8-K
Aclaris Therapeutics, Inc. (ACRS)
8-K
2025-10-14
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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of
The Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): October 14, 2025
Aclaris Therapeutics, Inc.
(Exact name of registrant as specified in its charter)
| | | | | |
|---|---|---|---|---|
| Delaware | | 001-37581 | | 46-0571712 |
| (State or other jurisdiction of incorporation) | | (Commission File Number) | | (IRS Employer<br>Identification No.) |
701 Lee Road , Suite 103
Wayne , PA **** 19087
(Address of principal executive offices, including zip code)
( 484 ) 324-7933
(Registrant’s telephone number, including area code)
N/A
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
| Title of Each Class: | Trading Symbol(s) | Name of Each Exchange on which Registered |
|---|---|---|
| Common Stock, $0.00001 par value | ACRS | The Nasdaq Stock Market, LLC |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01 Regulation FD Disclosure.
On October 14, 2025 at 8:00 a.m. ET, Aclaris Therapeutics, Inc. (the “Registrant”) will hold an in-person and virtual R&D Day. A webcast of the R&D Day will be available through the Events page of the Investors section of the Registrant’s website. A copy of the presentation that will accompany the R&D Day is furnished herewith as Exhibit 99.1 to this Current Report on Form 8-K.
In accordance with General Instruction B.2. of Form 8-K, the information in this Item 7.01 and Exhibit 99.1 hereto shall not be deemed “filed” for purposes of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference in any of the Registrant’s filings under the Securities Act of 1933, as amended, or under the Exchange Act, whether made before or after the date hereof, regardless of any incorporation language in such a filing, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit | **** | |
|---|---|---|
| Number | Exhibit Description | |
| 99.1 | | Company Presentation. |
| 104 | The cover page from Aclaris Therapeutics, Inc.’s Form 8-K filed on October 14, 2025, formatted in Inline XBRL. |
2
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| | | ACLARIS THERAPEUTICS, INC. |
|---|---|---|
| | | |
| | By: | /s/ Kevin Balthaser |
| Date: October 14, 2025 | | Kevin Balthaser |
| | | Chief Financial Officer |
3
Exhibit 99.1
| Patient Focused Innovation<br>Developing Therapeutic Franchises to Address Gaps<br>in Important I&I Diseases<br>2025 R&D Day<br>October 14, 2025 | |
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| 2<br>Any statements contained in this presentation that do not describe historical facts may constitute forward-looking statements as that term is defined in<br>the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “anticipate,” “believe,” “expect,” “intend,”<br>“may,” “plan,” “potential,” “will,” and similar expressions, and are based on Aclaris’ current beliefs and expectations. These forward-looking<br>statements include expectations regarding the therapeutic potential of Aclaris' product candidates, including bosakitug (ATI-045), ATI-052, ATI-2138,<br>next generation ITK selective inhibitors, and next generation bispecific and multispecific antibodies, including the potential for such product<br>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<br>therapies, the potential for bosakitug to have extended dosing, and the potential for the next-generation ITK inhibitors to have once-per-day dosing,<br>the development of such product candidates, including the potential targets and indications Aclaris may pursue, the timing and number of regulatory<br>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<br>Aclaris’ cash runway, including potential to extend the cash runway through non-dilutive opportunities. These statements involve risks and<br>uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual<br>results to differ materially include uncertainties inherent in the conduct of clinical trials, Aclaris’ reliance on third parties over which it may not always<br>have full control, Aclaris’ ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic<br>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<br>ended December 31, 2024, and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are<br>available under the “SEC Filings” page of the “Investors” section of Aclaris’ website at www.aclaristx.com. Any forward-looking statements speak only<br>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<br>obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.<br>This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and other data<br>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<br>addition, projections, assumptions and estimates of our future performance and the future performance of the markets in which we operate are<br>necessarily subject to a high degree of uncertainty and risk.<br>Tradenames, trademarks and service marks of other companies appearing in this presentation are the property of their respective owners.<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions, and are subject to change<br>based on a variety of factors.<br>Disclaimer and Cautionary Note Regarding<br>Forward-Looking Statements | |
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| Today’s Agenda<br>3<br>Patient Focused Innovation<br>Roland Kolbeck, Ph.D.<br>Chief Scientific Officer<br>World Class Development Engine<br>Zuzana Diamant, M.D, Ph.D., FERS<br>SAB member; Pulmonologist & Clinical<br>Pharmacologist, Department of Clinical<br>Pharmacy & Pharmacology, University<br>Medical Center Groningen, Netherlands<br>Michael Cameron, M.D., FAAD<br>Assistant Clinical Professor,<br>Department of Dermatology, Mount<br>Sinai, New York<br>Dr. Neal Walker<br>Chief Executive Officer<br>Introduction to Aclaris<br>Hugh Davis, Ph.D.<br>President & Chief Operating Officer<br>The Science of Antibody<br>Development<br>Jesse Hall, M.D.<br>Chief Medical Officer<br>Efficient Clinical Trial<br>Execution and Milestones<br>Joe Monahan, Ph.D.<br>Special Scientific Advisor<br>Founder, Confluence Discovery Technologies<br>Developing the Leading ITK Franchise | |
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| Aclaris Therapeutics<br>Developing Therapeutic Franchises to Address<br>Gaps in Important I&I Diseases<br>Neal Walker, MD<br>Chief Executive Officer<br>Patient Focused Innovation | |
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| Aclaris Therapeutics<br>Innovation<br>Driven<br>Patient<br>Focused<br>Three clinical programs in 2025; four anticipated<br>in 2026<br>2026 is an important year for Aclaris with four<br>anticipated inflection points<br>Validated targets; positioned in the oral and<br>antibody space<br>Bispecific and ITK oral programs could be<br>potential game changers in multiple indications<br>Advancing<br>potential<br>industry-leading<br>inhibitors<br>designed to<br>address<br>validated,<br>therapeutically-relevant<br>immune targets<br>5<br>Prudent capital management with a cash runway<br>expected into second half of 2028<br>Underpinned by state-of-the-art scientific<br>platform and world class people | |
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| Aclaris: Positioned for Significant Growth<br>6<br>Potential Best-in-Class<br>Clinical Assets<br>Continued Business<br>Execution<br>World Class<br>Expertise/Capability<br>• Bosakitug (ATI-045): Uniquely potent monoclonal antibody targeting TSLP<br>• ATI-052: Bispecific antibody (BsAb) targeting both TSLP and IL-4Rα<br>• ATI-2138: Potent and selective oral inhibitor of ITK/JAK3<br>• Discovery/preclinical lead candidate selection ongoing for novel ITK inhibitors and BsAbs<br>• ATI-2138: Phase 2a OL trial achieved primary and key secondary endpoints in AD;<br>further validated ITK as a therapeutic target<br>• Bosakitug: Dosing in two-arm placebo-controlled Phase 2 trial ongoing<br>• ATI-052: Phase 1a/1b SAD MAD program ongoing; dosing ongoing<br>• New INDs starting in 2026 expected from discovery engine<br>• World class development expertise<br>• Proprietary kinase small molecule discovery engine complemented by in-house<br>multidisciplinary team<br>• Innovative biologic discovery program incorporating dual-targeting strategies<br>addressing validated pathways<br>Well Financed with<br>Three-Year Cash Runway<br>• Strong balance sheet expected to fund operations into the second half of 2028<br>• Current cash runway expected to fully fund preclinical and clinical development plans<br>• Potential opportunities for additional non-dilutive financing and development partners | |
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| The Future Value of Drug Development<br>Addressing Th1, Th2 and Th17-Mediated Disorders<br>7<br>Sources: Eczema stats: National Eczema Association (accessed 07/31/25); National Alopecia Areata Foundation (Accessed 07/31/25); Vitiligo Facts: Global Vitiligo Foundation (accessed<br>07/31/25); Precedence Research; Forbes Business Insights; American Medical Association; American Lung Association; Global Initiative for Asthma; World Health Organization; The Centers for<br>Disease Control and Prevention (CDC); Business Research Company; peer research; Delveinsight; Cowen Categories Outlook 2024<br>0<br>10<br>20<br>30<br>40<br>50<br>60<br>70<br>Total Addressable Market (TAM)<br>Global, 2028-2034<br>($ billion)<br>Select Th1, Th2, Th17-Mediated Diseases<br>Significant opportunity<br>for new innovative<br>therapeutics for Th1,<br>Th2, and Th17-<br>mediated<br>dermatological and<br>respiratory diseases<br>including potent and<br>well tolerated<br>biologics and oral<br>inhibitors | |
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| Opportunities in the I&I Space<br>Potential to Address Significant Gaps in Unsatisfied I&I Indications<br>8<br>Opportunities for Orals<br>• Faster onset, durable, consistent effect<br>• Broader efficacy across heterogenous<br>populations<br>• Optimize symptom control: anti-itch<br>effect, FEV1<br>• Potential anti-fibrotic effect<br>• Convenience of oral<br>• Improved tolerability profile<br>Opportunities for Antibodies<br>• Raise efficacy ceiling<br>• Faster onset, durable, deeper, and<br>more consistent effect<br>• Improved tolerability<br>• Improved convenience and<br>practical dosing schedule | |
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| Aclaris Today<br>9<br>Patient Focused Innovation<br>• Unique State-of-the-Art R&D capabilities and World Class Scientists<br>• Four potential Best-in-Class clinical stage assets in 2026 targeting validated and therapeutically-relevant immune targets highlighted by a potential Best-in-Class bispecific and oral ITK inhibitor<br>• Rich calendar of data events expected throughout 2026 and 2027<br>• A cash runway expected to provide approximately three years of capital | |
