Vyne Therapeutics Inc. · NASDAQ:VYNE
Vyne Therapeutics — Investor Presentation (January 2025)
41 slides from Vyne Therapeutics's investor presentation, Jan 13, 2025
Slide 1: Corporate Presentation January 2025
Corporate Presentation January 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 Potential for Multiple Clinical Catalysts • Repibresib (VYN201): Phase 1b PoC data in vitiligo suggest VYN201 has the potential to be category le
Slide 4: Building a Leading Early-Stage Pipeline to Address Unmet Needs in I&I Conditions
Based on current estimates. 1. P1b initiation subject to adequate levels of funding 4 TLR = top-line results; SAD = Single Ascending Dose; MAD = Multiple Ascending Dose Building a Leading Early-Stage Pipeline to Address Unmet Needs in I&I Conditions Program Indication(s) Route of Administration Curr
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
6 BET Proteins: Key Epigenetic Regulators of NF-kB, a Master Orchestrator of Inflammation TCR (T cell receptor) and TLR (Toll-like receptor Adapted from Wang, N., Wu, R., Tang, D. et al. The BET family in immunity and disease (2021) • BET proteins are epigenetic regulators of transcription driven by
Slide 7: BET Inhibition: A Novel Mechanism for the Treatment of I&I Conditions
7 BET Inhibition: A Novel Mechanism for the Treatment of I&I Conditions 1. Cell types involved in inflammation and autoimmunity. Th1: Helper T cell Type 1; Tc1: Cytotoxic T cell Type 1; Th17: IL-17 producing helper T cell 2. Cytokines and key mediators involved in each cell type. NF-kB is involved i
Slide 8: Clinical Development Strategy
8 Clinical Development Strategy PoC studies in Vitiligo, PsO and RA serve as potential gateways to other large, strategically attractive markets unlocks potential for broad development strategy across range of immune-mediated diseases Vitiligo PsO RA NF-kB Regulated Disease Dermatology Dermatology R
Slide 9: VYNE's Drug Design Strategy
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 9 Dawson et
Slide 10: Repibresib (VYN201): Vitiligo
Repibresib (VYN201): Vitiligo
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: Repibresib (VYN201): Phase 1b Proof-of-Concept
Repibresib (VYN201): Phase 1 Proof-of-Concept
Slide 13: Repibresib (VYN201): Phase 1b Study in Active Vitiligo Patients
Repibresib (VYN201): Phase 1b Study in Active Vitiligo Patients 13 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% stren
Slide 14: 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 14 -7.5% -30.2% -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
Slide 15: Competitive Results at 16 Weeks vs. JAK Class at 24 Weeks
-7.5% -30.2% -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 Weeks JAK Class (P2b) Week 24 data End of treatment for VYN201 P1b Demonstrated Competitive Results at 16 Wee
Slide 16: Key Takeaways from Repibresib (VYN201) Phase 1b Results
Key Takeaways from Repibresib (VYN201) Phase 1b Results 16 1. Based on readily available public information such as clintrials.gov, academic publications and corporate websites/presentations • Significant clinical response demonstrated with once-daily dosing • Rapid onset of action with clear eviden
Slide 17: Repibresib (VYN201) Phase 2b in Non-Segmental Vitiligo
Repibresib (VYN201) Phase 2b in Non-Segmental Vitiligo (NSV) PART 1: Vehicle-controlled treatment period (24 weeks) Safety follow-up (4 weeks) Repibresib (VYN201) Gel 3% QD (N=~45) W24 Primary endpoint W52 PART 2: Extension treatment period (28 weeks) Repibresib (VYN201) Gel 2% QD (N=~45) Repibresib
Slide 18: VYN202: BD2 selective BET inhibitor
VYN202: BD2 selective BET inhibitor
Slide 19: VYNE's Drug Design Strategy
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 19 Dawson e
Slide 20: VYN202: A Novel BD2-Selective BET Inhibitor for Immune-Mediated Diseases
VYN202: A Novel BD2-Selective BET Inhibitor for Immune-Mediated Diseases 20 1. Based on readily available public information such as clintrials.gov, academic publications and corporate websites/presentations. • VYN202 is an innovative, oral BD2-Selective BET inhibitor • VYN202 is believed to be the
Slide 21: 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 Immune-Mediated Diseases 21 Compound ID Potency vs. BD2* (nM) Selectivity** (BD1/BD2) VYN202 (VYNE) 1 ~10,000 NUV-868 (Nuvation)2 2 1,460x (FRET) ABBV-744 (
Slide 22: VYN202: Preclinical Efficacy Models
VYN202: Preclinical Efficacy Models
Slide 23: VYN202 Comparable to Deucravacitinib in Preclinical Psoriasis Model
- 10 20 30 40 50 60 70 80 IL-17 IL-22 VYN202: Clinical and Biomarker Effects Comparable to Deucravacitinib in Preclinical in vivo Model of Psoriasis 23 Day 15 After 7 days of treatment IMI/Placebo IMI/VYN202 3mg/kg IMI/Deucravacitinib 3mg/kg - 5 10 15 IL-1β IL-6 TNF-α IL-23 >93% lower expression of
Slide 24: VYN202: Anti-Arthritic Effect Demonstrated in Preclinical Models of Arthritis
0 6 12 13 14 15 18 19 21 1.00 1.25 1.50 1.75 2.00 2.25 2.50 2.75 3.00 3.25 Day Left hind paw volume (mL) CIA+Placebo CIA+Dexamethasone (0.1mg/kg) CIA+GSK620 (10mg/kg) CIA+VYN202 (1mg/kg) CIA+VYN202 (3mg/kg) CIA+VYN202 (10mg/kg) Sham Control VYN202: Anti-Arthritic Effect and Decreased Antibody Levels
