Aclaris Therapeutics Announces ATI-450 (MK2 pathway Inhibitor) publication in Journal of Experimental Medicine
March 20 2018 - 7:00AM
Aclaris Therapeutics, Inc. (NASDAQ:ACRS), a dermatologist-led
biopharmaceutical company committed to identifying, developing, and
commercializing innovative therapies to address significant unmet
needs in aesthetic and medical dermatology and immunology, today
announced a publication in the Journal of Experimental Medicine
The title of the article is: "Selective inhibition of the p38α
MAPK-MK2 axis inhibits inflammatory cues, including inflammasome
priming signals".
ATI-450, an investigational drug formerly known as CDD-450, is a
unique p38α MAPK–MK2 pathway selective inhibitor used to uncover
the function of this protein complex in inflammasome priming
signals. Importantly, ATI-450 is as efficacious as global p38α MAPK
inhibitors in decreasing inflammation in disease models.
Cryopyrin-Associated Periodic Syndrome (CAPS) and the most severe
form of the disease, Neonatal-Onset Multisystem Inflammatory
Disease (NOMID) result from dysregulated inflammasome generating
elevated systemic levels of the cytokine IL-1β. As the
article elucidates:
- Selective inhibition of p38α MAPK –MK2 decreases IL-1β, IL-6,
and TNF-α production by promoting mRNA instability.
- ATI-450 attenuates NOMID-associated complications in a
transgenic mouse model of CAPS.
- ATI-450 prevents bone destruction in CAPS mice.
- ATI-450 inhibits IL-1β in blood cells from CAPS patients
- ATI-450 prevents inflammation and joint destruction in
inflammatory arthritis in rats.
ATI-450 selectively blocks p38α MAPK activation of the
proinflammatory kinase MK2 while sparing p38α activation of other
effectors such as PRAK and ATF2. Use of ATI-450 helped to reveal a
critical role of the p38α MAPK –MK2 pathway in NLRP3 inflammasome
priming. ATI-450 also inhibited other inflammatory pathways (e.g.,
TNF-α and IL-6), thus implying potential indications for this drug
candidate beyond inflammasopathies. These findings may have
potential clinical implications because ATI-450 is at least as
efficacious as clinically evaluated global p38α MAPK inhibitors in
suppressing inflammation in both animal disease models and
patients’ cells, and ATI-450’s offers the potential lack of
transient efficacy and safety issues associated with global p38α
MAPK inhibitors which may result from their inhibition of non-MK2
substrates involved in anti-inflammatory and housekeeping
functions.
This study was carried out by Aclaris Therapeutics, Inc. in
collaboration with the laboratory of Gabriel Mbalaviele, Ph.D.,
at Washington University Medical School.
The article is available at
http://jem.rupress.org/cgi/doi/10.1084/jem.20172063 and will appear
in print form on May 7th.
About Aclaris Therapeutics, Inc.
Aclaris Therapeutics, Inc. is a dermatologist-led
biopharmaceutical company committed to identifying, developing, and
commercializing innovative therapies to address significant unmet
needs in dermatology, both aesthetic and medical, and immunology.
Aclaris’ focus on market segments with no FDA-approved medications
or where treatment gaps exist has resulted in the first
FDA-approved treatment for raised seborrheic keratoses and several
clinical programs to develop medications for the potential
treatment of common warts, alopecia areata, and vitiligo. For
additional information, please visit www.aclaristx.com and follow
Aclaris on LinkedIn.
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
"believe", "expect", "may", "plan," "potential," "will," and
similar expressions, and are based on Aclaris' current beliefs and
expectations. These forward-looking statements include expectations
regarding Aclaris’ preclinical and clinical development of its drug
candidates. 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, 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, 2017 and other filings Aclaris makes with the
U.S. Securities and Exchange Commission from time to time. These
documents are available under the "Financial Information" section
of the Investors page of Aclaris' website at
http://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 ContactMichael Tung, M.D.Senior Vice
President Corporate Strategy/Investor
Relations484-329-2140mtung@aclaristx.com
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