Aclaris Therapeutics, Inc. · NASDAQ:ACRS
Aclaris Therapeutics — Investor Presentation (December 2019)
35 slides from Aclaris Therapeutics's investor presentation, Dec 3, 2019
Slide 1: Company Overview December 2019
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Company Overview December 2019 EMPOWERING PATIENTS THROUGH KINOME INNOVATION
Slide 2: Cautionary Note Regarding Forward-Looking Statements
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securit
Slide 3: Leadership, KINect Platform and Innovative Pipeline
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved LEADERSHIP • Physician/Scientist founded and led • Kinome experts - combined 300+ years of R&D experience immunology and inflammation • World class ex-Pfizer kinase and ex-
Slide 4: R&D Leadership Team
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved R&D Leadership Team Experienced team with deep scientific and operational experience Former VP Research & Global Head, Pfizer Inflammation, co-leader of Pfizer Licensing Te
Slide 5: Pipeline
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Pipeline Program Indication(s) Preclinical Phase 1 Phase 2 Phase 3 ATI-450 MK2 Inhibitor Oral Rheumatoid Arthritis + Additional Immuno- inflammatory Indication ATI-1777 JAK
Slide 6: The Kinase Opportunity and Challenge
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved The Kinase Opportunity and Challenge Creating New Medicines Targeting Previously Inaccessible Kinome Targets Science 2003 ~36 Marketed Drugs ~$48B* Annual Sales of Kinase D
Slide 7: KINect Platform: Developing Kinase Drug Candidates Rapidly & Efficiently
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved KINect™ Platform Developing Kinase Drug Candidates Rapidly & Efficiently Proprietary Portfolio • MK2 Inhibitor • JAK Inhibitors • ITK Inhibitors Strategic Partner(s) • Proj
Slide 8: KINect Platform Demonstrated Success
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved KINect™ Platform Demonstrated Success Reversible and Covalent Covalent ITK Inhibitors MK2 Inhibitor Tissue Restricted JAK and ITK Inhibitors • Oral anti-TNF, anti-IL1, and
Slide 9: Market Overview of Select Inflammatory Indications
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Market Overview of Select Inflammatory Indications * Auster M, et al. Something Big Is Getting Bigger [research note]. New York, NY: Credit Suisse Equity Research; 2019. 1
Slide 10: ATI-450: MK2 Inhibitor (Investigational Drug Candidate)
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved ATI-450: MK2 Inhibitor (Investigational Drug Candidate) 10
Slide 11: MK2 Inhibitor – Potential Oral Alternative to Injectable Biologics and JAK Inhibitors
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved MK2 Inhibitor – Potential ORAL Alternative to Injectable, Anti-Cytokine Biologics and JAK Inhibitors for Immuno-Inflammatory Diseases • MK2* is an attractive drug target be
Slide 12: MK2-driven Cytokines are Central to Many Diseases
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved MK2-driven Cytokines are Central to Many Diseases TNFα, IL1β, IL6 Psoriasis / psoriatic arthritis Gout Inflammatory bowel disease Rheumatoid arthritis / Juvenile idiopathic
Slide 13: Evolution in Understanding of a Well-Known Path: p38α to MK2
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Evolution in Understanding of a Well-Known Path The Path From p38α to MK2 p38α was the original therapeutic target for suppressing TNFα and other pro-inflammatory cytokines
Slide 14: Capturing MK2 in an Inactive State
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved 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 and p38α dock in a high af
Slide 15: ATI-450 Selectivity
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • 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 Assay Fold Selective p38α/MK
Slide 16: Animal Models Supporting the Development of ATI-450
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Animal Models Supporting the Development of ATI-450 in Inflammatory Diseases Therapeutic Area Animal Model Reference Rheumatoid Arthritis / Psoriatic Arthritis Rat streptoc
Slide 17: ATI-450 Blocks MK2 – Potential Effect in Rheumatoid Arthritis
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved ATI-450 Blocks MK2 – Potential Effect in Rheumatoid Arthritis MK2 is a key regulator of essential pathogenic signals in chronic inflammatory and autoimmune diseases Cells C
Slide 18: In vivo Preclinical Data of MK2 Pathway Inhibitor ATI-450
