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

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

ArQule And Daiichi Sankyo Present Final Phase 2 Results For ARQ 197 C-Met Inhibitor in Non-Small Cell Lung Cancer at ASCO

Woburn, Massachusetts and Tokyo, June 7, 2010 (ots/PRNewswire)

ArQule,
Inc.  and Daiichi Sankyo Co., Ltd. (TSE 4568) today announced the
presentation of data from a Phase 2 clinical trial at the 2010 Annual
Meeting of the American Society of Clinical Oncology (ASCO) showing
encouraging overall survival (OS) results with ARQ 197 in combination
with erlotinib among patients with advanced, refractory non-small
cell lung cancer.
One hundred sixty-seven patients participated in this Phase 2,
double-blind, randomized, signal generation trial. All patients were
EGFR (epidermal growth factor receptor) inhibitor-naïve, but had
progressed after at least one prior chemotherapy regimen. Patients
were randomized one-to-one to receive either the combination of ARQ
197 plus erlotinib or placebo plus erlotinib. The primary endpoint of
the study was comparison of Progression-Free Survival (PFS) between
treatment arms; secondary endpoints included PFS in pre-defined
patient subsets, overall survival, overall response rate, and safety.
The ASCO presentation (Abstract No: LBA7502), given by Joan H.
Schiller, M.D., Chief, Division of Hematology and Oncology at the
University of Texas Southwestern Medical Center, included data
showing that median OS in the intent to treat (ITT) population (n =
167) was 36.6 weeks in the ARQ 197 plus erlotinib arm, compared with
29.4 weeks in the erlotinib plus placebo arm, an improvement of 24
percent (unadjusted hazard ratio = 0.88, p = 0.50) as one of the
secondary endpoints.
In the pre-defined sub-group of patients with non-squamous cell
carcinoma histology (n = 117), median OS was 43.1 weeks in the
treatment arm, compared with 29.4 weeks in the placebo arm, an
improvement of 47 percent (unadjusted hazard ratio = 0.72, p = 0.19).
Based on an exploratory Cox regression analysis, the difference in
median OS achieved statistical significance (p < 0.05) in this
sub-group when adjusting for imbalances in key prognostic factors
that included EGFR status and KRAS status, both of which favored the
placebo arm.
As previously announced, the ARQ 197 plus erlotinib combination
demonstrated a 66 percent improvement in the primary endpoint, median
Progression-Free Survival (PFS), although the difference in PFS
between the two arms did not achieve statistical significance (p =
0.24, hazard ratio = 0.81) by applying a log-rank test. Improvement
in median PFS was more pronounced in the pre-defined sub-group of
patients with non-squamous histology (n = 117).
"These data from a well controlled trial signal potential patient
benefit, with promising overall survival and prolonged
progression-free survival," said Dr. Schiller. "In addition, the
combination of ARQ 197 plus erlotinib was shown to be well tolerated,
with manageable side effects similar to erlotinib alone."
The trial design allowed patients who failed on erlotinib
monotherapy to cross over into the erlotinib plus ARQ 197 arm. Of the
23 cross-over patients who were evaluable for response, two had a
partial response per Response Evaluation Criteria in Solid Tumors
(RECIST) and nine had stable disease.
"These OS results are consistent with the previously reported PFS
findings in both the ITT population and patients with non-squamous
histology, which gives us additional confidence in the strength of
the signal in this trial," said Glenn Gormley, MD, PhD, Chief
Scientific Officer & President, Daiichi Sankyo Pharma Development.
"The full set of data will now help guide planning for next-stage
clinical development activities, as well as discussions with
regulatory authorities."
About c-Met and ARQ 197
ARQ 197 is an orally available, small molecule inhibitor of the
c-Met receptor tyrosine kinase. Erlotinib, marketed as Tarceva(TM),
is an inhibitor of the EGFR tyrosine kinase.
ARQ 197 is also currently being evaluated in clinical trials as a
single agent and in combination with other anti-cancer therapies in a
number of indications, including c-Met-associated soft-tissue
sarcomas, hepatocellular carcinoma, pancreatic adenocarcinoma, germ
cell tumors and colorectal cancer.
The American Cancer Society's estimates of the impact of lung
cancer in the U.S. during 2009 include approximately 219,000 new
cases (both non-small cell and small cell) and 159,000 deaths
resulting from the disease, accounting for 28 percent of all cancer
deaths. Lung cancer is the leading cause of cancer death among both
men and women.
