Aclaris Therapeutics Announces ATI-450 (MK2 pathway Inhibitor) publication in the Journal Cancer Research
August 21 2018 - 7:00AM
Aclaris Therapeutics, Inc. (NASDAQ:ACRS), a dermatologist-led
biopharmaceutical company focused on 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 Cancer Research.
The title of the article is: "Inhibition of the stromal
p38MAPK/MK2 pathway limits breast cancer metastases and
chemotherapy-induced bone loss."
ATI-450, an investigational drug, is a selective inhibitor of
p38 mitogen-activated protein kinase-activated protein kinase 2
(p38MAPK/MK2) interface and an attractive candidate for
stromal-targeted therapy. Levels of p38MAPKα expressed by a tumor
and the surrounding stromal cells correlate with poor prognosis. In
addition, p38MAPK signaling plays a key role in regulating
osteoclast differentiation. In this paper, mouse models were
utilized to explore the stromal inhibition of p38MAPK/MK2 pathway
with oral ATI-450 in limiting breast cancer metastasis and
protecting against bone loss, a major comorbidity of breast
cancer.
Key Preclinical findings:
- Pharmacologically targeting the stromal p38MAPK/MK2 pathway
limits breast cancer metastasis, preserves bone quality, and
extends survival.
- The role of the stromal compartment in tumor progression is
strongly illustrated in breast cancer bone metastases, where the
stromal compartment supports tumor growth, albeit through poorly
defined mechanisms.
- p38MAPKα is frequently expressed in tumor cells and surrounding
stromal cells, and its expression levels correlate with poor
prognosis. This observation led the authors to investigate whether
inhibiting the p38MAPKα pathway could reduce breast cancer
metastases in a clinically relevant model.
- Orally administered ATI-450 limited outgrowth of metastatic
breast cancer cells in the bone and visceral organs.
- This effect was primarily mediated by p38MAPKα-MK2 pathway
inhibition within the stromal compartment. Beyond limiting
metastatic tumor growth, ATI-450 reduced tumor-associated and
chemotherapy-induced bone loss, a serious comorbidity that greatly
diminishes quality of life for cancer patients.
- These data: a) support a central role for stromal-derived
factors in tumor progression; and (b) identify the p38MAPK-MK2
pathway as a promising therapeutic target for treating metastatic
disease and preventing chemotherapy- and tumor-induced bone
loss.
Several studies have shown that the stroma plays a significant
role in tumor progression, thereby establishing a rationale for
developing stroma-targeted anti-tumor therapies. The findings
of Dr. Stewart and her colleagues suggest that stromal-targeted
therapies have the potential to provide durable responses, help
circumvent drug resistance, and synergize with tumor-targeted
therapies.
This study was carried out by the laboratory of Sheila Stewart,
Ph.D., at the Washington University School of Medicine in St. Louis
in collaboration with Aclaris Therapeutics, Inc.
The article is available at
http://cancerres.aacrjournals.org/content/early/2018/08/08/0008-5472.CAN-18-0234.full-text.pdf and
will appear in print form in the future.
About Aclaris Therapeutics, Inc.
Aclaris Therapeutics, Inc. is a dermatologist-led
biopharmaceutical company focused on identifying, developing, and
commercializing innovative therapies to address significant unmet
needs in aesthetic and medical dermatology 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 SKs 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.
About ATI-450
ATI-450, an investigational drug formerly known as CDD-450, is a
novel oral selective MK2 pathway inhibitor that is being studied in
relation to regulation of TNF-α and IL-1β via the p38/MK2 kinase
pathway. The p38/MK2 pathway is a transducer of inflammation.
Selective inhibitors of the MK2 pathway may block inflammatory
cytokine production and activity and have the potential to restore
balance to the body’s immune system. ATI-450 may have a role in
treating a variety of autoimmune diseases including dermatological
disorders, rheumatoid arthritis, inflammatory bowel disease,
respiratory diseases, and in oncology.
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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