Vyne Therapeutics Inc. · NASDAQ:VYNE
Vyne Therapeutics — Investor Presentation (October 2023)
52 slides from Vyne Therapeutics's investor presentation, Oct 30, 2023
Slide 1: Corporate Presentation October 2023
Corporate Presentation October 2023
Slide 2: Forward Looking Statements and Important Notes
Forward Looking Statements and Important Notes This presentation by VYNE Therapeutics Inc ..(" 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 devel
Slide 3: Investment Highlights
Investment Highlights (NASDAQ: VYNE) Advancing novel BET inhibitor platform to improve the lives of patients suffering from immuno-inflammatory conditions Potential for Multiple Clinical Catalysts • VYN201: Phase 1b PoC data in vitiligo suggest VYN201 has the potential to be category leader • VYN202
Slide 4: Building a Leading Early-Stage Pipeline to Address Unmet Needs in I&I Conditions
4 Based on current estimates. Building a Leading Early-Stage Pipeline to Address Unmet Needs in I&I Conditions Program Indication(s) Route of Administration Current Stage Status / Next Anticipated Milestones Rights Preclinical IND-Enabling Phase 1 Phase 2 InhiBETTM Platform - Library of NCE BET Inhi
Slide 5: Multiple Paths to Potential Value Creation Across BET Inhibitor Programs
5 Multiple Paths to Potential Value Creation Across BET Inhibitor Programs 2023 October Vitiligo P1b data Q1 Initiate P1a SAD/MAD 1H Initiate P2b Trial in Vitiligo 2025 Mid-Year TLR P2b Trial in Vitiligo Cash runway through the end of 2025 By Year End Submit IND 2024 Mid-Year 2H P1a SAD/MAD Results
Slide 6: InhiBET BET Inhibitor Platform
InhiBET™ BET Inhibitor Platform Bromodomain & Extra-Terminal Domain (BET) Inhibition for Immunology and Inflammatory Diseases 6
Slide 7: VYNE's Drug Design Strategy: BD2-selectivity
Improve efficacy and tolerability through BD2-selectivity • Class-leading BD2 vs. BD1 selectivity for systemic administration • BD2 activity more relevant to inflammatory gene expression • Minimize BD1 inhibition to protect against steady-state gene disruption VYNE’s Drug Design Strategy 7 Dawson et
Slide 8: VYN201: Vitiligo
VYN201: Vitiligo %VYNE’
Slide 9: BET Inhibition – A Differentiated Treatment Strategy for Non-Segmental Vitiligo
9 BET Inhibition – A Differentiated Treatment Strategy for Non-Segmental Vitiligo ACTIVE gene VYN201 Transcription machinery NF-Κb complex signal transduction Translation Transcription failure Fully expressed cytokine Cytokine down regulation e.g. IFNγ 3 1 BD1 & BD2 Inactive gene via BET inhibition
Slide 10: Vitiligo – Significant Unmet Need
Vitiligo – Significant Unmet Need Only one drug currently approved; treatment is dominated by non-specific therapeutics 10 1L Topicals (Corticosteroids, topical calcineurin inhibitors, ruxolitinib) Phototherapy Excimer Laser 2L Phototherapy + Topicals 3L+ Surgery (skin tissue grafting; hair follicle
Slide 11: Vitiligo Represents a Large and Growing Market Opportunity
Vitiligo Represents a Large and Growing Market Opportunity 11 Source: Gandhi et al. JAMA Dermatol. 2022;158(1):43-50; Kruger. 2012;51(10):1206-1212; Rangu. J Clin Dermatol Ther. 2021;7:070; Pandya. AAD 2023 Presentation; Incyte Corporate Pres. Aug. 2023; TD Cowen research dated Sept. 2023; Piper res
Slide 12: VYN201: Preclinical Data
VYN201: Preclinical Data %VYNE’
Slide 13: VYN201: Human Tissue Model of Vitiligo
13 VYN201: Human Tissue Model of Vitiligo Demonstrated reduction in melanocyte loss and lowering of key inflammatory biomarkers 100 894 34 63 725 880 73 0 100 200 300 400 500 600 700 800 900 1000 Untreated CTL Vehicle VYN201 - 1% VYN201 - 0.1% VYN201 - 0.01% VYN201 - 0.001% Rux 1.5% Ø TNF-α/IFN-γ TN
