ATI-2138 / Aclaris - LARVOL DELTA

Results from an Open-Label Phase 2 Trial of ATI-2138, an investigational oral covalent inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3), in patients with moderate-to-severe atopic dermatitis (AAD 2026) - "Proteome and transcriptome tape strip and biopsy analyses of lesional skin showed significant reduction of multiple inflammatory markers with downregulation of key ITK-dependent pathways (Th2, Th17, TCR and T-cell activation), along with reduction in fibrosis-related markers and changes in epidermal barrier genes suggesting restoration of skin homeostasis. In summary, results from this trial demonstrated ATI-2138 was generally well tolerated and reduced clinical signs/symptoms of AD."

Clinical • P2 data • Atopic Dermatitis • Dermatitis • Dermatology • Fibrosis • Immunology • Pruritus • IL2 • ITK • JAK3

Aclaris Therapeutics Announces Poster on Results from Phase 2a Trial of ATI-2138 at the 2026 American Academy of Dermatology (AAD) Annual Meeting (GlobeNewswire) - "The poster will include results not previously reported from Aclaris’ Phase 2a trial in patients with moderate-to-severe atopic dermatitis (AD)."

P2a data • Atopic Dermatitis

Aclaris Therapeutics’ Novel ITK/JAK3 Inhibitor ATI-2138 Demonstrates Rapid and Sustained Hair Regrowth in Validated Murine Model of Alopecia Areata (AA) (The Manila Times) - "Rapid onset of hair regrowth was observed at week 2 in mice receiving 300 ppm ATI-2138 (mean percent hair regrowth of 37%) and reached near peak effect at week 4 (mean percent hair regrowth of 87%) compared to 300 ppm ritlecitinib (25% and 48%, respectively). Mice receiving control chow showed no improvement in hair regrowth; At week 6, the mean percent hair regrowth was 93% for ATI-2138 (300 ppm) compared to 78% for ritlecitinib (300 ppm). Mice receiving control chow showed no improvement in hair regrowth....Given the uniquely potent and selective mechanism of ATI-2138, Aclaris is assessing additional indications for ATI-2138, including alopecias, and expects to initiate a Phase 2b trial in the first half of 2026."

New P2b trial • Preclinical • Alopecia

Molecular and Clinical Effects of Oral ATI-2138, an ITK/JAK3 inhibitor, in Moderate-to-Severe Atopic Dermatitis: Sub-study of a Phase 2a Open-Label, Single-Arm Trial (ISDS 2025) - P2 | "Treatment with ATI-2138 was associated with improvement in clinical measures and reductions in molecular markers of inflammation and fibrosis in skin and plasma. These findings suggest ATI-2138 as a new treatment for atopic dermatitis."

Clinical • P2a data • Atopic Dermatitis • Dermatitis • Dermatology • Fibrosis • Immunology • Inflammation • ADAMTS14 • CCL21 • CD4 • CD5 • COL1A1 • CXCL1 • CXCL12 • CXCL9 • IL13 • IL2 • IL33 • IL4R • IL6R • JAK3 • KRT7 • OASL • S100A9 • SPON1 • TGFB1 • TSLP

Additional Results on Robust Clinical Activity and Reductions in Fibrosis and Systemic Inflammation from ATI-2138 Phase 2a Trial Provided in Oral Presentation During the 2025 European Academy of Dermatology and Venereology (EADV) Congress (GlobeNewswire) - "Additional results included week 4 decreases (n=9) of 77% in Eczema Area and Severity Index (EASI) score (p<0.001), a 64% in Body Surface Area (BSA) score (p<0.001), and 45% in Peak Pruritus Numerical Rating Scale (PP-NRS) (p<0.01). These changes were maintained through end of treatment. Transcriptomic and proteomic analyses showed significant downregulation of the Th1, Th2 and Th17 markers along with downregulation of fibrosis. The observed reductions in inflammatory and fibrosis biomarkers in skin positively and strongly correlated with improvements in clinical scores."

P2a data • Atopic Dermatitis

Announced Anticipated Phase 2 Trial of ATI-2138, a Potent and Selective Investigational Inhibitor of ITK and JAK3, in an Additional Indication (GlobeNewswire) - "Aclaris expects to further assess ATI-2138 in additional unaddressed chronic, inflammatory, immune-mediated disorders, such as Lichen planus, scarring alopecias, and alopecia areata. The Company intends to initiate a Phase 2 trial in the first half of 2026."

