ArQule Announces Clinical Data from Ongoing Phase 1 Study of Reversible BTK Inhibitor, ARQ 531, in Patients with Relapsed/Refractory Hematologic Malignancies at the 2018 ASH Annual Meeting

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-ARQ 531 demonstrates anti-tumor activity and favorable safety profile
-Dose escalation to continue
– Call with management scheduled for 12/3 at 9:00 ET to discuss the
ArQule, Inc. (Nasdaq: ARQL) yesterday presented 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 2018 American Society of
Hematology (ASH) Annual Meeting in San Diego.

Dr. Brian Schwartz, Chief Medical Officer of ArQule commented, “We are
encouraged by the pace at which this trial is progressing and by the
level of target engagement we are observing as we continue to dose
escalate. Four out of the five heavily pretreated CLL patients enrolled
in the last two cohorts with the BTK-C481S mutation have experienced
tumor shrinkage.”

“These data provide further evidence of ARQ 531’s potential to become a
new therapeutic option for patients with B cell malignancies,” commented
Paolo Pucci, Chief Executive Officer of ArQule. “There is significant
unmet need for patients with relapsed or refractory B-cell malignancies
in particular those with the C481S-mediated resistance to irreversible
BTK inhibitors such as ibrutinib.”

The reported data are from the ongoing Phase 1, open label, single arm
dose escalation 3+3 study and include the first six cohorts (n=20) at
dose levels of 5, 10, 15, 20, 30 and 45 mg once a day in patients with
relapsed or refractory chronic lymphocytic leukemia (CLL), small
lymphocytic leukemia (SLL), Waldenstrom’s macroglobinemia and B-cell
Non-Hodgkin lymphomas.

Key findings presented include the following:

ARQ 531 has demonstrated a manageable safety profile with no
dose-limiting toxicities observed to date

Pharmacokinetic data are nearly dose proportional with a mean plasma
half-life that supports QD dosing

Pharmacodynamic biomarkers for cohorts 4 through 6 showed profound
pBTK inhibition

Anti-tumor activity, with reduction of tumor burden, was observed in 9
out of 20 patients

At the first assessment of tumor response, 80% of the ibrutinib
refractory, heavily pretreated CLL patients (4 out of 5) in the
highest dose cohorts (30 and 45 mg) experienced tumor shrinkages

Four out of 5 lymphoma patients derived benefit with shrinkages
between 27 and 58%, including 1 PR in a Follicular Lymphoma
patient who began at 5 mg, was dose escalated to 15 and then 45
mg, and remains on therapy after 70 weeks

The study is on-going and dose escalation continues

The presented poster, A Phase 1 Dose Escalation Study of ARQ 531 in
Selected Patients with Relapsed or Refractory Hematologic Malignancies,
is available on the company’s website at

The Company will hold a conference call and webcast today at 9:00 a.m.
ET to discuss these results. The live webcast can be accessed in the
“Investors and Media” section of our website,,
under “Events
& Presentations.” You may also listen to the call by dialing
(877) 868-1831 within the U.S. or (914) 495-8595 outside the U.S. A
replay will be available two hours after the completion of the call and
can be accessed in the “Investors & Media” section of our website,,
under “Events
and 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 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. ArQule’s current discovery efforts are
focused on the identification and development of novel kinase
inhibitors, leveraging the Company’s proprietary library of compounds.

Forward Looking Statements
This press release contains forward-looking statements, including
without limitation those regarding the current clinical trial 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

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Source: ArQule, Inc.
Corporate Contact:Marc Schegerin, M.D.Senior Vice
PresidentHead of Strategy, Finance and Communicationir@arqule.comMedia
Contact:Allison Blum, Ph.D.LifeSci Public Relations

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2018-12-04 05:11:27