Aclaris Therapeutics, Inc. · NASDAQ:ACRS
Aclaris Therapeutics — Investor Presentation (September 2020)
43 slides from Aclaris Therapeutics's investor presentation, Sep 15, 2020
Slide 1: Company Overview September 2020
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Company Overview September 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-0508 09/20) Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defin
Slide 3: Biotechnology Company Focused on the Kinome: People + Platform + Pipeline
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) LEADERSHIP Founded and Led by Physicians and Scientists • World class ex-Pfizer (kinase) and ex-GSK (immunology) leadership • Kinome experts skille
Slide 4: The Kinase Opportunity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) The Kinase Opportunity Unlocking the Potential of the Kinome ~36 Marketed Drugs1 ~$48B1,2 Annual Sales of Kinase Drugs Medically Important and Prod
Slide 5: Leadership team
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) •Former SVP, R&D at GSK. •Led discovery and development teams in Immuno-Inflammation and Dermatology leading to multiple successful NDAs, including
Slide 6: 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-0508 09/20) KINect™ Platform Developing Kinase Drug Candidates Rapidly & Efficiently Proprietary Portfolio • MK2 Inhibitors • JAK Inhibitors • ITK Inhibitors S
Slide 7: KINect Platform: Demonstrated Success in Reversible and Covalent MOA
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) KINect™ Platform Demonstrated Success in Reversible and Covalent MOA • Oral anti-TNF, anti-IL1, and anti-IL6 • Novel approach for a difficult to ta
Slide 8: Pipeline
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Pipeline Program Indication(s) Preclinical Phase 1 Phase 2 Phase 3 ATI-450 MK2 Inhibitor Oral Rheumatoid Arthritis COVID-19* Cryopyrin-Associated P
Slide 9: ATI-450: MK2 Inhibitor
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-450: MK2 Inhibitor (Investigational Drug Candidate) 9
Slide 10: ATI-450: Oral MK2 Inhibitor Blocks Same Targets as Biologics
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-450: Small Molecule, Oral MK2 Inhibitor Blocks the Same Targets as Broadly Used Biologics MK2* drives pro-inflammatory cytokine expression • In
Slide 11: 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-0508 09/20) Rheumatoid arthritis/ Juvenile idiopathic arthritis CAPS Inflammatory Bowel Disease Gout Cardiovascular/ Cerebrovascular Disease Ankylosing spondyl
Slide 12: Evolution in Understanding a Well-Known Inflammatory Pathway
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Evolution in Understanding a Well-Known Inflammatory Pathway The Path From p38α to MK2 INFLAMMATORY/STRESS STIMULI p38α Anti- inflammatory Negative
Slide 13: 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-0508 09/20) 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 14: ATI-450 Selectivity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) • 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: Mi
Slide 15: 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-0508 09/20) Animal Models Supporting the Development of ATI-450 in Immuno-Inflammatory Diseases Therapeutic Area Animal Model Reference Rheumatoid Arthritis/ P
Slide 16: 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-0508 09/20) 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 17: 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-0508 09/20) 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 18: Mouse Model: ATI-450 Inhibits Osteoclastogenesis
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) • In CAPS, osteoclastogenesis gives rise to low bone mass (osteopenia) •(a) When bone marrow derived macrophages (BMDM) from NOMID mice are stimula
Slide 19: Mouse Model: ATI-450 Efficacious in Collagen-Induced Arthritis
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Mouse Model: ATI-450 is Efficacious in Murine Collagen-Induced Arthritis (mCIA) 19 Clinical Arthritis Score Joint Histology Score ATI-450 demonstra
Slide 20: Mouse Model: ATI-450 Increases Treg Cells in mCIA
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) 20 Mouse Model: ATI-450 Increases Regulatory T (Treg) Cells in mCIA • The effect of ATI-450 treatment on T cell subsets was evaluated in the mCIA m
Slide 21: Mouse Model: LPS-Induced TNFα Production
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Mouse Model: LPS-Induced TNFα Production ATI-450 demonstrated durable response (no tachyphylaxis) 0 20 40 60 80 100 120 140 160 180 0.5 2 3 4 CDD11