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| ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>10<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>ITK/TXK ITK<br>TH1, TH2, and<br>TH17-driven diseases<br>TH2-driven atopic<br>and allergic diseases<br>IBD psoriasis GvHD<br>SO transplant<br>rejection vitiligo<br>Alopecia others<br>Asthma AD IBD<br>rhinitis GvHD others<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Ongoing<br>Next Gen<br>Multispecifics<br>Discovery<br>αTSLP/X (undisclosed 1)<br>αTSLP/X (undisclosed 2)<br>αTSLP/X (undisclosed 3)<br>Pruritis AD PN<br>psoriasis asthma chronic<br>urticaria IPF IBD<br>inflammation others<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Ongoing<br>Implicated in<br>Oral Kinase Inhibitors Biologics | |
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| World-Class Discovery<br>Engine<br>Leading Kinase and Antibody Innovation for the<br>Treatment of Autoimmune & Inflammatory Diseases<br>Roland Kolbeck, Ph.D.<br>Chief Scientific Officer<br>Patient Focused Innovation | |
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| What Makes Aclaris Stand Out<br>12<br>• Oral compounds targeting previously inaccessible parts of the Kinome<br>• Injectable potential best-in-class multi-specific antibodies designed to<br>address unmet clinical need and raise the efficacy ceiling<br>• World-class track record in drug discovery and development<br>• State-of-the-Art R&D capabilities<br>• Seamless execution by experienced drug developers | |
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| The Kinase Opportunity<br>13<br>The Aclaris Solution<br>KINect®<br>Technology<br>Platform<br>Proprietary chemical library and<br>integrated capabilities for<br>interrogating 60% of the Kinome<br><10%<br>of Kinome<br>targeted by the<br>80+ FDA<br>Approved Drugs<br>100s More to be Explored<br>500<br>Members<br>2% of the<br>Human<br>Genome<br>Most Members of the<br>Kinome Remain Unexplored<br>Medically Important and<br>Productive Target Class<br>$62.8B<br>Annual Sales<br>of Kinase<br>Drugs in 2024<br>$88.6B<br>Market<br>Opportunity in<br>2029<br>The Human Kinome<br>Challenges with Difficult to Drug Kinases<br>Selectivity<br>Biochemical efficiency<br>Sources: Kinase Inhibitors Market Overview (The Business Research Company); | |
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| Proprietary Chemical Library Design Specific to Each Kinase Faster Path to High Quality<br>Assets<br>Proprietary<br>Chemical<br>Library<br>Schrödinger<br>Enabled<br>Drug Design<br>Custom<br>Kinase<br>and<br>Immune<br>Assays<br>MODELING<br>DESIGN<br>SYNTHESIS<br>ANALYSIS<br>KINect Platform<br>Rapid and Efficient Development of Kinase Drug Candidates<br>14<br>KINect®<br>• Expands druggable Kinome:<br>Targets Type 1 (215 kinases),<br>Type 1.5 (68 kinases) and<br>Type 2 (128 kinases) kinases.<br>Competitors target<br>subgroups of Type 1 kinases<br>• Solves Class Challenges:<br>High affinity/selective drug<br>scaffolds<br>• Significantly decreases<br>time to Lead Optimization<br>• Proprietary Portfolio of<br>Inhibitors in development<br>• Expansion of target<br>opportunities | |
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| New Frontiers in Drug Discovery<br>Small Molecule Innovation<br>Innovation<br>Driven<br>Patient<br>Focused<br>Molecular glues<br>Small molecules that stabilize kinases in an inactive<br>confirmation or set them up for degradation<br>Covalent kinase inhibitors<br>Small molecules inhibiting kinases by forming irreversible<br>bonds with a cysteine at the active site<br>Tissue specific inhibitors<br>Small molecules that inhibit kinases in target<br>tissues with minimal systemic exposure<br>Protein degraders (PROTACs)<br>Small molecules that trigger the degradation of specific<br>kinases by the ubiquitin/proteasome pathway<br>“Drugging the<br>Undruggable”<br>Our approaches<br>allow us to<br>target<br>previously<br>inaccessible<br>parts of the<br>kinome and<br>beyond<br>15 | |
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| The Multi-Specific Antibody Opportunity<br>16<br>Multi-specific Antibodies<br>are a Successful Class of<br>Medicines for Cancers<br>$12.6B<br>Annual Sales of Multi-Specific<br>Antibodies in 2024<br>Number of Multi-Specific<br>Antibodies Approved<br>Opportunity:<br>Best-In-Class Multi-Specific<br>Antibodies for Autoimmune and<br>Inflammatory Diseases<br>$215B<br>Global health care<br>spending in<br>autoimmune<br>diseases in 2024<br>$396B<br>Global AI disease<br>therapeutics<br>market opportunity<br>by 2030<br>Unmet Clinical Need<br>Partial response; unresponsive<br>disease; refractory disease;<br>waning efficacy; safety; frequent<br>administrations<br>Increasing Health Burden<br>Over 100 autoimmune diseases; 50<br>million Americans affected;<br>Prevalence rising<br>18<br>Sources: Kuick Research Report: Global Multispecific Antibodies Market, Drug Sales, Dosage, Price and<br>Clinical Trials Insights; Autoimmune Disease Therapeutics Market – Global Forecast 2025-2032 | |
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| • Superior target affinity,<br>specificity, potency<br>• Combinations of 2 or more<br>clinically validated targets<br>with non-overlapping biology<br>• Combinations of clinically<br>validated targets with novel<br>biology<br>• Synergistic target<br>combinations: when one is<br>not enough<br>Format<br>– Fit-for-purpose multi-specific format<br>– Fully human/humanized<br>Fc Modifications<br>– Enhanced or reduced<br>effector function<br>– T1/2 extension<br>Developability<br>– High expression<br>– Stability<br>– Aggregation<br>Multi-Specificity/Potency<br>– High affinity<br>– Cellular potency<br>Developing Multi-Specific Antibodies<br>for Autoimmune Diseases<br>Working with world-class scientific partners<br>to identify opportunities and best-in-class technologies<br>17 | |
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| Proven Track Record of Discovery and Development<br>18<br>ITK is downstream of<br>the T cell receptor and<br>impacts T cell function<br>and differentiation<br>Covalent ITK/JAK3<br>Inhibitors (ATI-2138)<br>JAK3 is necessary for<br>signaling from γc<br>cytokines like IL-2<br>Covalently modifying<br>both targets interrupts<br>these pathways<br>simultaneously<br>impacting T cell<br>survival, function and<br>differentiation.<br>Next generation<br>compounds inhibit ITK<br>without JAK3 crossover<br>Next Generation ITK<br>Inhibitors<br>Compounds designed<br>to achieve sustained<br>ITK inhibition at trough<br>with QD dosing<br>Compounds with<br>different degrees of<br>TXK (RLK) selectivity are<br>under evaluation<br>Very high affinity to TSLP<br>Bosakitug (ATI-045)<br>Anti-TSLP mAb<br>70x more potent than<br>tezepelumab<br>Extremely low<br>dissociation rate from<br>TSLP, leading to long<br>residence time and<br>enhanced<br>neutralization activity<br>Bosakitug, combined<br>with anti-IL-4Rα<br>ATI-052<br>Anti-TSLP/IL4Rα BsAb<br>More potent than<br>combination of<br>tezepelumab +<br>dupilumab<br>Engineered for<br>extended T1/2<br>~23-day T1/2<br>potentially supporting<br>extended dosing<br>interval<br>Potential for superior<br>activity compared with<br>monotherapy<br>Dual ITK and JAK3 inhibition Selective inhibition of ITK Uniquely differentiated mAb Potential for Best-in-Class<br>bispecific antibody<br>Small Molecules Antibodies | |
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| State of the Art R&D Capabilities<br>Expertise in Small Molecules and Antibodies R&D<br>19<br>Biochemistry & Enzymology Bioanalytical Chemistry<br>Immunology<br>• Mechanistic Enzymology<br>• Compound - Target Interaction<br>• Enzyme Inhibitor Mechanisms<br>• Direct Binding Kinetics<br>• High Throughput Screening<br>• Non-GLP Analytical<br>• Bioanalytical Method<br>Development<br>• Bioanalytical Method Validation<br>• Pharmacokinetic / Toxicokinetic<br>Analysis<br>• Ab Solubility and Aggregation<br>• Cytokine Expression<br>• Th Cell Differentiation / Activation<br>• CTL Differentiation / Function<br>• B Cell and NK Cell Function<br>• Ag Specific Cell Activation<br>• HWB/PBMC/Monocyte Assays<br>Translational Research<br>Computational & Medicinal<br>Chemistry<br>In Vivo Pharmacology & PK<br>• Biomarker Assay Development<br>• Clinical Biomarker Assessment<br>• Release Assay Validation<br>• Schrödinger Enabled<br>Structure Based Drug Design<br>• AI Augmented Molecular<br>Modeling<br>• In Silico Antibody Engineering<br>• Scale-Up and Route<br>Optimization<br>• Inflammation Models (Mouse &<br>Rat)<br>• Immune Cell Phenotyping<br>• Cytokine Profiling<br>• Transcriptomics<br>• PK/PD Relationship | |
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| World Class Discovery Engine<br>Summary<br>20<br>• Oral compounds targeting previously inaccessible parts of the Kinome with<br>proprietary KINect platform<br>• Designing injectable multi-specific antibodies with superior target coverage and potency<br>to raise the efficacy ceiling<br>• Unique expertise in small and large molecule development<br>• State-of-the-Art R&D capabilities with broad unique expertise across spectrum of drug<br>design and development<br>• Seamless execution by experienced drug developers; anticipate new INDs starting in 2026<br>Leading Kinase and Antibody Innovation for<br>the Treatment of Autoimmune & Inflammatory Diseases | |
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| Developing the Leading<br>ITK Franchise<br>Innovation Through ITK Inhibition<br>Joe Monahan, Ph.D.<br>Special Scientific Advisor<br>Founder, Confluence Discovery Technologies<br>Patient Focused Innovation | |
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| ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>22<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>ITK/TXK ITK<br>TH1, TH2, and<br>TH17-driven diseases<br>TH2-driven atopic<br>and allergic diseases<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Next Gen<br>Multispecifics<br>Discovery<br>αTSLP/X(undisclosed 1)<br>αTSLP/X(undisclosed 2)<br>αTSLP/X(undisclosed 3)<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Oral Kinase Inhibitors Biologics | |
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| T Cell Receptor (TCR) Pathway<br>Interleukin-2-inducible T-cell kinase (ITK) is a Key Kinase Involved in TCR Signaling<br>Antigen-presenting cell<br>T-cell<br>Lck<br>LAT<br>Phosphorylation<br>Zap-70<br>CD3<br>CD4<br>MHC<br>Antigen<br>SLP-76<br>ITK<br>TCR<br>δ ε ε γ<br>α β<br>Ca2+<br>ER<br>Ca2+<br>Ca2+<br>Ca2+<br>Ca2+<br>Ca2+<br>Ca2+<br>Ca2+<br>Nucleus<br>Cytoplasm<br>Cytoplasm<br>ζ ζ<br>IRF4 IRF4<br>• TCR activation is critical for<br>T lymphocyte differentiation,<br>proliferation and activation<br>• TCR signaling proceeds<br>through a complex<br>intracellular pathway resulting<br>in the activation of key<br>transcription factors and<br>production of cytokines<br>• Central to TCR signaling is the<br>kinase ITK<br>Inhibiting/downregulating ITK shuts down TCR signaling under<br>inflamed/allergic conditions and impacts disease<br>23 | |