New P2 trial • Alopecia

Molecular and Clinical Effects of Oral ATI-2138, an ITK/JAK3 inhibitor, in Moderate-to-Severe Atopic Dermatitis: Sub-study of a Phase 2a Open-Label, Single-Arm Trial (EADV 2025) - P2 | "Conclusion Treatment with ATI-2138 was associated with improvement in clinical measures and reductions in molecular markers of inflammation and fibrosis in skin and plasma. These findings suggest ATI-2138 as a potential new treatment for clinical and molecular reversal of atopic dermatitis."

Clinical • Late-breaking abstract • P2a data • Atopic Dermatitis • Dermatitis • Dermatology • Fibrosis • Immunology • ADAMTS14 • CCL21 • CD4 • CD5 • COL1A1 • CXCL1 • CXCL12 • CXCL9 • IL13 • IL2 • IL33 • IL4R • IL6R • JAK3 • KRT7 • OASL • S100A9 • SPON1 • TGFB1 • TSLP

Aclaris Therapeutics Announces Late-Breaking Abstract and Oral Presentation On ATI-2138 Phase 2a Results at the 2025 European Academy of Dermatology and Venereology (EADV) Congress (GlobeNewswire) - "The presentation will include additional results from Aclaris’ Phase 2a trial in patients with moderate-to-severe atopic dermatitis (AD)."

Late-breaking abstract • P2a data • Atopic Dermatitis

Second Quarter 2025 and Year-to-Date 2025 (Aclaris Press Release) - "Research and development (R&D) expenses were $11.4 million and $23.0 million for the quarter and six months ended June 30, 2025, respectively, compared to $8.8 million and $18.6 million for the corresponding prior year periods. The increases were primarily driven by product candidate manufacturing costs, preclinical development activities, and clinical development expenses associated with the Phase 2 trial in AD for bosakitug and the Phase 1a/1b program for ATI-052. For the six-month comparison period, clinical development expenses associated with the Phase 2a trial in AD for ATI-2138 also contributed to the increase."

Commercial • Alopecia • Atopic Dermatitis

Aclaris Therapeutics Announces Positive Top-Line Results from Open-Label Phase 2a Trial of ATI-2138, a Potent and Selective Investigational Inhibitor of ITK and JAK3; Trial Achieves Primary and Key Secondary Endpoints (GlobeNewswire) - P2a | N=14 | NCT06585202 | Sponsor: Aclaris Therapeutics, Inc. | "ATI-2138 was very well tolerated in this Phase 2a trial. No severe adverse events (SAEs) or treatment-emergent adverse events (TEAEs) were observed....At week 12 (end of treatment), the mean improvement in EASI score in patients receiving 10mg BID of ATI-2138 (n=10) was 60.5% (median improvement = 76.8%). Patients in the trial experienced a rapid and sustained response, with measurable improvements observed starting at the first (week 1) office visit. At week 4, the mean improvement in EASI score (n=10) was 70.5% (median improvement = 71.9%). At week 8, the mean improvement in EASI score (n=10) was 70.7% (median improvement = 76.3%)....At week 12 (n=8), 62.5% of patients experienced a ≥4-point improvement in PP-NRS....Strong downregulation of key ITK-dependent markers including Th2, Th17, and TCR (ITK) pathways along with the Th1 pathway were observed at week 8 and week 12."

P2a data • Atopic Dermatitis

ATI-2138: Investigational oral covalent ITK/JAK3 inhibitor (GlobeNewswire) - "Top Line Results from Phase 2a Trial in AD Expected in June 2025: Dosing is complete in the single arm Phase 2a open-label trial of ATI-2138 designed to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 in patients with moderate-to-severe AD. The Company expects to report top line results in June 2025. Potential target indications under consideration include alopecia areata (AA) and vitiligo."

