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
Aclaris Therapeutics (NASDAQ: ACRS) announced positive top-line results from its Phase 2a trial of ATI-2138, an oral inhibitor targeting ITK and JAK3, for atopic dermatitis treatment. The trial met its primary endpoint, demonstrating a favorable safety profile with no severe adverse events.
Key efficacy results showed a 60.5% mean improvement in EASI score at week 12, reaching 77.1% when excluding one outlier patient. Additionally, 62.5% of patients achieved significant itch reduction. The drug demonstrated strong pharmacodynamic results, with 90% ITK target occupancy at peak and significant downregulation of inflammatory markers.
Based on these results, Aclaris plans to advance ATI-2138's development for alopecia areata and explore additional indications. The company is also developing next-generation ITK inhibitors, with new INDs expected in 2026.
Aclaris Therapeutics (NASDAQ: ACRS) ha annunciato risultati positivi preliminari dal suo studio di Fase 2a su ATI-2138, un inibitore orale che agisce su ITK e JAK3, per il trattamento della dermatite atopica. Lo studio ha raggiunto l'endpoint primario, evidenziando un profilo di sicurezza favorevole senza eventi avversi gravi.
I risultati chiave sull'efficacia hanno mostrato un miglioramento medio del 60,5% nel punteggio EASI alla settimana 12, che sale al 77,1% escludendo un paziente outlier. Inoltre, il 62,5% dei pazienti ha ottenuto una significativa riduzione del prurito. Il farmaco ha dimostrato forti risultati farmacodinamici, con una occupazione del target ITK del 90% al picco e una significativa riduzione dei marker infiammatori.
Basandosi su questi risultati, Aclaris intende proseguire lo sviluppo di ATI-2138 per la alopecia areata ed esplorare ulteriori indicazioni. L'azienda sta inoltre sviluppando inibitori ITK di nuova generazione, con nuove IND previste per il 2026.
Aclaris Therapeutics (NASDAQ: ACRS) anunci贸 resultados positivos preliminares de su ensayo de Fase 2a con ATI-2138, un inhibidor oral dirigido a ITK y JAK3, para el tratamiento de la dermatitis at贸pica. El ensayo cumpli贸 su objetivo primario, demostrando un perfil de seguridad favorable sin eventos adversos graves.
Los resultados clave de eficacia mostraron una mejora media del 60,5% en la puntuaci贸n EASI a la semana 12, alcanzando el 77,1% al excluir a un paciente at铆pico. Adem谩s, el 62,5% de los pacientes logr贸 una reducci贸n significativa del picor. El medicamento mostr贸 fuertes resultados farmacodin谩micos, con una ocupaci贸n del objetivo ITK del 90% en el pico y una regulaci贸n a la baja significativa de los marcadores inflamatorios.
Bas谩ndose en estos resultados, Aclaris planea avanzar en el desarrollo de ATI-2138 para la alopecia areata y explorar indicaciones adicionales. La compa帽铆a tambi茅n est谩 desarrollando inhibidores ITK de pr贸xima generaci贸n, con nuevas IND previstas para 2026.
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欤检殧 須姤 瓴瓣臣搿滊姅 12欤检皑鞐� EASI 鞝愳垬臧� 韽夑窢 60.5% 臧滌劆霅橃棃瓿�, 頃� 氇呾潣 鞚挫儊旃� 頇橃瀽毳� 鞝滌櫢頃橂┐ 77.1%旯岇 靸侅姽頄堨姷雼堧嫟. 霕愴暅, 62.5%鞚� 頇橃瀽臧� 臧�霠れ泙歃濎潣 順勳爛頃� 臧愳唽毳� 瓴巾棙頄堨姷雼堧嫟. 鞎诫鞚� 鞎诫鞐暀鞝侅溂搿滊弰 臧曤牓頃� 須臣毳� 雮橅儉雮挫柎, 斓滊寑 雴嶋弰 鞁� ITK 響滌爜 鞝愳湢鞙澊 90%鞐� 雼枅瓿� 鞐检 響滌鞛愳潣 鞙犾潣氙疙暅 頃橅枼 臁办爤鞚� 頇曥澑霅橃棃鞀惦媹雼�.
