ARQ 531 demonstrates best-in-class potential as a reversible,
non-covalent BTK inhibitor
BURLINGTON, Mass.--(BUSINESS WIRE)--
ArQule, Inc. (Nasdaq: ARQL) today announced that preclinical data was
presented on Bruton's tyrosine kinase (BTK) inhibitor, ARQ 531, in a
poster presentation by The Ohio State University at the American Society
of Hematology (ASH) Annual Meeting. The presentation highlighted
preclinical studies of ARQ 531 in Chronic Lymphocytic Leukemia (CLL).
ARQ 531 is an investigational, orally bioavailable, potent and
reversible BTK inhibitor.
ARQ 531 Poster Presentation Highlights
Title: The Bruton's Tyrosine Kinase (BTK) Inhibitor ARQ 531
Effectively Inhibits Wild Type and C481S Mutant BTK and Is Superior to
Ibrutinib in a Mouse Model of Chronic Lymphocytic Leukemia
Multi-targeted inhibition of cytokine, chemokine, and BCR pathways by
ARQ 531 decreases activation, migration, and viability of CLL cells.
Unlike ibrutinib, ARQ 531 inhibits activation of C481S mutated BTK
variants and maintains cytotoxicity in ibrutinib resistant clones.
ARQ 531 demonstrates remarkable efficacy in an in vivo TCL1
adoptive transfer model, improving survival to a greater extent than
ibrutinib and restoring granulocyte production.
The company plans to complete preclinical studies and file an
Investigational New Drug (IND) application in early 2017 to begin
clinical testing later in the year.
The presentation can be viewed at https://www.arqule.com/wp-content/uploads/ASH-2016-ARQ-531-in-CLL.pdf.
"Irreversible kinase inhibitors directed at BTK have really changed the
landscape of CLL but at extended follow up, we are beginning to see a
subset of high risk patients who are relapsing," said Dr. Jennifer
Woyach, M.D., of The Ohio State University College of Medicine. "Small
molecules that target BTK that are not dependent upon the C481 site
represent an exciting option for future clinical trials. We are excited
to be working with ArQule on this project and look forward to initiating
the first in man study with ARQ 531."
"We began our BTK discovery program in 2011 which ultimately lead to the
selection of ARQ 531, a potent reversible inhibitor of both wild type
and mutant BTK," said Dr. Giovanni Abbadessa, M.D., PhD., Vice President
of Clinical Development, Translational Medicine and Medical Affairs at
ArQule. "With the recent emergence in 2015 of BTK resistance we
concentrated our efforts in this growing CLL patient population. We are
pleased to be working with The Ohio State University to finish
preclinical studies on this exciting program. We remain on track to file
an IND application early next year."
About BTK and ARQ 531
ARQ 531 is an investigational, orally bioavailable, potent and
reversible Bruton's tyrosine kinase (BTK) inhibitor. Biochemical and
cellular studies have shown that ARQ 531inhibits both the wild type and
C481S-mutant forms of BTK. The C481S mutation is a known emerging
resistance mechanism for first generation irreversible BTK inhibitors.
ARQ 531 has high oral bioavailability as well as good ADME,
pharmacokinetic and metabolic properties. The company plans to file an
IND for ARQ 531 in early 2017. BTK is a therapeutic target that has been
clinically proven to inhibit B-cell receptor signaling in blood cancers.
is a biopharmaceutical company engaged in the research and development
of targeted therapeutics to treat cancers and rare diseases. Our mission
is to discover, develop and commercialize novel small molecule drugs in
areas of high unmet need that will dramatically extend and improve the
lives of our patients. Our clinical-stage pipeline consists of five drug
candidates, all of which are in targeted, biomarker-defined patient
populations, making ArQule
a leader among companies our size in precision medicine. ArQule's lead
product, in phase 3 clinical development, is tivantinib (ARQ 197), an
oral, selective inhibitor of the c-MET receptor tyrosine kinase, for
second-line treatment of hepatocellular carcinoma in partnership with
Daiichi Sankyo in the West and Kyowa Hakko Kirin in Asia. ArQule's
proprietary pipeline includes: ARQ 087, a multi-kinase inhibitor
designed to preferentially inhibit the fibroblast growth factor receptor
(FGFR) family, in phase 2 for iCCA and in phase 1b for multiple oncology
indications; ARQ 092, a selective inhibitor of the AKT serine/threonine
kinase, in phase 1 for multiple oncology indications as well as
ultra-rare Proteus syndrome, in partnership with the National Institutes
of Health (NIH); ARQ 751, a next generation AKT inhibitor, in phase 1
for patients with AKT1 and PI3K mutations; and ARQ 761, a β-lapachone
analog being evaluated as a promoter of NQO1-mediated programmed cancer
cell necrosis, in phase 1/2 in multiple oncology indications in
partnership with the University of Texas Southwestern Medical Center. In
addition, we have advanced ARQ 531, an investigational, orally
bioavailable, potent and reversible inhibitor of both wild type and
C481S-mutant BTK, into toxicology testing and plan to file an
Investigational New Drug Application in early 2017. ArQule's current
discovery efforts are focused on the identification and development of
novel kinase inhibitors, leveraging the Company's proprietary library of
compounds. You can follow us on Twitter
This press release contains forward-looking statements regarding
preclinical experiments and planned clinical trials with ARQ 531. These
statements are based on the Company's current beliefs and expectations,
and are subject to risks and uncertainties that could cause actual
results to differ materially. Positive information about
pre-clinical results does not ensure that clinical trials will be
successful. For example, ARQ 531 may not demonstrate promising
therapeutic effect in man; in addition, and ARQ 531 may not exhibit an
adequate safety profile in ongoing toxicology testing and may not
demonstrate appropriate safety in planned, current or later stage or
larger scale clinical trials as a result of known or as yet
unanticipated side effects. The results achieved in later stage trials
may not be sufficient to meet applicable regulatory standards or to
justify further development. Problems or delays may arise during
clinical trials or in the course of developing, testing or manufacturing
these compounds that could lead the Company to discontinue development.
Even if later stage clinical trials are successful, unexpected concerns
may arise from subsequent analysis of data or from additional data.
Obstacles may arise or issues may be identified in connection with
review of clinical data with regulatory authorities. Regulatory
authorities may disagree with the Company's view of the data or require
additional data or information or additional studies. Drug development
involves a high degree of risk. Only a small number of research and
development programs result in the commercialization of a product.
Furthermore, ArQule may not have the financial or human resources to
successfully pursue drug discovery in the future. For more detailed
information on the risks and uncertainties associated with the Company's
drug development and other activities, see the Company's periodic
reports filed with the Securities and Exchange Commission. The Company
does not undertake any obligation to publicly update any forward-looking
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Dawn Schottlandt, 781-994-0300
Investor Relations/Corp. Communications
Source: ArQule, Inc.
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