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| ITK Modulates T Cell Differentiation and Activation<br>Skews T Helper Cell Differentiation Towards Th2 and Th17 Phenotypes<br>• ITK has a nonredundant<br>role in the differentiation,<br>proliferation and<br>activation of TH2 and<br>TH17 cells<br>• ITK and the Tec kinase<br>TXK are both required for<br>Th1 function<br>Selective blockade of ITK impacts allergy and asthma<br>Dual blockade of ITK/TXK also impacts autoimmunity<br>24 | |
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| 25<br>Th2 Th17 ILC2 Th1<br>IL4 IL5 IL13 IL31 IL17 IL21 IL22 IL5 IL13 IFNγ IL2<br>ITK Inhibitor<br>ITK/TXK Inhibitor<br>αIL-4R<br>αIL-13<br>αIL-17<br>αIL-31R<br>JAK1<br>JAK3<br>STAT6 Inhibitor<br>Comparative Impact of ITK Inhibition<br>Broad Applicability in Inflammatory/Allergic Pathways | |
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| ITK is Therapeutically Relevant<br>But Historically Difficult to Drug<br>2002 2003 2004 2005 2006 2007 2008 2012 2013 2014 2015 2016 2017 2018<br>Reversible ATP Competitive Inhibitors Discontinued for Weak Cellular Potency, Poor ADME<br>Compounds<br>targeting the ATP<br>site of ITK have<br>been pursued since<br>the early 2000s<br>Only JTE-051 reached<br>development and<br>was discontinued<br>26<br>Japan Tobacco +<br>Akros Pharma<br>JTE-051<br>BMS Genentech<br>AstraZeneca Vertex GSK<br>Boehringer<br>Ingelheim<br>Pfizer<br>2009 2010 2011<br>O<br>N<br>N<br>NH<br>O<br>NH2<br>H2N<br>O<br>H<br>N<br>N<br>H<br>O<br>S<br>N<br>S<br>O<br>N<br>O<br>N<br>O<br>N<br>H<br>N<br>H<br>N<br>N<br>OH<br>O<br>S<br>N<br>H<br>N<br>N<br>H<br>N<br>NH<br>N<br>O<br>N<br>O<br>N<br>O S N<br>O<br>H<br>N<br>O<br>H<br>N N<br>F<br>F<br>N<br>N<br>HN S<br>N<br>N<br>H<br>OH<br>N<br>N<br>NH<br>H<br>N<br>O<br>N<br>H<br>O<br>N<br>N<br>N H<br>N<br>Cl<br>N<br>N<br>N<br>N | |
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| Issues with ATP Competitive ITK Inhibitors<br>27<br>• Generally large, lipophilic molecules with poor<br>physicochemical properties<br>• Poor pharmacokinetic properties in most series<br>• Reactive metabolites with gene tox issues<br>• Variable selectivity against kinome<br>• Ambiguous mechanisms of action in cells<br>• Large shift in potency between enzyme and cell<br>• Low biochemical efficiency<br>Known<br>concerns<br>require<br>alternative<br>to ATP<br>Competitive<br>inhibitors<br>Covalent<br>Kinase<br>Inhibitors | |
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| • Design guided by modeling and proprietary<br>crystal structures<br>• Crystal structure to confirm covalent binding<br>characteristics<br>– Designed to interact with the ATP site<br>and covalently modifies CYS442 in ITK<br>• Maximize reversible affinity and minimize<br>electrophile reactivity<br>• Approach overcomes issues with<br>biochemical efficiency and enhances<br>kinase selectivity<br>Structure of ITK: Inhibitor Complex<br>Covalent ITK Inhibition<br>Overcoming Issues with Biochemical Efficiency<br>28 | |
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| ATI-2138:<br>A First Generation<br>Novel ITK/JAK3 Inhibitor for<br>T Cell-Mediated Diseases<br>Potent and Selective Investigational Drug<br>Candidate with Strong Tolerability Profile<br>Patient Focused Innovation | |
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| TCR<br>APC<br>T Cell<br>Proliferation<br>Differentiation<br>Activation<br>γc cytokines<br>JAK3<br>pSTAT5<br>ATI-2138<br>T Cell<br>NK Cell<br>ATI-2138<br>Oral Small Molecule Covalent ITK & JAK3 Inhibitor for I&I Disease<br>• Investigational oral compound which interrupts<br>T cell receptor (TCR) signaling by inhibiting ITK and JAK3<br>signaling of common γ chain cytokines in lymphocytes<br>(including IL-2 & IL-15)<br>• Highly potent for both ITK and JAK3<br>(IC50: 0.2nM ITK; 0.5nM JAK3)<br>• Highly selective against other JAK isoforms<br>• Unique dual pharmacology; best-in-class potential<br>• Clinical data thus far demonstrate good safety and PK<br>characteristics; positive readout in a phase 2A AD study<br>30 | |
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| Why this Molecule is Unique<br>31<br>Regulation of T cell<br>development and<br>function both<br>upstream (ITK) and<br>downstream (JAK3)<br>High potency for<br>inhibiting both ITK<br>and JAK3<br>Inhibiting both<br>pathways may<br>provide a more<br>potent and complete<br>anti-inflammatory<br>response<br>As both targets are<br>restricted in expression<br>to immune cells,<br>inhibitors have the<br>potential for a<br>favorable safety profile<br>Unique Dual Pharmacology of ATI-2138 Provides Best-in-Class Potential | |
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| ATI-2138<br>Anti-inflammatory Activity in Mouse Models<br>IBD<br>Mouse T Cell Transfer<br>Vitiligo Score<br>3<br>0<br>6<br>9<br>12<br>15<br>18<br>Rheumatoid Arthritis<br>Mouse CIA Model<br>32<br>Mean ±SE Clinical Arthritis<br>Score (Scored 0-5)<br>Naïve/Chow<br>Vehicle Chow<br>Enbrel (10 mg/kg)<br>ATI-2138 (100 ppm)<br>ATI-2138 (300 ppm)<br>ATI-2138 (1000 ppm)<br>21 22 23 24 25 26 27 28 29 30 31 32 33 34 35<br>Study day<br>ATI-2138 has demonstrated robust anti-inflammatory activity in mouse models of disease:<br>Inflammatory Bowel Disease, Vitiligo, and Rheumatoid Arthritis<br>Vitiligo<br>Mouse T Cell Transfer | |
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| ATI-2138<br>Unique Dual Pharmacology and Best-in-Class JAK3 Inhibitor Potential<br>ITK: HWB αCD3<br>Stimulated IFNγ<br>Release<br>JAK3: HWB IL2<br>Stimulated IFNγ<br>Release<br>0.1 1 10 100 1000 10000<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>140<br>nM<br>IFNg Production (% Stim)<br>ATI-2138<br>Ritlecitinib<br>0.1 1 10 100 1000 10000<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>nM<br>IFNg Production (% Stim)<br>ATI-2138<br>Ritlecitinib<br>5.4x<br>44.4x<br>• ATI-2138 is 44.4x more potent than ritlecitinib for<br>inhibiting anti-CD3 induced IFNγ production (ITK) and<br>5.4x more potent for inhibiting JAK3 dependent IL-2<br>induced IFNγ production in human whole blood<br>• At the FDA recommended 50 mg QD dose for<br>alopecia areata, ritlecitinib plasma levels may not<br>impact ITK (anti-CD3 /IFNγ) for any appreciable time<br>33 | |
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| ATI-2138 and CPI-818 (Soquelitinib)<br>Best-in-Class ITK Inhibitor Potential<br>• ATI-2138 is 15-38x more potent than CPI-818<br>in inhibiting the ITK enzyme activity<br>• ATI-2138 is significantly more potent than<br>CPI-818 in blocking the Th2 derived<br>cytokines, IL-4, IL-5 and IL-13 (30-100x)<br>ITK, IC50,<br>nM<br>Kinact/Ki<br>(uM-1s-1)<br>ATI-2138 0.25 0.34<br>CPI-818 9.5 0.022<br>Potency Ratio 38x 15x<br>ITK Biochemical Enzyme Potency<br>Anti-CD3/CD28-Induced Cytokines from Human Th2 Cells<br>34 | |
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| 35<br>Safety<br>Pharmacokinetics<br>Pharmacodynamics<br>• ATI-2138 was generally well tolerated at all doses tested in the trial<br>• No serious adverse events were reported<br>• ATI-2138 was rapidly absorbed<br>• Multiple doses ranging from 10 to 80 mg daily over two weeks in healthy<br>volunteers showed linear PK and dose-dependent increases in exposure<br>• At 10-30 mg daily, ATI-2138 plasma concentration reached the targeted<br>level established using preclinical data<br>ATI-2138<br>Single and Multiple Ascending Dose (SAD/MAD) Studies: Summary<br>PK<br>PD<br>• Time, dose and concentration-dependent inhibition of both the ITK and<br>JAK3 pathways was observed with ATI-2138<br>• PD markers were inhibited across the dosing interval with the 5-40 mg BID<br>doses inhibiting up to 50%-90% of both ITK and JAK3 functional markers | |
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| Phase 2a Trial in Atopic Dermatitis<br>• Twelve-week, open-label study with ATI-2138 (10mg BID) in moderate to severe AD patients<br>• Favorable safety profile<br>• Efficacy observed across multiple measures comparable to drugs approved for AD<br>• Exposure similar to or slightly higher than predicted from MAD study<br>• Efficacy and PD results validate therapeutic potential of targeting ITK:<br>– Near complete and sustained inhibition and occupancy of ITK<br>– Downregulation of multiple ITK-dependent immune pathways in the skin<br>36 | |
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| PP-NRS: % of Pts with ≥4 Point Improvement in Worst Itch<br>over Prior 24 Hours<br>Phase 2a Trial in Atopic Dermatitis<br>After four weeks of treatment<br>• BSA decreased by 63.9%<br>• EASI scores dropped by 77.3%<br>• PP-NRS decreased by 44.7%<br>• These changes were statistically<br>significant and sustained through<br>study conclusion (W12)<br>At week 12, 63% of patients receiving a low dose (10mg BID) of<br>ATI-2138 experienced a ≥4-point improvement worst itch<br>in the past 24 hours<br>Molecular and Clinical Effects of oral ATI-2138, an ITK/JAK3<br>inhibitor, in Moderate-to-Severe Atopic Dermatitis: Sub-study<br>of a Phase 2a Open-Label, Single-Arm Trial. Beaziz-Tordjman, Jessica et al. European Academy of<br>Dermatology and Venereology, September 17, 2026.<br>A ≥4-point<br>improvement in<br>PP-NRS score is<br>considered a<br>clinically<br>meaningful<br>result<br>37<br>Efficacy Results Show Strong Consistent Response to ATI-2138<br>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<br>conducted. Differences exist between trial designs and subject characteristics, and caution should be exercised when comparing data across studies. Data collected on 8 of 10 PP patients. | |
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| ATI-2138 is<br>Mechanistically<br>Unique and PD<br>Supports Observed<br>Clinical Efficacy<br>38<br>Understanding PK/PD<br>• ITK Assay<br>– αCD3/aCD28 ex vivo<br>stim mRNA (IL-2 and<br>IFNγ) production<br>• ITK Target Occupancy<br>• JAK3 Assay<br>– IL-15 ex vivo stim IFNg<br>protein production<br>• Immunophenotyping<br>Relating PD to Efficacy<br>• Punch Biopsy Analysis<br>– Immunohistochemistry<br>– RNAseq Analysis<br>(>16,000 genes)<br>• Tape Strip Analysis<br>– RNAseq Analysis<br>(>16,000 genes)<br>– Olink Proteomics<br>(300+ analytes)<br>• Endogenous Biomarkers<br>in Plasma<br>– OLink Proteomics<br>(300+ analytes)<br>Phase 2a Trial in Atopic Dermatitis<br>Pharmacodynamic Assessment<br>Conducted to<br>Assess Target,<br>Pathway, and<br>Disease Markers<br>to Support<br>Mechanism of<br>Action | |
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| Phase 2a Trial in Atopic Dermatitis<br>Marked and Sustained ITK Inhibition Observed<br>39<br>Functional inhibition and target occupancy retained across the dosing interval;<br>>90% inhibition IFNγ mRNA and near complete target occupancy observed 1 hour post dose<br>Data collected on 8 of 10 per protocol patients | |
