Vyne Therapeutics Inc. · NASDAQ:VYNE
Vyne Therapeutics — Investor Presentation (July 2025)
52 slides from Vyne Therapeutics's investor presentation, July 2025
Slide 1: Corporate Presentation July 2025
Corporate Presentation July 2025
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 development plans and timeline
Slide 3: Investment Highlights
Investment Highlights (NASDAQ: VYNE) Advancing novel BET inhibitor platform to improve the lives of patients suffering from immuno-inflammatory conditions • BET inhibition represents a novel target for the treatment of immune-mediated diseases: Addressing the complex Innovative Target signaling of I
Slide 4: Building a Leading Early-Stage Pipeline to Address Unmet Needs in I&I Conditions
Building a Leading Early-Stage Pipeline to Address Unmet Needs in I&I Conditions Route of Current Stage Program Indication(s) Status / Next Anticipated Rights Administration Preclinical Phase 1 Phase 2 Phase 3 Milestones InhiBETTM Platform - Library of NCE BET Inhibitors for Any Indication Worldwide
Slide 5: InhiBET BET Inhibitor Platform
InhiBET BET Inhibitor Platform Bromodomain & Extra-Terminal Domain (BET) Inhibition for Immunology and Inflammatory Diseases 5
Slide 6: BET Proteins: Key Epigenetic Regulators of NF-kB
BET Proteins: Key Epigenetic Regulators of NF-kB, a Master Orchestrator of Inflammation Canonical NF-kB pathway IL23, IL12, TNFa, IL6, IL-1β TCR TLR Cytokine receptor Validated NF-kB targets: • Direct cytokine or receptor interaction (e.g., IL23, IL12, TNFa, IL6, IL-1β) NF-kB Pathway MyD88 Cytokine
Slide 7: BET Inhibition: A Novel Mechanism for the Treatment of I&I Conditions
BET Inhibition: A Novel Mechanism for the Treatment of I&I Conditions BET Inhibition’s Impact on Multiple Inflammatory Pathways Provides Potential to Address a Broad Range of Immune-Mediated Diseases Primary Cell nucleus Type1 Th1/Tc1 Th17 Myeloid cells B Cells NFκB BET-inhibition • TNF Cytokine RNA
Slide 8: VYNE's Drug Design Strategy
VYNE’s Drug Design Strategy Optimize benefit/risk profile of BET inhibitors to target immune-mediated diseases Repibresib (VYN201) VYN202 Pan-BD BET Inhibitor BD2-Selective BET Inhibitor Maximize local effect & Improve efficacy and tolerability minimize systemic exposure through BD2-selectivity • Ti
Slide 9: Repibresib (VYN201): Vitiligo
Repibresib (VYN201): Vitiligo
Slide 10: Vitiligo Represents a Large and Growing Market Opportunity
Vitiligo Represents a Large and Growing Market Opportunity Addressable Market : a Significant Unmet Need $ in millions • Market penetration: Opzelura is the U.S. vitiligo net sales 1.9M only product approved for treatment estimated ~$180M $725 of vitiligo ~2.5 years post-launch2 • Patient activation
Slide 11: Repibresib (VYN201): Phase 1 Proof-of-Concept
Repibresib (VYN201): Phase 1 Proof-of-Concept
Slide 12: Repibresib (VYN201): Phase 1b Study in Active Vitiligo Patients
Repibresib (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 T
Slide 13: Promising Onset of Action and F-VASI Response
Promising Onset of Action and F-VASI Response Repibresib (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-
Slide 14: Competitive Results at 16 Weeks vs. JAK Class at 24 Weeks
Demonstrated Competitive Results at 16 Weeks vs. JAK Class at 24 Weeks Repibresib (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 -3
Slide 15: Key Takeaways from Repibresib (VYN201) Phase 1b Results
