Vyne Therapeutics Inc. · NASDAQ:VYNE
Vyne Therapeutics — B&T Cell-Mediated Autoimmune Disease Drug Development Conference 2022
35 slides from Vyne Therapeutics's conference presentation, Jul 27, 2022
Slide 1: The InhiBET Platform: BET Inhibitors in Autoimmune Disease
The InhiBET TM Platform Bromodomain & End Terminal (BET) Inhibitors in Autoimmune Disease Iain Stuart, Ph.D Chief Scientific Officer B&T Cell - Mediated Autoimmune Disease Drug Development Conference, July 27, 2022 1
Slide 2: Forward Looking Statements
Forward Looking Statements This presentation includes forward - looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 , including, but not limited to statements regarding the development of VYNE’s product candidates, the timing of its clinical trials and regul
Slide 3: Bromodomain and end terminal proteins: Epigenetic enablers of transcription
Bromodomain and end terminal proteins: Epigenetic enablers of transcription 3 Shi & Vakoc , Mol. Cell 2014 • The bromodomain family (“ Brd ” or “BD”) is comprises of 4 members (BRD2 - 4, BRDT) and have two shared domains, bromodomain 1 and 2 (BD1 and BD2) with an extra - terminal domain • Both BD1 a
Slide 4: BET Proteins Play a Key Role in Regulation of Inflammatory and Oncogenic Genes
BET Proteins Play a Key Role in the Regulation of Inflammatory and Oncogenic Genes involved in Several Diseases Gene transcription stimulated Histones N - terminal of histones BRD4 Oncogenic genes, leading to: • Increased cell proliferation/survival • An increase in solid tumors and hematologic mali
Slide 5: How BET Proteins Influence Transcriptional Machinery
How BET Proteins Influence Transcriptional Machinery Role of BET proteins in Pro - Inflammatory Cytokine Production in Autoimmune Diseases Pro - inflammatory cytokines Cytokines bind to cytokine receptors 1 Activation of NF - kb kinase complex 2 Nuclear translocation 3 Recruitment of transcription f
Slide 6: BET Inhibitors Block BD1/BD2 Binding to Acetylated Lysines
cytokine transcription BET Inhibitors Block BD1/BD2 Binding to Acetylated Lysines and Stall Pro - inflammatory Protein Transcription BET INHIBITOR Binds BD1 and/or BD2 of BRD4 protein making it unable recognize acetylated histones & recruit transcription factors/form transcription complexes Pro - in
Slide 7: BET inhibitor biology – what have we learned?
BET inhibitor biology – what have we learned? 7 Dawson et al, Science 2020 Bromodomain functionality • Each BRD bromodomain plays distinct roles transcription regulation – they don’t do the same job - Steady - state gene expression primarily requires BD1. - Rapid increase of gene expression induced
Slide 8: InhiBET BET Inhibitor Platform Overview
InhiBET Œ BET Inhibitor Platform Overview 8 VYN201 Locally administered Pan - BD BET inhibitor VYN202 Oral BD2 - selective BET inhibitor BD1 BD2 Designed to selectively bind to BD2 and is being developed for major immuno - inflammatory diseases Focused BD activity: • Low nM Kd against BD2 domain • H
Slide 9: VYN202 Orally available BD2 selective BET inhibitor
Confidential – For Internal Use Only. VYN202 Orally available BD2 selective BET inhibitor
Slide 10: VYN202 Program Highlights & Molecular Profile
Potential Target Market 1 : • Immuno - inflammatory indications such as rheumatoid arthritis, systemic lupus erythematosus, ulcerative colitis/Crohn's and multiple sclerosis; additional potential in myeloproliferative neoplastic disorders 2 Focused activity: • Highly selective inhibition of BD2 doma
Slide 11: VYN201 Locally administered pan-BD BET inhibitor
Confidential – For Internal Use Only. VYN201 Locally administered pan - BD BET inhibitor Non - clinical efficacy program
Slide 12: VYN201 Pre-Clinical Efficacy Model Evaluations
