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Corporate Overview November 2025 EMPOWERING PATIENTS THROUGH THERAPEUTIC INNOVATION
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2 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 “anticipate,” “believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,” and similar expressions, and are based on Aclaris’ current beliefs and expectations. These forward-looking statements include expectations regarding the therapeutic potential of Aclaris' product candidates, including bosakitug (ATI-045), ATI-052, ATI-2138, next generation ITK selective inhibitors, and next generation bispecific and multispecific antibodies, including the potential for such product candidates to be first-in-class and/or best-in-class, the potential to increase the efficacy ceiling and show superior activity compared to other therapies, the potential for bosakitug to have extended dosing, and the potential for the next-generation ITK inhibitors to have once-per-day dosing, the development of such product candidates, including the potential targets and indications Aclaris may pursue, the timing and number of regulatory filings, the design of future clinical trials, the timing for the initiation of clinical trials, and the availability and timing of data from clinical trials, and Aclaris’ cash runway, including potential to extend the cash runway through non-dilutive opportunities. 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, Aclaris’ ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic environment 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, 2024, 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 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 the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. Tradenames, trademarks and service marks of other companies appearing in this presentation are the property of their respective owners. All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions, and are subject to change based on a variety of factors. Disclaimer and Cautionary Note Regarding Forward-Looking Statements
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Aclaris Therapeutics Innovation Driven Patient Focused Four anticipated clinical programs in 2026 2026 is an important year for Aclaris with multiple anticipated inflection points Validated targets; positioned in the oral and antibody space Bispecific and ITK oral programs could be potential game changers in multiple indications Advancing potential industry-leading inhibitors designed to address validated, therapeutically- relevant immune targets 3 Prudent capital management with a cash runway expected into second half of 2028 Underpinned by state-of-the-art scientific platform and world class people
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Aclaris: Positioned for Significant Growth 4 Potential Best-in-Class Clinical Assets Continued Business Execution World Class Expertise/Capability • Bosakitug (ATI-045): Uniquely potent monoclonal antibody targeting TSLP • ATI-052: Bispecific antibody (BsAb) targeting both TSLP and IL-4Rα • ATI-2138: Potent and selective oral inhibitor of ITK/JAK3 • Discovery/preclinical lead candidate selection ongoing for novel ITK inhibitors and BsAbs • ATI-2138: Phase 2a OL trial achieved primary and key secondary endpoints in AD, further validated ITK as a therapeutic target; additional Phase 2 initiation expected in 1H 2026 • Bosakitug: Dosing in two-arm placebo-controlled Phase 2 trial ongoing • ATI-052: Phase 1a/1b SAD MAD program ongoing; dosing ongoing • New INDs starting in 2026 expected from discovery engine • World class development expertise • Proprietary kinase small molecule discovery engine complemented by in-house multidisciplinary team • Innovative biologic discovery program incorporating dual-targeting strategies addressing validated pathways Well Financed with Three-Year Cash Runway • Strong balance sheet expected to fund operations into the second half of 2028 • Current cash runway expected to fully fund preclinical and clinical development plans • Potential opportunities for additional non-dilutive financing and development partners
