Vyne Therapeutics Inc. · NASDAQ:VYNE
Vyne Therapeutics — Investor Presentation (November 2022)
53 slides from Vyne Therapeutics's investor presentation, Nov 10, 2022
Slide 1: Investor Presentation November 2022
INVESTOR PRESENTATION November 2022
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 199 including, but not limited to, statements regarding clinical development and timelines for VYNE’s BET inhibitor platform, VYNE’s development st
Slide 3: Investment Highlights
3 Investment Highlights (NASDAQ: VYNE) VYNE is focused on developing proprietary, innovative, and differentiated therapies for the treatment of immuno - inflammatory conditions Innovative Pipeline • Pipeline focused on major markets in inflammation and immunology with high unmet medical need • Key T
Slide 4: Pipeline: compounds, targets, indications and stage of development
Compound Target Indication / Therapeutic Area Stage of Development VYN201 “Soft” pan - BD BET inhibitor (Topical Administration) Vitiligo • IND submitted • Q4 2022: Phase 1a/b 1 FPI • 1H 2023: Phase 1a/b 1 TLR VYN201 “Soft” pan - BD BET inhibitor (Non - topical Administrations) Indications benefitin
Slide 5: InhiBET BET Inhibitor Platform
InhiBET ΠBET Inhibitor Platform Bromodomain & Extra - Terminal Domain (BET) Inhibition for Immunology and Inflammatory Diseases 5
Slide 6: 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 7: How BET Proteins Fuel the Vicious Cycle of Pro-Inflammatory Cytokine Production
How BET Proteins Fuel the “Vicious Cycle” of 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 factors 4 5 6 BRD4 active cytokin
Slide 8: 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 and release pro - inflammatory cytokin
Slide 9: InhiBET BET Inhibitor Platform Overview
InhiBET ΠBET Inhibitor Platform Overview Platform includes global rights to a library of NCEs for any indication 9 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 - infla
Slide 10: VYN201 Locally administered pan-BET inhibitor
VYN201 Locally administered pan - BET inhibitor
Slide 11: VYN201 Pre-Clinical Efficacy Model Evaluations
VYN201 Pre - Clinical Efficacy Model Evaluations 11 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 12: VYN201: Preclinical Proof-of-Concept Data Summary
VYN201: Preclinical Proof - of - Concept Data Summary Potential “pipeline in a product” with broad utility across multiple routes of administration 12 1. Idiopathic pulmonary Fibrosis (IPF) 2. Data on file Arthritis Model (Intra - articular Injection) IPF 1 & Fibrotic Tissue Models (Intra - Nasal an
Slide 13: VYN201: Vitiligo Disease / Market Overview
VYN201: Vitiligo Disease / Market Overview
Slide 14: Vitiligo – Disease Overview
Vitiligo – Disease Overview An acquired disorder of dermatologic pigmentation with high impact on self - esteem 14 Pathophysiology & Clinical Presentation • Vitiligo is a depigmenting skin disorder characterized by the loss of melanocytes, which causes typical non - scaly, chalky - white macules • P
Slide 15: Vitiligo – Treatment Paradigm
Vitiligo – Treatment Paradigm Only one drug currently approved; Treatment is dominated by non - specific therapeutics 15 Current Treatment Paradigm 1L Corticosteroids Phototherapy Topical Calcineurin Inhib . Excimer Laser 2L Phototherapy + Combo Agent(s) 3L+ Surgery Depigmentation Therapy Treatment
Slide 16: Vitiligo – Epidemiology and Pricing
Vitiligo – Epidemiology and Pricing Large market with high unmet need and lack of approved prescription treatment options 16 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; Incyte Corporate Pres.; Redbook; Rxlist.co
Slide 17: VYN201: Vitiligo Preclinical data and Clinical Plan
VYN201: Vitiligo Preclinical data and Clinical Plan
Slide 18: VYN201: Human Tissue Model of Vitiligo – Demonstrated Inhibition of MMP9