P2a data • Pipeline update • Trial status • Alopecia • Atopic Dermatitis • Vitiligo

Study of ATI-2138 in Adult Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=14 | Completed | Sponsor: Aclaris Therapeutics, Inc. | Active, not recruiting ➔ Completed

Trial completion • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Study of ATI-2138 in Adult Participants with Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=14 | Active, not recruiting | Sponsor: Aclaris Therapeutics, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Aclaris Therapeutics Reports Fourth Quarter and Full Year 2024 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Confirmed Expectation of Phase 2 Data in the First Half of 2025 for Bosakitug in Chinese Patients with Certain Pulmonary Disorders:..Data from trials in severe asthma and CRSwNP expected in first half of 2025 to inform internal development programs. Initiated Clinical Trial Activities for a Phase 2b Trial of Bosakitug in Atopic Dermatitis (AD); Enrollment Expected to Begin in the First Half of 2025...Confirmed Expectation of Top Line Results in the First Half of 2025 for Phase 2a Trial in AD of ATI-2138, an Investigational Oral Covalent ITK/JAK3 Inhibitor...Announced Plan to File an Investigational New Drug (IND) Application for ATI-052 in the First Quarter of 2025..."

IND • New P2b trial • P2 data • Asthma • Chronic Obstructive Pulmonary Disease • Chronic Rhinosinusitis With Nasal Polyps • Pulmonary Disease • Ulcerative Colitis

Characterization of the dual ITK/JAK3 small molecule covalent inhibitor ATI-2138. (PubMed, J Pharmacol Exp Ther) - "ATI-2138 inhibits JAK3 and ITK in enzyme and functional cellular assays, demonstrates disease-modifying activity in rodent models of arthritis and colitis, and inhibits biomarkers linked to both ITK and JAK3 activity in healthy human participants. With this dual kinase activity against components of these inflammatory signaling pathway, ATI-2138 has the potential for enhanced therapeutic efficacy in the treatment of autoimmune and chronic inflammatory disease."

Clinical • Journal • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Rheumatology • IL2 • ITK • JAK3

New Publication Highlights Unique Properties of ATI-2138, a Potent and Selective Inhibitor of ITK and JAK3 (GlobeNewswire) - "ATI-2138 covalently inhibits ITK...more potently than the other Tec kinase family members and is selective for JAK3 inhibition relative to the other JAK isoforms...ATI-2138 dose-dependently decreased JAK1/JAK3-dependent IL-2-stimulated STAT5 phosphorylation in human peripheral blood mononuclear cells (PBMCs) with low-nanomolar potency...The functional cellular data demonstrating the impact of ATI-2138 on ITK and JAK3 biology translated into efficacy in multiple rodent models of chronic inflammation...In healthy human participants, ATI-2138 was generally well tolerated at all doses tested in both the SAD and MAD trials."

Clinical data • Preclinical • Immunology • Inflammation

Aclaris Therapeutics Announces First Patient Dosed in Phase 2a Clinical Trial of ATI-2138, an Investigational Oral Covalent ITK/JAK3 Inhibitor for the Treatment of Moderate to Severe Atopic Dermatitis (GlobeNewswire) - "Aclaris Therapeutics...today announced that the first patient has been dosed in Aclaris' Phase 2a clinical trial of ATI-2138, an investigational oral covalent inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase (JAK) 3, for the treatment of moderate to severe atopic dermatitis (AD)....Aclaris expects topline data from this trial in the first half of 2025."

P2a data • Trial status • Atopic Dermatitis

Study of ATI-2138 in Adult Participants With Moderate to Severe Atopic Dermatitis (clinicaltrials.gov) - P2 | N=15 | Recruiting | Sponsor: Aclaris Therapeutics, Inc.

New P2 trial • Atopic Dermatitis • Dermatitis • Dermatology • Immunology

Aclaris Therapeutics Reports Fourth Quarter and Full Year 2023 Financial Results and Provides a Corporate Update (GlobeNewswire) - "R&D expenses were $98.4 million for the year ended December 31, 2023 compared to $77.8 million for the prior year period....ATI-2138 development expenses, including costs associated with the Phase 1 MAD trial and other preclinical activities..."