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Broad Immunology Development Pipeline 5 Preclinical Phase 1 Phase 2 Phase 3 Partner Bosakitug (ATI-045) TSLP mAb Subcutaneous Atopic Dermatitis (moderate-to-severe) Severe Asthma CTTQ (China)* Chronic Rhinosinusitis with Nasal Polyps CTTQ (China)* COPD CTTQ (China)* ATI-2138 ITK/JAK3 Inhibitor Oral Atopic Dermatitis (AD) (moderate-to-severe) Additional Indication (e.g., Lichen planus) ATI-052 TSLP x IL-4R BsAb Subcutaneous Respiratory/ Dermatology ITK Selective Inhibitor Oral Autoimmune Undisclosed BsAb Subcutaneous Autoimmune Positive Phase 2a Results Presented July 2025 SAD/MAD Enrollment Ongoing 1st IND: 2H26 Enrollment Ongoing Phase 2 trial initiation: 1H26 1st IND: 2027 Further global (excluding China) development in respiratory indications is dependent on partnerships Aclaris programs Partner programs *This trial is sponsored and conducted by Chia Tia Tianquing Pharmaceuticals Group, Co., Ltd. (“CTTQ”) or its affiliates; Aclaris will not develop bosakitug in this indication on its own. All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions, and are subject to change based on a variety of factors POC initiation: 1H26
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6 Sources: Eczema stats: National Eczema Association (accessed 07/31/25); National Alopecia Areata Foundation (Accessed 07/31/25); Vitiligo Facts: Global Vitiligo Foundation (accessed 07/31/25); Precedence Research; Forbes Business Insights; American Medical Association; American Lung Association; Global Initiative for Asthma; World Health Organization; The Centers for Disease Control and Prevention (CDC); Business Research Company; peer research; Delveinsight; Cowen Categories Outlook 2024 Significant opportunity for new innovative therapeutics for Th1, Th2, and Th17- mediated dermatological and respiratory diseases including potent and well tolerated biologics and oral inhibitors The Future Value of Drug Development Addressing Th1, Th2 and Th17-Mediated Disorders
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Opportunities in the I&I Space Potential to Address Significant Gaps in Unsatisfied I&I Indications 7 Opportunities for Orals • Faster onset, durable, consistent effect • Broader efficacy across heterogenous populations • Optimize symptom control: anti-itch effect, FEV1 • Potential anti-fibrotic effect • Convenience of oral • Improved tolerability profile Opportunities for Antibodies • Raise efficacy ceiling • Faster onset, durable, deeper, and more consistent effect • Improved tolerability • Improved convenience and practical dosing schedule
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ATI-2138: A First Generation Novel ITK/JAK3 Inhibitor for T Cell-Mediated Diseases Potent and Selective Investigational Drug Candidate with Strong Tolerability Profile
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T Cell Receptor (TCR) Pathway Interleukin-2-Inducible T-cell Kinase (ITK) is a Key Kinase Involved in TCR Signaling Antigen- presenting cell T-cell Lck LAT Phosphorylation Zap-70 CD3 CD4 MHC Antigen SLP-76 ITK TCR δ ε ε γ α β Ca2+ ER Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Ca2+ Nucleus Cytoplasm Cytoplasm ζ ζ IRF4IRF4 • TCR activation is critical for T lymphocyte differentiation, proliferation and activation • TCR signaling proceeds through a complex intracellular pathway resulting in the activation of key transcription factors and production of cytokines • Central to TCR signaling is the kinase ITK Inhibiting/downregulating ITK shuts down TCR signaling under inflamed/allergic conditions and impacts disease 9
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10 Comparative Impact of ITK Inhibition Broad Applicability in Inflammatory/Allergic Pathways
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TCR APC T Cell Proliferation Differentiation Activation γc cytokines JAK3 pSTAT5 ATI-2138 T Cell NK Cell ATI-2138 Oral Small Molecule Covalent ITK & JAK3 Inhibitor for I&I Disease • Investigational oral compound which interrupts T cell receptor (TCR) signaling by inhibiting ITK and JAK3 signaling of common γ chain cytokines in lymphocytes (including IL-2 & IL-15) • Highly potent for both ITK and JAK3 (IC50: 0.2nM ITK; 0.5nM JAK3) • Highly selective against other JAK isoforms • Unique dual pharmacology; best-in-class potential • Clinical data thus far demonstrate good safety and PK characteristics; positive readout in a phase 2A AD study 11