18 • 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 19: 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 20: VYN201: Human Tissue Model of Vitiligo – Effect on Melanocyte Retention
VYN201: Human Tissue Model of Vitiligo – Effect on Melanocyte Retention 20 • Stimulated and vehicle - treated RHE demonstrated a significant loss in melanin content, relative to unstimulated control • VYN201 substantially prevents the loss of melanin pigment in the basal layers of skin in a dose dep
Slide 21: 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 22: VYN201: Human Tissue Model of Vitiligo – Gene regulation
Stimulated control Stimulated and VYN201 1% treated Preliminary data suggest that VYN201 regulates genes relevant to Vitiligo including impacting WNT pathway which is believed to play a key role in melanocyte regeneration Significant upregulation of cytokines IL6, IL1A and IL1B and TNF Melanocyte mi
Slide 23: VYN201: Phase 1a/b Study Design in Vitiligo
Phase 1b Portion (N=30: 3 Cohorts with 10 patients each) Treatment on the face and target lesion(s) on trunk of vitiligo patients for 8 weeks of once - daily treatment with planned extension. Primary objective: Evaluation of the safety and pharmacokinetics of VYN201 in vitiligo patients • Dose level
Slide 24: Vitiligo Represents an Exciting Opportunity for VYN201
Large Market 24 Vitiligo Represents an Exciting Opportunity for VYN201 • 0.5 to 2.0% of worldwide population • Non - segmental sub - type represents ~90% of patients • Est. U.S. prevalence is between 1.9 and 3.2 million cases (diagnosed/undiagnosed) Significant Unmet Need • Vitiligo is a disabling d
Slide 25: VYN201: Th17 Inflammation Model
VYN201: Th17 Inflammation Model
Slide 26: VYN201 in Imiquimod-Induced Th17 Inflammation Model
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 27: 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 28: VYN201 Significantly 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 29: VYN201: Fibrotic Tissue & IPF Models
VYN201: Fibrotic Tissue & IPF Models
Slide 30: VYN201: Murine Skin Healing and Fibrosis Model
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 31: 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 32: VYN201: Bleomycin-induced mouse model of IPF - Histology
VYN201: Bleomycin - induced mouse model of IPF - Histology Histology images indicate positive impact of VYN201 0.06mg/ml on fibrosis in lungs. Additional preclinical exploration planned 32 Healthy sham control Bleomycin control Bleomycin + 0.06mg/ml VYN201 A: Normal lung parenchyma with open airways
Slide 33: VYN201: Arthritis
VYN201: Arthritis ¥VYNE
Slide 34: 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 35: 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 36: 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 dose - dependent effect -0.50 0.00 0.50 1.0
Slide 37: VYN201: CAIA Mouse Model of Arthritis – Histopathology
VYN201: CAIA Mouse Model of Arthritis – Histopathology Joint histopathology confirmed arthritis clinical scoring & local effect 37 VYN201 10mg/kg treatment group Untreated right paw • Arthritis score 4 “severe” • Severe inflammation with destruction of both cartilage and bone Inflammation marked wit
Slide 38: VYN202: BD2 selective BET inhibitor
VYN202: BD2 selective BET inhibitor
Slide 39: 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 40: FMX114 Tofacitinib and Fingolimod Topical Gel for Atopic Dermatitis
FMX114 Tofacitinib and Fingolimod Topical Gel for Atopic Dermatitis 40
Slide 41: FMX114: Atopic Dermatitis Market
FMX114: Atopic Dermatitis Market Significant and rapidly growing Market Opportunity 1. Data on file 2. Globaldata and includes U.S., France, Germany, Italy, Spain, UK and Japan 3. Auster M, et al. Something Big Is Getting Bigger [research note]. Credit Suisse Equity Research; 2019 41 High prevalence
Slide 42: FMX114: Two Validated Modes of Action
