Aclaris Therapeutics, Inc. · NASDAQ:ACRS
Aclaris Therapeutics — Investor Presentation (May 2020)
43 slides from Aclaris Therapeutics's investor presentation, May 15, 2020
Slide 1: Company Overview May 2020
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Company Overview May 2020 EMPOWERING PATIENTS THROUGH KINOME INNOVATION
Slide 2: Forward-looking statements
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defin
Slide 3: Leadership, KINect platform and innovative pipeline
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) LEADERSHIP • Physician/Scientist founded and led • Kinome experts - combined 300+ years of R&D experience immunology and inflammation • World class
Slide 4: R&D Leadership Team
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) R&D Leadership Team Experienced team with deep scientific and operational experience Former VP Research & Global Head, Pfizer Inflammation, co-lead
Slide 5: Pipeline
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Pipeline Program Indication(s) Preclinical Phase 1 Phase 2 Phase 3 ATI-450 MK2 Inhibitor Oral Rheumatoid Arthritis Additional Immuno- inflammatory
Slide 6: The Kinase Opportunity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) The Kinase Opportunity Creating New Medicines Targeting Previously Inaccessible Kinome Targets Science 2003 ~36 Marketed Drugs ~$48B* Annual Sales
Slide 7: KINect Platform: Developing Kinase Drug Candidates Rapidly & Efficiently
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) KINect Platform Developing Kinase Drug Candidates Rapidly & Efficiently Proprietary Portfolio • MK2 Inhibitor • JAK Inhibitors • ITK Inhibitors Str
Slide 8: KINect Platform Demonstrated Success
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) KINect™ Platform Demonstrated Success Reversible and Covalent • Oral anti-TNF, anti-IL1, and anti-IL6 MK2 kinase inhibitor drug • Novel approach fo
Slide 9: Market Overview of Select Inflammatory Indications
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Market Overview of Select Inflammatory Indications * Auster M, et al. Something Big Is Getting Bigger [research note]. New York, NY: Credit Suisse
Slide 10: ATI-450: MK2 Inhibitor
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-450: MK2 Inhibitor (Investigational Drug Candidate) 10
Slide 11: MK2 Inhibitor – Potential Alternative to Injectable Biologics and JAK Inhibitors
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) MK2 Inhibitor – Potential Alternative to Injectable, Anti-Cytokine Biologics and JAK Inhibitors for Immuno-Inflammatory Diseases • MK2* is an attra
Slide 12: MK2-driven Cytokines are Central to Many Diseases
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) MK2-driven Cytokines are Central to Many Diseases TNFα, IL1β, IL6 Psoriasis / psoriatic arthritis Gout Inflammatory bowel disease Rheumatoid arthri
Slide 13: Evolution in Understanding of a Well-Known Path
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Evolution in Understanding of a Well-Known Path The Path From p38α to MK2 INFLAMMATORY/STRESS STIMULI p38α Anti- inflammatory Negative Feedback TNF
Slide 14: Capturing MK2 in an Inactive State
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Capturing MK2 in an Inactive State Crystal structure of the p38α/MK2 complex ATI-450 (yellow) docked in the pocket • In the nucleus, inactive MK2 a
Slide 15: ATI-450 selectivity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • ATI-450 (5µM) was tested vs 193 kinases • >350-fold binding selectivity on all kinases in this panel except p38α and p38β ATI-450 selectivity Ass
Slide 16: Animal Models Supporting Development of ATI-450
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Animal Models Supporting the Development of ATI-450 in Immuno-Inflammatory Diseases Therapeutic Area Animal Model Reference Rheumatoid Arthritis /
Slide 17: MK2 – Potential Effect in Rheumatoid Arthritis
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) MK2 – Potential Effect in Rheumatoid Arthritis ATI-450 regulates cells and cytokines involved in RA MK2 is a key regulator of pathogenic signals in
Slide 18: In vivo Preclinical Data of ATI-450
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) In vivo Preclinical Data of MK2 Pathway Inhibitor ATI-450 Normal Vehicle 450 (5 mpk) Joint Protection in Rat Arthritis Model1 Cytokine Modulation i
Slide 19: ATI-450 Inhibits RANKL-induced Osteoclastogenesis
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • In CAPS, osteoclastogenesis gives rise to low bone mass (osteopenia) •(a) When bone marrow derived macrophages (BMDM) from NOMID mice are stimula
Slide 20: Mouse Model: LPS-Induced TNFa Production
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Mouse Model: LPS-Induced TNFa Production ATI-450 demonstrated durable response (no tachyphylaxis) • CDD-111 and ATI-450 administered to mice in fee
Slide 21: Ex vivo Data: ATI-450 Inhibits IL1β in CAPS PBMCs
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Ex vivo Preclinical Data: ATI-450 Inhibits IL1β Expression in PBMCs from a Patient with CAPS • Peripheral blood mononuclear cells (PBMCs) were isol
Slide 22: ATI-450 Clinical Development