Slide 25: 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) 25 VYN202 Results Show Strong Correlation with VYN201 Results Reinforcing BET potential and rol
Slide 26: VYN202: Phase 1a SAD/MAD Data
VYN202: Phase 1a SAD/MAD Data
Slide 27: VYN202 Phase 1a SAD/MAD Trial Design and Key Objectives
VYN202 Phase 1a SAD/MAD Trial Design and Key Objectives 27 Placebo-controlled study evaluating safety, tolerability, PK and PD First-in-human trial in healthy volunteers complete 1. Intended to approximate 0.25mg QD dosing; DDI = drug-drug interaction Assess: Safety, Tolerability, Exposure Explorato
Slide 28: VYN202 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1
VYN202 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1 28 VYN202 was generally well tolerated in Phase 1 MAD with no drug related AEs of special interest historically associated with BET inhibitor class Treatment Emergent AEs Number of Subjects Reporting (%) Placebo (n=6) VYN202
Slide 29: VYN202 Phase 1 MAD Results: Selected Laboratory Data
VYN202 Phase 1 MAD Results: Selected Laboratory Data 29 All laboratory results within normal limits throughout treatment and follow-up period 0 100 200 300 400 PD 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Mean 103/uL (±SE) Day 20 25 30 35 PD 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Me
Slide 30: VYN202 Phase 1 SAD and 14-Day MAD Pharmacokinetics
VYN202 Phase 1 SAD and Day 14 MAD Pharmacokinetics 30 • Dose-dependent exposure from dose 0.5 QOD to 4mg, with low variability • ~4-fold accumulation observed, steady state reached after 7 QD doses • VYN202 exposure remained above key inhibitory levels vs. BD2 BRD4 for 24 hours post-dose on Day 14 •
Slide 31: Pharmacokinetics Showed Strong Correlation with Target Engagement
Pharmacokinetics Showed Strong Correlation with Target Engagement 31 • Inhibition of BET proteins release pTEFb* which activates transcription of pTEFb-dependent genes such as HEXIM-1 leading to higher expression of the HEXIM-1 protein • Induction of HEXIM-1 closely follows corresponding pharmacokin
Slide 32: Demonstrated Impact on Pro-Inflammatory and Disease Related Cytokines
Demonstrated Impact on Pro-Inflammatory and Disease Related Cytokines 32 -60% -50% -40% -30% -20% -10% 0% 10% 20% 30% 40% Mean % Change from Baseline Ex Vivo Inhibition of Disease Related Cytokines1, Day 14 1Using TLR4/TLR7 stimulation and analysis from whole blood samples Th17 Th1/Myeloid Cells Th1
Slide 33: Majority of Cytokine Suppression Occurred in Concentrations at 1 mg or Below
Majority of Cytokine Suppression Occurred in Concentrations at 1 mg or Below 33 in preclinical in vitro tests at fixed concentrations of VYN202 ranging from 0 to 10 ng/mL 1. 0.5mg QOD intended to approximate 0.25mg QD dose 2. Mean clinical concentration range of VYN202 is approximately 0.5 ng/mL (0.
Slide 34: VYN202 Phase 1a MAD Data Summary
VYN202 Phase 1a MAD Data Summary 34 • Demonstrated favorable safety and tolerability profile • No drug-related adverse events historically associated with earlier generation, less selective BET inhibitors, including thrombocytopenia, neutropenia or gastrointestinal toxicity findings • No serious adv
Slide 35: VYN202 Enhanced Phase 1b Study Design in Moderate-to-Severe Plaque Psoriasis
VYN202 Enhanced Phase 1b Study Design in Moderate-to-Severe Plaque Psoriasis W12 Primary endpoint Top-line results from 12-week placebo-controlled treatment period expected YE 2025 N = up to 80 subjects with moderate-to-severe plaque psoriasis 35 Key Inclusion Criteria • 18-75 y • BMI 18-40 • PASI ≥
Slide 36: Multiple Paths to Potential Value Creation Across BET Inhibitor Programs
36 Multiple Paths to Potential Value Creation Across BET Inhibitor Programs P1a MAD Results Q4 LPI P2b Trial in Vitiligo Mid-Year Top-line Results P2b Trial in Vitiligo VYN201 VYN202 Top-line Results P1b PsO Q1 Q1 2024 2025 2026 Initiate P1b PsO P2b Extension Readout YE Cash Runway into 2H 2026 Base
Slide 37: MM THeRApeutics
4 MM THeRApeutics NASDAQ: VYNE
Slide 38: Appendix
Appendix “VY
Slide 39: VYN201 is superior to ruxolitinib in inhibiting CD8+ T-cell proliferation
VYN201 is superior to ruxolitinib in inhibiting CD8+ t-cell proliferation VYN201 IC50 for IFNγ release superior to ruxolitinib VYN201 does not impart a cytotoxic effect on CD8+ t-cells at levels similar to ruxolitinib Pathogenesis of Vitiligo is Primarily Linked to CD8+ T-Cell Proliferation and Hype
Slide 40: Repibresib (VYN201) P1b 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 41: Demonstrated Favorable Safety & Tolerability Profile in P1b
Demonstrated Favorable Safety & Tolerability Profile in P1b 41 Adverse Events No serious adverse events reported No treatment related discontinuations All TEAEs classified as mild (>70%) or moderate; except for 2 severe events of application site pain reported for 1 subject in 2% cohort which resolv
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