FMX114: Two Validated Modes of Action Designed to address both the source & cause of inflammation in AD Image Sources: Leung DY, Guttman - Yassky E. J Allergy Clin Immunol . 2014;134(4):769 - 779 and Hodge JA, Kawabata TT, Krishnaswami S et al. Clin & Exper Rheum . 2016; 34(2): 318 - 328 1. Schwartz
Slide 43: FMX114: Potential for a series of firsts in atopic dermatitis
FMX114: Potential for a series of firsts in the treatment of atopic dermatitis 43 FMX114 has the potential to be the: • 1 st topical combination product for the treatment of atopic dermatitis • 1 st topical product containing a sphingosine 1 - phosphate receptor modulator (S1PRM) • S1PRM’s that are
Slide 44: FMX114: Targeting a Multi-factorial Solution for a Multi-factorial Disease
Characteristic FMX114 Target Profile JAK Inhibitors PDE4 Inhibitors Aryl hydrocarbon receptor Agonists Gluco - Corticosteroids Calcineurin Inhibitors Moderate - to - severe patient indication Multiple validated modes of action Rapid onset of treatment effect Potential for direct skin barrier repair
Slide 45: FMX114 Phase 1b/2a Proof of Concept Study Design
FMX114 Phase 1b/2a Proof of Concept Study Design Randomized, double - blinded, vehicle - controlled Phase 1b/2a trial with separate open - label active treatment phase evaluating the safety, pharmacokinetics & efficacy of FMX114 gel vs. vehicle gel in the treatment of mild - to - moderate atopic der
Slide 46: FMX114 Phase 1b Safety and Pharmacokinetics
FMX114 Phase 1b Safety and Pharmacokinetics 46 Safety • FMX114 and vehicle generally well tolerated with no treatment - emergent SAEs. • No clinically - significant adverse events of special interest related to either tofacitinib or fingolimod. • Local application site tolerance to both treatments r
Slide 47: FMX114 Phase 1b Efficacy Data
FMX114 Phase 1b Efficacy Data 47 ADSI = Atopic Dermatitis Severity Score; NRS = Numeric Rating Scale Absolute and percent change relative to baseline in ADSI score at week 2 : • Mean ADSI scores for FMX114 and vehicle treated lesions were 7.8 and 8.0, respectively, at baseline. • Mean reduction in A
Slide 48: FMX114 Phase 2a Efficacy Data
• Efficacy data for the Phase 2a trial was measured based on the absolute and percent change relative to baseline in the ADSI s cor ing assessment at week 4: • FMX114 was statistically superior to vehicle up to and including week 3; numerically superior at week 4 (primary endpoint mis sed ) • FMX114
Slide 49: FMX114 Phase 2a Subanalyses Secondary Endpoints
FMX114 Phase 2a Subanalyses 49 Secondary Endpoints (Percent Reduction in TLSS Score and WI - NRS) - 22.0 - 40.1 - 45.9 - 46.8 - 72.4 - 3.9 - 18.4 - 26.3 - 36.5 - 69.2 -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 0 1 2 3 4 5 6 Treatment Period (Week) Change in TLSS (n = 21 pts.; 42 lesions) * * * • Com
Slide 50: FMX114 Phase 2a Subanalyses
FMX114 Phase 2a Subanalyses 50 ADSI = Atopic Dermatitis Severity Score 1. Inclusive *p<0.05 – FMX114 treated lesions vs. vehicle treated lesions Percent Reduction in ADSI Score by Baseline Score - 41.3 - 54.5 - 57.4 - 64.7 - 85.1 - 16.9 - 29.5 - 31.1 - 47.9 - 82.5 -100.0 -90.0 -80.0 -70.0 -60.0 -50.
Slide 51: FMX114 Phase 1b/2a Results Summary
FMX114 Phase 1b/2a Results Summary 51 x FMX114 drug effect and proof - of - concept established • On target PK and safety profile met • Statistically significant efficacy results at weeks 1, 2 and 3; Primary efficacy endpoint at week 4 not met but numerically superior • Continued effect demonstrated
Slide 52: FMX114 Next Phase 2b Study Design
• 2 - arm double - blind intra - lesional design with patient acting as self - control with 2 lesions of similar size and severity • Eliminate risk of patients using active drug on lesions assigned to vehicle • Conventional 4 - arm double blind design (pivotal enabling) • Active Drug: tofacitinib 0.
Slide 53: A Therapeutics
rd A Therapeutics NASDAQ: VYNE
VYNE Therapeutics — Investor Presentation (November 2022) on 6ix