Key Takeaways from Repibresib (VYN201) Phase 1b Results • Believed to be first clinical demonstration of BET inhibitor’s effect in I&I disease1 • Significant clinical response demonstrated with once-daily dosing • Rapid onset of action with clear evidence of dose response • Upregulation of WNT pathw
Slide 16: Repibresib (VYN201) Phase 2b in Non-Segmental Vitiligo
Repibresib (VYN201) Phase 2b in Non-Segmental Vitiligo (NSV) Top-line results from 24-week vehicle-controlled treatment period expected mid-2025 N = ~180 subjects with NSV (active and stable disease) PART 1: Vehicle-controlled treatment period PART 2: Extension treatment period Safety follow-up (24
Slide 17: VYN202: BD2 selective BET inhibitor
VYN202: BD2 selective BET inhibitor
Slide 18: VYNE's Drug Design Strategy
VYNE’s Drug Design Strategy Optimize benefit/risk profile of BET inhibitors to target immune-mediated diseases Repibresib (VYN201) VYN202 Pan-BD BET Inhibitor BD2-Selective BET Inhibitor Maximize local effect & Improve efficacy and tolerability minimize systemic exposure through BD2-selectivity • Ti
Slide 19: VYN202: A Novel BD2-Selective BET Inhibitor for Immune-Mediated Diseases
VYN202: A Novel BD2-Selective BET Inhibitor for Immune-Mediated Diseases • VYN202 is an innovative, oral BD2-selective BET inhibitor • VYN202 is believed to be the most potent and BD2-selective BET Inhibitor in clinical development1 which is designed to improve efficacy and tolerability • Program su
Slide 20: Drug Design Approach: Maximize On-target Potency and BD2-Selectivity
Drug Design Approach: Maximize On-target Potency and BD2-Selectivity to Optimize the Benefit/Risk Profile of BET Inhibitors VYN202 is believed to be the most potent and BD2-selective BET Inhibitor in clinical development1 which is designed to improve efficacy and tolerability Potency vs. BD2* Select
Slide 21: VYN202: Phase 1a SAD/MAD Data
VYN202: Phase 1a SAD/MAD Data
Slide 22: VYN202 Phase 1a SAD/MAD Trial Design and Key Objectives
VYN202 Phase 1a SAD/MAD Trial Design and Key Objectives First-in-human trial in healthy volunteers complete Healthy Volunteers SAD MAD Placebo-controlled study evaluating safety, tolerability, PK and PD Key Objectives Trial size: N=40 Trial size: N=32 Assess: Evaluated 4 doses of VYN202 Evaluated 3
Slide 23: VYN202 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1
VYN202 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1 VYN202 was generally well tolerated in Phase 1 MAD with no drug related AEs of special interest historically associated with BET inhibitor class MAD Results Treatment Emergent AEs Placebo VYN202 Number of Subjects Reporting (
Slide 24: VYN202 Phase 1 MAD Results: Selected Laboratory Data
VYN202 Phase 1 MAD Results: Selected Laboratory Data All laboratory results within normal limits throughout treatment and follow-up period Platelets Neutrophils Lymphocytes 7.0 5.0 400 6.0 4.0 Mean 10^3/uL (±SE) Mean 10^3/uL (±SE) Mean 10^3/uL (±SE) 5.0 300 4.0 3.0 200 3.0 2.0 Grade 1 (<150-75) 2.0
Slide 25: VYN202 Phase 1 SAD and MAD Pharmacokinetics
VYN202 Phase 1 SAD and Day 14 MAD Pharmacokinetics Single Ascending Dose PK Multiple Ascending Dose PK, Day 14 4.5 4.5 4.0 IC90 4.0 IC90 Mean (±SEM) Concentration (ng/mL) Mean (±SEM) Concentration (ng/mL) 3.5 4.0mg QD 3.5 1mg QD 2.0mg QD 0.5mg QD 3.0 3.0 1mg QD 0.5mg QOD 2.5 0.5mg QD 2.5 2.0 2.0 1.5
Slide 26: Pharmacokinetics Showed Strong Correlation with Target Engagement
