Aclaris Therapeutics : Overview – January 2023

EMPOWERING PATIENTS THROUGH KINOME INNOVATION

41st Annual J.P. Morgan Healthcare Conference

January 2023

© Copyright 2023 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0782 1/09)

Cautionary Note Regarding Forward-Looking Statements

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 statements may be identified by words such as "believe," "expect," "may," "plan," "potential," "will," and similar expressions, and are based on Aclaris' current beliefs and expectations. These forward-looking statements include expectations regarding Aclaris' development of its drug candidates, including the timing of its clinical trials and regulatory submissions, and its expected cash runway. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Aclaris' reliance on third parties over which it may not always have full control, the uncertainty regarding the COVID-19 pandemic including its impact on the timing of Aclaris' regulatory and research and development activities, and other risks and uncertainties that are described in the Risk Factors section of Aclaris' Annual Report on Form 10-K for the year ended December 31, 2021 and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are available under the "SEC Filings" page of the "Investors" section of Aclaris' website at http://www.aclaristx.com. Any forward-looking statements speak only as of the date of this presentation and are based on information available to Aclaris as of the date of this presentation, and Aclaris assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise

This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data about our industry. These data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk

© Copyright 2023 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0782 1/09)

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Biotechnology Company Focused on the Kinome

People + Platform + Pipeline

Leadership

Scientific Discovery led by World Class Kinase Expertise

• Kinome experts skilled at developing novel kinase targeted medicines

Proven Operational and

Clinical Development Leadership

Team in Place

KINect® Platform

Proprietary Kinase

Discovery Engine

• Versatile discovery platform
• Fully integrated discovery and development team
• Advancing small molecule drug candidates designed to parallel or exceed efficacy of high-value biologics

Innovative pipeline

(investigational drug candidates)

Zunsemetinib (ATI-450) - MK2i

• Oral anti-TNFα,anti-IL17, anti- IL1, anti-IL6

ATI-1777 - Topical "Soft" JAK1/3i

• Tissue specific therapy

ATI-2138 - ITK/JAK3i

• Oral dual inhibitor of T cell and cytokine receptors

Development of Small Molecule Therapeutics for Immuno-inflammatory Diseases

Note: KINect® is the registered trademark of Aclaris Therapeutics, Inc.

© Copyright 2023 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0782 1/09)

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The Kinase Opportunity

Unlocking the Potential of the Kinome

Medically Important and Productive Target Class

Oncology

Non-Oncology

>70 Marketed Drugs1 ~$48B2,3

Annual Sales of Kinase Drugs

Most Members of the Kinome Remain Unexplored

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518 Members

>90% of the Human Kinome remains undrugged5

Creating New Medicines Targeting Previously Inaccessible Kinome Targets

Note: All trademarks are the property of their respective owners.

1. GoodRx. Accessed January 4, 2023. https://www.goodrx.com/kinase-inhibitors; 2. Data on file; 3. Oprea TI, et al. Unexplored opportunities in the druggable human genome. Nature Rev Drug Discov. Poster Jan. 2017; 4. Manning G, et al. Science. 2002;298(5600):1912-1934; 5. Oprea TI, et al. Nat Rev Drug Discov. 2018;17(5):317-332.

© Copyright 2023 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0782 1/09)

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Precision Immunology with the KINect Platform

Demonstrated Success in Reversible and Covalent MOA

MK2 Inhibitors

• Zunsemetinib (ATI-450),ATI-2231: Oral anti-TNF,anti-IL17,anti-IL1, and anti-IL6
• Novel approach for a difficult to target kinase
• Broad potential in several immuno- inflammatory diseases

Unique kinase complex inhibitor

Tissue Restricted JAK Inhibitors

• ATI-1777:Skin specific (Soft) topical JAK1/3
• Oral Gut-biased JAK inhibitors
• Goal: Comparable clinical efficacy with improved safety profile

Tailoring physico-chemical and potency properties

Covalent ITK Inhibitors

• ATI-2138:ITK/JAK3 Oral T cell kinase inhibitor for autoimmune diseases

Covalent inhibition for difficult-to-target kinase

Small Molecule Therapeutics Targeting Multi-billion Dollar Immunology and Inflammation Markets

© Copyright 2023 Aclaris Therapeutics, Inc. All rights reserved (PP--US-0782 1/09)

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