Slide 14: VYN201: Human Tissue Model of Vitiligo
VYN201 1% treated Vehicle treated TRV: tyrosinase-related protein 1 (important enabler of melanogenesis) Keratinocytes (blue), melanocytes (green) Melanocyte detachment / migration Retention of melanocytes at the basal layer VYN201: Human Tissue Model of Vitiligo VYN201 prevents melanocyte detachmen
Slide 15: VYN201: Phase Proof-of-Concept
VYN201: Phase 1 Proof-of-Concept
Slide 16: VYN201: Phase 1b Study in Active Vitiligo Patients
VYN201: Phase 1b Study in Active Vitiligo Patients 16 F-VASI = Facial Vitiligo Area Scoring Index Study 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
Slide 17: Baseline Demographic and Clinical Characteristics
Age - year mean 49.2 53.2 57.0 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 60% 7 70% 7 78% 20 69% Race or ethnic group Hispanic or Latino 0 0% 2 20% 7 78% 9 31% Not Hispanic or Latino 10 100
Slide 18: Demonstrated Favorable Safety & Tolerability Profile
Demonstrated Favorable Safety & Tolerability Profile 18 1. Data available as of 10/13/23 Adverse Events No serious adverse events reported No treatment related discontinuations All treatment emergent adverse events classified as mild (>70%) or moderate; no severe AEs No dose/exposure-dependent incre
Slide 19: Low Systemic Exposure with No Impact on Platelet Counts
VYN201 Phase 1b: Low Systemic Exposure in Vitiligo Subjects Correlates with No Impact on Platelet Counts 19 Available data for treatment up to 16 weeks supports “soft” drug approach for topical pan-BD BET inhibitor LLOQ = Lower Limit of Quantification 0.001 0.01 0.1 1 10 100 1000 1 2 3 Log VYN201 pl
Slide 20: Vitiligo Disease Activity within PoC Study Designs
Vitiligo Disease Activity within PoC Study Designs 20 Patients with Active Disease Will Continue to Depigment in Areas that Show High Activity without Therapy5 VYNE expects to enroll patients with active and stable disease in P2b study Patient Population and Asset Development Status Fig 1: Vitiligo
Slide 21: 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 21 -7.5% -30.3% -39.0% -45% -40% -35% -30% -25% -20% -15% -10% -5% 0% 0 4 8 12 16 Mean % CFB in F-VASI Weeks VYN201 0.5% (N = 10) VYN201 1% (N = 10) VYN201 2% (N=9) (p = 0.0137 vs. VYN
Slide 22: Competitive Efficacy at 16 Weeks vs. JAK Class at 24 Weeks
-7.5% -30.3% -39.0% Litfulo -18.5% Povorcitinib -36.4% Opzelura -37.8% Rinvoq -35.6% -45.0% -40.0% -35.0% -30.0% -25.0% -20.0% -15.0% -10.0% -5.0% 0.0% 0 4 8 12 16 20 24 Mean % CFB in F-VASI Time (Weeks) JAK Class (P2b) Week 24 data End of treatment for VYN201 P1b Demonstrated Competitive Efficacy a
Slide 23: Potential for Differentiated Product Profile
Characteristic VYN201 Opzelura (Ruxolitinib) Cream 1.5% Litfulo (Ritlecitinib) 50mg1 Povorcitinib 45mg2 1% 2% Novel MOA / JAK Class Alternative Targeted Dosing Posology QD BID QD QD Rapid Onset of Action Moderate Moderate Efficacy, % CFB F-VASI, Week 16 100% active disease study Active & stable dise
Slide 24: Key Takeaways from VYN201 Phase 1b Results
Key Takeaways from VYN201 Phase 1b Results 24 Notes: Data through 10/13/23; Based on readily available public information such as clintrials.gov, academic publications and corporate websites/presentations • Significant clinical response shown with rapid onset of action • Clear evidence of dose respo
Slide 25: VYN202: BD2 selective BET inhibitor
VYN202: BD2 selective BET inhibitor
Slide 26: VYNE's Drug Design Strategy: BD2-selectivity
