ArQule Announces First Patient Dosed in Phase 1 Trial of BTK Inhibitor, ARQ 531, for B-cell Malignancies
July 11 2017 - 7:00AM
Business Wire
Trial is enrolling patients refractory to
standard of care, including ibrutinib
ArQule, Inc. (Nasdaq: ARQL) today announced that the first
patient has been dosed in a phase 1a/b trial with its BTK
inhibitor, ARQ 531, in patients with B-cell malignancies refractory
to other approved therapies. The trial can enroll up to 120
patients. ARQ 531 is an investigational, orally bioavailable,
potent and reversible inhibitor of both wild type and C481S-mutant
Bruton’s tyrosine kinase (BTK).
The phase 1 trial is designed to enroll patients with B-cell
malignancies including B-cell lymphomas, chronic lymphocytic
leukemia, and Waldenstrom’s macroglobulinemia. The phase 1a portion
of the trial will be a dose escalation study open to all refractory
patients, with the aim of establishing a recommended dose. Upon
completion of the phase 1a trial, the company plans to begin the
phase 1b portion of trial that will consist of a number of
expansion cohorts including patients with the C481S mutation who
are refractory to other approved therapies. The goal of the phase
1b portion would be to establish proof of concept and early signs
of activity.
“There is a clear clinical need to address the refractory
population in B-cell malignancies, particularly those with the BTK
C481S mutation,” said Dr. Brian Schwartz, M.D., Head of Research
and Development and Chief Medical Officer at ArQule. “Our clinical
strategy is to rapidly identify a recommended dose and then begin
to enroll a number of expansion cohorts including one dedicated to
patients with the C481S mutation.”
B-cell malignancies, like chronic lymphocytic leukemia,
Waldenstrom’s macroglobulinemia, diffuse large B-cell lymphoma and
mantle cell lymphoma are driven by BTK. The only approved BTK
inhibitor, ibrutinib, is irreversible and makes a covalent bond
with the C481 residue of the targeted protein. Although ibrutinib
has demonstrated excellent responses in patients with elevated
B-cell receptor signaling, clinical resistance has been observed,
and the BTK C481S mutation is emerging as a predominant mechanism
of resistance. As a reversible inhibitor, ARQ 531 does not require
interaction with the C481 residue, a binding site essential for
irreversible ibrutinib binding to BTK, thus positioning ARQ 531 as
a targeted therapy for patients harboring C481S-mutant BTK who have
developed resistance to irreversible BTK inhibitors.
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 531 inhibits 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. In preclinical studies ARQ 531 has demonstrated high
oral bioavailability as well as good ADME, pharmacokinetic and
metabolic properties. A phase 1 trial commenced in the third
quarter of 2017. BTK is a therapeutic target that has been
clinically proven to inhibit B-cell receptor signaling in blood
cancers.
About ArQule
ArQule is a biopharmaceutical company engaged in the research
and development of targeted therapeutics to treat cancers and rare
diseases. ArQule’s 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 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 a phase
1/2 company sponsored study for Overgrowth Diseases, in a phase 1
study for ultra-rare Proteus syndrome conducted by the National
Institutes of Health (NIH), as well as in multiple oncology
indications; 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, in phase 1 for
patients with B-cell malignancies refractory to other therapeutic
options. 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 and LinkedIn.
Forward Looking Statements
This press release contains forward-looking statements regarding
preclinical experiments and 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, it may not
exhibit an adequate safety profile in planned 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 ARQ 531 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. 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 statements.
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version on businesswire.com: http://www.businesswire.com/news/home/20170711005306/en/
ArQule, Inc.Dawn Schottlandt, 781-994-0300Vice President,
Investor Relations/Corp. Communicationswww.ArQule.com
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