Slide 1: VYN202 P1a SAD/MAD Data December 2024
VYN202 P1a SAD/MAD Data December 2024
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 timel
Slide 3: BET Proteins: Key Epigenetic Regulators of NF-kB, a Master Orchestrator of Inflammation
3 BET Proteins: Key Epigenetic Regulators of NF - kB, a Master Orchestrator of Inflammation Indication Cell type / Cytokine pathway Vitiligo , Lichen Planus, Alopecia Areata Th1/Tc1 IL - 12, IFN , BATF Psoriasis , PsA, IBD Th17 IL - 17, IL - 23, IL - 21, RORC Autoantibody - mediated diseases (e.g.
Slide 4: VYN202: A Novel BD2-Selective BET Inhibitor for Immune-Mediated Diseases
VYN202: A Novel BD2 - Selective BET Inhibitor for Immune - Mediated Diseases 4 1. Based on readily available public information such as clintrials.gov, academic publications and corporate websites/present ati ons. • VYN202 is an innovative, oral BD2 - Selective BET inhibitor • VYN202 is believed to
Slide 5: Maximizing On-target Potency vs. BD2 and Minimizing Affinity to BD1
Maximizing On - target Potency vs. BD2 and Minimizing Affinity to BD1 May B e T he Key to Optimizing the Benefit/Risk Profile of BET Inhibitors for Autoimmune Diseases 5 Selectivity ** (BD1/BD2) Potency vs. BD2 * ( nM ) Compound ID ~10,000 1 VYN202 (VYNE) 1,460x (FRET) 2 NUV - 868 ( Nuvation ) 2 753
Slide 6: VYN202: Clinical and Biomarker Effects 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 6 Day 15 After 7 days of treatment IMI/VYN202 3mg/kg IMI/Placebo IMI/Deucravacitinib 3mg/kg - 5 10 15 IL - 1 β IL-6 TNF - α IL-23 >93% lower expression
Slide 7: Anti-Arthritic Effect and Decreased Antibody Levels Demonstrated in Preclinical Models of Arthritis
VYN202: Anti - Arthritic Effect and Decreased Antibody Levels Demonstrated in Preclinical Models of Arthritis, including a Comparable Effect to Upadacitinib 7 79% >98% lower expression of anti - CII IgG1 vs. CIA+placebo Collagen - Induced Arthritis Model Adjuvant - Induced Arthritis Model *: P<0.05
Slide 8: VYN202 Results Show Strong Correlation with VYN201 Results
8 VYN202 Results Show Strong Correlation with VYN201 Results Reinforcing BET potential and role of BD2 inhibition in treatment of autoimmune diseases 0 10 20 30 40 50 60 70 80 90 100 % Improvement from Baseline at Day 15 Psoriasis Model VYN201 Locally - administered 0.01% 0.1% 1% 1 (mg/kg) 3 10 3 VY
Slide 9: Phase 1a SAD/MAD Data
VYN202: Phase 1a SAD/MAD Data
Slide 10: Phase 1a SAD/MAD Trial Design and Key Objectives
VYN202 Phase 1a SAD/MAD Trial Design and Key Objectives 10 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 E
Slide 11: Demonstrated a Favorable Safety and Tolerability Profile in Phase 1
VYN202 Demonstrated a Favorable Safety and Tolerability Profile in Phase 1 11 VYN202 was generally well tolerated in Phase 1 MAD with no drug related AEs of special interest historically associated with BET inhibitor class VYN202 Placebo (n=6) Treatment Emergent AEs Number of Subjects Reporting (%)
Slide 12: Phase 1 MAD Results: Selected Laboratory Data
VYN202 Phase 1 MAD Results: Selected Laboratory Data 12 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 10^3/ 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
Slide 13: Phase 1 SAD and 14 Day MAD Pharmacokinetics
VYN202 Phase 1 SAD and Day 14 MAD Pharmacokinetics 13 • 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 D
Slide 14: Pharmacokinetics Show Strong Correlation with Target Engagement
Pharmacokinetics Show Strong Correlation with Target Engagement 14 • 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 phar
Slide 15: Demonstrated Impact on Pro-Inflammatory and Disease Related Cytokines
Demonstrated Impact on Pro - Inflammatory and Disease Related Cytokines 15 -60% -50% -40% -30% -20% -10% 0% 10% 20% 30% 40% Mean % Change from Baseline Ex Vivo Inhibition of Disease Related Cytokines 1 , Day 14 1U sing TLR4/TLR7 stimulation and analysis from whole blood samples Th1/Tc1 Th1/Myeloid C
Slide 16: Majority of Cytokine Suppression Occurs in Concentrations at 1mg or Below
Majority of Cytokine Suppression Occurs in Concentrations at 1mg or Below 16 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 (0.5mg
Slide 17: Phase 1a MAD Data Summary
VYN202 Phase 1a MAD Data Summary 17 • 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 a