Aclaris Therapeutics, Inc. · NASDAQ:ACRS

Aclaris Therapeutics — Technical Presentation (March 2019)

26 slides from Aclaris Therapeutics's technical presentation, Mar 18, 2019

1. Slide 1: R&D Clinical Update March 18, 2019

   © Copyright 2019 Aclaris Therapeutics. All rights reserved R&D Clinical Update March 18, 2019

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

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. 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 Securities Litigat

3. Slide 3: Pipeline

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Pipeline Program Indication(s) Preclinical Phase 1 Phase 2 Phase 3 A-101(45%) Topical Common Warts ATI-502 JAK1/JAK3 Inhibitor Topical Alopecia Areata Vitiligo Androgenetic Alopecia (

4. Slide 4: ATI-502-AUATB-201 - Australian Eyebrow

   © Copyright 2019 Aclaris Therapeutics. All rights reserved © Copyright 2019 Aclaris Therapeutics. All rights reserved 4 ATI-502-AUATB-201 - Australian Eyebrow

5. Slide 5: Subject 01-008 (33/M)

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Subject 01-008 (33/M) 5 • The onset date for the current episode of eyebrow loss was 2010, and the onset of Alopecia Areata was 2009. • No previous therapies for eyebrow hair loss. •

6. Slide 6: Subject 01-008: Baseline vs Visit 12 (250 Days on Drug)

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 6 Visit 2 (Baseline) Visit 12 (250 Days on Drug)

7. Slide 7: Subject 01-008: Baseline vs Visit 12 (250 Days on Drug)

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 7 Visit 2 (Baseline) Visit 12 (250 Days on Drug)

8. Slide 8: Subject 01-008: Baseline vs Visit 12 (250 Days on Drug)

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 8 Visit 2 (Baseline) Visit 12 (250 Days on Drug)

9. Slide 9: Subject 02-010 (23/F)

   © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Subject 02-010 (23/F) 9 • The onset date for the current episode of eyebrow loss and the onset of Alopecia Areata was May 2017. • The subject has previously used an undefined “other”

10. Slide 10: Subject 02-010: Baseline vs Visit 12 (268 Days on Drug)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 10 Visit 2 (Baseline) Visit 12 (268 Days on Drug)

11. Slide 11: Subject 02-010: Baseline vs Visit 12 (268 Days on Drug)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 11 Visit 2 (Baseline) Visit 12 (268 Days on Drug)

12. Slide 12: Subject 02-010: Baseline vs Visit 12 (268 Days on Drug)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 12 Visit 2 (Baseline) Visit 12 (268 Days on Drug)

13. Slide 13: Subject 02-007 (45/F)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Subject 02-007 (45/F) 13 • The onset date for the current episode of eyebrow loss was 2013, and the onset of Alopecia Areata was 1986. • Prior therapies for eyebrow hair loss include

14. Slide 14: Subject 02-007: Baseline vs Visit 12 (289 Days on Drug)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Visit 2 (Baseline) Visit 12 (289 Days on Drug*) 14

15. Slide 15: Subject 02-007: Baseline vs Visit 12 (289 Days on Drug)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Visit 2 (Baseline) Visit 12 (289 Days on Drug*) 15

16. Slide 16: Subject 02-007: Baseline vs Visit 12 (289 Days on Drug)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Visit 2 (Baseline) Visit 12 (289 Days on Drug*) 16

17. Slide 17: Spectrum of Hair Loss

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Spectrum of Hair Loss 17 24% 43%34% 51% 100%

18. Slide 18: Current treatment paradigm

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Current treatment paradigm 18 https://www.naaf.org/alopecia-areata/alopecia-areata-treatments - Last accessed 3-14-19

19. Slide 19: Alopecia Areata: Potential Treatment Paradigms

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Topical Treatments Systemic Treatments Oral JAK inhibitor Adult / Pediatric Patchy AA Adult AT/AU patients Alopecia Areata: Potential Treatment Paradigms 19 Topical JAK inhibitor Pedi

20. Slide 20: ATI-450 (MK-2 Inhibitor)

    © Copyright 2019 Aclaris Therapeutics. All rights reserved © Copyright 2019 Aclaris Therapeutics. All rights reserved 20 ATI-450 (MK-2 Inhibitor)

21. Slide 21: MK-2 Pathway Inhibitor (MK-2 PI) ATI-450

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved • Pharmacologically unique MOA • MK-2 pathway inhibitors target the production and activity of key inflammatory cytokines including TNFα, IL-1α, IL-1β and IL-6 • ATI-450 inhibits the

22. Slide 22: The MK2 Pathway Drives Key Inflammatory Cytokines: TNFα, IL-1β and IL-6

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 22 INFLAMMATION Activated MK-2 up-regulates key pro-inflammatory signals (TNFα, IL1β, IL6) that drive further inflammatory signalingp38α MK-2 TNFα /IL-1β /IL-6 Cytokines/ Chemokines/

23. Slide 23: ATI-450 Inhibits the Expression of Key Inflammatory Cytokines

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved 23 INFLAMMATION ATI-450 does NOT block the activation of anti-inflammatory pathways (e.g., IL-10) thereby preserving this homeostatic dampening of the immune response p38α MK-2 TNFα /

24. Slide 24: Mouse LPS-Induced TNFa Production

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved Mouse LPS-Induced TNFa Production ATI-450 demonstrated durable response (no tachyphylaxis) • Conventional p38 (CDD-111) and MK-2PI (ATI- 450) administered to mice in feed starting day

25. Slide 25: In vivo Results of MK-2 Pathway Inhibitor ATI-450

    © Copyright 2019 Aclaris Therapeutics. All rights reserved© Copyright 2019 Aclaris Therapeutics. All rights reserved In vivo Results of MK-2 Pathway Inhibitor ATI-450 Normal Vehicle 450 (5 mpk) Joint Protection in Rat Arthritis Model1 Cytokine (IL-1 Beta) Modulation in Orphan Autoinflammatory Diseas

26. Slide 26: Thank You

    © Copyright 2019 Aclaris Therapeutics. All rights reserved THANK YOU © Copyright 2019 Aclaris Therapeutics. All rights reserved

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