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ATI-2138 is a Unique Molecule 12 Regulation of T cell development and function both upstream (ITK) and downstream (JAK3) High potency for inhibiting both ITK and JAK3 Inhibiting both pathways may provide a more potent and complete anti-inflammatory response As both targets are restricted in expression to immune cells, inhibitors have the potential for a favorable safety profile Unique Dual Pharmacology of ATI-2138 Provides Best-in-Class Potential
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ATI-2138 Anti-inflammatory Activity in Mouse Models IBD Mouse T Cell Transfer Vitiligo Score 3 0 6 9 12 15 18 13 ATI-2138 has demonstrated robust anti-inflammatory activity in mouse models of disease: Inflammatory Bowel Disease, Vitiligo, and Rheumatoid Arthritis Vitiligo Mouse T Cell Transfer
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ATI-2138 Unique Dual Pharmacology and Best-in-Class JAK3 Inhibitor Potential ITK: HWB αCD3 Stimulated IFNγ Release JAK3: HWB IL2 Stimulated IFNγ Release 0.1 1 10 100 1000 10000 0 20 40 60 80 100 120 140 nM IFNg Production (% Stim) ATI-2138 Ritlecitinib 0.1 1 10 100 1000 10000 0 20 40 60 80 100 120 nM IFNg Production (% Stim) ATI-2138 Ritlecitinib 5.4x 44.4x • ATI-2138 is 44.4x more potent than ritlecitinib for inhibiting anti-CD3 induced IFNγ production (ITK) and 5.4x more potent for inhibiting JAK3 dependent IL-2 induced IFNγ production in human whole blood • At the FDA recommended 50 mg QD dose for alopecia areata, ritlecitinib plasma levels may not impact ITK (anti-CD3 /IFNγ) for any appreciable time 14
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ATI-2138 and CPI-818 (Soquelitinib) Assessing the Potency Advantage of ATI-2138 • ATI-2138 is 15-38x more potent than CPI-818 in inhibiting the ITK enzyme activity • ATI-2138 is significantly more potent than CPI-818 in blocking the Th2 derived cytokines, IL-4, IL-5 and IL-13 (30-100x) ITK, IC50, nM Kinact/Ki (uM-1s-1) ATI-2138 0.25 0.34 CPI-818 9.5 0.022 Potency Ratio 38x 15x ITK Biochemical Enzyme Potency Anti-CD3/CD28-Induced Cytokines from Human Th2 Cells 15
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Phase 2a Trial in Atopic Dermatitis: Complete • Favorable safety profile • Efficacy observed across multiple measures comparable to drugs approved for AD • Exposure similar to or slightly higher than predicted from MAD study • Efficacy and PD results validate therapeutic potential of targeting ITK: – Near complete and sustained inhibition and occupancy of ITK – Downregulation of multiple ITK-dependent immune pathways in the skin 16 ATI-2138 (10mg BID) Screening/ Washout up to 30 days Two Weeks Follow-up Week 12 Primary endpoint analysisEnrolled: 14 subjects Moderate-to-Severe Atopic Dermatitis Treatment Period: 12 Weeks
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PP-NRS: % of Pts with ≥4 Point Improvement in Worst Itch over Prior 24 Hours Phase 2a Trial in Atopic Dermatitis: Efficacy Results After four weeks of treatment • BSA decreased by 63.9% • EASI scores dropped by 77.3% • PP-NRS decreased by 44.7% • These changes were statistically significant and sustained through study conclusion (W12) At week 12, 63% of patients receiving a low dose (10mg BID) of ATI-2138 experienced a ≥4-point improvement worst itch in the past 24 hours Molecular and Clinical Effects of oral ATI-2138, an ITK/JAK3 inhibitor, in Moderate-to-Severe Atopic Dermatitis: Sub-study of a Phase 2a Open-Label, Single-Arm Trial. Beaziz- Tordjman, Jessica et al. European Academy of Dermatology and Venereology, September 17, 2026. A ≥4-point improvement in PP-NRS score is considered a clinically meaningful result 17 Efficacy Results Show Strong Consistent Response to ATI-2138 Each other compound efficacy is the average percent improvement from multiple studies, at week 12 or 16 data from Phase 2 and Phase 3 published sources; head-to-head clinical studies have not been conducted. Differences exist between trial designs and subject characteristics, and caution should be exercised when comparin g data across studies. Data collected on 8 of 10 PP patients.