VYN201 Pre - Clinical Efficacy Model Evaluations 12 Indication/area Model Administration Route Status Th17 autoimmune diseases IMI - induction mouse model Topical Complete Th2 autoimmune diseases DNCB - induction mouse model Topical Complete Fibrosis Wound healing outcomes mouse model Topical Comple
Slide 13: VYN201 Psoriasis murine model (topical)
Confidential – For Internal Use Only. VYN201 Psoriasis murine model (topical)
Slide 14: VYN201 Psoriasis model: reduction in composite inflammation score
IMI – Imiquimod. *Composite Inflammation Severity Score is a composite mean score of erythema and peeling severity scored on a 4 - point ordinal sc ale per domain (0=none, 1=mild, 2=moderate and 3=severe for a maximum score of 6), data expressed as a mean percentage change from initiation of treatme
Slide 15: VYN201: Normal Skin Physiology in Th17-Mediated Murine Inflammation Model
VYN201 0.1% VYN201 Vehicle Clobetasol Cream 0.05% • No appreciable improvement in clinical signs • Substantial resolution of clinical signs • Skin presents with normal physiology with no evidence of striae rubrae or atrophy • No evidence suggestive of intolerance • Substantial resolution of clinical
Slide 16: VYN201 Reduced Expression of Key Pro-Inflammatory Proteins in Human Tissue
VYN201 Significantly Reduced Expression of Several Key Pro - Inflammatory Proteins Relevant to Th17 - mediated Autoimmune Diseases in Human Tissue 1 Interleukin 36 - gamma IL36 γ is implicated in upregulating IL - 17A signaling - related genes and so able to amplify keratinocyte inflammatory respons
Slide 17: VYN201 Rheumatoid Arthritis murine model (intra-articular)
Confidential – For Internal Use Only. VYN201 Rheumatoid Arthritis murine model (intra - articular)
Slide 18: VYN201: CAIA Mouse Model of Arthritis – Paw Thickness
VYN201: CAIA Mouse Model of Arthritis – Paw Thickness Marked inhibition of paw thickening/swelling CAIA = Collagen Antibody Induced Arthritis; IA = Intra - articular; IP = Intraperitoneal 1.75 2.00 2.25 2.50 2.75 3.00 3.25 3.50 Baseline Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 Day 10 Day 12 Paw thickness
Slide 19: VYN201: CAIA Mouse Model of Arthritis – Arthritis Score
VYN201: CAIA Mouse Model of Arthritis – Arthritis Score Demonstrated dose dependent reduction in disease severity *Scoring based on a five - point composite severity scale of redness, swelling of the ankles and wrists, and paw thickness. Scorin g ranges from 0 (normal) to 4 (extensive signs and symp
Slide 20: VYN201: CAIA Mouse Model of Arthritis – Systemic Impact
VYN201 1 & 10mg/kg results demonstrated the highest localized effect in the treated limb when compared to the untreated limbs (largest delta between treated and untreated limbs) VYN201: CAIA Mouse Model of Arthritis – Systemic Impact Demonstrated localized effect -0.50 0.00 0.50 1.00 1.50 2.00 Basel
Slide 21: VYN201: CAIA Mouse Model of Arthritis – Histopathology
VYN201: CAIA Mouse Model of Arthritis – Histopathology Joint histopathology confirmed arthritis clinical scoring & local effect 21 VYN201 10mg/kg treatment group Untreated right paw Arthritis score 4 “severe” Severe inflammation with destruction of both cartilage and bone. Inflammation marked with a
Slide 22: VYN201 Anti-fibrosis/scarring murine model (topical)
Confidential – For Internal Use Only. VYN201 Anti - fibrosis/scarring murine model (topical)
Slide 23: VYN201 wound healing model: healing and fibrotic tissue scores
Female hairless mice (n=4/group) had two identical 10mm incisions made either side of the flank. Animals were topically dosed 1X daily with 100mg VYN201 vehicle, VYN201 1% or a hydroalcoholic gel* until each wound had completely healed • Statistically significant difference (p<0.05) in composite glo