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| Gene Set Variation Analysis (GSVA)<br>Tape Strip Proteomics Data<br>Immune Genes (Extended)<br>Th17 Th2<br>IgFCH vs Baseline IgFCH vs Baseline<br>Week 4 Week 8 Week 12<br>Black stars: significance vs baseline<br>Red stars: significance between change in<br>lesional vs. change in non-lesional<br>Th1<br>Week 4 Week 8 Week 12<br>Week 4 Week 8 Week 12<br>Week 4 Week 8 Week 12<br>• Proteomic results corroborate<br>genomics findings<br>• Immune-related gene or protein<br>profile improved over time, with<br>reduction of inflammation<br>• Variability between weeks 8 and<br>12 may be attributed to<br>noncompliance by two patients<br>Non-lesional Lesional<br>40<br>Data collected on 8 of 10 per protocol patients | |
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| Correlation B/W Change in Clinical Scores & in Key Gene Expression<br>Decreases in<br>inflammatory<br>and fibrosis-related markers<br>positively and<br>strongly<br>correlated with<br>improvements<br>in clinical<br>scores<br>CXCL12 TSLP CCL21<br>R=0.71<br>p=0.029<br>R=0.8<br>p=0.009<br>R=0.67<br>p=0.05<br>GENERAL INFLAMMATION Th2 Th17<br>SPON1 LUM ELN<br>FIBROSIS<br>R=0.68<br>p=0.042<br>R=0.8<br>p=0.009<br>R=0.8<br>p=0.009<br>41 Data collected on 8 of 10 per protocol patients | |
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| Phase 2a Trial in Atopic Dermatitis<br>ITK Pathway Mediated Anti-Inflammatory Activity in Skin and Plasma<br>• ATI-2138 significantly downregulated multiple immune pathways in skin and plasma<br>• Strong downregulation of key ITK dependent pathway markers such as:<br>– Th2 (e.g., CCL17, CCL24, IL13, TSLP)<br>– Th17 (e.g., CXCL1, IL17A, IL6R)<br>– TCR (ITK) Pathway (e.g., ITK, IL-13, CD3, ZAP70, LCK, PLCg1)<br>– Th1 (e.g., CXCL11, CXCL9, IL2RA, TNF)<br>– Fibrosis related markers (e.g., MMP9, TNFRSF9)<br>• Safety profile and expected incremental increase in PD with greater exposure may<br>support higher dosing in subsequent studies<br>42 | |
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| Next Generation ITK<br>Inhibitors<br>Novel ITK and ITK/TXK Selective Inhibitors<br>Designed to Limit JAK Inhibitory Activity<br>Patient Focused Innovation | |
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| Aclaris ITK Inhibitor Program Status Summary<br>1 Next Generation Inhibitors st Generation<br>Inhibitors<br>Phase 2a AD study met<br>primary and secondary<br>key endpoints<br>Well tolerated at all doses<br>Validated ITK MOA and<br>corroborates our work on<br>next-generation ITK<br>selective compounds<br>Translatable JAK3 Selectivity<br>Low dose for total ITK occupancy<br>JAK3 and TXK selectivity<br>Total ITK occupancy<br>demonstrated in vivo<br>ITK TXK<br>ATI-2138 ACRS-1 ACRS-2<br>ITK TXK JAK3 ITK<br>ACRS-3<br>44<br>Highly potent ITK/TXK dual<br>inhibitors<br>Extended half-life<br>Potent ITK-selective<br>inhibitor<br>Extended half-life | |
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| JAK3 Kinase Domain<br>Exploit collapse in<br>G-loop to increase<br>ITK selectivity<br>ITK Kinase Domain<br>Strong interaction<br>with gatekeeper<br>Phe435 increases<br>ITK Potency Phe435<br>JAK3 G-loop<br>ITK G-loop<br>CYS442<br>ACRS-2 modeled into ITK kinase domain 3QGY and JAK3 kinase<br>domain 5TOZ SP covalent dock<br>Next Generation ITK Inhibitors<br>Designing ITK Potency and JAK3 Selectivity<br>• Aclaris compounds designed to<br>form strong interactions in the ITK<br>kinase domain with gatekeeper<br>Phe435 leading to an increase in<br>potency for ITK (Ki)<br>• The position and orientation of<br>the G-loop is different between<br>the ITK and JAK3 Kinase domains<br>• ACRS Next Generation<br>compounds designed to take<br>advantage of these structural<br>differences to decrease potency<br>for JAK3 compared to ITK<br>45 | |
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| • Next Generation compounds have<br>decreased efficiency against JAK3<br>and variable efficiency against TXK<br>• Aclaris compounds are significantly<br>more efficient inactivators of ITK as<br>compared to CPI-818<br>46<br>Efficiency and Selectivity in Enzyme-Based Assays<br>Aclaris Next Generation Compounds<br>CPI-818 | |
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| Human PBMC Cell Data Human Whole Blood<br>Data<br>Compound Target ITK Occupancy<br>(OC90)<br>aCD3 stim IL-2<br>(IC50)<br>ITK/JAK3<br>(IC50 Ratio)<br>HWB ITK IC50<br>CD3/CD28 stim<br>IL-2 mRNA<br>ATI-2138 ITK/TXK/JAK3<br>1st Generation 17 nM 10 nM 0.1x 17 nM<br>ACRS-1<br>ITK/TXK<br>7 nM 7 nM 79x 51 nM<br>ACRS-2 69 nM 34 nM 95x 33 nM<br>ACRS-3 ITK 16 nM 16 nM 109x 61 nM<br>CPI-818 Corvus<br>ITK-selective 117 nM 167 nM >40x 408 nM<br>47<br>Aclaris compounds show significant increase in cell potencies<br>for ITK as compared to CPI-818<br>Next Generation compounds show limited inhibition of JAK3<br>Potency, Occupancy and Selectivity<br>In Human Primary Cells | |
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| Correlation B/W Occupancy & Functional Inhibition in PBMC<br>48<br>Good correlation between<br>functional ITK inhibition and<br>target occupancy<br>Demonstrates potency<br>and occupancy superiority<br>for the ACRS ITK inhibitors<br>vs competitors | |
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| Differential Inhibitor Impact<br>Th1 and Th2 Cell Function<br>• Impact of inhibitors on canonical<br>cytokines from human differentiated<br>Th1 and Th2 cells<br>• ACRS 1 and ACRS 2 block Th1 and Th2<br>responses through dual inhibition of ITK<br>and TXK<br>• ACRS 3 blocks Th2 responses and spares<br>Th1 through selective inhibition of ITK<br>Th1/IFNg Th2/IL4 Th2/IL5 Th2/IL13<br>0<br>0<br>0<br>0<br>0<br>0<br>0<br><br> <br> <br> <br>Next generation inhibitors potently block Th2 function and differentially modulate Th1 activation<br>49<br><br>Average IC50 nM<br> <br> <br> | |
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| Why is Potency Important with Covalent Drugs?<br>50<br>• Enzyme inactivation efficiency drives drug potency<br>• Higher potency results in lower and less frequent dosing<br>• Lower and less frequent dosing decreases drug burden<br>• Lower drug burden increases selectivity and supports a superior safety profile<br>• Covalent drugs contain reactive electrophiles:<br>– Low potency covalent inhibitors require high drug levels in blood and tissue<br>– High drug concentrations increase probability of the electrophile reacting with non-target proteins,<br>potentially increasing safety liabilities | |
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| Next Gen ITK Inhibitors Demonstrate JAK3 Selectivity in Vivo<br>Veh<br>ACRS-2, 10mpk<br>ACRS-2, 30mpk<br>ACRS-2, 100mpk<br>ATI-2138, 45mpk<br>0<br>2<br>4<br>6<br>8<br>10<br>NK, % of CD45+<br>✱✱✱✱<br>ACRS-1 ACRS-2 ACRS-3<br>Veh<br>ACRS-1, 10mpk<br>ACRS-1, 30mpk<br>ACRS-1, 100mpk<br>ATI-2138, 45mpk<br>0<br>2<br>4<br>6<br>8<br>NK, % of CD45+<br>✱✱✱<br>✱✱✱✱<br>Vehicle<br>ACRS-1 - 10MPK<br>ACRS-1 - 30MPK<br>ACRS-1 - 100MPK<br>ATI-2138 - 45MPK<br>-50<br>0<br>50<br>100<br>150<br>ACRS-1 ITK Occupancy<br>in Mouse Spleen<br>% ITK Occupancy<br>Vehicle<br>ACRS-2 - 10MPK<br>ACRS-2 - 30MPK<br>ACRS-2 - 100MPK<br>ATI-2138 - 45MPK<br>-25<br>0<br>25<br>50<br>75<br>100<br>125<br>ACRS-2 ITK Occupancy<br>in Mouse Spleen<br>% ITK Occupancy<br>Veh<br>ACRS-3, 10mpk-BID<br>ACRS-3, 30mpk-BID<br>ACRS-3, 100mpk-BID<br>ATI-2138, 45mpk-BID<br>0<br>2<br>4<br>6<br>NK, % of CD45+<br>✱✱✱✱<br>Complete ITK<br>occupancy<br>achieved without<br>impacting JAK3<br>function<br>51<br>ACRS-3 ITK Occupancy<br>In Mouse Spleen<br>JAK 3 functional activity assessed by NK<br>cell frequency in mouse spleen<br>JAK 3 functional activity assessed by NK<br>cell frequency in mouse spleen<br>JAK 3 functional activity assessed by NK<br>cell frequency in mouse spleen | |
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| Half-Life Comparison of Compounds<br>Elimination Half-Lives in Mice<br>Aclaris Next Generation compounds demonstrate a significant increase in half-lives<br>in mice as compared to ritlecitinib and CPI-818<br>More amenable to once-per-day dosing<br>ritlecitinib<br>CPI 818<br>ACRS 1<br>ACRS 2<br>ACRS 3<br>52 | |
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| Profiling of Next Generation Compounds<br>ACRS-1 ACRS-2 ACRS-3<br>Patent applications<br>have been filed on<br>Next Generation<br>compounds<br>Biochemical IC50 and kinact/Ki<br>(ITK, TXK, BTK, and JAK3)<br>hPBMC Cell-Based Assays<br>(Functional and Occupancy)<br>ITK and JAK3<br>ITK Cell Cytotox IC50<br>HWB Translatable Functional<br>Biomarker IC50 (ITK and JAK3)<br>Solubility in Biorelevant Media<br>Permeability and Efflux<br>Cross-species Stability (Liver,<br>Hepatocytes, Blood, and Plasma)<br>Cross-species Plasma Protein<br>Binding and Blood-to-Plasma Ratio<br>In vivo Pharmacokinetics in Rodent<br>and Non-rodent Species<br>Kinase Selectivity<br>Human PK Projections (PBPK)<br>hERG, and CEREP Panel<br>CYP (Inhibition, TDI, and Induction)<br>Transporter Inhibition<br>Pharmacology<br>DMPK<br>Safety<br>53 | |
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| Aclaris ITK Inhibitor Program<br>Summary<br>• Successfully generated a portfolio of covalent ITK inhibitors with differentiated<br>pharmacological properties and selectivity profiles<br>• These inhibitors expected to differentially modulate T cell biology across a broad<br>range of disease indications and have best-in-class/first-in-class potential<br>• ATI-2138 has demonstrated:<br>– Favorable safety profile<br>– Clear understanding of PK and PD<br>– ITK pathway and T cell modulation<br>– Early signs of efficacy in a 12-week AD study<br>• Next Generation JAK-sparing compounds progressing toward initial IND in 2026<br>54 | |
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| Aclaris Next Generation ITK Inhibitor Program<br>Potentially beneficial<br>in Th1, Th2,<br>and Th17-driven<br>diseases<br>55<br>• IBD<br>• Psoriasis<br>• Chronic GvHD<br>• SO Transplant Rejection<br>• Vitiligo<br>• Alopecia<br>• Celiac disease<br>• Eosinophilic esophagitis<br>• Prurigo nodularis<br>• Others<br>IL-4R: Dupixent® (dupilumab)<br>IL-31R: Nemluvio® (nemolizumab)<br>IL-17A: Cosentyx® (secukinumab)<br>Taltz® (ixekizumab)<br>Bimzelx® (bimekizumab)<br>Siliq® (brodalumab)<br>JAK1: Oluminant® (baricitinib)<br>JAK1/2: Opzelura® (ruxolitinib)<br>JAK3: Litfulo® (ritlecitinib)<br>Alopecia areata: $7B<br>Vitiligo: $3B<br>Psoriasis: $60B<br>EoE: $5B<br>Prurigo nodularis: $2B<br>COPD: $31B<br>Potentially<br>beneficial in Th2-<br>driven atopic and<br>allergic diseases<br>• Asthma<br>• Atopic Dermatitis<br>• Rhinitis<br>• COPD<br>• CSU<br>• Others<br>IL-4R: Dupixent® (dupilumab)<br>IL-13: Ebglyss® (lebrikcizumab)<br>Adbry® (tralokinumab)<br>IL-31R: Nemluvio® (nemolizumab)<br>JAK1: Rinvoq® (upadacitinib)<br>Cibinqo® (abrocitinib)<br>Asthma: $36B<br>Atopic dermatitis: $31B<br>Rhinitis: $19B<br>CSU: $6B<br>Sources: Eczema stats: National Eczema Association (accessed 07/31/25); National Alopecia Areata Foundation (Accessed 07/31/25); Vitiligo Facts: Global Vitiligo Foundation (accessed<br>07/31/25); Precedence Research; Forbes Business Insights; American Medical Association; American Lung Association; Global Initiative for Asthma; World Health Organization; The Centers for<br>Disease Control and Prevention (CDC); Business Research Company; peer research; Delveinsight; Cowen Categories Outlook 2024<br>Potential Indications Approved Inhibitors TAMs*<br>*TAM=Total Addressable Markets: Estimates, 2028-2034<br>ITK/TXK<br>ITK | |
