New Publication Highlights Unique Properties of ATI-2138, a Potent and Selective Inhibitor of ITK and JAK3
Aclaris Therapeutics (NASDAQ: ACRS) announced a new publication highlighting the properties of ATI-2138, their novel investigational covalent inhibitor of ITK and JAK3 for treating autoimmune and inflammatory diseases. The drug demonstrates potent and selective blocking of both ITK and JAK3, effectively inhibiting key T cells involved in conditions like atopic dermatitis, alopecia areata, and vitiligo.
The publication details ATI-2138's performance in biochemical target inhibition, cellular systems, and animal models. Key findings show the drug's unique pharmacological profile with high potency in inhibiting both ITK and JAK3. In initial clinical trials, ATI-2138 was generally well-tolerated, with no serious adverse events reported. The drug showed dose- and time-dependent modulation of biomarkers linked to both ITK and JAK3 activity in healthy participants.
Aclaris Therapeutics (NASDAQ: ACRS) ha annunciato una nuova pubblicazione che evidenzia le proprietà di ATI-2138, il loro nuovo inibitore covalente sperimentale di ITK e JAK3 per il trattamento di malattie autoimmuni e infiammatorie. Il farmaco dimostra un blocco potente e selettivo di entrambi ITK e JAK3, inibendo efficacemente le cellule T chiave coinvolte in condizioni come la dermatite atopica, l'alopecia areata e il vitiligine.
La pubblicazione dettaglia le prestazioni di ATI-2138 nell'inibizione dei target biochimici, nei sistemi cellulari e nei modelli animali. I risultati chiave mostrano il profilo farmacologico unico del farmaco con alta potenza nell'inibire sia ITK che JAK3. Nei primi studi clinici, ATI-2138 è stato generalmente ben tollerato, senza eventi avversi gravi segnalati. Il farmaco ha mostrato una modulazione dipendente dalla dose e dal tempo dei biomarcatori collegati all'attività di ITK e JAK3 in partecipanti sani.
Aclaris Therapeutics (NASDAQ: ACRS) anunció una nueva publicación que destaca las propiedades de ATI-2138, su nuevo inhibidor covalente en investigación de ITK y JAK3 para el tratamiento de enfermedades autoinmunes e inflamatorias. El fármaco demuestra un bloqueo potente y selectivo de ITK y JAK3, inhibiendo efectivamente las células T clave involucradas en condiciones como la dermatitis atópica, la alopecia areata y el vitíligo.
La publicación detalla el rendimiento de ATI-2138 en la inhibición de objetivos bioquímicos, sistemas celulares y modelos animales. Los hallazgos clave muestran el perfil farmacológico único del fármaco con alta potencia en la inhibición de ITK y JAK3. En los primeros ensayos clínicos, ATI-2138 fue generalmente bien tolerado, sin eventos adversos graves reportados. El fármaco mostró una modulación dependiente de la dosis y del tiempo de biomarcadores relacionados con la actividad de ITK y JAK3 en participantes sanos.
Aclaris Therapeutics (NASDAQ: ACRS)는 자가면역 및 염증 질환 치료를 위한 새로운 실험적 공유 결합 억제제 ATI-2138의 특성을 강조하는 새로운 발표를 했습니다. 이 약물은 ITK와 JAK3를 모두 강력하고 선택적으로 차단하여 아토피 피부염, 원형 탈모증 및 백반증과 같은 질환에 관여하는 주요 T 세포를 효과적으로 억제합니다.
발표에서는 ATI-2138의 생화학적 표적 억제, 세포 시스템 및 동물 모델에서의 성능을 상세히 설명합니다. 주요 발견은 ITK와 JAK3를 모두 억제하는 높은 효능을 가진 약물의 독특한 약리학적 프로필을 보여줍니다. 초기 임상 시험에서 ATI-2138은 일반적으로 잘 견디는 것으로 나타났으며, 심각한 부작용은 보고되지 않았습니다. 이 약물은 건강한 참가자에서 ITK와 JAK3 활동과 관련된 바이오마커의 용량 및 시간 의존적 조절을 보여주었습니다.
