Improvement in Clinical Presentation of Disease
VYN202: Marked Improvement in Clinical Presentation of Disease Comparable to deucravacitinib in resolving induced dermal inflammation at an identical dose after 7 days of treatment IMI/Placebo IMI/VYN202 3mg/kg IMI/Deucravacitinib 3mg/kg Day 8 Before treatment Day 15 After 7 days of treatment 41 IMI
Slide 42: VYN202: Rheumatoid Arthritis Model
VYN202: Rheumatoid Arthritis Model
Slide 43: VYN202: Collagen-Induced Arthritis Model in the Rat – Arthritis Score
VYN202: Collagen-Induced Arthritis Model in the Rat – Arthritis Score • VYN202 demonstrated highly potent anti-inflammatory activity • VYN202 statistically superior to GSK620 (BD2-selective BET inhibitor) at all dose levels 16 3.25 71% 79% Left hind paw volume (mL) Sham Control 14 3.00 12 CIA+Placeb
Slide 44: VYN202: Collagen-Induced Arthritis Rat Model – Histology Score & Biomarkers
VYN202: Collagen-Induced Arthritis Rat Model – Histology Score & Biomarkers • Treatment with VYN202 at 10mg/kg PO QD results in near normal joint histopathology • VYN202 demonstrated near complete inhibition of IgG1* expression at all doses Histology Scores - Day 21 IgG1 (units/ml) - Day 21 180 20,0
Slide 45: VYN202: Collagen-Induced Arthritis Rat Model – Pathology Images
VYN202: Collagen-Induced Arthritis Rat Model – Pathology Images Treatment with VYN202 at 10mg/kg PO QD results in near normal joint pathology CIA+Placebo CIA+VYN202 10mg/kg E B D C A A. Inflammation; mixed cell, marked • Normal joint presentation B. Granulation tissue; marked C. Increased bone, peri
Slide 46: VYN202 Results Show Strong Correlation with VYN201 Results
VYN202 Results Show Strong Correlation with VYN201 Results Reinforcing BET potential and role of BD2 inhibition in treatment of autoimmune diseases Psoriasis Model Psoriasis Model Arthritis Model 16 VYN202 VYN201 Sham Control VYN202 Deucra 14 100 Locally-administered 71% 12 CIA+Placebo Clinical scor
Slide 47: VYN202 Program Summary
VYN202 Program Summary • Novel, highly differentiated MOA - acting at the point of gene transcription in T Cells to directly address the complex signaling of immuno- & fibro-inflammatory diseases • BET Inhibition’s impact on multiple inflammatory pathways unlocks potential across broad range of immu
Slide 48: VYN202 Clinical Development Plan
VYN202 Clinical Development Plan 1. Moderate-to-Severe Psoriasis 2. Moderate-to-Severe Active Rheumatoid Arthritis
Slide 49: VYN202 Planned Study Designs
VYN202 Planned Study Designs Healthy Volunteers PoC Studies in Patients with Disease SAD MAD Psoriasis (Mod/Severe) Rheumatoid Arthritis (Mod/Severe) Placebo-controlled study evaluating safety, tolerability, PK and PD • Multicenter, double-blind, placebo- • Multicenter, double-blind, placebo- contro
Slide 50: Financial Update
Confidential – For Internal Use Only. Confidential – For Internal Use Only. Financial Update
Slide 51: Well Capitalized and Supported by Leading Fundamental Healthcare Investors
Well Capitalized and Supported by Leading Fundamental Healthcare Investors Cash, cash equivalents and restricted cash (in millions) $103.7 • $103.7M pro forma cash balance1; No debt Successful equity raise in October 2023 with premier syndicate of fundamental investors • Cash runway through end of 2
Slide 52: Multiple Paths to Potential Value Creation Across BET Inhibitor Programs
Multiple Paths to Potential Value Creation Across BET Inhibitor Programs 2023 2024 2025 October By Year End Q1 1H Mid-Year 2H Mid-Year TLR P2b Trial in VYN201 Vitiligo P1b Initiate P2b data Trial in Vitiligo Vitiligo Initiate 2 P1b TLR P1b Trial in Announce P1a SAD/MAD VYN202 Initiate P1a PoC Trials
Slide 53: Q&A Session
Q&A Session