Aclaris Therapeutics, Inc. · NASDAQ:ACRS

Aclaris Therapeutics — Technical Presentation (January 2021)

32 slides from Aclaris Therapeutics's technical presentation, Jan 19, 2021

  1. Slide 1: ATI-450 Preliminary Topline Analyses, January 2021

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-RA-201 ATI-450-PKPD-102 Preliminary Topline Analyses January 2021 EMPOWERING PATIENTS THROUGH KINOME INNOVATION

  2. Slide 2: Forward-looking statements

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) 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: Biotechnology Company Focused on the Kinome: People + Platform + Pipeline

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) LEADERSHIP Founded and Led by Physicians and Scientists • World class ex-Pfizer (kinase) and ex-GSK (immunology) leadership • Kinome experts skilled at developing kinase targeted medicines Biotechnology Company Focus

  4. Slide 4: Leadership team

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) •Former SVP, R&D at GSK. •Led discovery and development teams in Immuno-Inflammation and Dermatology leading to multiple successful NDAs, including NUCALA® & BENLYSTA® David Gordon Chief Medical Officer •Former Execu

  5. Slide 5: Leverage Kinome Target Discovery to Address Unmet Needs

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Advance the process of identifying and targeting key kinome-based enzymes involved in chronic inflammation and autoimmune disease. Model, elaborate and assess compounds through a unique combination of our proprietary

  6. Slide 6: ATI-450: Investigational Oral MK2 Inhibitor

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450: Investigational Small Molecule, Oral MK2 Inhibitor Designed to Block the Targets of Broadly-Used Biologics • MK2* drives pro- inflammatory cytokine expression • By inhibiting multiple cytokines, ATI-450 may

  7. Slide 7: Evolution in Understanding a Well-Known Inflammatory Pathway

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Evolution in Understanding a Well-Known Inflammatory Pathway The Path From p38a to MK2 INFLAMMATION/STRESS p38α Anti- inflammatory Negative Feedback TNFa IL1b IL6 IL8 MK2 Cellular Function Pro- inflammatory We believ

  8. Slide 8: p38 Inhibitors: Tachyphylaxis in RA Clinical Trials

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) p38 Inhibitors: Tachyphylaxis in RA Clinical Trials Transient CRP Reduction SCIO-469 vs. Placebo2 304: VX-702 + MTX vs. Placebo + MTX3 Pamapimod + MTX vs. Placebo + MTX1 Transient CRP reduction in multiple trials 8 1

  9. Slide 9: Overview

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) • ATI-450 development program consists of: – Rheumatoid Arthritis – CAPS – COVID-19 – MAD cohort extension (80mg BID, 120mg BID) • Today’s update: – Progress on RA-201: summary of topline data – MAD cohort extension

  10. Slide 10: ATI-450-RA-201 Preliminary Topline Data Analysis

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-RA-201 Preliminary Topline Data Analysis 10

  11. Slide 11: Trial Design

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Trial Design • Diagnosis of adult-onset RA (ACR/EULAR classification criteria) • DAS28-CRP ≥3.2 defined as moderate to high disease activity • Moderately to severely active RA defined by at least 4/28 tender and 4/28

  12. Slide 12: Key Demographics

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Key Demographics Parameter Placebo (n=3) Median (Min – Max) ATI-450 (n=16) Median (Min – Max) Age (years) 53 (50 – 63) 59.5 (32 – 65) Gender (F) 3/3 (100%) (M) 0/0 (0%) (F) 11/16 (68.75%) (M) 5/16 (31.25%) Weight (kg

  13. Slide 13: DAS28-CRP Mean Change From Baseline

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) DAS28-CRP Mean Change From Baseline Numbers on lines = no. of subjects at each timepoint 13 * Data on file

  14. Slide 14: Swollen Joint Count Median Percent Change From Baseline

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Swollen Joint Count Median Percent Change From Baseline Numbers on lines = no. of subjects at each timepoint 14 * Data on file

  15. Slide 15: Tender Joint Count Median Percent Change From Baseline

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Tender Joint Count Median Percent Change From Baseline Numbers on lines = no. of subjects at each timepoint 15 * Data on file

  16. Slide 16: Subjective Physician & Patient VAS Scores

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Subjective Physician & Patient VAS Scores Median Percent Change -30 -10 10 30 1 28 56 84 Patient: Arthritic Pain ATI-450 placebo -30 -10 10 30 1 7 14 28 42 56 84 Patient: Disease Activity ATI-450 placebo -90 -70 -50

  17. Slide 17: ACR20/50/70: Responder Analysis over time

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ACR20/50/70: Responder Analysis over time 17 * Data on file