鞚� 瓴瓣臣毳� 氚旐儠鞙茧 Aclaris電� ATI-2138鞚� 鞗愴槙 韮堧歃� 旃橂 臧滊皽鞚� 歆勴枆頃橁碃 於旉皜 鞝侅潙歃濎潉 韮愳儔頃� 瓿勴殟鞛呺媹雼�. 霕愴暅 須岇偓電� 彀劯雽� ITK 鞏奠牅鞝� 臧滊皽霃� 歆勴枆 欷戩澊氅�, 2026云�鞐� 靸堧鞖� IND 鞁犾箔鞚� 鞓堨儊霅╇媹雼�.
Aclaris Therapeutics (NASDAQ : ACRS) a annonc茅 des r茅sultats positifs pr茅liminaires de son essai de phase 2a sur ATI-2138, un inhibiteur oral ciblant ITK et JAK3, destin茅 au traitement de la dermatite atopique. L鈥檈ssai a atteint son crit猫re principal, d茅montrant un profil de s茅curit茅 favorable sans 茅v茅nements ind茅sirables graves.
Les r茅sultats cl茅s d鈥檈fficacit茅 ont montr茅 une am茅lioration moyenne de 60,5% du score EASI 脿 la semaine 12, atteignant 77,1% en excluant un patient atypique. De plus, 62,5% des patients ont obtenu une r茅duction significative des d茅mangeaisons. Le m茅dicament a pr茅sent茅 de solides r茅sultats pharmacodynamiques, avec une occupation de la cible ITK 脿 90% au pic et une r茅gulation significative 脿 la baisse des marqueurs inflammatoires.
Sur la base de ces r茅sultats, Aclaris pr茅voit de poursuivre le d茅veloppement d鈥橝TI-2138 pour la pelade et d鈥檈xplorer d鈥檃utres indications. La soci茅t茅 d茅veloppe 茅galement des inhibiteurs ITK de nouvelle g茅n茅ration, avec de nouvelles demandes d鈥橧ND attendues en 2026.
Aclaris Therapeutics (NASDAQ: ACRS) gab positive Zwischenergebnisse aus seiner Phase-2a-Studie mit ATI-2138 bekannt, einem oralen Inhibitor, der ITK und JAK3 bei der Behandlung von atopischer Dermatitis hemmt. Die Studie erreichte ihren prim盲ren Endpunkt und zeigte ein g眉nstiges Sicherheitsprofil ohne schwere unerw眉nschte Ereignisse.
Wesentliche Wirksamkeitsergebnisse zeigten eine durchschnittliche Verbesserung von 60,5% im EASI-Score nach 12 Wochen, die auf 77,1% anstieg, wenn ein Ausrei脽erpatient ausgeschlossen wurde. Zudem erreichten 62,5% der Patienten eine signifikante Juckreizreduktion. Das Medikament zeigte starke pharmakodynamische Effekte mit einer 90%igen ITK-Zielbindung zum Spitzenwert und einer signifikanten Herunterregulierung entz眉ndlicher Marker.
Auf Basis dieser Ergebnisse plant Aclaris, die Entwicklung von ATI-2138 f眉r Alopecia areata voranzutreiben und weitere Indikationen zu erforschen. Das Unternehmen entwickelt zudem neue Generationen von ITK-Inhibitoren, mit neuen IND-Anmeldungen im Jahr 2026.
- Strong safety profile with no severe adverse events (SAEs) or treatment-emergent adverse events (TEAEs)
- Significant efficacy with 77.1% mean EASI score improvement at week 12 (excluding outlier)
- 62.5% of patients achieved clinically meaningful itch reduction
- Near complete ITK target occupancy (90% at peak)
- Strong downregulation of key inflammatory markers
- Small study size with only 14 patients enrolled
- One patient identified as statistical molecular outlier affecting overall results
- Current dosing (10mg BID) considered low, suggesting higher doses may be needed
Insights
Aclaris' ATI-2138 shows promising safety and efficacy in atopic dermatitis trial, validating ITK as therapeutic target with potential advantages over JAK inhibitors.