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ATI-2138 is Mechanistically Unique and PD Supports Observed Clinical Efficacy 18 Understanding PK/PD • ITK Assay – αCD3/aCD28 ex vivo stim mRNA (IL-2 and IFNγ) production • ITK Target Occupancy • JAK3 Assay – IL-15 ex vivo stim IFNg protein production • Immunophenotyping Relating PD to Efficacy • Punch Biopsy Analysis – Immunohistochemistry – RNAseq Analysis (>16,000 genes) • Tape Strip Analysis – RNAseq Analysis (>16,000 genes) – Olink Proteomics (300+ analytes) • Endogenous Biomarkers in Plasma – OLink Proteomics (300+ analytes) Phase 2a Trial in Atopic Dermatitis Pharmacodynamic Assessment Conducted to Assess Target, Pathway, and Disease Markers to Support Mechanism of Action
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Phase 2a Trial in Atopic Dermatitis Marked and Sustained ITK Inhibition Observed 19 Functional inhibition and target occupancy retained across the dosing interval; >90% inhibition IFNγ mRNA and near complete target occupancy observed 1 hour post dose Data collected on 8 of 10 per protocol patients
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Gene Set Variation Analysis (GSVA) Tape Strip Proteomics Data Immune Genes (Extended) Th2 Th17 IgFCH vs Baseline IgFCH vs Baseline Week 4 Week 8 Week 12 Black stars: significance vs baseline Red stars: significance between change in lesional vs. change in non-lesional Th1 Week 4 Week 8 Week 12 Week 4 Week 8 Week 12 Week 4 Week 8 Week 12 • Proteomic results corroborate genomics findings • Immune-related gene or protein profile improved over time, with reduction of inflammation • Variability between weeks 8 and 12 may be attributed to noncompliance by two patients Non-lesional Lesional 20 Data collected on 8 of 10 per protocol patients
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Correlation B/W Change in Clinical Scores & in Key Gene Expression Decreases in inflammatory and fibrosis- related markers positively and strongly correlated with improvements in clinical scores CXCL12 TSLP CCL21 R=0.71 p=0.029 R=0.8 p=0.009 R=0.67 p=0.05 GENERAL INFLAMMATION Th2 Th17 ELN LUMSPON1 FIBROSIS R=0.68 p=0.042 R=0.8 p=0.009 R=0.8 p=0.009 21 Data collected on 8 of 10 per protocol patients
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Phase 2a Trial in Atopic Dermatitis ITK Pathway Mediated Anti-Inflammatory Activity in Skin and Plasma • ATI-2138 significantly downregulated multiple immune pathways in skin and plasma • Strong downregulation of key ITK dependent pathway markers such as: – Th2 (e.g., CCL17, CCL24, IL13, TSLP) – Th17 (e.g., CXCL1, IL17A, IL6R) – TCR (ITK) Pathway (e.g., ITK, IL-13, CD3, ZAP70, LCK, PLCg1) – Th1 (e.g., CXCL11, CXCL9, IL2RA, TNF) – Fibrosis related markers (e.g., MMP9, TNFRSF9) • Safety profile and expected incremental increase in PD with greater exposure may support higher dosing in subsequent studies 22
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Potential Next Clinical Steps with ATI-2138 The Lichen Planus Opportunity 23 An unaddressed chronic, inflammatory, immune-mediated disorder • Affects skin, mucous membrane, hair and nails; multiple clinical subtypes • Most common symptoms: severe itch, sores, scales/plaques, hair loss, fatigue • Oral lichen planus (OLP) (50%+ of cases) is of particular clinical significance due to malignant potential • Prevalence = 0.2-1% worldwide; associated with hepatitis C, autoimmune conditions, certain medications • Market opportunity – U.S. addressable patients: ~200K systemic-eligible – Global addressable: ~2–3M – Peak U.S. revenue potential: $500M–1B – Global peak revenue: $1.2–1.4B – No approved oral LP therapy → white space opportunity • Unsatisfied market; management focuses on immunosuppression and symptom control Large unsatisfied market; ample “white space”
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24 ATI-2138 in Lichen Planus Dual Pharmacology Creates Ideal Mechanistic Fit • Chronic inflammatory skin disease • Aberrant activation of TH1/2/17 and cytotoxic CD8 T-cells • IFN mediated pathology in affected skin • Severe itch associated with IL31 up- regulation • Fibrosis common • Activity demonstrated in open-label AD study suggests strong fit for LP • Downregulation of Th1/2/17 activation markers • Inhibition of biomarkers down-stream of IFNy (CXCL11, CXCL9) • Significant reductions in itch • Strong downregulation of fibrosis markers • Efficacy of calcineurin inhibitors in LP support T-cell mediated pathology Lichen planus ATI-2138
