Aclaris reports potential of ATI-2138 as a dual inhibitor for inflammatory diseases, with promising preclinical and clinical trial results.
Quiver AI Summary
Aclaris Therapeutics, Inc. has announced the publication of findings related to ATI-2138, a novel investigational drug aimed at treating autoimmune and inflammatory diseases by inhibiting interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3). The publication highlights ATI-2138's unique mechanism of action, demonstrating its potency and selectivity in blocking key T cell signal transduction pathways involved in various inflammatory conditions, including atopic dermatitis and alopecia areata. Preclinical studies indicate promising efficacy in animal models, and early clinical trials show that the drug is well-tolerated among healthy participants. Aclaris is currently advancing ATI-2138 in a Phase 2a clinical trial for atopic dermatitis and aims to explore its broader therapeutic potential in multiple inflammatory diseases.
Potential Positives
- Data generated to date support the potential for ATI-2138 to impact several human inflammatory diseases, highlighting the drug's promising therapeutic applications.
- The new publication demonstrates that ATI-2138 exhibits a unique mechanism of action as a dual inhibitor of ITK and JAK3, suggesting it may be a best-in-class treatment option.
- Results from preclinical studies indicate that ATI-2138 effectively inhibits key T cell activities, which are crucial in various autoimmune and inflammatory conditions.
- The initial clinical trials of ATI-2138 showed that it was well tolerated, with no serious adverse events reported, providing a positive outlook for its safety profile in further development.
Potential Negatives
- The press release relies heavily on preclinical data and forward-looking statements, which may not guarantee future success in clinical trials for ATI-2138.
- Potential risks and uncertainties are noted, including the conduct of clinical trials and reliance on third parties, which could negatively impact the development and commercialization of ATI-2138.
- There is no mention of definitive clinical trial results, which may raise concerns about the efficacy and safety of ATI-2138 compared to existing treatments.
FAQ
What is ATI-2138 developed for?
ATI-2138 is in development to treat autoimmune and inflammatory diseases by inhibiting ITK and JAK3 signaling pathways.
How does ATI-2138 work?
ATI-2138 acts as a covalent inhibitor targeting interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3).
What diseases could ATI-2138 potentially impact?
ATI-2138 may impact various autoimmune and inflammatory diseases, including atopic dermatitis, alopecia areata, and vitiligo.
What were the results of ATI-2138 clinical trials?
Initial clinical trials showed that ATI-2138 was well-tolerated among healthy participants with no serious adverse events.
Where can I find more information on ATI-2138?
More information on ATI-2138 can be found in the publication available in The Journal of Pharmacology and Experimental Therapeutics.
Disclaimer: This is an AI-generated summary of a press release distributed by GlobeNewswire. The model used to summarize this release may make mistakes. See the full release here.
$ACRS Insider Trading Activity
$ACRS insiders have traded $ACRS stock on the open market 1 times in the past 6 months. Of those trades, 1 have been purchases and 0 have been sales.
Here’s a breakdown of recent trading of $ACRS stock by insiders over the last 6 months:
- ANAND MEHRA purchased 666,666 shares for an estimated $1,499,998
To track insider transactions, check out Quiver Quantitative's insider trading dashboard.
$ACRS Hedge Fund Activity
We have seen 26 institutional investors add shares of $ACRS stock to their portfolio, and 59 decrease their positions in their most recent quarter.
Here are some of the largest recent moves:
- TRIUM CAPITAL LLP removed 1,912,990 shares (-100.0%) from their portfolio in Q4 2024, for an estimated $4,744,215
- BAIN CAPITAL LIFE SCIENCES INVESTORS, LLC removed 1,000,000 shares (-100.0%) from their portfolio in Q3 2024, for an estimated $1,150,000
- JACOBS LEVY EQUITY MANAGEMENT, INC added 915,509 shares (+inf%) to their portfolio in Q3 2024, for an estimated $1,052,835
- QUBE RESEARCH & TECHNOLOGIES LTD removed 647,907 shares (-68.9%) from their portfolio in Q3 2024, for an estimated $745,093
- ACUITAS INVESTMENTS, LLC removed 578,139 shares (-100.0%) from their portfolio in Q4 2024, for an estimated $1,433,784
- CONNOR, CLARK & LUNN INVESTMENT MANAGEMENT LTD. added 576,413 shares (+173.4%) to their portfolio in Q4 2024, for an estimated $1,429,504
- STONEPINE CAPITAL MANAGEMENT, LLC added 531,427 shares (+27.6%) to their portfolio in Q3 2024, for an estimated $611,141
To track hedge funds' stock portfolios, check out Quiver Quantitative's institutional holdings dashboard.
Full Release
- 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
This article was originally published on Quiver News, read the full story.
The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.