Aclaris Therapeutics (NASDAQ: ACRS) a annoncé une nouvelle publication mettant en lumière les propriétés de ATI-2138, leur nouvel inhibiteur covalent expérimental de l'ITK et de la JAK3 pour le traitement des maladies auto-immunes et inflammatoires. Le médicament démontre un blocage puissant et sélectif des deux, ITK et JAK3, inhibant efficacement les cellules T clés impliquées dans des conditions telles que la dermatite atopique, l'alopécie areata et le vitiligo.
La publication détaille les performances de ATI-2138 en matière d'inhibition des cibles biochimiques, de systèmes cellulaires et de modèles animaux. Les principales conclusions montrent le profil pharmacologique unique du médicament avec une forte puissance pour inhiber à la fois l'ITK et la JAK3. Lors des premiers essais cliniques, ATI-2138 a été généralement bien toléré, sans événements indésirables graves signalés. Le médicament a montré une modulation dépendante de la dose et du temps des biomarqueurs liés à l'activité de l'ITK et de la JAK3 chez des participants en bonne santé.
Aclaris Therapeutics (NASDAQ: ACRS) hat eine neue Veröffentlichung angekündigt, die die Eigenschaften von ATI-2138, ihrem neuartigen experimentellen kovalenten Inhibitor von ITK und JAK3 zur Behandlung von Autoimmun- und Entzündungserkrankungen, hervorhebt. Das Medikament zeigt eine potente und selektive Blockierung von sowohl ITK als auch JAK3 und inhibiert effektiv die Schlüssel-T-Zellen, die an Bedingungen wie atopischer Dermatitis, Alopecia areata und Vitiligo beteiligt sind.
Die Veröffentlichung beschreibt die Leistung von ATI-2138 bei der biochemischen Zielinhibition, in zellulären Systemen und Tiermodellen. Wichtige Ergebnisse zeigen das einzigartige pharmakologische Profil des Medikaments mit hoher Wirksamkeit bei der Hemmung von ITK und JAK3. In den ersten klinischen Studien wurde ATI-2138 im Allgemeinen gut vertragen, ohne schwerwiegende unerwünschte Ereignisse. Das Medikament zeigte eine dosis- und zeitabhängige Modulation von Biomarkern, die mit der Aktivität von ITK und JAK3 bei gesunden Teilnehmern verbunden sind.
- Drug demonstrated high potency and selectivity in cellular systems
- Showed efficacy in multiple rodent models of chronic inflammation
- Well-tolerated in clinical trials with no serious adverse events
- Successfully modulated target biomarkers in human participants
- None.
Insights
The publication reveals several important aspects that position ATI-2138 as a potentially significant advancement in the treatment of inflammatory diseases. The compound's dual inhibition of ITK and JAK3 represents a novel approach that could offer superior efficacy compared to existing treatments.
Three key differentiating factors stand out: First, the high selectivity profile demonstrated in biochemical and cellular assays suggests a potentially better safety profile than broader-spectrum JAK inhibitors currently on the market. The compound showed selective inhibition of JAK3 while sparing other JAK isoforms, which could translate to fewer off-target effects.
Second, the preclinical efficacy data across multiple inflammatory disease models, combined with favorable safety results from both SAD and MAD studies, provides a strong foundation for continued development. The absence of serious adverse events and demonstration of dose-dependent biomarker modulation are particularly encouraging at this stage.
Third, ATI-2138's unique mechanism targeting both ITK and JAK3 pathways could provide more comprehensive control of inflammatory processes, potentially leading to better clinical outcomes in conditions like atopic dermatitis, where existing treatments may have efficacy.
The market implications are significant, considering the growing $7+ billion atopic dermatitis market. If ATI-2138 can demonstrate superior efficacy or safety compared to existing JAK inhibitors, it could capture meaningful market share. However, investors should note that the compound is still in early clinical development (Phase 2a), and substantial clinical validation will be required to confirm these promising preliminary results.
- Data Generated to Date Support Potential for Aclaris’ ATI-2138 to Impact Several Human Inflammatory Diseases -
WAYNE, Pa., Feb. 12, 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 the availability of a new publication describing the unique properties of Aclaris Therapeutics’ ATI-2138, a novel investigational covalent inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3) in development for the treatment of autoimmune and inflammatory diseases. This was published in The Journal of Pharmacology and Experimental Therapeutics and can be found here.
