ArQule Announces First Patient Dosed in Phase 1 Trial of BTK Inhibitor, ARQ 531, for B-cell
Malignancies
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.
ArQule, Inc.
Dawn Schottlandt, 781-994-0300
Vice President, Investor Relations/Corp. Communications
www.ArQule.com
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