When abnormally activated, the c-Met receptor tyrosine kinase
plays multiple roles in aspects of human cancer, including cancer
cell growth, survival, angiogenesis, invasion and metastasis.
Pre-clinical data have demonstrated that ARQ 197 inhibits c-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 ARQ 197 has been well tolerated and has
resulted in tumor responses and prolonged stable disease across broad
ranges of tumors and doses.
On December 19, 2008, ArQule and Daiichi Sankyo, Co., Ltd. signed
a license, co-development and co-commercialization agreement to
co-develop ARQ 197 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 clinical development, is
ARQ 197, an inhibitor of the c-Met receptor tyrosine kinase. The
Company is also conducting Phase 1 clinical testing with ARQ 621,
designed to inhibit the Eg5 kinesin motor protein. The Company's
pre-clinical pipeline includes a compound designed to inhibit the
B-RAF kinase. ArQule's current discovery efforts, which are based on
the ArQule Kinase Inhibitor Platform (AKIP(TM)), 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. The most advanced AKIP(TM) program is focused on the
discovery of inhibitors of fibroblast growth factor receptor (FGFR).
About Daiichi Sankyo
The Daiichi Sankyo Group is dedicated to the creation and supply
of innovative pharmaceutical products to address the diversified,
unmet medical needs of patients in both mature and emerging markets.
While maintaining its portfolio of marketed pharmaceuticals for
hypertension, hyperlipidemia, and bacterial infections, the Group is
engaged in the development of treatments for thrombotic disorders and
focused on the discovery of novel oncology and
cardiovascular-metabolic therapies. Furthermore, the Daiichi Sankyo
Group has created a "Hybrid Business Model," which will respond to
market and customer diversity and optimize growth opportunities
across the value chain. For more information, please visit
http://www.daiichisankyo.com.
Daiichi Sankyo, Inc., headquartered in Parsippany, New Jersey, is
a member of the Daiichi Sankyo Group. For more information on Daiichi
Sankyo, Inc., please visit http://www.dsi.com.
This press release contains forward-looking statements regarding
the progress of the Company's clinical trials, including its Phase 2
trial with ARQ 197 in non-small cell lung cancer (NSCLC) and trials
which may be conducted by Daiichi Sankyo and/or Kyowa Hakko Kirin
under their agreements with the Company. 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 early stage clinical trial
results is not necessarily indicative of clinical efficacy and does
not ensure that later stage or larger scale clinical trials will be
successful. For example, ARQ 197 may not demonstrate promising
therapeutic effect; in addition, this compound may not demonstrate an
appropriate safety profile in further pre-clinical testing and in
current, 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. Problems or delays may arise during clinical
trials or in the course of developing, testing or manufacturing these
compounds that could lead the Company or its partner to discontinue
development. Even if later stage clinical trials are successful, the
risk exists that unexpected concerns may arise from analysis of data
or from additional data or that obstacles may arise or issues be
identified in connection with review of clinical data with regulatory
authorities or that regulatory authorities may disagree with the
Company's view of the data or require additional data, information or
studies. In addition, the planned timing of initiation and completion
of clinical trials for ARQ 197 are subject to the ability of the
Company or Daiichi Sankyo, its partner, and Kyowa Hakko Kirin, a
licensee of ARQ 197, to enroll patients, enter into agreements with
clinical trial sites and investigators, and other technical hurdles
and issues that may not be resolved. Moreover, Daiichi Sankyo has
certain rights to unilaterally terminate the ARQ 197 license,
co-development and co-commercialization agreement. Drug development
involves a high degree of risk. 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
pursue drug discovery successfully in the future. 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:

CONTACT: Contact: William B. Boni, ArQule, Inc., VP,
InvestorRelations/Corp. Communications, +1(781)-994-0300,
http://www.ArQule.com,Dr. Michaela Paudler-Debus, DAIICHI SANKYO
EUROPE GmbH, CorporateCommunications and Public Affairs,
+49(0)-89-7808-685; Patients,physicians and other healthcare
professionalsseeking additional information regarding trials
involving ARQ 197 may call+1-800-373-7827.