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ArQule Announces Clinical Proof-of-Concept Data from Ongoing Phase 1 Study of Reversible BTK Inhibitor, ARQ 531, in Patients with Relapsed/Refractory Hematologic Malignancies at the 2019 EHA Annual Meeting

June 14, 2019 Off By BusinessWire

-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

BURLINGTON, Mass.–(BUSINESS WIRE)–$ARQL #arql–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, Waldenström
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 C_min
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 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 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 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 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 Statements
This 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.