Slide 24: VYN201: Little Evidence of Residual Swelling in Murine Skin Healing Model
VYN201 1% VYN201 Vehicle Hydroalcoholic gel • Still evidence of minor swelling around incision sites • Little evidence of residual swelling • Wound appears more macular in nature compared to VYN201 vehicle or the hydroalcoholic gel • Incision sites appear less distinct and leave a more aesthetic out
Slide 25: VYN201 Idiopathic pulmonary fibrosis murine model (intra-nasal)
Confidential – For Internal Use Only. VYN201 Idiopathic pulmonary fibrosis murine model (intra - nasal)
Slide 26: VYN201: Bleomycin-induced Mouse Model of IPF Histopathology Images
VYN201: Bleomycin - induced mouse model of idiopathic pulmonary fibrosis Histopathology Images Lung fibrosis is induced in C57bl/6 mice using bleomycin at a dose of 4U/kg once daily by intranasal administration (N=10/treatment group). VYN201 treatment groups received nebulized, intra - nasal doses a
Slide 27: VYN201 Ex vivo human skin explant vitiligo model (topical)
Confidential – For Internal Use Only. VYN201 Ex vivo human skin explant vitiligo model (topical)
Slide 28: VYN201: Human Tissue Model of Vitiligo – Inhibition of MMP9
28 • Stimulated and vehicle treated RHE demonstrated a significant upregulation of MMP9, relative to unstimulated and untreated control • VYN201 markedly reduced the expression of MMP9 in a dose - dependent manner with a maximal effect at the 1% concentration • VYN201 1% reduced the secretion of MMP
Slide 29: VYN201: Human Tissue Model of Vitiligo – Reduction of Soluble E-cadherin
VYN201: Human Tissue Model of Vitiligo – Reduction of Soluble E - cadherin • Stimulated and vehicle - treated RHE demonstrated a significant upregulation of soluble E - cadherin, relative to unstimulated control • VYN201 affects a dose - dependent reduction in solubilized E - cadherin • VYN201 was n
Slide 30: VYN201: Human Tissue Model of Vitiligo – Effect on Melanocyte Retention
VYN201: Human Tissue Model of Vitiligo – Effect on Melanocyte Retention 30 498 100 35 367 290 36 9 0 100 200 300 400 500 600 700 Unstimulated control Stimulated control Stimulated + Vehicle Stimulated + VYN201 1% Stimulated + VYN201 0.1% Stimulated + VYN201 0.01% Stimulated + VYN201 0.001% Relative
Slide 31: VYN201: Human Tissue Model of Vitiligo – Histology
TRV: tyrosinase - related protein 1 (important enabler of melanogenesis) Keratinocytes (blue), melanocytes (green) Basal layer Melanocyte migration Retention of melanocytes at the basal layer Stimulated and Vehicle treated Unstimulated and untreated control Stimulated and VYN201 1% treated Melanocyt
Slide 32: VYN201: Human Tissue Model of Vitiligo – Gene regulation
Stimulated control Stimulated and VYN201 1% treated Transcriptome volcano plots of genes relevant to vitiligo (preliminary findings) Significant upregulation of cytokines IL6, IL1 α and β and TNF Basal layer VYN201: Human Tissue Model of Vitiligo – Gene regulation Significant downregulation of cytok
Slide 33: VYN201: First-in-Human Phase 1a/b Study Design
*Pending concurrence with US FDA. Phase 1a/b design comprising of: Phase 1a Part A single ascending / multiple ascending dose cohort in healthy volunteer participants for up to 2 weeks of once daily treatment. • Primary objective is to identify safe starting doses for vitiligo patients in Phase 1b p
Slide 34: Targeted Clinical Milestones through 2023
Target Candidate Selection Preclinical Clinical Trials Near - Term Catalysts FMX114 (tofacitinib/fingolimod gel) Mild - to - moderate Atopic Dermatitis Phase 1b: Completed Phase 2a: Enrollment Complete; TLR expected end of July/early Aug. 2022 VYN201 Locally administered Pan - BD BET inhibitor 2H 20
Slide 35: Thank you!
Confidential – For Internal Use Only. Thank you!
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