  18. Slide 18: DAS28-CRP: Responder Analysis over time

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) DAS28-CRP: Responder Analysis over time Percentage response 0 5 10 15 20 25 30 35 40 45 1 7 14 28 42 56 84 DAS-28 Responders DAS28<2.6 DAS28<=3.2 DAS28<2.6 DAS28<=3.2 ATI-450 placebo 18 * Data on file

  19. Slide 19: hsCRP Median Percent Change From Baseline

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) hsCRP (mg/L) Median Percent Change From Baseline Numbers on lines = no. of subjects at each timepoint 19 * Data on file

  20. Slide 20: Durable Dependence on MK2 for Cytokine Production

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) RA Patients Treated with ATI-450 for 12 Weeks Ex Vivo LPS-Stimulated Cytokines Day 1 vs Day 84 Hypothesis: p38 transient efficacy (tachyphylaxis) may be associated with feedback loops and pathway reprogramming. Selec

  21. Slide 21: Impact of ATI-450 on Endogenous Plasma Cytokine Levels in RA-201

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Impact of ATI-450 on Endogenous Plasma Cytokine Levels in RA-201 TNFa, IL6, IL8 and MIP1b • Cytokines with endogenous levels <0.5 pg/ml predose:IL1b, IL10, IL4 and GM-CSF 21 * Data on file

  22. Slide 22: Adverse Events: Subjects with at least one event

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Adverse Events: Subjects with at least one event ATI-450 50 mg BID (N = 16) Placebo (N = 3) Preferred Term Mild n(%) Moderate n(%) Mild n(%) Moderate n(%) Blood cholesterol increased 1(6.25) 0 Blood creatine phosphok

  23. Slide 23: ATI-450-PKPD-102 Preliminary Topline Data Analysis

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-PKPD-102 Preliminary Topline Data Analysis 23

  24. Slide 24: ATI-450-PKPD-102 Evaluation of Safety, PK and PD of Higher Doses

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) Background: – ATI-450-PKPD-101: Phase 1 SAD/MAD trial in male and female healthy volunteers o No SAEs or AEs that led to discontinuation o All AEs were mild in severity and did not interfere with everyday activities

  25. Slide 25: Day 7 Steady State Pharmacokinetics

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-PKPD-101 & ATI-450-PKPD-102 Day 7 Steady State • t½ 9-14 hours • 80mg cohort dose proportional with previous cohorts • No significant increased exposure in 120mg cohort 25 * Data on file

  26. Slide 26: Ex vivo LPS stimulated pHSP27 and TNFa Day 7

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-PKPD-101 & ATI-450-PKPD-102 Ex vivo LPS stimulated pHSP27 and TNFa Day7 Peak and Trough TNF a pHSP27 (*) = All placebo samples (all time points) Day 7 Peak and Trough Dose Response Day 7 Peak 26 * Data on fil

  27. Slide 27: Ex vivo LPS stimulated IL1b and IL8 Day 7

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-PKPD-101 & ATI-450-PKPD-102 Ex vivo LPS stimulated IL1b and IL8 Day7 Peak and Trough IL8 IL1 b (*) = All placebo samples (all time points) Day 7 Peak and Trough Dose Response Day 7 Peak 27 * Data on file

  28. Slide 28: Ex vivo LPS stimulated IL6 Day 7

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-PKPD-101 & ATI-450-PKPD-102 Ex vivo LPS stimulated IL6 Day7 Peak and Trough IL6 (*) = All placebo samples (all time points) Day 7 Peak and Trough Dose Response Day 7 Peak 28 * Data on file

  29. Slide 29: Differential Modulation of IL10 vs. TNFa and IL1b by ATI-450

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) (*) = All placebo samples (all time points) Phase 1 MAD Extension Differential Modulation of Ex Vivo LPS-Stimulated IL10 vs. TNFa and IL1b by ATI-450 Day 7 (4 hr) The anti-inflammatory cytokine, IL10, was only modula

  30. Slide 30: MAD Extension: Ex Vivo IL1b Stimulation of HWB

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) (*) = All placebo samples (all time points) ATI-450 Phase 1 MAD Extension: 80mg and 120mg Ex Vivo IL1b Stimulation of HWB Day 7 (4 hr) ATI-450 potently inhibited ex vivo IL1b-induced proinflammatory cytokines, TNFa,

  31. Slide 31: ATI-450-PKPD-102 Adverse Events

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) ATI-450-PKPD-102 Adverse Events • No SAEs • No withdrawal for AEs • No significant ECG, Laboratory findings # only 1st or 2nd day + 7 cases resolved on drug * After stopping drug Cohort 1 80mg BID N=8 Cohort 1 Pbo N=

  32. Slide 32: Topline Analyses Summary

    © Copyright 2021 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0544 01/21) • Main objectives of POC trial were achieved – Potent and durable clinical activity with 50mg BID o Rapid reduction in median percentage of tender and swollen joint count, which persisted o DAS28-CRP reduction persis

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