Pharmacokinetics Showed Strong Correlation with Target Engagement Dose-dependent induction of HEXIM-1 with maximum effect observed at 0.5-1 mg QD Multiple Ascending Dose PK, Day 14 Multiple Ascending Dose HEXIM-1 Induction, Day 14 4.5 1.6 0.5mg QOD Mean (±SEM) Fold Induction vs. Predose 4.0 IC90 1.5
Slide 27: Demonstrated Impact on Pro-Inflammatory and Disease Related Cytokines
Demonstrated Impact on Pro-Inflammatory and Disease Related Cytokines Ex Vivo Inhibition of Disease Related Cytokines1, Day 14 40% Mean % Change from Baseline 30% 20% 10% Significant inhibition of key cytokines 0% relevant to several immune-mediated diseases -10% -20% -30% -40% Comparable inhibitory
Slide 28: Majority of Cytokine Suppression Occurred in Concentrations at 1 mg or Below
Majority of Cytokine Suppression Occurred in Concentrations at 1 mg or Below in preclinical in vitro tests at fixed concentrations of VYN202 ranging from 0 to 10 ng/mL 0 VYN202 exhibited steep exposure/response curves, consistent -25 with preclinical disease models % Inhibition -50 Majority of inhib
Slide 29: VYN202 Phase 1a MAD Data Summary
VYN202 Phase 1a MAD Data Summary Safety Pharmacokinetics Pharmacodynamics • Demonstrated favorable safety and • Favorable PK profile • Robust pharmacodynamic activity on target tolerability profile engagement and inflammatory biomarkers • Data supports once-daily dosing regimen in ex vivo assays • N
Slide 30: VYN202: Phase 1b Moderate-to-Severe PsO
VYN202: Phase 1b Moderate-to-Severe PsO
Slide 31: VYN202 Phase 1b Study Design in Moderate-to-Severe Plaque Psoriasis
VYN202 Phase 1b Study Design in Moderate-to-Severe Plaque Psoriasis No longer enrolling or dosing patients in study - 7 subjects enrolled Screening period Placebo-controlled treatment period Safety follow-up (30 days) (12 weeks) (4 weeks) Key Inclusion Criteria • 18-75 y VYN202 1 mg QD • BMI 18-40 •
Slide 32: VYN202 Phase 1b Study: 7 Patients Enrolled
VYN202 Phase 1b Study: 7 Patients Enrolled Demographic and Patient Characteristics Duration of treatment Subject Dose Parameter Value BL Week 1 Week 2 Week 4 Week 6 Week 8 Week 12 Week 16 ID (mg) Mean Age, yr (min-max) 47.1 (30-59) A Pbo 24 Days Sex, M/F 5/2 B 0.25 64 Days Race White (7) C 0.50 14 D
Slide 33: Individual PASI Score Changes
Individual PASI Score Changes Subject 0% A (Placebo) B (0.25mg) PASI % Change from Baseline C (0.5mg) -20% D (0.5mg) E (1mg) Individual Patient F (1mg) G (1mg) -40% PASI50 -60% PASI75 -80% PASI90 -100% 0 1 2 4 6 8 10 12 14 16 Rapid onset of action within 4 weeks Weeks for all subjects on active drug
Slide 34: Serum Inflammatory Biomarkers
Serum Inflammatory Biomarkers IL19 IL17A IL17F IL22 20 20 20 20 10 10 10 10 Maximum % Change from Baseline 0 N/A N/C 0 N/A N/C 0 N/C N/A N/C 0 N/A N/C -10 -10 -10 -10 -20 -20 -20 -20 -30 -30 -30 -30 -40 -40 -40 -40 -50 -50 -50 -50 -60 -60 -60 -60 -70 -70 -70 -70 -80 -80 -80 -80 -90 -90 -90 -90 A B C
Slide 35: Selected Laboratory Data
Preliminary Data available as of 6/20 Selected Laboratory Data • All data within Upper and Lower Limits of Normal (ULN/LLN) Platelet Count (103/mm3) • No grades of thrombocytopenia and trends in platelet counts reach a nadir between 4 and 6 weeks and increase during treatment • No grades of Neutrope
Slide 36: Visual Improvements in Psoriasis in 6 weeks
Visual Improvements in Psoriasis in 6 weeks Confidential – For Internal Use Only. Subject B (0.25mg) Last Dose Administered Day 64 Right Elbow Day 1 Week 6 Week 12 (PASI 13.9) (PASI 6.9) (PASI 5.4) 36
Slide 37: Visual Improvements in Psoriasis in 6 weeks