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| ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>56<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Next Gen<br>Multispecifics<br>Discovery<br>αTSLP/X(undisclosed 1)<br>αTSLP/X(undisclosed 2)<br>αTSLP/X(undisclosed 3)<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b ITK | ITK/TXK<br>Next Gen IND:<br>2H 2026<br>Oral Kinase Inhibitors Biologics<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors |
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| The Science of Antibody<br>Development<br>Validating TSLP as an Effective Therapeutic Target<br>Hugh Davis, Ph.D.<br>President and Chief Operating Officer<br>Patient Focused Innovation | |
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| ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>58<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Ongoing<br>Next Gen<br>Multispecifics<br>Discovery<br>αTSLP/X(undisclosed 1)<br>αTSLP/X(undisclosed 2)<br>αTSLP/X (undisclosed 3)<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Ongoing<br>Oral Kinase Inhibitors Biologics<br>ITK | ITK/TXK<br>Next Gen IND:<br>2H 2026<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors |
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| • Pleiotropic and broad activity<br>– Master regulator of type 2 (Th2) immune<br>responses at the barrier surfaces of skin<br>and the respiratory/ gastrointestinal tract<br>– Drives eosinophilic and neutrophilic<br>inflammation and acts on a wide variety<br>of adaptive, innate, and structural cells<br>– Broad activity: Involved in induction<br>phase and effector phase as well as non-Th2 processes<br>– Proven biology: The expression of TSLP is<br>elevated in individuals with respiratory<br>and skin disease<br>59<br>Targeting Thymic Stromal Lymphopoietin (TSLP)<br>Therapeutically Relevant Immune Target<br>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<br>High Potency Therapeutics are Key to Effectiveness<br>• Abs must engage ligands at the site of action<br>• Key variables related to efficacy<br>– TSLP concentration at site of lesion<br>– Antibody concentration at site of lesion<br>• Concentration of mAb in general circulation<br>• Skin penetration of mAb<br>• Dose<br>• Potency<br>– Binding Mechanism of mAb to TSLP<br>• Binding affinity<br>• Residence Time<br>– Degree of TSLP reduction needed at site of lesion<br>Only 15% of mAb serum levels reach skin/site of lesion: Potency is Key to Efficacy<br>60<br>mAb mAb TSLP<br>TSLP<br>Tissue<br>Penetration<br>Antibody<br>Concentration TSLP<br>Concentration<br>Binding<br>Mechanism<br>Adapted from Lavers et al., Int J Aes Nursing 2017 | |
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| Bosakitug (ATI-045):<br>Highly Differentiated<br>Anti-TSLP Antibody<br>Backbone<br>Best-in-Class Potential<br>Patient Focused Innovation | |
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| Bosakitug Key Properties<br>• Very high affinity to TSLP<br>• Extremely low dissociation rate<br>from TSLP* leading to long<br>residence time and enhanced<br>neutralization activity<br>• Very high potency<br>• Unique binding characteristics<br>to TSLP<br>• ~23-day half-life that can<br>potentially support an extended<br>dosing interval of up to 3 months<br>~70x Inhibition of CCL17 Produced by hPBMCs<br>Stimulated with TSLP<br>mean % stim, R&D TSLP @ 0.1ng/mL<br>IC50<br>Bosakitug is ~70x More Potent than Tezepelumab, the Only Marketed Anti-TSLP mAb<br>62 * Quantification of dissociation rate limited by the surface plasmon resonance instrument sensitivity<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>Antibody (nM)<br>ATI-045<br>Tezepelumab<br>Bosakitug | |
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| Dissociation of TSLP from mAbs (TR-FRET)<br>0 1000 2000 3000 4000<br>0.0<br>0.5<br>1.0<br>Time (min)<br>Fractional Response (yi/yo)<br> ATI-045<br> ATI-052<br> GSK-5784283 V1 (hu3-13)*<br> GSK-5784283 V2 (hu179-33)*<br> Solrikitug/MK-8226**<br> Tezepelumab**<br>bosakitug<br>Residence Time<br>(hours)<br>416 402<br>14.3 8.11 22.1 3.59 20.7<br>ATI-052<br>ATI-045<br>Tezepelumab**<br>Solrikitug/MK-8226**<br>GSK-5784283 V2 (hu179-<br>33)*<br>GSK-5784283 V1 (hu3-13)*<br>UPB-101<br>TSLPR1<br>(n=2)<br>TSLP<br>(n=3)<br>bosakitug<br>Bosakitug (and ATI-052) demonstrates very slow dissociation kinetics from TSLP<br>Residence time for Bosakitug (and ATI-052) is ~20-100x longer than comparator antibodies<br>63<br>Bosakitug Key Properties<br>Lower Dissociation Rate = Longer Residence Time<br>1. SPR: Residence Time based on apparent kd using standard TSLPR immobilization density and bivalent fit; *Analog mAb; **Biosimilar mAb | |
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| 70X<br>6X<br>5X<br>9X<br>2X<br>3X<br>1X<br>Tezepelumab*<br>hu3-13 (GSK1)**<br>UPB-101*<br>MK-8226*<br>hu179-33 (GSK2)**<br>ATI-052<br>ATI-045<br>IC50 (X∆) vs bosakitug<br>bosakitug<br>0.1ng/ml TSLP<br>TSLP Stimulated CCL17 Production from hPBMC<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>1000<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>140<br>Antibody (nM)<br> UPB-101 (Verekitug anti-TSPLR)*<br>ATI-045<br> Tezepelumab*<br> hu3-13 (GSK-5784283 v1)**<br> MK-8226 (Solikritug)*<br> hu179-33 (GSK-5784283 v2)**<br>ATI-052<br>Bosakitug is the most potent of the TSLP/TSLPR antibodies evaluated<br>in blocking CCL17 production<br>ATI-052 retains much of the potency for TSLP functional blockade<br>64<br>Bosakitug Key Properties<br>Greater Potency Than Other TSLP/TSLPR Antibodies<br>*Biosimilar; **Analog | |
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| 65<br>Bosakitug<br>High affinity,<br>long residence<br>time, high<br>potency<br>Best-in-Class<br>Potential<br>Greater Potency Requires Lower Concentration<br>to Exhibit the Same Effect | |
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| Tezepelumab vs Bosakitug<br>Relationship of Potency and Exposure to Extent of TSLP Inhibition<br>• The highest dose of<br>Tezepelumab may not cover<br>the IC99 for TSLP at the site of<br>action based on in vitro<br>potency<br>• Bosakitug is expected to cover<br>multiples over the<br>concentration needed for<br>99% inhibition of TSLP at the site<br>of action based on its in vitro<br>potency<br>Bosakitug Potency Allows for Substantial Exposure Above 99% Inhibition of TSLP<br>66<br>BAF3 Proliferation 1 ng/mL TSLP<br>PBMC CCL17 1 ng/mL TSLP<br>Kd<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>Exposure and In Vitro Potency<br>ATI-045<br>mAb Concentration (nM)<br>300Q2W<br>IC90<br>IC99<br>280Q2W<br>210Q2W<br>420Q2W<br>IC90<br>IC99<br>Tezepelumab Bosakitug | |
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| MKCLGQSKKEEVSFRKIFILQLVGLVLT28YDFTNCDFEKIKAAYLSTISKDLITYMSGTKSTEFNNTVSCSNRPHCLTEI<br>QSLTFNPTAGCASLAKEMFAMKTKAALAIWCPGYSETQINATQAMKKRRKRKVTTNKCLEQVSQLQGLWRRFNRPLLKQQ159<br>Signal peptide<br>TSLP binding AA to TSLPR<br>TSLP Hot spot(R149/150/153L156) to TSLPR<br>Projected Bosakitug(ATI-045)binding site<br>Tezepelumab binding site<br>TSLP AA Sequence<br>Dual Binding Provides High Avidity and Low Dissociation<br>67<br>Bosakitug Key Properties<br>Uniquely Binds Both the N- and C-Terminus of TSLP<br>The high affinity and low dissociation observed with Bosakitug/TSLP is a result of biparatopic<br>binding that includes an N-terminal recognition site not observed with tezepelumab<br>N-Terminus<br>C-Terminus | |
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| Bosakitug<br>Potential Best-in-Class Anti-TSLP Antibody<br>68<br>• Key properties support best-in-class potential<br>– Greater potency than other TSLP/TSLPR antibodies<br>– High affinity anti-TSLP mAb with long, natural half-life of 23 days<br>– Unique binding mechanism, providing very low dissociation from TSLP<br>– Very high residence time on TSLP, allowing for more sustained neutralization of TSLP<br>• In Vitro potency translated to substantial clinical activity in Phase 2a open label AD trial<br>• Clinically derisked: Data generated to date reinforce clinical confidence<br>– Sustained clinical response after last dose<br>– Pharmacokinetic (PK) data indicates long half-life; could support an extended dosing interval<br>– Consistently strong safety and tolerability profile<br>ATI-052 utilizes the same Bosakitug anti-TSLP binding regions | |
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| ATI-052: Anti-TSLP x IL-4Rα<br>First Generation Bispecific<br>Antibody Program<br>Patient Focused Innovation<br>Highly Potent and Bioactive Investigational<br>Product Candidate | |
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| Advantages of Multispecific Antibodies<br>Superior therapeutic window: Enhanced efficacy with<br>favorable safety profile<br>Increased efficacy ceiling via multi-target engagement<br>Reduced therapy resistance<br>Extended dosing regimens drive simplified treatment protocols<br>70<br>Access to a projected BsAb global market of $112 billion (2030*)<br>*Precedence Research | |
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| ATI-052: Key Asset Highlights<br>Potential Best-in-Class Bispecific Anti-TSLP/IL-4Rα mAb<br>ATI-052<br>YTE mutation<br>Anti-TSLP Fab<br>Anti-IL4Rα scFv<br>CH2 CH3<br>CH2 CH3<br>71<br>• Bispecific utilizing same antibody binding regions of<br>Bosakitug combined with anti-IL-4Rα, inhibiting TSLP<br>upstream and immune cells downstream of the Th2<br>cascade<br>– Retains dissociation kinetics, residence time, and<br>potency advantages of bosakitug over comparator Abs<br>• Anti-TSLP mAb component has Fc engineered to bind<br>more tightly to FcRn, potentially extending half-life<br>• The AQQ mutation in the Fc silences effector<br>functionality, thereby reducing off-target binding and<br>potential toxicity<br>• Potential to show superior activity in certain<br>dermatological and respiratory I&I disorders<br>compared to approved therapies<br>AQQ mutation | |
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| 72<br>ATI-052<br>Bispecific Binding Attributes Clinical Opportunity<br>Multispecific Binding Potential Clinical Efficacy<br>Simultaneous Binding<br>of TSLP and IL-4Rα<br>High affinity to both<br>ligands simultaneously:<br>ATI-052 binds two<br>molecules of TSLP and<br>sIL4Rα<br>Effective Binding of<br>TSLP and IL-4Rα<br>ATI-052 binds both<br>targets effectively; high<br>affinity of either ligand is<br>not altered by the<br>binding of the other<br>Higher Potency than<br>Competitor Antibodies<br>Exhibits greater cellular<br>bioactivity on CCL17<br>release than the<br>combination of<br>Tezepelumab and<br>Dupilumab<br>Effective Blockade<br>of IL-4 and IL-13<br>ATI-052 antagonism<br>of IL4Rα blocks<br>signaling of both IL-4<br>and IL-13 | |