Commercial • Immunology • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis

Aclaris Therapeutics Reports Third Quarter 2023 Financial Results and Provides a Corporate Update (Yahoo Finance) - "ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor:...Based on analysis of the PK, PD and safety, Aclaris is progressing ATI-2138 into Phase 2a clinical development in ulcerative colitis, which it expects to initiate in early 2024....Research and development (R&D) expenses were $23.9 million for the quarter ended September 30, 2023 compared to $23.7 million for the prior year period. The $0.2 million increase was primarily the result of: An increase in ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial and other preclinical activities..."

Commercial • New P2a trial • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Aclaris Therapeutics Announces Positive Results from Phase 1 Multiple Ascending Dose Trial of ATI-2138, an Investigational Oral Covalent ITK/JAK3 Inhibitor (GlobeNewswire) - P1 | N=60 | "Aclaris Therapeutics, Inc...today announced positive results from ATI-2138-PKPD-102, a Phase 1 Multiple Ascending Dose (MAD) trial of the investigational compound ATI-2138. Preliminary data from the MAD trial demonstrated: that ATI-2138 was generally well tolerated at all doses tested in the trial; that ATI-2138 had dose proportional pharmacokinetics (PK); and a dose-dependent inhibition of both ITK and JAK3 exploratory pharmacodynamic (PD) biomarkers, with near maximal inhibition achieved at the 30 mg total daily dose. Based on these results, Aclaris will progress this program into a Phase 2a proof of concept study in patients with ulcerative colitis, its previously announced intended first clinical development target, and anticipates initiation of the trial in early 2024."

New P2a trial • P1 data • Immunology • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis

Aclaris Therapeutics Reports Second Quarter 2023 Financial Results and Provides a Corporate Update (Yahoo Finance) - "Healthy Volunteers (ATI-2138-PKPD-102): This two-week Phase 1 MAD (multiple ascending dose) trial to investigate the safety, tolerability, PK and PD of ATI-2138 in healthy volunteers has been completed....Aclaris expects to report the data in September 2023....Research and development (R&D) expenses were $25.3 million for the quarter ended June 30, 2023 compared to $18.8 million for the prior year period....ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial and other preclinical activities."

Commercial • P1 data • PK/PD data • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Dr. Vince Clinical Research Announces Dosing of Aclaris Therapeutics’ Phase I MAD Study of ATI-2138 (Businesswire) - “Dr. Vince Clinical Research (DVCR)…announced that it has administered the first dose of Aclaris Therapeutics’ ATI-2138 in a Phase I multiple ascending dose (MAD) study for an investigational oral compound being developed for the treatment of autoimmune diseases. The Phase I MAD study in healthy volunteers is being conducted at DVCR’s world-class clinical pharmacology unit. The study will enroll 60 participants across five cohorts.”

Trial status • Immunology • Inflammatory Bowel Disease • Psoriasis • Ulcerative Colitis

Aclaris Therapeutics Reports Third Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - "Successfully Completed ATI-2138 Phase 1 SAD (single ascending dose) Trial in November; Selected Ulcerative Colitis as First Clinical Development Target...Aclaris submitted a new IND for this program to the U.S. Food and Drug Administration’s (FDA) Gastroenterology Division in October 2022 for the treatment of ulcerative colitis. If allowed, Aclaris intends to initiate a Phase 1 MAD trial of ATI-2138 in healthy subjects by the end of 2022."

IND • New P1 trial • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Aclaris Therapeutics Reports Second Quarter 2022 Financial Results and Provides a Corporate Update (GlobeNewswire) - “Research and Development Highlights: Rheumatoid Arthritis (ATI-450-RA-202): This Phase 2b dose ranging trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics…of zunsemetinib in combination with methotrexate in subjects with moderate to severe rheumatoid arthritis (RA) is ongoing. Aclaris continues to expect topline data in 2023….Psoriatic Arthritis (ATI-450-PsA-201): Aclaris initiated study activities in the second quarter in this Phase 2a trial to investigate the efficacy, safety, tolerability, pharmacokinetics and pharmacodynamics of zunsemetinib…Aclaris continues to expect topline data in the first half of 2023; ATI-2138: If the Phase 1 SAD trial is successful, Aclaris currently plans to initiate a Phase 1 multiple ascending dose (MAD) trial of ATI-2138 in subjects with psoriasis in 2022.”

New P1 trial • P2 data • Immunology • Psoriasis • Psoriatic Arthritis • Rheumatoid Arthritis