ArQule Presents Results from Ongoing Phase 1 Dose Escalation Study of its Reversible BTK Inhibitor, ARQ 531

ArQule, Inc. (Nasdaq:ARQL) today is presenting preliminary results from
the Company’s Phase 1 dose escalation study for ARQ 531, an orally
bioavailable, potent and reversible inhibitor of both wild type and
C481S-mutant Bruton’s tyrosine kinase (BTK) in patients with relapsed or
refractory hematologic malignancies at the 23rd Congress of European
Hematological Association (EHA) in Stockholm, Sweden.

“Preliminary data from our Phase 1 dose escalation trial highlights the
potential of ARQ 531 to become a new therapeutic option for patients
with B-cell malignancies,” commented ArQule Chief Medical Officer and
Head of Research and Development, Brian Schwartz, M.D. “There is a
significant unmet need for patients with relapsed or refractory B-cell
malignancies, in particular those with C481S-mediated resistance to
irreversible BTK inhibitors such as ibrutinib. We are especially
encouraged by the early signs of anti-tumor activity observed in the
first three cohorts.”

The reported data from the ongoing Phase 1, open label, single arm dose
escalation 3+3 study are from the first three cohorts at dose levels of
5 (n=3), 10 (n=4) and 15 mg (n=4) in patients with relapsed or
refractory chronic lymphocytic leukemia (CLL), small lymphocytic
leukemia (SLL), Waldenstrom’s macroglobinemia and B-cell Non-Hodgkin

ARQ 531 demonstrated preliminary anti-tumor activity at all dose levels,
resulting in an observed tumor reduction of 35% at 5mg, 33% at 10mg, and
29% at 15mg doses. The 29% tumor reduction in the 15mg cohort was
achieved after 8 weeks of treatment in a patient with the BTK
C481S-mutation, after 5 prior systemic regimens including ibrutinib and
venetoclax, with treatment still ongoing. Overall treatment duration
ranged from 1 to 46 weeks with 4 of 11 patients treated still ongoing.

ARQ 531 was well tolerated at all three dose levels, supporting
continued dose escalation. No dose limiting toxicities or ARQ
531-related Grade 3 or greater adverse events were observed, and the
maximum tolerated dose has not been reached.

The half-life of ARQ 531 was between 22-27 hours suggesting the
potential for sustained target inhibition and supporting a once daily
dosing regimen with preliminary pharmacokinetics showing increases in
exposure that are approximately dose proportional.

The poster, A Phase 1 Dose Escalation Study of ARQ 531 in Selected
Patients with Relapsed or Refractory Hematologic Malignancies, is
available on ArQule’s website, www.arqule.com,
under “Publications and Presentations”: https://www.arqule.com/publications-presentations/.

About BTK and ARQ 531

Bruton’s tyrosine kinase, BTK, is a therapeutic target that has been
clinically proven to inhibit B-cell receptor signaling in blood cancers.
ARQ 531 is an orally bioavailable, potent and reversible 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 resistance mechanism for first generation irreversible BTK
inhibitors. In preclinical studies, ARQ 531 has demonstrated good oral
bioavailability as well as favorable pharmacokinetic, pharmacodynamic
and metabolic properties.

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 pipeline includes:
ARQ 531, an 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; Miransertib (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), and in Phase 1b in combination with the
hormonal therapy, anastrozole, in patients with advanced endometrial
cancer; ARQ 751 a next generation AKT inhibitor, in Phase 1 for patients
with AKT1 and PI3K mutations; Derazantinib, a multi-kinase inhibitor
designed to preferentially inhibit the fibroblast growth factor receptor
(FGFR) family, in a registrational trial for iCCA; and ARQ 761, a
?-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. 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, including
without limitation those regarding current 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 from those set
forth in this press release. Positive information about early stage
clinical trial results does not ensure that later stage or larger scale
clinical trials will be successful. For example, ARQ 531 may not
demonstrate promising therapeutic effect; in addition, it may not
demonstrate an appropriate safety profile in 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 prior to the
initiation of planned clinical trials, during clinical trials or in the
course of developing, testing or manufacturing 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 or
its collaborators’ view of data or require additional data or
information or additional studies. In addition, the planned timing of
completion of clinical trials is subject to the ability of the Company
and, in certain cases, its collaborators to enroll patients, enter into
agreements with clinical trial sites and investigators, and overcome
technical hurdles and other issues related to the conduct of the trials
for which each of them is responsible. There is a risk that these issues
may not be successfully resolved. In addition, we expect to utilize
diagnostic tools in ongoing and future biomarker-guided clinical trials
with ARQ 531. We or our collaborators may encounter difficulties in
developing and obtaining approval for companion diagnostics, including
issues relating to access to certain technologies,
selectivity/specificity, analytical validation, reproducibility, or
clinical validation. Any delay or failure by our collaborators or us to
develop or obtain regulatory approval of companion diagnostics could
delay or prevent approval of our product candidates. 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, financial condition 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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