Aclaris Therapeutics, Inc. · NASDAQ:ACRS

Aclaris Therapeutics — Technical Presentation (June 2020)

23 slides from Aclaris Therapeutics's technical presentation, Jun 17, 2020

  1. Slide 1: ATI-450: A Potential Treatment for Patients with COVID-19

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) ATI-450: A Potential Treatment for Patients with COVID-19 ATI-450, an investigational oral MK2 inhibitor June 17, 2020 EMPOWERING PATIENTS THROUGH KINOME INNOVATION

  2. Slide 2: Cautionary Note Regarding Forward-Looking Statements

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) 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 Securities Litigation Reform Act of 1995. These sta

  3. Slide 3: ATI-450: Potential Treatment for COVID-19-Induced Cytokine Storm

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) • Mortality in COVID-19 disease is driven, in large part, by cytokine release syndrome (CRS), resulting in acute respiratory distress syndrome (ARDS)1,2 • CRS is characterized by elevated levels of cytokines and chem

  4. Slide 4: MK2 Pathway Regulates Key Cytokines Involved in COVID-19-Induced Cytokine Release Syndrome

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) MK2 Pathway Regulates Key Cytokines Involved in COVID-19-Induced Cytokine Release Syndrome 4

  5. Slide 5: The MK2 Pathway is Activated by Coronaviruses

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) The MK2 Pathway is Activated by Coronaviruses TLR activation, unfolded protein stress response, ER stress response 5 IBV: infectious bronchitis virus MHV: murine hepatitis virus TGEV: transmissible gastroenteritis co

  6. Slide 6: In Vitro: The MK2 Pathway Drives Coronavirus-Induced Cytokines

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) 6 p38MAPK/MK2 inhibition reduces IL-6 production in MHV infected cells9 p38MAPK/MK2 inhibition reduces TNFa and IL-1b production in FIPV infected cells10 • IL-6 and IL-8 induction are dependent on the p38MAPK/MK2 pat

  7. Slide 7: ATI-450 Inhibited TNFa and IL-6 Production In Vivo and In Vitro

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) 7 0 20 40 60 80 100 120 140 Vehicle 0.1 MPK 0.3 MPK 1 MPK 3 MPK p38i - 1 MPK % Control <---------------CDD450--------------> TNFa IL6 LPS, IP ATI-450 (CDD-450) dosed orally (n=5/cohort) min 0 60 150 Draw blood Serum

  8. Slide 8: SARS-CoV-2-Induced CRS Signals Through MK2

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) SARS-CoV-2-Induced CRS Signals Through MK2 8 Spike Protein ssRNA dsRNA AngII MK2 MK2 MK2 MK2 TLR4 TLR7/8 TLR3 AR1 Inflammatory Cytokines: CRS ACE2 12

  9. Slide 9: In Vitro: ATI-450 Blocked TLR3/4/7/8 Stimulated Cytokines in HWB

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) 9 TLR4: LPS-Stimulated HWB % Control (LPS - Stim) TLR7/8: R848-Stimulated HWB % Control (R848 - Stim) ATI-450 (mM) 100ng/ml LPS ATI-450 0 1hr 4hr Cytokines quantified by MSD TLR3: poly(I:C)-Stimulated HWB 0.5ug/ml R8

  10. Slide 10: Rat Model: MK2 Inhibition Blocked Pulmonary Inflammation

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) Rat Model: MK2 Inhibition Blocked Pulmonary Inflammation ATI-450 reduced neutrophil influx into lungs 10 p value relative to vehicle * * Aerosol LPS ATI-450 dosed orally (n=x/cohort) hr 0 1 5 Lung Lavage * Data on fi

  11. Slide 11: ATI-450 Impact on Human Blood Cytokines & Chemokines: Ex Vivo LPS-Stimulated HWB

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) 11 • LPS (TLR4) stimulated cytokine and chemokine production – Blood samples from the ATI-450-PKPD-101 Trial – Cytokines and chemokines elevated in patients with COVID-19 were analyzed including: IL1-b, IL-2, IL-6, I