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| Concurrent Binding of TSLP and sIL4Rα to ATI-052<br>High Affinity to Both TSLP and IL-4Rα<br>73<br>a<br>ATI-052 Binds<br>Both Targets<br>Effectively<br>High affinity of<br>either ligand is<br>not altered by<br>the binding of<br>the other<br>Comparison of Affinity for sIL-4Rα Binding to<br>ATI-052 or ATI-052:TSLP Complex<br>Comparison of Affinity for TSLP Binding to<br>ATI-052 or ATI-052:sIL-4Rα Complex<br>Parameter ATI-052 ATI-052:TSLP<br>KD (pM) 348 215<br>Parameter ATI-052 ATI-052:sIL-4Rα<br>KD (pM) 41.2 33.9 | |
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| Concurrent Binding of TSLP and sIL4Rα to ATI-052<br>Simultaneous Binding of TSLP and IL-4Rα<br>74<br>a<br>High Affinity to<br>Both Ligands<br>Simultaneously:<br>ATI-052 binds<br>two molecules<br>of TSLP and<br>sIL4Rα<br>TSLP:ATI-052 sIL-4Rα:ATI-052<br>Binding Sequence Stoichiometry* Stoichiometry*<br>ATI-052 capture / sIL-4Rα dose-response n/a 2.25<br>ATI-052 capture / TSLP load / sIL-4Rα dose-response 1.82 2.10<br>ATI-052 capture / TSLP dose-response 2.04 n/a<br>ATI-052 capture / sIL-4Rα load / TSLP dose-response 1.82 1.97<br>* determined using molecular weights based on AA sequence, does not account for glycosylated species<br>• ~2 molecules of sIL-4Rα bound to ATI-052 in the absence (2.25:1) and<br>presence (2.10:1) of TSLP<br>• ~2 molecules of TSLP bound to ATI-052 in the absence (2.04:1) and<br>presence (1.82:1) of sIL-4Rα | |
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| Comparison of ATI-052 vs Dupilumab + Tezepelumab<br>ATI-052 Demonstrates Greater Potency than the mAb Combination<br>ATI-052 is Significantly More Potent than the Combination<br>of Dupilumab and Tezepelumab<br>mAb Concentration [nM]<br>Antibody IC50 (nM)<br>ATI-052 0.016<br>Dupilumab +<br>Tezepelumab 0.069<br>Fold change 4.3<br>75 | |
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| Impact of ATI-052 on IL-4 and IL-13 Receptor Activation<br>• IL-4 and IL-13 both bind to a<br>receptor complex composed<br>of the IL-4Rα and IL-13Rα1<br>• IL-4 also signals through the<br>IL-4Rα and common gamma-chain (γc)<br>• Upon binding, the receptor<br>complex activates the<br>receptor-associated kinases<br>(JAK1 and Tyk2), leading to<br>the recruitment and<br>phosphorylation of STAT6<br>76<br>or<br>Hematopoietic Cells Non-hematopoietic Cells<br>Adapted from Shi et al., nt. J. Mol. Sci. 2021, 22(6), 2998<br>a<br>Hypothesis:<br>If IL-4Rα is required for<br>both IL-4 and IL-13<br>mediated signaling,<br>then ATI-052 antagonism<br>of the IL4Rα should block<br>signaling of both IL-4<br>and IL-13<br>JAK3 | |
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| IL-4 Stimulation<br>N=3 Donors<br>IL-13 Stimulation<br>N=4 Donors<br>Stim Concentration [ng/mL]<br>0.01 0.1 1 10 100<br>CCL17 [pg/mL]<br>0<br>500<br>1000<br>1500<br>2000<br>IL-4 Appears to be a More Dominant and Consistent Driver of Downstream<br>Chemokine Activation Compared to IL-13<br>Comparison of CCL17 Levels Induced by IL-4 or IL-13<br>• IL-4 is ~10 fold more potent than<br>IL-13 in stimulating CCL17<br>production from PBMCs (EC80 of<br>~1.5 ng/mL for IL-4 compared to<br>11.1 ng/mL for IL-13)<br>• IL-4 elicits consistently high<br>concentration of CCL17 whereas<br>IL-13 exhibits lower and greater<br>subject-to-subject variability<br>77 | |
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| Comparison to Marketed Biologics that Inhibit<br>IL-4 +/- IL-13 Signaling<br>78<br>Adapted from Lylvyn and Gooderham; Pharmaceutics 2023, 15(2), 568<br>Markovic and Savvides; Front. Immunol., Vol 11 - 2020<br>Dupilumab<br>Anti-IL4Rα<br>Lebrikizumab<br>Anti-IL13<br>Tralokinumab<br>Anti-IL13<br>TSLP IL-4 IL-13<br>ATI-052<br>Anti-TSLP and Anti-IL-4Rα<br>Data Support the Need for Inhibition of Both IL-4 and IL-13<br>to be Effective in Respiratory Indications | |
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| Comparison of IL-4/IL-13 Monoclonal Antibodies<br>IL-4-induced<br>CCL17 release<br>IL-13-induced<br>CCL17 release<br>TSLP-induced<br>CCL17 release<br>IL-4+IL-13-induced<br>CCL17 release<br>Antibody concentration [nM]<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>CCL17 (% stim)<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>140<br>160<br>Antibody concentration [nM]<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>CCL17 (% corr stim)<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>140<br>Antibody concentration [nM]<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>CCL17 (% corr stim)<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>140<br>Antibody concentration [nM]<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>CCL17 (% stim)<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>TSLP/IL-4/IL-13-induced<br>CCL17 release<br>Antibody concentration [nM]<br>0.00001<br>0.0001<br>0.001<br>0.01<br>0.1<br>1<br>10<br>100<br>CCL17 (% stim)<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>ATI-052<br>Dupilumab<br>Tezepelumab<br>Tralokinumab<br>Lebrikizumab<br>IgG1<br>IgG4k<br>IgG4l<br>79<br>Antibody IC50 [nM]<br>ATI-052 0.0077<br>Dupilumab >100<br>Lebrikizumab >100<br>Tezepelumab 0.4083<br>Tralokinumab >100<br>Antibody IC50 [nM]<br>ATI-052 0.18<br>Dupilumab 0.09<br>Lebrikizumab >100<br>Tezepelumab >100<br>Tralokinumab >100<br>Antibody IC50 [nM]<br>ATI-052 0.74<br>Dupilumab 0.57<br>Lebrikizumab 0.55<br>Tezepelumab >100<br>Tralokinumab 1.83<br>Antibody IC50 [nM]<br>ATI-052 0.97<br>Dupilumab 0.27<br>Lebrikizumab >100<br>Tezepelumab N/A<br>Tralokinumab >100<br>Antibody IC50 [nM]<br>ATI-052 0.3625<br>Dupilumab 2.0217<br>Lebrikizumab >100<br>Tezepelumab >100<br>Tralokinumab >100<br>ATI-052 Exhibits Broadest Activity Among the Biologics Tested | |
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| ATI-052<br>Summary<br>• Bispecific antibodies are engineered to have two distinct binding domains that can<br>efficiently bind to two targets simultaneously<br>– ATI-052 has two distinct binding domains that independently bind both TSLP and IL-4Rα<br>with high affinity, efficiency and completeness<br>• YTE mutation in the Fc to allow for enhanced half-life<br>• AQQ mutation in the Fc silences effector functionality, reducing off-target binding<br>and potential toxicity<br>• Inhibits TSLP and antagonism of IL-4Rα also blocks the signaling of both IL-4 and IL-13<br>• Highly potent; more potent than the combination of Tezepelumab and Dupilumab<br>in inhibiting CCL17 production from the combination of TSLP and IL-4 treated PBMCs<br>80 | |
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| Developing Next-Generation Bispecific<br>Antibodies<br>Patient Focused Innovation | |
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| Next Generation Bispecific Antibodies<br>Designing Optimal Synergies with TSLP for I&I Diseases<br>82<br>a<br>Critical role of<br>epithelium-derived cytokines<br>in dermatological<br>and respiratory /<br>airway I&I<br>disorders guides<br>design of potent<br>and selective<br>bispecific<br>antibodies<br>Modified from Divekar et al., 2015 | |
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| 83<br>0<br>Pruritis (Itch)<br>Alarmin Combinations<br>Eosinophil-Driven Diseases<br>• TSLP combinations with itch mediators may have a positive impact on itch and<br>QoL in AD and other dermatological diseases<br>• Could impact initiation of allergic response and associated downstream<br>inflammation and enhance anti-viral immunity during respiratory virus infections<br>• Allergic disorders, skin conditions, fungal infections, autoimmune diseases, others<br>• Causes multiple disorders including eosinophilic cystitis, fasciitis, pneumonia,<br>gastrointestinal disorders, granulomatosis with polyangiitis, hypereosinophilic syndrome<br>Opportunities for Aclaris Next Generation BsAbs<br>Multispecific Antibodies Can Expand Therapeutic Optionality<br>Synergistic Effect with TSLP • May amplify immune responses, particularly the development of Type 2<br>inflammation, which is central to allergic diseases like asthma, AD, and others | |
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| Next Generation Bispecific Antibodies<br>Progressing Toward IND<br>Multispecific Ab<br>development<br>Progressing<br>Toward<br>IND<br>Multispecific approach enables synergistic<br>target binding and addresses<br>shortcomings of multi-drug administration<br>Additional bispecific and trispecific<br>modalities under initial consideration<br>Initial assessment of bispecific targets<br>completed (αTSLP + undisclosed)<br>Campaigns progressing: Hit optimization<br>toward lead candidate selection ongoing<br>Targeting first<br>IND from<br>bispecific<br>antibody<br>development<br>efforts in 2027<br>84 | |
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| ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>85<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Ongoing<br>Next Gen<br>Multispecifics<br>Discovery<br>αTSLP/X (undisclosed 1)<br>αTSLP/X (undisclosed 2)<br>αTSLP/X (undisclosed 3)<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Ongoing<br>Oral Kinase Inhibitors Biologics<br>ITK | ITK/TXK<br>Next Gen IND:<br>2H 2026<br>Other<br>multispecific<br>antibodies in<br>discovery<br>Initial IND: 2027<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors |
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| Efficient Clinical Trial<br>Execution and Milestones<br>Derisking Small and Large Molecule Assets with<br>Time- and Cost-Efficient Clinical Evaluation<br>Jesse Hall, MD<br>Chief Medical Officer<br>Patient Focused Innovation | |
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| ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>87<br>First<br>Generation Next Generation Monoclonal<br>Antibodies<br>Multispecific<br>Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Ongoing<br>Next Gen<br>Multispecifics<br>Discovery<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Ongoing<br>Oral Kinase Inhibitors Biologics<br>ITK | ITK/TXK<br>Next Gen IND<br>2H 2026<br>Other<br>multispecific<br>antibodies in<br>discovery<br>αTSLP/X (undisclosed 1)<br>αTSLP/X (undisclosed 2)<br>αTSLP/X (undisclosed 3)<br>Initial IND: 2027<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors |
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| Aclaris Therapeutics<br>Innovating in Immuno-Inflammatory Disorders<br>Innovation<br>Driven<br>Patient<br>Focused<br>Leadership in I&I/immuno-dermatology<br>Potential Best-in-Class molecules and<br>“white space”<br>Multiple shots on goal with a diversified<br>pipeline<br>Near term catalysts expected in next 6-12<br>months and beyond<br>Advancing<br>potential<br>industry-leading<br>inhibitor<br>franchises<br>designed to<br>address<br>validated,<br>therapeutically-relevant<br>immune targets<br>88<br>Strong cash runway to execute on Aclaris<br>clinical programs | |