The Phase 2a trial results for ATI-2138 represent a significant milestone for Aclaris Therapeutics' ITK inhibition platform. This novel dual inhibitor of ITK and JAK3 demonstrated a favorable safety profile with no severe adverse events and minimal treatment-related adverse events - a crucial differentiator from other JAK inhibitors that typically carry more significant safety concerns.
The efficacy data is particularly compelling despite the small sample size (n=14). Patients achieved a mean EASI improvement of 60.5% at 12 weeks (76.8% median), with one statistical outlier affecting these numbers. When excluding this non-compliant outlier with systemic findings inconsistent with atopic dermatitis, the improvements reached 77.1% mean and 82.1% median - comparable to approved therapies in this indication.
What's mechanistically important are the pharmacodynamic results showing 90% target occupancy at peak and 60-70% at trough, confirming strong target engagement. The molecular data validates ITK as a therapeutic target through demonstrated downregulation of Th2, Th17, and TCR pathways - all critical in immune-mediated skin conditions.
Most notably, these results were achieved at a relatively low dose (10mg BID), suggesting potential for dose optimization in future trials. This creates a promising development pathway for ATI-2138 not only in atopic dermatitis but potentially in other conditions like alopecia areata, where the company plans to focus future development efforts.
The anti-fibrotic effects observed add another interesting dimension to this compound's potential therapeutic profile, possibly expanding its utility across multiple immune-inflammatory conditions.
- Primary Endpoint Analysis Confirms Favorable Tolerability Profile of ATI-2138 Without Certain Risks Associated with Other Agents in the Class -
- Efficacy Results Show Comparable Outcomes to Approved Therapies with Potential for Improved Tolerability, Supporting Exploration of Higher Doses in Future Clinical Trials -
- Pharmacodynamic Results Validate Therapeutic Potential of ITK Inhibition and Corroborate Potential of Aclaris鈥� ITK Franchise -
- Management to Host a Conference Call to Discuss Results Today at 5:00PM EDT -
WAYNE, Pa., July 29, 2025 (GLOBE NEWSWIRE) -- Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel product candidates for immuno-inflammatory diseases, today announced positive top-line results from its open-label, single-arm Phase 2a trial of ATI-2138, a potent and selective investigational oral covalent inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3), in 14 patients with moderate-to-severe atopic dermatitis (AD). Based on the growing body of supportive non-clinical and clinical evidence, Aclaris intends to further develop ATI-2138 in alopecia areata and is also exploring other indications relevant to the mechanism of action.
鈥淭hese Phase 2a trial results represent a significant achievement for our ITK franchise by confirming the mechanism and corroborating our work on next-generation ITK selective compounds,鈥� said Dr. Neal Walker, Chief Executive Officer of Aclaris. 鈥淭he objectives of this trial were to confirm the strong tolerability profile across multiple doses of ATI-2138 over 12 weeks, to test the mechanism in AD before initiating our work in other diseases including alopecia areata, and to further validate ITK as an important therapeutic target; we accomplished each of these. Consistent with prior results, ATI-2138 was shown to be well tolerated. The observed efficacy results across a variety of validated scoring tools 鈥� even at this low dose 鈥� suggest responses that are in line with, if not better than, that seen with approved therapies. And finally, the PD results confirmed the potential of targeting ITK, including strong downregulation of key ITK-dependent markers and an interesting antifibrotic effect.鈥�
The results observed in this trial include a favorable tolerability profile of ATI-2138, clinically meaningful improvements from baseline in assessments of disease severity including extent and severity of AD (Eczema Area and Severity Index (EASI)) and percent of patients experiencing a greater than or equal to four point improvement in worst itch in the last 24 hours (Peak Pruritus Numerical Rating Scale (PP-NRS)) in patients receiving low doses (10mg BID, 12 weeks) of ATI-2138, and PD results that validate ITK as a therapeutic target. Overall, these results provide evidence that the contribution of ITK has the potential to enable ATI-2138, even at low doses, to confer efficacy comparable to that observed in clinical trials of approved JAK and IL-4/13 inhibitors in moderate-to-severe AD, with improved tolerability and without the significant safety risks typically associated with JAK inhibition.