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Opportunity in Alopecia Market is Rapidly Evolving but Opportunities Remain • Market and competitive landscape dynamics shape indication selection process • Strong mechanistic rationale: JAK3 inhibition shown to be effective in alopecia areata • Multiple types of alopecia exist, some of which are under evaluation – Scarring (cicatricial) alopecia – Alopecia areata – Others 25
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ATI-2138: Next Steps Oral Small Molecule Covalent ITK & JAK3 Inhibitor for I&I Disease 26 Potential applicability in a variety of I&I indications based on dual pharmacology / MOA Next Steps • Complete trial design, market analysis, and TPP of Lichen planus • Finalize assessment of additional potential future targets • Initiate Phase 2 in additional indication (e.g., Lichen planus) in 1H 2026 Prioritized potential areas of focus: Targets evolve with competitive dynamics
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Next Generation ITK Inhibitors Novel ITK and ITK/TXK Selective Inhibitors Designed to Limit JAK Inhibitory Activity
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Next Generation ITK-Specific Inhibitor Program Progressing Toward IND Next Gen ITK Inhibitor Program Progressing Toward IND Developing highly potent ITK or ITK/TXK selective compounds; significantly more efficient at inactivating ITK than CPI-818 Opportunity for total ITK occupancy at low doses without impacting JAK3 function Extended half life compared to first generation ATI-2138 and competitor molecules Potent blockade of Th2 function and differential modulation of Th1 activation Targeting first IND from ITK selective program in 2026 28
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Aclaris ITK Inhibitor Program Summary • First Generation ATI-2138 has demonstrated: – Favorable safety profile – Clear understanding of PK and PD – ITK pathway and T cell modulation – Early signs of efficacy in a 12-week AD study • Successfully generated a portfolio of next generation covalent ITK inhibitors with differentiated pharmacological properties and selectivity profiles; lead candidate selection ongoing • Expected to differentially modulate T cell biology across a broad range of disease indications and have best-in-class/first-in-class potential • Next Generation JAK-sparing compounds progressing toward initial IND in 2026 29
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Bosakitug (ATI-045): Highly Differentiated Anti-TSLP Antibody Investigational Product Candidate with Best-in-Class Potential
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• Pleiotropic and broad activity – Master regulator of type 2 (Th2) immune responses at the barrier surfaces of skin and the respiratory/ gastrointestinal tract – Drives eosinophilic and neutrophilic inflammation and acts on a wide variety of adaptive, innate, and structural cells – Broad activity: Involved in induction phase and effector phase as well as non- Th2 processes – Proven biology: The expression of TSLP is elevated in individuals with respiratory and skin disease 31 Targeting Thymic Stromal Lymphopoietin (TSLP) Therapeutically Relevant Immune Target Adapted from Pelia et al., Int J Mol Sci. 2021 Apr 22;22(9):4369
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Driving High Efficacy in Dermatological Disease High Potency Therapeutics are Key to Effectiveness • Abs must engage ligands at the site of action • Key variables related to efficacy – TSLP concentration at site of lesion – Antibody concentration at site of lesion • Concentration of mAb in general circulation • Skin penetration of mAb • Dose • Potency – Binding Mechanism of mAb to TSLP • Binding affinity • Residence Time – Degree of TSLP reduction needed at site of lesion Only 15% of mAb serum levels reach skin/site of lesion: Potency is Key to Efficacy 32 mAb mAbTSLP TSLP Tissue Penetration Antibody Concentration TSLP Concentration Binding Mechanism Adapted from Lavers et al., Int J Aes Nursing 2017