Slide 22: 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-0508 09/20) Ex Vivo Preclinical Data: ATI-450 Inhibits IL1β Expression in PBMCs from a Patient with CAPS • PBMCs were isolated from patients with CAPS and heal
Slide 23: ATI-450 Clinical Development
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-450 Clinical Development Phase 2a Clinical Trials Rheumatoid Arthritis Psoriasis Psoriatic Arthritis Hidradenitis Suppurativa Inflammatory Bowe
Slide 24: Phase 1 Trial Design and Demographics
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Part A: single ascending dose (SAD) plus food effect (n=32) • 4 cohorts: 10mg, 30mg, 50mg, 100mg (100mg repeated with high fat meal) • 8 subjects p
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-0508 09/20) Most Common Adverse Events (≥2 subjects in the trial) ATI-450-PKPD-101 Safety: ATI-450 Generally Well-Tolerated Preferred Term ATI-450 n (%) (n=48)
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-0508 09/20) 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: MAD PD Marker Time Dependence: pHSP27, TNFα, IL1β
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-450-PKPD-101: Day 7 MAD PD Marker Time Dependence Target Biomarker pHSP27 and Cytokines TNFα and IL1β • ATI-450 dosed orally BID for 7 days in
Slide 28: MAD PD Biomarker Time Dependence: IL8 and IL6
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-450-PKPD-101: Day 7 MAD PD Biomarker Time Dependence Cytokines IL8 and IL6 • ATI-450 dosed orally BID for 7 days in healthy subjects at doses o
Slide 29: 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-0508 09/20) 29 *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 30: In Vitro Model: ATI-450 Inhibited IL1b-Stimulated Cytokines
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) In Vitro Model: ATI-450 Inhibited IL1b-Stimulated Cytokines in Human Whole Blood 30 IL1b-Stimulated HWB • ATI-450 was added to freshly isolated hum
Slide 31: ATI-450 Inhibited Additional CRS-Related Proteins
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-450 Inhibited Additional CRS-Related Proteins in HWB Ex Vivo LPS-Stimulated HWB from SAD/MAD Study 31 Marked Inhibition of CRS Cytokines by ATI
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-0508 09/20) ATI-1777 (Topical “Soft” JAK Inhibitor) (Investigational Drug Candidate) 32
Slide 33: Atopic Dermatitis Opportunity
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Atopic Dermatitis Opportunity • Comparable efficacy to other topical JAKs but “soft” drug to minimize the potential for systemic immunosuppression
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-0508 09/20) • Single application of 2% ATI-1777 development formulation significantly inhibits IL15 (JAK1/3) induced gene induction (CCL8). Porcine Model: ATI-
Slide 35: Minipig Model: ATI-1777 Non-clinical Safety Program
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) • 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 36: 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-0508 09/20) ATI-2138 (ITK/TXK/JAK3 Inhibitor) (Investigational Drug Candidate) 36
Slide 37: 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-0508 09/20) • ATI-2138 covalently blocks ITK/TXK/JAK31 ✓ Potential for synergistic efficacy • ITK/TXK required for T-cell receptor (TCR) signaling • JAK3 requi
Slide 38: 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-0508 09/20) 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 39: Rat Adjuvant Induced Arthritis Model
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) ATI-2138 reduced inflammation and bone mineral density loss Rat Adjuvant Induced Arthritis (AIA) Model: ATI-2138 Reduced Inflammation and Protected
Slide 40: Mouse Model: ATI-2138 is Efficacious in mCIA
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Mouse Model: ATI-2138 is Efficacious in mCIA 40 Clinical Arthritis Score Joint Histology Score In the gold standard mCIA model, ATI-2138 demonstrat
Slide 41: Empowering Patients Through Kinome Innovation
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Empowering Patients Through Kinome Innovation Cash Position $68 million as of June 30, 2020 Commitment to Patients Focus on addressing the needs of
Slide 42: Key Milestones
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) Key Milestones Program/Milestone 2020 2021 1Q 2Q 3Q 4Q 1Q 2Q ATI-450 (MK2 Inhibitor) Phase 1 Data (SAD/MAD) ✓ Initiate Phase 2a Trial in Rheumatoid
Slide 43: Thank You
© Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (XX) © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0508 09/20) EMPOWERING PATIENTS THROUGH KINOME INNOVATION THANK YOU
Aclaris Therapeutics — Investor Presentation (September 2020) on 6ix