鈥淎lthough this is a small study, the pharmacodynamic results are quite compelling; I鈥檓 excited about the anti-inflammatory activity we observed and the therapeutic potential for ATI-2138, and more broadly, ITK as a potential therapeutic target,鈥� said Emma Guttman, M.D., Ph.D., Waldman Professor of Dermatology and Immunology and Health System Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai in New York City. 鈥淲e observed strong downregulation of key inflammatory markers, including those associated with ITK including Th2 and Th1/Th17-related markers, as well as certain ITK pathway- and fibrosis-related markers. Overall, these are important results that define the potential of ATI-2138 and ITK inhibition to address Th2 and Th1/Th17 mediated diseases like alopecia areata, vitiligo, and atopic dermatitis.鈥�
Patient Demographics
Twenty-six (26) patients were screened for inclusion in this single-arm Phase 2a trial. Of the 14 that were enrolled, 12 completed treatment. Excluding two protocol violations, 10 patients were available for the per protocol analysis. The enrolled population was split evenly between male and female participants. Consistent with published demographics, half of the enrolled population self-identified as African American. Mean baseline EASI score was 22.7.
Primary Endpoint: Safety Results
ATI-2138 was very well tolerated in this Phase 2a trial. No severe adverse events (SAEs) or treatment-emergent adverse events (TEAEs) were observed. A majority of the adverse events were mild and resolved spontaneously during treatment; there were no discontinuations due to adverse events. Three patients experienced a combined total of four adverse events determined to be related to study drug (TRAE); all but one (moderate myalgia; starting on day 24 with no elevation in CPK) were mild, transient, and resolved during treatment. No safety signal over the extent of the trial was observed in chemistry, creatine phosphokinase (CPK), hematology (e.g., leukocytes, lymphocytes, neutrophils), lipids, electrocardiogram (ECG), ECG with corrected QT (ECG-QTcF), or vital signs.
Secondary Endpoints: Efficacy Results
Mean and median change from baseline in Eczema Area and Severity Score (EASI) over time:
The EASI score is a validated tool used to assess the severity of AD. It measures the extent and severity of lesional skin associated with AD across different body regions and assigns a composite score from 0 to 72, with higher scores indicating severe (21.1 to 50.0) or very severe (50.1 to 72.0) disease.
- 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) was70.7% (median improvement =76.3% ). - The week 12 results were skewed by a single patient who was identified by an independent lab as being a statistical molecular outlier by more than four standard deviations compared to others. This patient demonstrated systemic findings inconsistent with AD alone including significant non-lesional inflammation, based on various PD measures. In addition, this patient was not fully compliant with study drug administration. Excluding this patient, the mean improvement in EASI score at week 12 (end of treatment) was
77.1% (median improvement =82.1% ). At week 4, the mean improvement in EASI score was77.3% (median improvement =72.9% ), and at week 8, the mean improvement in EASI score was81.0% (median improvement =77.1% ).
All other assessed efficacy response curves showed similar mean and median improvements from baseline, starting at the first (week 1) office visit.
Percent of patients with a greater than or equal to four-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS):
The PP-NRS assesses the severity of itch at the worst moment during the previous 24 hours on a scale of 0 (鈥渘o itch鈥�) to 10 (鈥渨orst itch imaginable鈥�). A 鈮�4-point improvement in PP-NRS score is considered a clinically meaningful reduction in itch intensity and severity.
- At week 12 (n=8),
62.5% of patients experienced a 鈮�4-point improvement in PP-NRS.
Secondary Endpoint: Pharmacodynamic Results
The clinical activity was supported by pharmacodynamic analyses clearly demonstrating modulation of both the ITK and JAK3 pathways as evidenced by inhibition of ex vivo pathway-specific stimulation of patient whole blood. Near complete and sustained ITK target occupancy was observed across the dosing interval ranging from ~
Next Steps for ITK Franchise
Positive results from this Phase 2a single-arm, open-label trial help validate Aclaris鈥� ITK franchise. The Company intends to further develop ATI-2138 in alopecia areata and is also exploring other indications relevant to the mechanism of action. In addition, preclinical work is ongoing for next-generation ITK inhibitors, which Aclaris expects to provide the basis for new INDs starting in 2026.
