Data Presented at European Cancer Congress Suggest Clinical Benefit of Tivantinib in Patients with MET High Non-Squamous Non

  Data Presented at European Cancer Congress Suggest Clinical Benefit of
  Tivantinib in Patients with MET High Non-Squamous Non-Small Cell Lung Cancer

    Treatment with tivantinib and erlotinib improved overall survival and
 progression free survival in key sub-group of patients from Phase 3 MARQUEE
                                    trial

ECC 2013

Business Wire

WOBURN, Mass. -- September 30, 2013

Data presented at the European Cancer Congress demonstrated clinical benefits
of treatment with the combination of tivantinib and erlotinib in patients with
non-squamous, non-small cell lung cancer (NSCLC) whose tumors expressed high
levels of MET protein (Abstract number 3410, MARQUEE: a randomized,
double-blind, placebo-controlled, phase 3 trial of tivantinib [ARQ 197] plus
erlotinib versus placebo plus erlotinib in previously treated patients with
locally advanced or metastatic, non-squamous, non-small cell lung cancer).

In the intent-to-treat (ITT) population of 1048 patients in MARQUEE, median
overall survival (OS) in the treatment arm of tivantinib plus erlotinib was
8.5 months versus 7.8 months in the erlotinib only control arm (hazard ratio =
0.98, p = 0.81), while median progression free survival (PFS) was 3.6 months
in the treatment arm versus 1.9 months in the control arm (hazard ratio =
0.74, p < 0.001). Objective response rate (ORR) was 10.3 percent in the
treatment arm compared to 6.5 percent in the control arm.

Median OS for patients with MET High NSCLC in the treatment arm was 9.3 months
compared to 5.9 months in the control arm (hazard ratio = 0.70, p = 0.03), and
median PFS for the treatment arm was 3.6 months compared to 1.9 months for the
control arm (hazard ratio = 0.72, p = 0.01). ORR was 10.6 percent for patients
with MET-high NSCLC in the treatment arm versus 6.5 percent in the control
arm.

Median OS for patients with MET Low NSCLC in the treatment arm was 8.5 months
compared to 7.7 months in the control arm (hazard ratio = 0.90, p = 0.53), and
median PFS for the treatment arm was 3.7 months compared to 1.9 months for the
control arm (hazard ratio = 0.66, p = 0.006). ORR was 11.2 percent for
patients with MET-low NSCLC in the treatment arm versus 5.5 percent in the
control arm.

“The final data analyses from the MARQUEE trial demonstrate the substantial
impact of tivantinib treatment for MET High NSCLC, as measured primarily by
improvements in OS and PFS,” said Professor Giorgio Scagliotti, MD, PhD, Head
of the Department of Clinical and Biological Sciences at S. Luigi Hospital,
Orbassano (Torino). “Patients with MET Low disease, on the other hand, did not
experience significantly improved OS despite their increased PFS. These
findings represent intriguing signals of clinical benefit among a
pre-specified sub-group within the broad population of non-squamous NSCLC
patients in this trial. We believe they underscore the therapeutic effects of
MET inhibition with tivantinib in patients with tumors expressing high levels
of MET protein.”

The overall safety profile among patients receiving tivantinib (360 milligrams
twice daily) and erlotinib (150 milligrams daily) was manageable and
consistent with findings at the interim analysis.

MET protein expression was measured using immunohistochemistry. Patients
classified as MET-high had 50 percent or more of tumor tissue stained with an
intensity of 2+ and/or 3+, and the MET analysis must have taken place within
90 days following tissue sectioning. Of the 1048 patients in the trial, 445
were evaluable for MET status. Patients with MET-high NSCLC numbered 211, and
the number with MET-low disease was 234.

The MARQUEE trial was stopped in the fall of 2012 after a planned interim
analysis. Data analyzed at that time showed significant improvement in the
secondary endpoint of PFS but not in the primary endpoint of OS in the broad
ITT population. Following the interim analysis, treatment in the trial was
allowed to be continued in patients whose disease had not yet progressed. The
data cut-off for full study analysis was December 15, 2012.

Additional data on other molecular subgroups enrolled in MARQUEE are planned
for presentation at an upcoming peer-reviewed forum.