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Bosakitug Key Properties • Very high affinity to TSLP • Extremely low dissociation rate from TSLP* leading to long residence time and enhanced neutralization activity • Very high potency • Unique binding characteristics to TSLP • ~23-day half-life that can potentially support an extended dosing interval of up to 3 months ~70x Inhibition of CCL17 Produced by hPBMCs Stimulated with TSLP mean % stim, R&D TSLP @ 0.1ng/mL IC50 Bosakitug is ~70x More Potent than Tezepelumab, the Only Marketed Anti-TSLP mAb 33 * Quantification of dissociation rate limited by the surface plasmon resonance instrument sensitivity 0.00001 0.0001 0.001 0.01 0.1 1 10 100 0 20 40 60 80 100 120 Antibody (nM) ATI-045 Tezepelumab Bosakitug
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Bosakitug (and ATI-052) demonstrates very slow dissociation kinetics from TSLP Residence time for Bosakitug (and ATI-052) is ~20-100x longer than comparator antibodies 34 1. SPR: Residence Time based on apparent kd using standard TSLPR immobilization density and bivalent fit; *Analog mAb; **Biosimilar mAb Bosakitug Key Properties Lower Dissociation Rate = Longer Residence Time
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Bosakitug is the most potent of the TSLP/TSLPR antibodies evaluated in blocking CCL17 production ATI-052 retains much of the potency for TSLP functional blockade 35 *Biosimilar; **Analog Bosakitug Key Properties Greater Potency Than Other TSLP/TSLPR Antibodies
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Tezepelumab vs Bosakitug Relationship of Potency and Exposure to Extent of TSLP Inhibition • The highest dose of Tezepelumab may not cover the IC99 for TSLP at the site of action based on in vitro potency • Bosakitug is expected to cover multiples over the concentration needed for 99% inhibition of TSLP at the site of action based on its in vitro potency Bosakitug Potency Allows for Substantial Exposure Above 99% Inhibition of TSLP 36
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Clinical Translation Phase 2a (US-Based) POC Monotherapy Trial 37 Bosakitug 300 mg QW Bosakitug 300 mg Q2W Screening/ Washout up to 30 days 12 Week Follow-up Week 26 (2 weeks after last dose) Primary endpoint analysisEnrolled: 22 subjects (17 completed treatment) at 7 US-based sites Primary Objective (Week 24) To evaluate the efficacy, safety and tolerability of bosakitug as monotherapy in subjects with moderate to severe AD W1-W4 W4-W24 W24-W36 Secondary Objectives (Week 24) To evaluate the pharmacokinetics, immunogenicity and pharmacodynamic biomarkers of ATI- 045 in subjects with moderate to severe AD Eligibility Diagnosis of AD (present for at least 6 months); EASI ≥12; IGA ≥3; total AD BSA ≥10% Baseline Characteristics Mean EASI of 17.6, Mean PP-NRS of 6.5; majority had prior medication prior to screening
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Bosakitug Exposure and Efficacy Time Profile Demonstrated Sustained Clinical Response After the Last Dose 0 4 8 12 16 20 24 28 32 0.01 0.1 1 10 100 0 20 40 60 80 100 Time (Week) Concentration (μg/mL) Percent Change from Baseline of EASI Score (%) Last Dose Simulated Mean Conc. Observed Conc. Observed Efficacy 95% Confidence Interval • A time lag in efficacy response relative to exposure was observed both while the drug was onboard and after the last dose • EASI-75 sustained response after the last dose supports the possibility of longer dosing intervals • Favorable safety and immunogenicity profile 38
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Phase 2a (US-Based) POC Monotherapy Trial Bosakitug Demonstrated Improvement in Efficacy Measures 39
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Phase 2 Monotherapy Trial Ongoing Dosing Proceeding to Plan 40 Placebo Week 0 & 2 Bosakitug Week 0 & 2 Placebo Q2W, Week 4 through Week 22 Bosakitug 300 mg Q2W, Week 4 through Week 22 Screening/ Washout up to 30 days 12 Week Follow-up Randomization 2:1 Active to Placebo Week 24 (2 weeks after last dose) Primary endpoint analysis~90 Patients Moderate-to-Severe AD Treatment Period: 24 Weeks Loading dose Primary Objective (Week 24) To evaluate the efficacy of Bosakitug compared to placebo, as measured by the change in Eczema Area and Severity Index (EASI) score in patients with moderate-to-severe AD Secondary Objectives (Week 24) To evaluate the safety, tolerability & treatment effect of Bosakitug compared to placebo, on additional clinical outcome measures • EASI response (EASI-50, EASI-75, EASI-90) • Validated Investigator Global Assessment (IGA) response • Body Surface Area (BSA) response • Peak Pruritus Numerical Rating Scale (PP-NRS) score