About the Phase 2a Trial
The Phase 2a trial is an open-label, single-arm study designed to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of 10mg of ATI-2138 administered twice daily (BID) for 12 weeks in patients with moderate-to-severe AD. The primary endpoints were safety-related parameters. Secondary endpoints included pharmacodynamic assessments and efficacy as measured by scoring tools including the Eczema Area and Severity Index (EASI), Peak Pruritus Numerical Rating Scale (PP-NRS), and other pertinent efficacy related measures.
Webcast and Conference Call
Aclaris will host a webcast and conference call with slides at 5:00 p.m. EDT today to discuss the results of this Phase 2a trial. The live and archived webcast will be available on the Events page of the Company鈥檚 website: . The webcast will be archived on the same page for 30 days following the event. Please note the following process if you would rather access the call via telephone: To register and receive a dial in number and unique PIN to access the live conference call, please follow to register online. Upon registering you will receive the dial-in info and a unique PIN to join the call as well as an email confirmation with the details.
About ATI-2138
ATI-2138 is a highly potent and selective novel investigational pharmacologic agent that acts as a dual inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3). ITK regulates T cell receptor signal transduction and inhibition of this kinase can affect T cell differentiation and activation. JAK3 is a key signal transduction kinase that forms a heterodimer with JAK1, modulates JAK1 phosphorylation of signal transducer and activator of transcription 5 (STAT5), and regulates cytokines that signal through the IL-2 receptor common gamma chain (IL-2蠏肠) to affect lymphocyte proliferation and activation. The efficacy results exhibited in preclinical animal models of inflammation and autoimmune diseases, coupled with the favorable safety, PK, and PD profile in healthy human SAD and MAD studies and the top-line results of the Phase 2a trial in AD support the potential for ATI-2138 to affect several human inflammatory diseases and further investigation of this molecule in patients with atopic and autoimmune diseases that are dependent on T cell function and/or IL-2蠏肠 signaling.
About Aclaris Therapeutics, Inc.
Aclaris Therapeutics, Inc. is a clinical-stage biopharmaceutical company developing a pipeline of novel product candidates to address the needs of patients with immuno-inflammatory diseases who lack satisfactory treatment options. The company has a multi-stage portfolio of product candidates powered by a robust R&D engine. For additional information, please visit 聽and follow Aclaris on (formerly Twitter) at @AclarisTx and on .
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Cautionary Note Regarding Forward-Looking Statements
Any statements contained in this press release that do not describe historical facts may constitute forward-looking statements as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as 鈥渁nticipate,鈥� 鈥渂elieve,鈥� 鈥渆xpect,鈥� 鈥渋ntend,鈥� 鈥渕ay,鈥� 鈥減lan,鈥� 鈥減otential,鈥� 鈥渨ill,鈥� and similar expressions, and are based on Aclaris鈥� current beliefs and expectations. These forward-looking statements include expectations regarding its development plans for ATI-2138, and its next-generation ITK inhibitors, including plans to develop ATI-2138 in alopecia areata and potentially other indications and plans to have INDs in 2026 for its next-generation ITK inhibitors, and the therapeutic potential for ATI-2138 and its next-generation ITK inhibitors. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Aclaris鈥� reliance on third parties over which it may not always have full control, Aclaris鈥� ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic environment and other risks and uncertainties that are described in the Risk Factors section of Aclaris鈥� Annual Report on Form 10-K for the year ended December 31, 2024, and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are available under the 鈥淪EC Filings鈥� page of the 鈥淚nvestors鈥� section of Aclaris鈥� website at www.aclaristx.com. No head-to-head clinical studies have been conducted against JAK or IL4/13 inhibitors. Differences exist between data and trial designs, and caution should be exercised when comparing data across studies. Any forward-looking statements speak only as of the date of this press release and are based on information available to Aclaris as of the date of this release, and Aclaris assumes no obligation to, and does not intend to, update any forward-looking statements, whether as a result of new information, future events or otherwise.
Aclaris Therapeutics Contact:
Will Roberts
Senior Vice President
Corporate Communications and Investor Relations
(484) 329-2125
FAQ
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