Improve efficacy and tolerability through BD2-selectivity • Class-leading BD2 vs. BD1 selectivity for systemic administration • BD2 activity more relevant to inflammatory gene expression • Minimize BD1 inhibition to protect against steady-state gene disruption VYNE’s Drug Design Strategy 26 Dawson e
Slide 27: Maximizing BD2 Potency and Minimizing BD1 Affinity
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 27 Compound ID Potency vs. BD2* (nM) Selectivity** (BD1/BD2) VYN202 (VYNE) < >>>> NUV-868 (Nuvation)2 2 1,460x (FRET) ABBV-744 (AbbVie)3
Slide 28: Strategies to Control Dysregulated TH17 Immune Cell Activity
Strategies to Control Dysregulated TH17 Immune Cell Activity Inhibitors of receptor signal transduction (JAK/TYK2 inhibitors via IL23/TNFα mediation: tofacitinib, upadacitinib, deucravacitinib, TAK-279) Inhibitors of TH17 cell differentiation (risankizumab, tildrakizumab, guselkumab, ustekinumab) IL
Slide 29: BET Inhibitors Disrupt Inflammatory Gene Transcription in T Cells
29 BET Inhibitors Disrupt Inflammatory Gene Transcription in T Cells to Directly Address the Complex Signaling of Immuno- & Fibro-inflammatory Diseases ACTIVE gene VYN202 Transcription machinery NF-Κb complex signal transduction Translation Transcription failure Fully expressed cytokine Cytokine dow
Slide 30: Demonstrated Potency Against Th17 Cytokines
-6 -5 -4 -3 -2 -1 0 0 20 40 60 80 100 BA83_IL17 log [Compound] (uM) Percent inhibition Demonstrated Potency Against Th17 Cytokines 30 Source: Data on file; Summary basis of approval for Cosentyx, pharmacology review, CDER, FDA, August 2014; Dice Therapeutics Corporate Presentation March 2023 VYN202
Slide 31: Selectivity of Cytokine Expression vs. CXCL10
Cytokine VYN202 IC50 (nM) Selectivity vs. CXCL10 IL-17A 0.27 >13,000 IL-22 0.21 >17,000 CXCL10 3637 - Minimal Inhibition on Key Innate Immune Chemokine Demonstrates Selectivity of Cytokine Expression (IL-17A and IL-22 vs. CXCL10) 31 Source: Data on file Analysed by ELISA with media supernatant from
Slide 32: Preclinical Safety Data
Preclinical Safety Data %VYNE’
Slide 33: 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 33 1 10 100 1000 10000 100000 0.5 1 2 4 8 24 Log VYN202 plasma concentration (ng/ml) Timepoint (Hours) 1mg/kg/day 3mg/kg/day 10m
Slide 34: Effect on Gastrointestinal (GI) System
Effect on Gastrointestinal (GI) System 34 VYN202 (BD2 Selective) Vehicle ABBV-075 (Pan-BD BET inhibitor) Depleted goblet cells VYN202 (BD2 Selective) 10mg/kg Goblet cells GI villus Images for VYN202 representative from histopathology of the duodenum (H&E stain). Comparable results obtained for ileum
Slide 35: Preclinical Efficacy Models
Preclinical Efficacy Models
Slide 36: VYN202: Psoriasis Model
VYN202: Psoriasis Model %VYNE’
Slide 37: VYN202: Comparable Onset of Action and Efficacy to Deucravacitinib
1Sotyktu® (deucravacitinib) was approved in the U.S. in September 2022. PASI-90 = 90% improvement from baseline in PASI score 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 trea
Slide 38: VYN202 Reduced Key Cytokines in Psoriasis Model
VYN202 Reduced Key Cytokines Associated with Pathogenesis of Psoriasis in Preclinical in vivo Model 38 - 10 20 30 40 50 60 70 80 IL-17 IL-22 Pg/ml IMI/Placebo IMI/VYN202 (1mg/kg) IMI/VYN202 (3mg/kg) IMI/VYN202 (10mg/kg) IMI/Deucra (3mg/kg) - 5 10 15 IL-1β IL-6 TNF-α IL-23 Pg/ml IMI/Placebo IMI/VYN20
Slide 39: VYN202: Marked Improvement in Clinical Presentation of Disease
VYN202: Marked Improvement in Clinical Presentation of Disease IMI/Placebo IMI/VYN202 3mg/kg 39 Day 8 Before treatment Day 15 After 7 days of treatment IMI/Deucravacitinib 3mg/kg IMI = imiquimod; Comparable to deucravacitinib in resolving induced dermal inflammation at an identical dose after 7 days