Visual Improvements in Psoriasis in 6 weeks Confidential – For Internal Use Only. Subject B (0.25mg) Last Dose Administered Day 64 Left Elbow Day 1 Week 6 Week 12 (PASI 13.9) (PASI 6.9) (PASI 5.4)
Slide 38: Visual Improvements in Psoriasis in 6 weeks
Visual Improvements in Psoriasis in 6 weeks Confidential – For Internal Use Only. Subject B (0.25mg) Back Scalp Day 1 (PSSI 14) Week 6 Week 12 (PSSI 4) (PSSI 1) 38
Slide 39: Visual Improvements in Psoriasis in 6 weeks
Visual Improvements in Psoriasis in 6 weeks Confidential – For Internal Use Only. Subject E (1mg) Last Dose Administered Day 65 Right Elbow Day 1 Week 6 Week 12 (PASI 12.1) (PASI 2.0) (PASI 3.0) 39
Slide 40: Visual Improvements in Psoriasis in 6 weeks
Visual Improvements in Psoriasis in 6 weeks Confidential – For Internal Use Only. Subject E (1mg) Last Dose Administered Day 65 Left Elbow Day 1 Week 6 Week 12 (PASI 12.1) (PASI 2.0) (PASI 3.0) 40
Slide 41: Data Summary
Data Summary Confidential – For Internal Use Only. Safety and Tolerability Exploratory Efficacy • No TESAEs or discontinuation due to a clinical TEAE • All subjects receiving VYN202 had an improvement in signs and symptoms of disease, including scalp psoriasis: • No treatment interruptions due to a
Slide 42: Multiple Paths to Potential Value Creation Across BET Inhibitor Programs
Multiple Paths to Potential Value Creation Across BET Inhibitor Programs 2024 2025 2026 Q4 Q1 Mid-Year YE Q1 LPI Top-line VYN201 P2b Trial in Results P2b P2b Extension Vitiligo Trial in Readout Vitiligo P1a MAD P1b Trial in Preliminary VYN202 Results PsO Pso Data Initiated Released Cash Runway into
Slide 43: NASDAQ: VYNE
ld A THeRAPEuTics NASDAQ: VYNE
Slide 44: Appendix
Appendix %VYNE’
Slide 45: Repibresib (VYN201): Vitiligo
Repibresib (VYN201): Vitiligo
Slide 46: 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 Repibresib (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 Viabili
Slide 47: Repibresib (VYN201) P1b Baseline Demographic and Clinical Characteristics
Repibresib (VYN201) P1b 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 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%
Slide 48: Demonstrated Favorable Safety & Tolerability Profile in P1b
Demonstrated Favorable Safety & Tolerability Profile in P1b 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 TEAEs classified as mild
Slide 49: VYN202: Preclinical Efficacy Models
VYN202: Preclinical Efficacy Models
Slide 50: VYN202: Clinical and Biomarker Effects Comparable to Deucravacitinib in Preclinical Psoriasis Model
VYN202: Clinical and Biomarker Effects Comparable to Deucravacitinib in Preclinical in vivo Model of Psoriasis Day 15 After 7 days of treatment 150 IMI/Placebo IMI/VYN202 3mg/kg IMI/Deucravacitinib 3mg/kg % Change in PASI Score 125 100 VYN202 and Deucravacitinib 75 surpassed PASI-90 by day 7 of trea
Slide 51: VYN202: Anti-Arthritic Effect and Decreased Antibody Levels in Preclinical Arthritis Models
VYN202: Anti-Arthritic Effect and Decreased Antibody Levels Demonstrated in Preclinical Models of Arthritis Collagen-Induced Arthritis Model Adjuvant-Induced Arthritis Model • VYN202’s increased potency and selectivity led to improved outcomes • Comparable effect on paw volume and IgG1 expression to
Slide 52: 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 I&I diseases Psoriasis Model Psoriasis Model Arthritis Model (CIA) 16 VYN202 Sham Control VYN201 VYN202 Deucra 14 100 Locally-administered 71% CIA+Placebo 12 CIA+Dexamethas
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