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-450 Clinical Development Rheumatoid Arthritis Phase 2a Clinical Trial • 12 wks: ATI-450 vs placebo • Assess CRP dynamics • Clinical Disease Act
Slide 23: ATI-450-PKPD-101 SAD/MAD Phase 1 Trial
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • First-in-human, randomized, observer-blind, placebo- controlled trial ✓Single Ascending Doses and Multiple Ascending Doses (SAD/MAD) • Objectives
Slide 24: Trial Design and Demographics
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • Three-Part Study: ✓ Part A: single ascending dose (SAD) plus food effect (n=32) • 4 cohorts: 10mg, 30mg, 50mg, 100mg (100mg repeated with high fa
Slide 25: Safety: ATI-450 Generally Well-Tolerated
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Most Common Adverse Events (≥2 subjects in the trial) • No serious adverse events • No adverse events led to discontinuation of study medication •
Slide 26: MAD Pharmacokinetics: Dose Proportional PK
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-450-PKPD-101 MAD Pharmacokinetics: Dose Proportional PK 26 Mean (SD) plasma concentration-time profiles of ATI-450: Day 7 t½ = 9-12 hours * Dat
Slide 27: PD Marker Time Dependence: pHSP27, TNFa and IL1b
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-450 PD: Day 7 MAD PD Marker Time Dependence Target Biomarker pHSP27 and Cytokines TNFa and IL1b • ATI-450 dosed orally BID for 7 days in health
Slide 28: PD Biomarker Time Dependence: IL6 and IL8
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-450 PD: Day 7 MAD PD Biomarker Time Dependence Cytokines IL6 and IL8 • ATI-450 dosed orally BID for 7 days in healthy subjects at doses of 10mg
Slide 29: Plasma Levels Greater Than IC80 Throughout Dosing Interval
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Biomarker Dose Level (mg BID) Parameter Ctrough Cmax IL-1β 10 Fold IC80 0.3 1.3 IL-6 10 Fold IC80 0.0 0.1 IL-8 10 Fold IC80 0.3 1.3 pHSP27 10 Fold
Slide 30: ATI-450-RA-201 Phase 2a Trial
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • Rheumatoid Arthritis Trial ✓PD/safety study with early look at efficacy given small patient numbers • A Phase 2a, Randomized, Investigator and Pa
Slide 31: MK2 inhibitor ATI-450 Summary
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • Discovered an approach to drug the target ✓ Lock MK2 in a catalytically inactive state – a unique MOA ✓ Multiple relevant inflammatory cytokines
Slide 32: ATI-1777 (Topical Soft-JAK Inhibitor)
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-1777 (Topical Soft-JAK Inhibitor) (Investigational Drug Candidate) 32
Slide 33: Atopic dermatitis and topical soft-JAK inhibitor opportunity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • Atopic dermatitis (AD) is a disease of unknown origin that usually starts in early infancy and is typified by pruritus, eczematous lesions, xeros
Slide 34: Minipig Model: ATI-1777 Nonclinical Safety Program
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • No adverse effects noted (10% body surface area, QD) • Bleeds at 0.5, 1, 2, 4, 8, 12, and 24 hours post-application: Days 1 and 6 • All plasma sa
Slide 35: Porcine Model: ATI-1777 Blocks IL15 Induced CCL8 mRNA
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • Single application of 2% ATI- 1777 development formulation significantly inhibits IL15 induced gene induction (CCL8). • Clinical topical formulat
Slide 36: ATI-1777: Topical Soft-JAK Inhibitor to Target Moderate-to-Severe AD
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Formulate a topical therapy for atopic dermatitis which meets the medical, aesthetic and compliance needs of patients and physicians ATI-1777: Topi
Slide 37: ATI-2138 (ITK/TXK/JAK3 Inhibitor)
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-2138 (ITK/TXK/JAK3 Inhibitor) (Investigational Drug Candidate) 37
Slide 38: ATI-2138: Covalent ITK/TXK/JAK3 Inhibitor
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) • ATI-2138 (investigational compound) covalently blocks ITK/TXK/JAK3* ✓ ITK/TXK required for T-cell receptor (TCR) signaling ✓ JAK3 required for gc
Slide 39: ATI-2138 is a Potent Covalent Inhibitor
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-2138 is a Potent Covalent Inhibitor ATI-2138 potently inhibits ITK/TXK and JAK3 in cells and in whole blood Assay Description ATI-2138 IC50 (nM
Slide 40: Rat AIA Model: ATI-2138 Reduced Inflammation and Protected Bone
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) ATI-2138 reduced inflammation and bone mineral density loss Rat Adjuvant Induced Arthritis (AIA) Model: ATI-2138 Reduced Inflammation and Protected
Slide 41: Biopharmaceutical Company Cash Position
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Biopharmaceutical Company Cash Position $79 million as of March 31, 2020 Commitment to Patients Focus on addressing the needs of patients with immu
Slide 42: Catalysts
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) Catalysts Milestone 2020 2021 1Q 2Q 3Q 4Q 1Q 2Q ATI-450 (MK2 Inhibitor) Phase 1 Data (SAD/MAD) ✓ Initiate Phase 2a Trial in Rheumatoid Arthritis ✓
Slide 43: Thank You
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0458 05/20) THANK YOU EMPOWERING PATIENTS THROUGH KINOME INNOVATION
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