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Next Steps with Bosakitug Competitively Positioned as Potential Best-in-Class TSLP mAb • Preclinical and clinical data generated to date reinforce the enhanced potency of bosakitug and support further development in dermatological conditions – Two-arm placebo-controlled Phase 2 trial of bosakitug in moderate-to-severe AD ongoing (initiated 2Q 2025); dosing underway • Results expected in 2H 2026 • Aclaris is seeking partners to develop bosakitug in respiratory indications; further global (excluding China) development in these indications is dependent on entering into potential partnerships 41
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ATI-052: Anti-TSLP x IL-4Rα First Generation Bispecific Antibody Program Highly Potent and Bioactive Investigational Product Candidate
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ATI-052: Key Asset Highlights Potential Best-in-Class Bispecific Anti-TSLP/IL-4Rα mAb ATI-052 YTE mutation Anti-TSLP Fab Anti-IL4Rα scFv CH2CH3 CH2CH3 43 • Bispecific utilizing same antibody binding regions of Bosakitug combined with anti-IL-4Rα, inhibiting TSLP upstream and immune cells downstream of the Th2 cascade – Retains dissociation kinetics, residence time, and potency advantages of bosakitug over comparator Abs • Anti-TSLP mAb component has Fc engineered to bind more tightly to FcRn, potentially extending half-life • The AQQ mutation in the Fc silences effector functionality, thereby reducing off-target binding and potential toxicity • Potential to show superior activity in certain dermatological and respiratory I&I disorders compared to approved therapies AQQ mutation
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44 ATI-052 Bispecific Binding Attributes Clinical Opportunity Multispecific Binding Potential Clinical Efficacy Simultaneous Binding of TSLP and IL-4Rα High affinity to both ligands simultaneously: ATI-052 binds two molecules of TSLP and sIL4Rα Effective Binding of TSLP and IL-4Rα ATI-052 binds both targets effectively; high affinity of either ligand is not altered by the binding of the other Higher Potency than Competitor Antibodies Exhibits greater cellular bioactivity on CCL17 release than the combination of Tezepelumab and Dupilumab Effective Blockade of IL-4 and IL-13 ATI-052 antagonism of IL4Rα blocks signaling of both IL-4 and IL-13
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Placebo Controlled Phase 1a/1b Program Ongoing 45 Cohort 1: SC, N=8 D1-113 Screening Randomization 3:1 Cohort 3: SC, N=8 D1-113 Cohort 4: SC, N=8 D1-113 Cohort 2: SC, N=8 D1-113 Part A Single Ascending Dose (SAD) in Healthy Volunteers Part B Multiple Ascending Dose (MAD) in Healthy Volunteers Screening Randomization 3:1 D1 D8 D15 D22 D29 D1 D8 D15 D22 D29 D141 D141 Cohort 1: SC, Q7D Cohort 2: SC, Q7D Treatment and Follow-up Period Treatment and Follow-up Period
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46 Key Learnings Expected in 2025 Expected Milestones • Initial PK • Safety and Tolerability • TMDD role • Indications of prolonged exposure • Complete SAD/MAD assessment YE 2025 • SAD/MAD results 1Q 2026 • Phase 1b top line POC results 4Q 2026 • Full PK profile (half-life, ADA, etc.) • Pathway engagement ex-vivo from HV study • Pathway engagement in diseased population • Initiate Phase 1b POC trial in asthma 1H 2026 • Initiate Phase 1b POC trial in AD 1H 2026 Phase 1a/1b ATI-052 Program Anticipated Key Learnings and Next Steps
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Next-Generation Multispecific Antibodies
