Aclaris Therapeutics, Inc. · NASDAQ:ACRS
Aclaris Therapeutics — Investor Presentation (May 2020)
41 slides from Aclaris Therapeutics's investor presentation, May 27, 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-0480 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-0480 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-0480 05/20) LEADERSHIP • Physician/Scientist founded and led • World class ex-Pfizer kinase and ex-GSK immunology leadership • Kinome experts skilled at develo
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-0480 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-0480 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-0480 05/20) The Kinase Opportunity Creating New Medicines Targeting Previously Inaccessible Kinome Targets Science 2003 ~36 Marketed Drugs ~$48B* Annual Sales
Slide 7: 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-0480 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 8: 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-0480 05/20) KINect Platform Developing Kinase Drug Candidates Rapidly & Efficiently Proprietary Portfolio • MK2 Inhibitor • JAK Inhibitors • ITK Inhibitors Str
Slide 9: KINect Platform Demonstrated Success
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) KINect™ Platform Demonstrated Success Reversible and Covalent • Oral anti-TNF, anti-IL1, and anti-IL6 • Novel approach for a difficult to target ki
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-0480 05/20) ATI-450: MK2 Inhibitor (Investigational Drug Candidate) 10
Slide 11: MK2 Inhibitor: Oral Small Molecule Inhibitor of TNFα, IL1, and IL6
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) MK2 Inhibitor: Oral Small Molecule Inhibitor of TNFα, IL1, and IL6 • MK2* drives pro-inflammatory cytokine expression • The effects of inhibiting M
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-0480 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-0480 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: Novel mechanism: 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-0480 05/20) Novel mechanism: Capturing MK2 in an Inactive State Crystal structure of the p38α/MK2 complex ATI-450 (yellow) docked in the pocket • In the nucleu
Slide 15: ATI-450 Selectivity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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 the Development of ATI-450
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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-0480 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 MK2 Pathway Inhibitor ATI-450
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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: Mouse Model: 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-0480 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-0480 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 Preclinical Data: IL1β Expression in CAPS PBMCs
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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-0480 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 Trial Design and Demographics
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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 24: 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-0480 05/20) Most Common Adverse Events (≥2 subjects in the trial) • No serious adverse events or adverse events that led to discontinuation of study medication
Slide 25: MAD Pharmacokinetics: Dose Proportional PK
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) ATI-450-PKPD-101 MAD Pharmacokinetics: Dose Proportional PK 25 Mean (SD) plasma concentration-time profiles of ATI-450: Day 7 t½ = 9-12 hours * Dat
Slide 26: MAD PD Marker Time Dependence: pHSP27, TNFa, IL1b
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) ATI-450-PKPD-101: Day 7 MAD PD Marker Time Dependence Target Biomarker pHSP27 and Cytokines TNFa and IL1b • ATI-450 dosed orally BID for 7 days in
Slide 27: MAD 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-0480 05/20) ATI-450-PKPD-101: Day 7 MAD PD Biomarker Time Dependence Cytokines IL6 and IL8 • ATI-450 dosed orally BID for 7 days in healthy subjects at doses o
Slide 28: Multiples of Cytokine IC80 Across Dosing Interval
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) 28 *IC80 values generated with all SAD/MAD exposure data using the Emax model in WinNonlin ** 50 mg BID MAD Cohort 50 mg BID Ctrough = 87.9 ng/ml 5
Slide 29: In Vitro Model: IL1b-Stimulated Cytokines in Human Whole Blood
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) In Vitro Model: ATI-450 Inhibits IL1b-Stimulated Cytokines in Human Whole Blood 29 IL1b-Stimulated HWB ATI-450 was added to freshly isolated human
Slide 30: MK2 inhibitor ATI-450 Summary
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) • Discovered a novel approach to drug the target • Potential alternative for diseases treated by biologics and JAK inhibitors ✓ Robust efficacy in
Slide 31: 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-0480 05/20) ATI-1777 (Topical Soft-JAK Inhibitor) (Investigational Drug Candidate) 31
Slide 32: Atopic Dermatitis Opportunity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) Atopic Dermatitis Opportunity • Positioning: • Comparable efficacy to other topical JAKs but “soft” drug to minimize the potential for systemic imm
Slide 33: 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-0480 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 34: 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-0480 05/20) • Single application of 2% ATI-1777 development formulation significantly inhibits IL15 (JAK1/3) induced gene induction (CCL8). Porcine Model: ATI-
Slide 35: 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-0480 05/20) ATI-2138 (ITK/TXK/JAK3 Inhibitor) (Investigational Drug Candidate) 35
Slide 36: ATI-2138: Covalent ITK/TXK/JAK3 (ITJ) Inhibitor
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) • ATI-2138 covalently blocks ITK/TXK/JAK3* ✓ Potential for synergistic efficacy • ITK/TXK required for T-cell receptor (TCR) signaling • JAK3 requi
Slide 37: 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-0480 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 38: ATI-2138 reduced inflammation and bone mineral density loss
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) ATI-2138 reduced inflammation and bone mineral density loss Rat Adjuvant Induced Arthritis (AIA) Model: ATI-2138 Reduced Inflammation and Protected
Slide 39: Biopharmaceutical Company Cash Position
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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 40: Catalysts
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 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 41: Thank You
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0480 05/20) THANK YOU EMPOWERING PATIENTS THROUGH KINOME INNOVATION
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