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| Broad Immunology Development Pipeline<br>89<br>Preclinical Phase 1 Phase 2 Phase 3 Partner<br>Bosakitug (ATI-045)<br>TSLP mAb<br>Subcutaneous<br>Atopic Dermatitis<br>(moderate-to-severe)<br>Severe Asthma CTTQ (China)*<br>Chronic Rhinosinusitis<br>with Nasal Polyps CTTQ (China)*<br>COPD CTTQ (China)*<br>ATI-2138<br>ITK/JAK3 Inhibitor<br>Oral<br>Atopic Dermatitis (AD)<br>(moderate-to-severe)<br>Second Indication<br>ATI-052<br>TSLP x IL-4R BsAb<br>Subcutaneous<br>Respiratory/<br>Dermatology<br>ITK Selective Inhibitor<br>Oral Autoimmune<br>Undisclosed BsAb<br>Subcutaneous Autoimmune<br>Positive Phase 2a Results Presented July 2025<br>Enrollment Ongoing<br>1st IND: 2H 2026<br>Enrollment Ongoing<br>Trial initiation: 1H 2026<br>1st IND: 2027<br>Further global<br>(excluding<br>China)<br>development<br>in respiratory<br>indications<br>is dependent<br>on partnerships<br>Aclaris programs Partner programs<br>*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.<br>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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| Clinical Focus in 2025<br>Fully integrated<br>Biosion molecules and<br>team members and<br>have continued to<br>build out our clinical<br>capabilities<br>2025 clinical goals:<br>• Program<br>execution,<br>financial discipline<br>• Establishment of<br>foundation for<br>continued<br>execution in 2026<br>and beyond<br>Derisking of clinical programs:<br>• Clinical validation of<br>ITK pathway<br>• Focused on enrolling<br>patients that meet the<br>strict enrollment criteria<br>• Advancing the ATI-052<br>program in HV<br>• Preparing for new INDs<br>in 2026 and beyond<br>90<br>2025 provides foundation for multiple ongoing clinical<br>programs and data readouts in 2026 | |
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| Portfolio Execution<br>Strong Execution in 2025 Creates Packed 2026<br>91<br>Target Engagement (ex-vivo assay in HV)<br>Top line results from AD Phase 2<br>Initiation of Phase 2 in 2nd Indication<br>6-month tox dosing started 3Q25<br>Phase 1a LPI: complete dosing<br>Preliminary PK results in house<br>IND filed and cleared<br>Phase 2 FPI in NA<br>AD Positive Phase 2a top line results<br>IND filed and cleared<br>2025 2026<br>Phase 1a SAD/MAD (PK Profile, ADA, etc.) top line results<br>Phase 1a FPI in NA<br>Completion of chronic tox studies<br>ATI-052<br>Bosakitug<br>ATI-2138<br>Initiation of Phase 1b POC<br>IND and prep for clinical start<br>ATI-052<br>Bosakitug<br>ATI-2138<br>ITK selective<br>Phase 1b top line results<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors | |
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| ATI-052: Anti-TSLP x<br>IL-4Rα Bispecific<br>Antibody Program<br>Highly Potent and Bioactive Investigational<br>Product Candidate | |
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| ATI-052: Key Asset Highlights<br>Potential Best-in-Class Bispecific Anti-TSLP/IL-4R mAb<br>ATI-052<br>YTE mutation<br>Anti-TSLP Fab<br>Anti-IL4Rα scFv<br>CH2 CH3<br>CH2 CH3<br>93<br>• Same antibody binding regions of ATI-045 + IL-4Rα<br>– Retains dissociation kinetics, residence time, and potency<br>advantages<br>• Half-life enhanced: Engineered to bind more tightly to FcRn<br>• Reduced off-target binding: Engineered to silence effector<br>functionality<br>• Significantly more potent than the combination<br>of dupilumab and tezepelumab<br>• Potential to show superior activity in certain dermatological<br>and respiratory I&I disorders<br>AQQ mutation | |
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| Placebo Controlled Phase 1a/1b Program Ongoing<br>94<br>Cohort 1: SC, N=8 D1-113<br>Screening Randomization<br>3:1 Cohort 3: SC, N=8 D1-113<br>Cohort 4: SC, N=8 D1-113<br>Cohort 2: SC, N=8 D1-113<br>Part A Single Ascending Dose (SAD) in Healthy Volunteers<br>Part B Multiple Ascending Dose (MAD) in Healthy Volunteers<br>Screening Randomization<br>3:1<br>D1 D8 D15 D22 D29<br>D1 D8 D15 D22 D29 D141<br>D141<br>Cohort 1: SC, Q7D<br>Cohort 2: SC, Q7D<br>Treatment and Follow-up Period<br>Treatment and Follow-up Period | |
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| 95<br>Key Learnings Expected<br>in 2025<br>Expected Milestones<br>• Initial PK<br>• Safety and Tolerability<br>• TMDD role<br>• Indications of prolonged exposure<br>• Complete SAD/MAD assessment YE 2025<br>• SAD/MAD results 1Q 2026<br>• Initiate Phase 1b POC trial in asthma 1H 2026<br>• Initiate Phase 1b POC trial in AD 1H 2026<br>• Phase 1b top line POC results 4Q 2026<br>• Full PK profile (half-life, ADA, etc.)<br>• Pathway engagement ex-vivo from HV study<br>• Pathway engagement in diseased population<br>Phase 1a/1b ATI-052 Program<br>Anticipated Key Learnings and Milestones | |
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| 96<br>Placebo (single dose)<br>ATI-052 (single dose)<br>Screening/<br>Washout Follow-up<br>Randomization<br>3:1 Active<br>to Placebo<br>Day 28<br>Efficacy Assessment<br>Primary Endpoint To evaluate the safety and tolerability of ATI-052 compared to placebo in patients with<br>moderate-to-severe asthma<br>Next Steps with ATI-052<br>Expected Asthma Phase 1b POC Study Design<br>16 Patients<br>Moderate-to-Severe<br>Asthma<br>Key Clinical Efficacy Assessment Other endpoints<br>Day 28<br>Emphasis on PD assessments: FeNO, FEV1, Blood Eos,<br>TARC (CCL17), Periostin, IGE, Cytokines (IL-4,IL-5,IL-13)<br>Patient Selection<br>Moderate-to-severe defined as<br>(GINA 3-5) adult asthmatics,<br>excluding prior biologics<br>Type 2 asthma with active inflammation:<br>FeNO baseline ≥ 25 ppb, Blood Eos ≥ 150<br>Asthma Trial Expected to Initiate 1H 2026 | |
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| 97<br>Screening/<br>Washout<br>Randomization<br>3:1 Active<br>to Placebo<br>Primary Endpoint To evaluate the safety and tolerability of ATI-052 compared to placebo in patients with<br>moderate-to-severe atopic dermatitis<br>Next Steps with ATI-052<br>Expected Atopic Dermatitis (AD) Phase 1b POC Study Design<br>12 Patients<br>Moderate-to-Severe<br>AD<br>Placebo Q1wk (five doses)<br>ATI-052 Q1wk (five doses)<br>Follow-up<br>Day 57<br>Efficacy Assessment<br>Other Endpoints AD clinical efficacy assessments (EASI, BSA, IGA)<br>PD endpoints measured by assays including lesional and non-lesional skin tape strips<br>Patient Screening Central photography to confirm diagnosis and extent of disease<br>Atopic Dermatitis Trial Expected to Initiate 1H 2026 | |
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| Bosakitug (ATI-045)<br>Anti-TSLP<br>Monoclonal<br>Antibody Program<br>Differentiated Investigational Product<br>Candidate with Best-in-Class Potential | |
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| Clinical Translation<br>Phase 2a (US-Based) POC Monotherapy Trial<br>99<br>Bosakitug<br>300 mg QW<br>Bosakitug<br>300 mg Q2W<br>Screening/<br>Washout<br>up to 30 days<br>12 Week<br>Follow-up<br>Week 26<br>(2 weeks after last dose)<br>Primary endpoint analysis Enrolled: 22 subjects<br>(17 completed treatment)<br>at 7 US-based sites<br>Primary Objective<br>(Week 24)<br>To evaluate the efficacy, safety and tolerability of bosakitug as monotherapy in subjects with<br>moderate to severe AD<br>W1-W4 W4-W24 W24-W36<br>Secondary<br>Objectives (Week 24)<br>To evaluate the pharmacokinetics, immunogenicity and pharmacodynamic biomarkers of ATI-045 in subjects with moderate to severe AD<br>Eligibility Diagnosis of AD (present for at least 6 months); EASI ≥12; IGA ≥3; total AD BSA ≥10%<br>Baseline<br>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<br>Demonstrated Sustained Clinical Response After the Last Dose<br>0 4 8 12 16 20 24 28 32<br>0.01<br>0.1<br>1<br>10<br>100<br>0<br>20<br>40<br>60<br>80<br>100<br>Time (Week)<br>Concentration (μg/mL)<br>Percent Change from Baseline of EASI Score (%)<br>Last<br>Dose<br>Simulated Mean Conc.<br>Observed Conc.<br>Observed Efficacy<br>95% Confidence Interval<br>• A time lag in efficacy response<br>relative to exposure was<br>observed both while the drug<br>was onboard and after the last<br>dose<br>• EASI-75 sustained response after<br>the last dose supports the<br>possibility of longer dosing<br>intervals<br>• Favorable safety and<br>immunogenicity profile<br>100 | |
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| Phase 2a (US-Based) POC Monotherapy Trial<br>Bosakitug Demonstrated Improvement in Efficacy Measures<br>101<br>EASI 75 %<br>@ Week 26<br>EASI 90 %<br>@ Week 26<br>EASI 100 %<br>@ Week 26<br>IGA 0/1<br>@ Week 26<br>94% 65% 24% 88%<br>% of Patients Achieving Clinical Endpoint<br>0<br>10<br>20<br>30<br>40<br>50<br>60<br>70<br>80<br>90<br>100<br>0 4 8 12 16 20 24 28 32 36<br> EASI75<br> EASI90<br> IGA0/1<br>(N=17) | |
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| Phase 2 Monotherapy Trial Ongoing<br>Dosing Proceeding to Plan<br>102<br>Placebo<br>Week 0 & 2<br>Bosakitug<br>Week 0 & 2<br>Placebo<br>Q2W, Week 4 through Week 22<br>Bosakitug 300 mg<br>Q2W, Week 4 through Week 22 Screening/<br>Washout<br>up to 30 days<br>12 Week<br>Follow-up<br>Randomization<br>2:1 Active<br>to Placebo<br>Week 24<br>(2 weeks after last dose)<br>~90 Patients Primary endpoint analysis<br>Moderate-to-Severe<br>AD<br>Treatment Period: 24 Weeks<br>Loading dose<br>Primary Objective<br>(Week 24)<br>To evaluate the efficacy of Bosakitug compared to placebo, as measured by the change in<br>Eczema Area and Severity Index (EASI) score in patients with moderate-to-severe AD<br>Secondary<br>Objectives (Week 24)<br>To evaluate the safety, tolerability & treatment<br>effect of Bosakitug compared to placebo, on<br>additional clinical outcome measures<br>• EASI response (EASI-50, EASI-75, EASI-90)<br>• Validated Investigator Global Assessment (IGA) response<br>• Body Surface Area (BSA) response<br>• Peak Pruritus Numerical Rating Scale (PP-NRS) score | |
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| Derisking High Placebo Rates in Atopic Dermatitis<br>Defining a New Industry Standard in Eligibility Review<br>Enrolling Patients That Meet Strict Eligibility Criteria<br>Three step process provides robust patient screening prior to randomization<br>Step 1<br>Standardized<br>Lesion and BSA<br>Photography<br>Step 2<br>Review by<br>Central Reader<br>Step 3<br>Review by Aclaris<br>Dermatologists<br>• Central vendor provides standardized photographic equipment and trains each site<br>to support consistent inter-site photographic proof of disease<br>• All patients screened serially by multiple readers for lesion severity and affected body<br>surface area (extent of disease) consistent with moderate-to-severe AD<br>Enrollment<br>Process designed to enable trials to (1) only enroll patients with AD<br>(2) with moderate-to-severe disease based on disease extent and severity<br>103 | |