Slide 40: VYN202: Rheumatoid Arthritis Model
VYN202: Rheumatoid Arthritis Model
Slide 41: 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 41 Inflammatory arthritis was induced in Lewis rats using a mixture of colla
Slide 42: Collagen-Induced Arthritis Rat Model – Histology Score & Biomarkers
- 2,000 4,000 6,000 8,000 10,000 12,000 14,000 16,000 18,000 20,000 Placebo CIA+Placebo CIA+Dex 0.1% CIA+GSK620 10mg/kg CIA+VYN202 1mg/kg CIA+VYN202 3mg/kg CIA+VYN202 10mg/kg IgG1 (units/ml) - Day 21 VYN202: Collagen-Induced Arthritis Rat Model – Histology Score & Biomarkers 42 • Treatment with VYN2
Slide 43: Collagen-Induced Arthritis Rat Model – Pathology Images
VYN202: Collagen-Induced Arthritis Rat Model – Pathology Images 43 A. Inflammation; mixed cell, marked B. Granulation tissue; marked C. Increased bone, periosteum; marked D. Increased eroded surface, bone; moderate E. Erosion/ulcer; cartilagenous, moderate • Normal joint presentation B A D C E CIA+P
Slide 44: VYN202 Results Show Strong Correlation with VYN201 Results
0 6 12 13 14 15 18 19 21 -2 0 2 4 6 8 10 12 14 16 Day Clinical score Sham Control CIA+Placebo CIA+Dexamethasone (0.1mg/kg) CIA+GSK620 (10mg/kg) CIA+VYN202 (1mg/kg) CIA+VYN202 (3mg/kg) CIA+VYN202 (10mg/kg) 44 VYN202 Results Show Strong Correlation with VYN201 Results Reinforcing BET potential and rol
Slide 45: VYN202 Clinical Development Plan
VYN202 Clinical Development Plan 1. Moderate-to-Severe Psoriasis 2. Moderate-to-Severe Active Rheumatoid Arthritis
Slide 46: Clinical Development Strategy
37 14 37 14 7 3 2 46 Source: 1. Global Data; ABBV 2020 Long-term Strategy Corporate Presentation; Data on file 2. Alotaibi HM Clin Cosmet Investig Dermatol. 2023; MacGearailt C., Fitzgerald, G. EMJ Rheumatol. 2021; Ogdie A, Weiss P. Rheum Dis Clin North Am. 2015; Armstrong, et al. JAMA Dermatol. 202
Slide 47: Psoriasis: Rationale and Preclinical Proof-of-Concept
Psoriasis: Rationale and Preclinical Proof-of-Concept 47 Sources: Young M et al. JAANP. 2017; 2: Ben Abdallah H et, al. Psoriasis (Auckl). 2021; 3: Sugaya M. Int J Mol Sci. 2020; 4:Sun, X., Yang, P. BioMed Eng OnLine. 2021 Proof of Concept / Rationale Fig 1: Mechanism of Psoriasis underscores the im
Slide 48: Rheumatoid Arthritis: Rationale and Preclinical Proof-of-Concept
Rheumatoid Arthritis: Rationale and Preclinical Proof-of-Concept 48 Sources: 1. Yafei J. et al, BBA – Molecular Basis of Disease, 2017; 2. Yuanji, D. et al. Frontiers in Immunology. 2022; 3. Zhang QG, Qian J, Zhu YC. Immunol Lett. 2015 BET proteins have dual effects on HMGB1 and NF-kB signaling path
Slide 49: VYN202 Planned Study Designs
• Trial size: N=~40 Evaluating 5 strengths of VYN202 (N=8 / cohort) and food effect • MRSD to be determined based on final IND-enabling non-clinical safety program VYN202 Planned Study Designs 49 Healthy Volunteers • Multicenter, double-blind, placebo-controlled phase 1b study • Trial size: N=~40 3:
Slide 50: VYN202 Program Summary
VYN202 Program Summary 50 • 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 i
Slide 51: Multiple Paths to Potential Value Creation Across BET Inhibitor Programs
51 Multiple Paths to Potential Value Creation Across BET Inhibitor Programs 2023 October Vitiligo P1b data Q1 Initiate P1a SAD/MAD 1H Initiate P2b Trial in Vitiligo 2025 Mid-Year TLR P2b Trial in Vitiligo Cash runway through the end of 2025 By Year End Submit IND 2024 Mid-Year 2H P1a SAD/MAD Results
Slide 52: VYNE Therapeutics
J Wy Therapeutics NASDAQ: VYNE
VYNE Therapeutics — Investor Presentation (October 2023) on 6ix