  12. Slide 12: ATI-450-PKPD-101: Day 7 MAD PD Marker Time Dependence

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) ATI-450-PKPD-101: Day 7 MAD PD Marker Time Dependence Target Biomarker pHSP27 and Cytokines TNFa and IL-1b • ATI-450 dosed orally BID for 7 days in healthy subjects at doses of 10mg, 30mg and 50mg • Day 1 (predose) i

  13. Slide 13: ATI-450-PKPD-101: Day 7 MAD PD Biomarker Time Dependence Cytokines IL-6 and IL-8

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) • ATI-450 dosed orally BID for 7 days in healthy subjects at doses of 10mg, 30mg and 50mg • Day 1 (pre-dose) is from blood taken on day 1 just prior to the first dose of ATI-450 • Samples ex vivo stimulated with LPS

  14. Slide 14: ATI-450 Inhibited Additional CRS-Related Proteins in HWB

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) ATI-450 Inhibited Additional CRS-Related Proteins in HWB Ex Vivo LPS-Stimulated HWB from Phase 1 SAD/MAD Trial 14 0 25 50 75 100 125 GMCSF IL2 MIP1a IFNg Analyte Production (% Predose) Analyte: Cytokine or Chemokine

  15. Slide 15: The MK2 Pathway Regulates Coronavirus Replication/Pathology

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) The MK2 Pathway Regulates Coronavirus Replication/Pathology 15

  16. Slide 16: In Vitro: The p38/MK2 Pathway is Involved in Viral Replication

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) 16 MHV Replication is p38 Dependent9 MHV infected J774.1 Cells RSV Infectivity is MK2 Dependent13 RSV infected A549 Cells • p38 inhibition blocked murine hepatitis virus (coronavirus) replication in murine macrophage

  17. Slide 17: Mouse Model: p38MAPK/MK2 Inhibition Increased Survival of SARS-CoV Infected Mice

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) Mouse Model: p38MAPK/MK2 Inhibition Increased Survival of SARS-CoV Infected Mice 17 • Mice infected with SARS-CoV intranasal • p38MAPKi dosed 8mpk ip BID for 8 days • Mortality measured daily p38MAPK/MK2 Inhibition I

  18. Slide 18: MK2 Inhibition Prevents Pulmonary Fibrosis

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) MK2 Inhibition Prevents Pulmonary Fibrosis 18

  19. Slide 19: COVID-19 Induced ARDS and Pulmonary Fibrosis

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) • Severe cases of respiratory SARS-CoV-2, SARS-CoV and MERS-CoV coronavirus infections often result in ARDS and the development of pulmonary fibrosis17 • A substantial number of ARDS survivors die as a result of prog

  20. Slide 20: Mouse Model: MK2 Inhibition Protected Mice from Bleomycin-Induced Pulmonary Fibrosis

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) Mouse Model: MK2 Inhibition Protected Mice from Bleomycin-Induced Pulmonary Fibrosis 20 • The MK2 inhibitor MMI-0100 inhibited murine bleomycin-induced pulmonary fibrosis (above)22 • Murine tissue specific MK2 KO in

  21. Slide 21: ATI-450 as a Potential Treatment for COVID-19 Summary

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) • ATI-450 has the potential to: – Inhibit multiple key inflammatory cytokines associated with CRS in patients with COVID-19; – Inhibit coronavirus replication and infectivity; and – Block COVID-19-induced pulmonary f

  22. Slide 22: IIT-2020-ATI-450-COVID-19: University of Kansas Medical Center

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) Eligibility • COVID-19 positive confirmed • Hospitalized as a result of COVID-19 infection • Evidence of pulmonary involvement by chest imaging or exam, or respiratory failure: • SpO2 ≤ 93% on room air; or • SpO2 > 9

  23. Slide 23: References

    © Copyright 2020 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0484 06/20) References 23 1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. doi: 10.1016/S0140-6736(20)30183-5 2. Zhou F, Yu T, Du R, e

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