About the MARQUEE trial

The MARQUEE trial was a randomized, double-blinded, controlled Phase 3 study
of previously treated patients with locally advanced or metastatic,
non-squamous NSCLC who received tivantinib plus erlotinib or placebo plus
erlotinib. The primary objective was to evaluate OS in the ITT population.
Secondary endpoints included OS in the subpopulation of patients with
epidermal growth factor receptor (EGFR) wild type, PFS in the ITT population,
and further assessment of the safety of tivantinib in combination with
erlotinib. The trial was conducted under a Special Protocol Assessment
agreement with the U.S. Food and Drug Administration.

About MET and Tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor
tyrosine kinase, which is currently in Phase 2 and Phase 3 clinical trials. In
certain healthy adult cells, MET is present in low to normal levels to support
natural cellular function, but in some cancer cells, MET is inappropriately
and continuously activated. When abnormally activated, MET plays multiple
roles in aspects of human cancer, including cancer cell growth, survival,
angiogenesis, invasion and metastasis. The activation of certain cell
signaling pathways, including MET, has also been associated with the
development of resistance to EGFR (epidermal growth factor receptor)
inhibitors such as erlotinib.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in
a range of human tumor cell lines and shows anti-tumor activity against
several human tumor xenografts. In clinical trials to date, treatment with
tivantinib has been generally well tolerated and has shown clinical activity
in the tumors studied. Tivantinib has not yet been approved for any indication
in any country.

About ArQule, Inc. and Daiichi Sankyo, Co., Ltd.

On December 19, 2008, ArQule and Daiichi Sankyo, Co., Ltd. signed a license,
co-development and co-commercialization agreement to co-develop tivantinib in
the U.S., Europe, South America and the rest of the world, excluding Japan,
China (including Hong Kong), South Korea and Taiwan, where Kyowa Hakko Kirin
Co., Ltd. has exclusive rights for development and commercialization.

About ArQule

ArQule is a biotechnology company engaged in the research and development of
next-generation, small-molecule cancer therapeutics. The Company’s targeted,
broad-spectrum products and research programs are focused on key biological
processes that are central to human cancers. ArQule’s lead product, in Phase 2
and Phase 3 clinical development, is tivantinib (ARQ 197), an oral, selective
inhibitor of the c-MET receptor tyrosine kinase. The Company’s pipeline
includes: ARQ 092, designed to inhibit the AKT serine/threonine kinase; ARQ
087, designed to inhibit fibroblast growth factor receptor (FGFR); ARQ 621,
designed to inhibit the Eg5 kinesin motor protein; and ARQ 736, designed to
inhibit the RAF kinases. ArQule’s current discovery efforts, which are based
on the ArQule Kinase Inhibitor Platform (AKIP™), are focused on the
identification of novel kinase inhibitors that are potent, selective and do
not compete with ATP (adenosine triphosphate) for binding to the kinase.

This press release contains forward-looking statements regarding the Company’s
clinical trials with tivantinib (ARQ 197) and its ability to fund operations
with current cash and marketable securities. 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 and early stage clinical trial results does not
ensure that later stage or larger scale clinical trials will be successful.
For example, tivantinib may not demonstrate promising therapeutic effects; in
addition, it may not demonstrate appropriate safety profiles 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 during clinical trials or in the
course of developing, testing or manufacturing tivantinib that could lead the
Company or its partners 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. In
addition, the planned timing of initiation and completion of clinical trials
for tivantinib is subject to the ability of the Company as well as Daiichi
Sankyo, Inc. and Kyowa Hakko Kirin, a licensee of tivantinib, 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. Drug development involves a high
degree of risk. Only a small number of research and development programs
result in the commercialization of a product. Positive pre-clinical data may
not be supported in later stages of development. Furthermore, ArQule may not
have the financial or human resources to successfully pursue drug discovery in
the future. Moreover, with respect to partnered programs, even if certain
compounds show initial promise, Daiichi Sankyo or Kyowa Hakko Kirin may decide
not to license or continue to develop them, as the case may be. In addition,
Daiichi Sankyo and Kyowa Hakko Kirin have certain rights to unilaterally
terminate their agreements with ArQule. If either company were to do so, the
Company might not be able to complete development and commercialization of the
applicable licensed products on its own. 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.

Contact:

ArQule
William B. Boni, 781-994-0300
VP, Investor Relations/Corp. Communications
www.ArQule.com