ArQule Announces Clinical Proof-of-Concept Data from Ongoing Phase 1 Study of Reversible BTK Inhibitor, ARQ 531, in Patients ...
June 14 2019 - 3:30AM
Business Wire
-ARQ 531 demonstrates substantial anti-tumor
activity and favorable safety profile
-Four of six evaluable CLL patients, all with
the BTK-C481S mutation, from cohort 7 (65 mg) experienced a Partial
Response
-Partial Response also observed in the study’s
first Richter’s Transformation patient
-Call with management and Dr. Jennifer Woyach,
Principal Investigator, scheduled for today, June 14, at 8:00 am
EDT to discuss these results
ArQule, Inc. (Nasdaq: ARQL) today announced preliminary results
from the Company’s phase 1 dose escalation study for ARQ 531, an
orally bioavailable, potent and reversible dual inhibitor of both
wild type and C481S-mutant Bruton’s tyrosine kinase (BTK) in
patients with relapsed or refractory hematologic malignancies at
the 2019 European Hematology Association (EHA) Annual Meeting in
Amsterdam, the Netherlands.
“The profile of ARQ 531 continues to strengthen, and we are
delighted to be able to demonstrate such compelling clinical
activity at a well-tolerated dose in patients who have already
exhausted available therapies,” commented Dr. Brian Schwartz, Chief
Medical Officer of ArQule. “We are now focused on finalizing the
recommended phase 2 dose and planning for the expansion of our
clinical efforts with ARQ 531 into later stage trials across
multiple indications as a single agent and as a combination
therapy.”
“ARQ 531 was selected and extensively tested preclinically to
address the emerging therapeutic need for patients who have become
resistant to covalent BTK inhibitors,” commented Dr. Jennifer
Woyach, Associate Professor of Medicine at The Ohio State
University and the Principal Investigator of the study. “The data
presented in this poster provide compelling clinical
proof-of-concept for this novel class of reversible BTK inhibitors
and was predicted by the preclinical studies published in Cancer
Discovery1 last year.”
The reported data are from the ongoing phase 1, open label,
single arm dose escalation study and include the first eight
cohorts (n=34) at dose levels of 5, 10, 15, 20, 30, 45, 65 and 75
mg once a day in patients with relapsed or refractory chronic
lymphocytic leukemia (CLL), small lymphocytic leukemia (SLL),
Richter’s Transformation, Waldenstr�m macroglobulinemia and other
B-cell Non-Hodgkin lymphomas. Cohort 8 (75 mg) enrollment is
ongoing.
Key findings presented include the following:
- ARQ 531 is well-tolerated through 65 mg
QD
- Pharmacokinetic data demonstrate a
steady-state mean Cmin of above 1 µM in patients receiving ≥45 mg
QD. The plasma half-life ranges from 20-30 hours
- Pharmacodynamic data at doses above
20-30 mg QD is associated with complete pBTK inhibition and
substantial CCL3 suppression
- Robust, dose-dependent, anti-tumor
activity was observed
- ORR of 66% (4 responses in 6 evaluable
patients) was observed in heavily pretreated R/R CLL patients, all
with the BTK-C481S mutation, from cohort 7
- A partial response was observed in the
first patient with Richter’s Transformation, who had progressed on
ibrutinib and R-CHOP, suggesting that ARQ 531’s distinct MOA is
amenable to target this highly unmet medical need
- A Follicular Lymphoma patient remains a
confirmed PR and has been on therapy approximately two years,
providing valuable initial insights into long- term safety as well
as durability of response
The poster at EHA presenting these data entitled, “A Phase 1
Dose Escalation Study of ARQ 531 in Patients with Relapsed or
Refractory B-Cell Lymphoid Malignancies,” is available on the
company’s website at
www.arqule.com/publications-presentations/.
ArQule will host a conference call and webcast for investors on
Friday, June 14, 2019 at 8:00 a.m. EDT to discuss the ARQ 531
clinical data. The live webcast can be accessed in the “Investors
and Media” section of our website, www.arqule.com, under
“Events & Presentations” or by clicking here. You may also
listen to the call by dialing 1-800-239-9838 within the U.S. or
1-323-794-2551 outside the U.S. and providing conference ID
3110780. 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, www.arqule.com, under “Events and
Presentations.”
About BTK and ARQ 531Bruton’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 dual inhibitor of both wild
type and C481S-mutant BTK. The C481S-mutation is a known resistance
mechanism for first generation irreversible BTK inhibitors. ARQ 531
has demonstrated a good safety profile, predictable PK, profound
pharmacodynamic effects and emerging signs of dose-proportional
clinical activity in phase 1 clinical testing.
About ArQuleArQule 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 four 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 dual 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 potent and selective inhibitor of the AKT
serine/threonine kinase, in a planned registrational trial with
cohorts in Proteus syndrome and PROS to initiate in 2019, and in
phase 1b in combination with the hormonal therapy, anastrozole, in
patients with advanced endometrial cancer; ARQ 751, a next
generation highly potent and selective AKT inhibitor, in phase 1
for patients with AKT1 and PI3K mutations; and derazantinib, a
multi-kinase inhibitor designed to preferentially inhibit the
fibroblast growth factor receptor (FGFR) family, in a
registrational trial for iCCA in collaboration with Basilea and
Sinovant. ArQule’s current discovery efforts are focused on the
identification and development of novel kinase inhibitors,
leveraging the Company’s proprietary library of compounds.
1Reiff et al. The BTK Inhibitor ARQ 531 Targets
Ibrutinib-Resistant CLL and Richter Transformation. Cancer
Discovery. 2018, 8:1300-1315
Forward Looking StatementsThis press release contains
forward-looking statements, including without limitation those
regarding the current clinical trial with ARQ 531 and plans for
future trials. 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 adequate 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 current or
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 or
intellectual property, 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 diagnostic could delay or prevent approval of
ARQ 531. 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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version on businesswire.com: https://www.businesswire.com/news/home/20190614005037/en/
Corporate Contact:Kathleen FarrenInvestor Relations&
Executive Assistant to the CFOir@arqule.comMedia
Contact:Cait Williamson, Ph.D.LifeSci Public Relations(646)
751-4366cait@lifescipublicrelations.comwww.ArQule.com
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