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| Next Steps with Bosakitug<br>Competitively Positioned as Potential Best-in-Class TSLP mAb<br>• Preclinical and clinical data generated to date reinforce the enhanced potency<br>of bosakitug and support further development in dermatological conditions<br>– Two-arm placebo-controlled Phase 2 trial of bosakitug in moderate-to-severe AD<br>ongoing (initiated 2Q 2025); dosing underway<br>• Results expected in 2H 2026<br>• Aclaris is seeking partners to develop bosakitug in respiratory indications; further<br>global (excluding China) development in these indications is dependent on<br>entering into potential partnerships<br>104 | |
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| ATI-2138: A First-Generation Novel<br>ITK/JAK3 Inhibitor for T<br>Cell-Mediated Diseases<br>Potent and Selective Investigational Drug<br>Candidate with Strong Tolerability Profile | |
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| ATI-2138<br>Positive Phase 2a Results Inform Trials in Additional Indications<br>106<br>• Positive results from single arm OL Phase 2a trial in AD provide proof of concept:<br>– PD results that validate ITK as a therapeutic target<br>– Favorable tolerability profile of ATI-2138<br>– Clinically meaningful improvements from baseline in assessments of disease severity<br>including:<br>• Extent and severity of AD (Eczema Area and Severity Index (EASI))<br>• Percent of patients experiencing a greater than or equal to four-point improvement in worst itch<br>in the last 24 hours (Peak Pruritus Numerical Rating Scale (PP-NRS))<br>• Body Surface area (BSA)<br>• Aclaris is exploring further development of ATI-2138 in indications relevant to the<br>mechanism of action with ample available white space | |
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| ATI-2138<br>Oral Small Molecule Covalent ITK & JAK3 Inhibitor for I&I Disease<br>• Unique dual pharmacology; best-in-class potential<br>• Potent compound that interrupts TCR signaling by inhibiting ITK and JAK3 signaling of<br>common γ chain cytokines in lymphocytes<br>• Highly selective for both ITK and JAK3<br>• Isoform specificity spares JAK1 and JAK2 signaling<br>• Potential applicability in a variety of I&I indications based on its mechanism of action;<br>targets evolve with competitive dynamics<br>107<br>Vitiligo<br>cGvHD<br>Genital<br>Psoriasis<br>Acute<br>Inflammatory<br>Psoriasis<br>Asthma<br>RA<br>Crohn’s<br>Disease<br>Ulcerative<br>Colitis<br>Psoriatic<br>Arthritis<br>Atopic<br>Palmoplantar Dermatitis Pustulosis<br>Alopecia<br>Areata<br>Peripheral<br>T cell<br>Lymphoma<br>Celiac<br>Disease<br>Fibrosing<br>Interstitial<br>Lung<br>Disease<br>Acute<br>Severe<br>Ulcerative<br>Colitis<br>Vitiligo<br>PSC<br>SLE<br>Prioritized<br>potential areas of<br>focus<br>Wide array of<br>potential targets<br>for 2138<br>PN<br>Lichen<br>planus<br>Lichen<br>planus<br>Prurigo<br>nodularis<br>Scarring<br>Alopecia<br>Alopecia<br>areata | |
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| Next Clinical Steps with ATI-2138<br>The Lichen Planus Opportunity<br>108<br>An unaddressed chronic,<br>inflammatory, immune-mediated<br>disorder<br>• Affects skin, mucous membrane, hair<br>and nails; multiple clinical subtypes<br>• Most common symptoms: severe<br>itch, Wickham’s striae, sores,<br>scales/plaques, hair loss, fatigue<br>• Oral lichen planus (OLP) (50%+ of<br>cases) is of particular clinical<br>significance due to malignant<br>potential<br>• Prevalence = 0.2-1% worldwide;<br>associated with hepatitis C,<br>autoimmune conditions, certain<br>medications<br>• Market opportunity<br>– U.S. addressable patients: ~200K<br>systemic-eligible<br>– Global addressable: ~2–3M<br>– Peak U.S. revenue potential:<br>$500M–1B<br>– Global peak revenue: $1.2–1.4B<br>– No approved oral LP therapy →<br>white space opportunity<br>• Unsatisfied market; management<br>focuses on immunosuppression<br>and symptom control<br>Large unsatisfied market;<br>ample “white space” | |
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| 109<br>ATI-2138 in Lichen Planus<br>Dual Pharmacology Creates Ideal Mechanistic Fit<br>• Chronic inflammatory skin disease<br>• Aberrant activation of TH1/2/17 and<br>cytotoxic CD8 T-cells<br>• IFN mediated pathology in affected skin<br>• Severe itch associated with IL31 up-regulation<br>• Fibrosis common<br>• Activity demonstrated in open-label AD<br>study suggests strong fit for LP<br>• Downregulation of Th1/2/17 activation<br>markers<br>• Inhibition of biomarkers down-stream of<br>IFNy (CXCL11, CXCL9)<br>• Significant reductions in itch<br>• Strong downregulation of fibrosis markers<br>• Efficacy of calcineurin inhibitors in LP<br>support T-cell mediated pathology<br>Lichen planus<br>ATI-2138 | |
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| 110<br>Potential Lichen Planus Clinical Program<br>Next Steps<br>• Complete trial design, market analysis, and TPP<br>of Lichen planus<br>• Finalize assessment of additional potential<br>future targets<br>– Other immunological disorder opportunities<br>based on mechanism may include Hidradenitis<br>suppurativa, Prurigo nodularis, scarring<br>alopecia, vitiligo, etc.<br>• Initiate Phase 2 in 1H 2026<br>Dose ranging three indication basket<br>study (mucosal and cutaneous LP,<br>Lichen planopilaris)<br>Proposed efficacy endpoints<br>• Primary: Investigator’s Global Assessment<br>(IGA); 0 (clear) to 4 (severe)<br>• Secondary: Numeric Rating Scale (NRS)<br>for itch; 0 (none) to 10 (worst imaginable)<br>Target indication for ATI-2138 based on current development strategy | |
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| Opportunity in Alopecia<br>Market is Rapidly Evolving but Opportunities Remain<br>• Market and competitive landscape dynamics shape indication selection process<br>• Strong mechanistic rationale: JAK3 inhibition shown to be effective in alopecia areata<br>• Multiple types of alopecia exist, some of which are under evaluation<br>– Scarring (cicatricial) alopecia<br>– Alopecia areata<br>– Others<br>111 | |
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| Continued Clinical Momentum in 2026<br>Four Expected Clinical Programs<br>Bosakitug (ATI-045)<br>Phase 2 in atopic<br>dermatitis ongoing<br>Top line results in 2H 2026<br>ATI-052<br>Top line SAD/MAD results in<br>1Q 2026<br>Top line Proof-of-Concept<br>results in asthma<br>and AD in 2H 2026<br>ATI-2138<br>Phase 2b initiation in<br>second indication,<br>likely Lichen planus, in<br>1H 2026<br>Top line results in 2027<br>Next generation<br>ITK inhibitors<br>First IND from ITK selective<br>program in<br>2H 2026<br>Advancing<br>potentially<br>industry-leading<br>inhibitor franchises<br>designed to<br>address validated,<br>therapeutically-relevant immune<br>targets<br>Innovation<br>Driven<br>Patient<br>Focused<br>112 All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors | |
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| Results:<br>ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>113<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Ongoing<br>Next Gen<br>Multispecifics<br>Discovery<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Ongoing<br>Oral Kinase Inhibitors Biologics<br>ITK | ITK/TXK<br>Next Gen IND:<br>2H 2026<br>Other<br>multispecific<br>antibodies in<br>discovery<br>Phase 2<br>Lead: Lichen Planus<br>Initiation: 1H 2026<br>POC<br>Asthma<br>AD<br>Results<br>in 2H 2026<br>Results in 2027 Initial IND: 2027<br>αTSLP/X (undisclosed 1)<br>αTSLP/X (undisclosed 2)<br>αTSLP/X (undisclosed 3)<br>POC<br>Asthma<br>AD<br>SAD/MAD 1Q26<br>POC 2H 2026<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors |
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| Aclaris Therapeutics<br>Developing Therapeutic Franchises to Address<br>Gaps in Important I&I Diseases<br>Neal Walker, MD<br>Chief Executive Officer<br>Patient Focused Innovation | |
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| z<br>Results:<br>ITK Franchise Antibody Franchise<br>Broad Clinical and Preclinical I&I Pipeline<br>Potential Best-in-Class Inhibitors of Immunoinflammatory Cascade<br>115<br>First<br>Generation Next Generation Monoclonal<br>Antibodies Multispecific Antibodies<br>ATI-2138<br>ITK/JAK3<br>Phase 2a<br>Complete<br>ITK Selectives<br>Preclinical Development<br>Bosakitug<br>(ATI-045)<br>αTSLP<br>Phase 2<br>Ongoing<br>Next Gen<br>Multispecifics<br>Discovery<br>ATI-052<br>αTSLP/IL-4Rα<br>Phase 1a/1b<br>Ongoing<br>Oral Kinase Inhibitors Biologics<br>ITK | ITK/TXK<br>Next Gen IND:<br>2H 2026<br>Other<br>multispecific<br>antibodies in<br>discovery<br>Phase 2<br>Lead: Lichen Planus<br>Initiation: 1H 2026<br>POC<br>Asthma<br>AD Results<br>in 2H 2026<br>Results in 2027<br>Initial IND: 2027<br>αTSLP/X (undisclosed 1)<br>αTSLP/X (undisclosed 2)<br>αTSLP/X (undisclosed 3)<br>SAD/MAD 1Q26<br>POC 2H 2026<br>All future development, clinical, and regulatory timelines are expectations, are based on current beliefs and assumptions,<br>and are subject to change based on a variety of factors |
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| 2025/2026: Executing on Rich Clinical Catalyst Calendar<br>2025<br>ATI-052<br>IND Clearance by FDA<br>Bosakitug (ATI-045)<br>Initiation of Phase 2 Trial in Atopic Dermatitis<br>ATI-052<br>Initiation of Phase 1a/1b Program<br>ATI-2138<br>Atopic Dermatitis Phase 2a Top Line Data<br>July 2025<br>ATI-052<br>Completion of dosing in Phase 1a SAD/MAD HV Portion<br>Year-end 2025<br>2026<br>All timelines are expectations, are based on current beliefs and assumptions, and are subject to change based on a variety of factors.<br>ATI-052<br>Phase 1a/1b Top Line Data<br>Phase 1a SAD/MAD: Early 2026<br>Phase 1b POC: 2H 2026<br>Bosakitug (ATI-045)<br>Atopic Dermatitis Phase 2 Top Line Data<br>2H 2026<br>ATI-2138<br>Initiation of Phase 2 in Second Indication (e.g., Lichen Planus)<br>1H 2026<br>ITK Next Generation Program<br>IND Submission and Start of Phase 1 Program<br>2026<br>116 | |
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| Aclaris Today<br>117<br>• Unique State-of-the-Art R&D capabilities<br>and World Class Scientists<br>• Four potential Best-in-Class clinical stage assets<br>in 2026 targeting validated and therapeutically-relevant immune targets highlighted by a<br>potential Best-in-Class bispecific and oral ITK<br>inhibitor<br>• Rich calendar of data events expected<br>throughout 2026 and 2027<br>• A cash runway expected to provide<br>approximately three years of capital, with<br>opportunities to expand it further without dilution<br>Patient Focused Innovation | |
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| Patient Focused Innovation<br>Developing Therapeutic Franchises to Address Gaps<br>in Important I&I Diseases<br>2025 R&D Day<br>October 14, 2025 | |
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