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved In vivo Preclinical Data of MK2 Pathway Inhibitor ATI-450 Normal Vehicle 450 (5 mpk) Joint Protection in Rat Arthritis Model1 Cytokine Modulation in Orphan Autoinflammatory
Slide 19: Ex vivo Preclinical Data: ATI-450 Inhibits IL1β Expression in CAPS PBMCs
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Ex vivo Preclinical Data: ATI-450 Inhibits IL1β Expression in PBMCs from a CAPS Patient • Peripheral blood mononuclear cells (PMBCs) were isolated from CAPS patients and he
Slide 20: Mouse Model: ATI-450 Inhibits RANKL-induced Osteoclastogenesis
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • In CAPS, osteoclastogenesis gives rise to low bone mass (osteopenia) •(a) When bone marrow derived macrophages (BMDM) from NOMID mice are stimulated with RANKL (RANK liga
Slide 21: Mouse Model: LPS-Induced TNFa Production
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Mouse Model: LPS-Induced TNFa Production ATI-450 demonstrated durable response (no tachyphylaxis) • Conventional p38 (CDD-111) and MK2i (ATI- 450) administered to mice in f
Slide 22: ATI-450 Clinical Development
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved ATI-450 Clinical Development Rheumatoid Arthritis Phase 2 Clinical Trial • 12 wks: ATI-450 vs placebo • Assess CRP dynamics • Clinical Disease Activity/PD Biomarkers • MRI:
Slide 23: MK2 Inhibitor ATI-450 Summary
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • Well-known pathway • Discovered an approach to drug the target • Novel mechanism designed to block inflammation ✓ Multiple inflammatory cytokines impacted ✓ Key RA inflam
Slide 24: ATI-1777 (Topical Soft-JAK Inhibitor) (Investigational Drug Candidate)
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved ATI-1777 (Topical Soft-JAK Inhibitor) (Investigational Drug Candidate) 24
Slide 25: Atopic Dermatitis and Topical Soft-JAK Inhibitor Opportunity
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • Atopic dermatitis (AD) is a disease of unknown origin that usually starts in early infancy and is typified by pruritus, eczematous lesions, xerosis (dry skin), and lichen
Slide 26: Minipig Model: ATI-1777 Nonclinical Safety Program
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • 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 samples were below limit of
Slide 27: Porcine Model: ATI-1777 Blocks IL15 Induced CCL8 mRNA
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • Single application of 2% ATI- 1777 development formulation significantly inhibits IL15 induced gene induction (CCL8). • Clinical topical formulation of 1.5% ruxolitinib d
Slide 28: ATI-1777: Topical Soft-JAK Inhibitor to Target Moderate-to-Severe AD
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Formulate a topical atopic dermatitis therapy which meets the medical, aesthetic and compliance needs of patients and physicians ATI-1777: Topical Soft-JAK Inhibitor to Tar
Slide 29: ATI-2138 (ITK/TXK/JAK3) (Investigational Drug Candidate)
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved ATI-2138 (ITK/TXK/JAK3) (Investigational Drug Candidate) 29
Slide 30: ATI-2138: Covalent ITK/TXK/JAK3 Inhibitor
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved • ATI-2138 covalently blocks ITK/TXK/JAK3* ✓ ITK/TXK required for T-cell receptor signaling ✓ JAK3 required for gc cytokines (IL-2/4/7/9/15/21) ✓ Targeting both with a sing
Slide 31: ATI-2138 is a Potent Covalent Inhibitor
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved 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) Assay ITK/TXK activity
Slide 32: ATI-2138 Reduced Inflammation and Bone Mineral Density Loss
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved ATI-2138 reduced inflammation and bone mineral density loss Rat Adjuvant Induced Arthritis (AIA) Model: ATI-2138 Reduced Inflammation and Protected Bone VEH QD ATI-2138-10-
Slide 33: Biopharmaceutical Company Cash Position
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Biopharmaceutical Company Cash Position $91 million as of September 30, 2019 Commitment to Patients Focus on addressing the needs of patients with immuno-inflammatory disea
Slide 34: Catalysts
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved Catalysts Milestone 2019 2020 Q3 Q4 Q1 Q2 Q3 Q4 A-101 45% Common Warts Phase 3 Data (THWART-1, THWART-2) ✓ Immuno-Inflammatory ATI-450 (MK2 Inhibitor) - Initiate Phase 1 Tr
Slide 35: Thank You
© Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved © Copyright 2019 Aclaris Therapeutics, Inc. All rights reserved THANK YOU EMPOWERING PATIENTS THROUGH KINOME INNOVATION
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