“This publication provides important clinical and non-clinical evidence of the potential for ATI-2138 to be a best-in-class inhibitor of key signal transduction kinases as a result of its unique mechanism of action,” said Dr. Joseph Monahan, Ph.D., Aclaris’ Chief Scientific Officer. “ATI-2138 potently and selectively blocks both ITK and JAK3. Through this mechanism, ATI-2138 has been shown in preclinical studies to effectively inhibit Th1, Th2 and Th17 cell activity, which are key T cells involved in a wide range of autoimmune, chronic inflammatory and allergic diseases, including atopic dermatitis (AD), alopecia areata, and vitiligo. In addition, JAK inhibitors have been approved in multiple diseases including AD. Data generated to date support our ongoing clinical efforts including our ongoing Phase 2a trial of ATI-2138 in AD.”
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-2Rγc) to affect lymphocyte proliferation and activation (Leonard and O'Shea, 1998; Rochman et al., 2009; Agashe et al., 2022).
The publication, entitled “Characterization of the dual ITK/JAK3 small molecule covalent inhibitor ATI-2138,” describes in vitro and in vivo assessments and the clinical translation of ATI-2138 on ITK and JAK3 signaling. It describes the evaluation of the efficacy of ATI-2138 in three animal models of inflammatory disease, as well as the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) results of ATI-2138 in healthy human participants from single ascending dose (SAD) and multiple ascending dose (MAD) studies. The results in the publication include:
- Biochemical Target Inhibition: ATI-2138 covalently inhibits ITK, a TCR-activated Tec family kinase, more potently than the other Tec kinase family members and is selective for JAK3 inhibition relative to the other JAK isoforms.
- Potency and Selectivity in Cellular Systems: ATI-2138 dose-dependently decreased JAK1/JAK3-dependent IL-2-stimulated STAT5 phosphorylation in human peripheral blood mononuclear cells (PBMCs) with low-nanomolar potency while having no inhibitory effect on the JAK1/JAK2-dependent IFNγ-induced STAT1 phosphorylation or the JAK2/Tyk2-dependent IL-12-induced STAT4 phosphorylation, consistent with JAK3 selectivity.
- Unique Pharmacological Profile: In biochemical and cellular assays, ATI-2138 demonstrated a similar high potency for inhibiting both ITK and JAK3, compared to ritlecitinib which was markedly less potent in inhibiting T-cell receptor (TCR)-mediated ITK signaling.
- Demonstrated Efficacy in Animal Models: 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.
- Well Tolerated in Initial Clinical Trials: In healthy human participants, ATI-2138 was generally well tolerated at all doses tested in both the SAD and MAD trials. There were no clinically significant findings for laboratory results, vital signs, and ECGs. No participants experienced a serious adverse event (AE), serious AE related to the study drug, or an AE leading to death.
- Activity on Target Biomarkers: ATI-2138 demonstrated dose- and time-dependent modulation of biomarkers linked to both ITK and JAK3 activity in healthy human participants.
ATI-2138 is a novel pharmacologic agent that acts as a dual inhibitor of ITK and JAK3. The efficacy 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, 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-2Rγc 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 www.aclaristx.com.
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 “anticipate,” “believe,” “expect,” “intend,” “may,” “plan,” “potential,” “will,” and similar expressions, and are based on Aclaris’ current beliefs and expectations. These forward-looking statements include expectations regarding its development plans for ATI-2138, the potential for ATI-2138 to be a best-in-class inhibitor of key signal transduction kinases and the therapeutic potential of ATI-2138. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements. Risks and uncertainties that may cause actual results to differ materially include uncertainties inherent in the conduct of clinical trials, Aclaris’ reliance on third parties over which it may not always have full control, Aclaris’ ability to enter into strategic partnerships on commercially reasonable terms, the uncertainty regarding the macroeconomic environment and other risks and uncertainties that are described in the Risk Factors section of Aclaris’ Annual Report on Form 10-K for the year ended December 31, 2023, and other filings Aclaris makes with the U.S. Securities and Exchange Commission from time to time. These documents are available under the “SEC Filings” page of the “Investors” section of Aclaris’ website at www.aclaristx.com. Any forward-looking statements speak only as of the date of this 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
wroberts@aclaristx.com
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