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48 0 Pruritis (Itch) Alarmin Combinations Eosinophil-Driven Diseases • TSLP combinations with itch mediators may have a positive impact on itch and QoL in AD and other dermatological diseases • Could impact initiation of allergic response and associated downstream inflammation and enhance anti-viral immunity during respiratory virus infections • Allergic disorders, skin conditions, fungal infections, autoimmune diseases, others • Causes multiple disorders including eosinophilic cystitis, fasciitis, pneumonia, gastrointestinal disorders, granulomatosis with polyangiitis, hypereosinophilic syndrome Opportunities for Aclaris Next Generation BsAbs Multispecific Antibodies Can Expand Therapeutic Optionality Synergistic Effect with TSLP • May amplify immune responses, particularly the development of Type 2 inflammation, which is central to allergic diseases like asthma, AD, and others
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Next Generation Bispecific Antibodies Progressing Toward IND Multispecific Ab development Progressing Toward IND Multispecific approach enables synergistic target binding and addresses shortcomings of multi-drug administration Additional bispecific and trispecific modalities under initial consideration Initial assessment of bispecific targets completed (αTSLP + undisclosed) Campaigns progressing: Hit optimization toward lead candidate selection ongoing Targeting first IND from bispecific antibody development efforts in 2027 49
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z Results: Antibody FranchiseITK Franchise Broad Clinical and Preclinical I&I Pipeline Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade 50 First Generation Next Generation Monoclonal Antibodies Multispecific Antibodies ATI-2138 ITK/JAK3 Phase 2a Complete ITK Selectives Preclinical Development Bosakitug (ATI-045) αTSLP Phase 2 Ongoing Next Gen Multispecifics Discovery ATI-052 αTSLP/IL-4Rα Phase 1a/1b Ongoing Oral Kinase Inhibitors Biologics ITK | ITK/TXK Next Gen IND: 2H 2026 Other multispecific antibodies in discovery Phase 2 Additional indication (e.g., Lichen planus, etc.) Initiation: 1H 2026 POC Asthma ADResults in 2H 2026 Results in 2027 Initial IND: 2027 αTSLP/X (undisclosed 1) αTSLP/X (undisclosed 2) αTSLP/X (undisclosed 3) SAD/MAD 1Q26 POC 2H 2026 All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions, and are subject to change based on a variety of factors
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Continued Clinical Momentum in 2026 and 2027 Four Expected Clinical Programs in 2026 Bosakitug (ATI-045) Phase 2 in AD ongoing Top line results in 2H 2026 ATI-052 Top line SAD/MAD results in 1Q 2026 Top line Proof-of-Concept results in asthma and AD in 2H 2026 ATI-2138 Phase 2 initiation in additional indication, e.g., Lichen planus, in 1H 2026 Top line results in 2027 Next generation Therapeutics First IND from ITK selective program in 2H 2026 First IND from multispecific antibody program in 2027 Advancing potentially industry-leading inhibitor franchises designed to address validated, therapeutically- relevant immune targets Innovation Driven Patient Focused 51 All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions, and are subject to change based on a variety of factors
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52 * Without giving effect to additional business development transactions or financing activities. Proven track record of R&D, business development, and scientific leadership in immuno- inflammatory diseases Integrated approach to small and large molecule discovery enables targeted design of novel drug candidates from concept through lead optimization Executing on multiple therapeutic programs from discovery to clinical development Multiple milestones expected in 2026 and beyond Executive Team State-of-the-Art Discovery Platform Diversified Pipeline Intellectual Property Financial Strength Global IP estate Cash, cash eq., and marketable securities as of 3Q25 of $167M Cash runway expected into the second half of 2028* Potential to extend runway further through non-dilutive opportunities Focus on addressing the needs of patients with immuno- inflammatory diseases who lack satisfactory treatment options Commitment to Patients Company Summary
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Corporate Overview November 2025 EMPOWERING PATIENTS THROUGH THERAPEUTIC INNOVATION