Daiichi Sankyo and ArQule Enroll First Hepatocellular Carcinoma Patient into Global Phase 3 Trial for Tivantinib

  Daiichi Sankyo and ArQule Enroll First Hepatocellular Carcinoma Patient into
  Global Phase 3 Trial for Tivantinib

Business Wire

TOKYO & WOBURN, Mass. -- January 31, 2013

Daiichi Sankyo Company, Limited (TSE 4568) and ArQule, Inc. (Nasdaq: ARQL)
today announced that the first patient has been enrolled in the pivotal Phase
3 METIV-HCC (MET-high patients with tivantinib in HCC) trial of tivantinib
(ARQ 197). Tivantinib, an investigational selective inhibitor of MET, a
receptor tyrosine kinase, is being evaluated for the treatment of patients
diagnosed with hepatocellular carcinoma (HCC) who have received one or two
prior systemic anti-cancer therapies.

The METIV-HCC trial is a randomized, double-blinded, controlled study of
previously treated patients with MET-high inoperable HCC who will receive
tivantinib or placebo. The primary endpoint is overall survival (OS), and the
secondary endpoint is progression-free survival (PFS). Approximately 300
patients are planned to be enrolled at approximately 120 clinical centers
worldwide. Additional details of the trial are available on
www.clinicaltrials.gov.

“We are very pleased to begin this Phase 3 trial to advance our understanding
of the potential role of tivantinib in the treatment of HCC,” said Glenn
Gormley, MD, PhD, Global Head of Research and Development and Senior Executive
Officer, Daiichi Sankyo. “It is our hope that this late-stage study will
confirm the positive results we saw in Phase 2 in time to progression (TTP)
and overall survival (OS) observed in patients whose tumors were MET-high.”

“Hepatocellular carcinoma is a devastating disease, and patients with advanced
HCC are in need of new therapies that can help extend their lives,” said Paolo
Pucci, chief executive officer of ArQule. “The METIV-HCC trial follows
positive Phase 2 results that demonstrated improvements in overall survival
and time to progression observed among MET-high patients.”

In October 2012, agreement was reached with the U.S. Food and Drug
Administration (FDA) on a Special Protocol Assessment (SPA) for this pivotal
Phase 3 trial. The SPA process is a procedure by which the FDA provides
official evaluation and written guidance on the design and size of proposed
protocols that are intended to form the basis for a New Drug Application.
Final marketing approval depends on the results of the trial.

About Hepatocellular Carcinoma (HCC)

Globally, liver cancer is the sixth most common cancer (749,000 new cases),
accounting for 7 percent of all cancers, and is the third leading cause of
cancer related death (692,000 cases).^1 HCC represents more than 90 percent of
primary liver cancers.^2 Chronic hepatitis B and C are recognized as the major
factors worldwide increasing the risk of HCC, with risk being even greater in
the presence of co-infection with these viruses.^3 Cirrhosis is also a risk
factor for development of HCC.

About Tivantinib and the MET pathway

Tivantinib is an orally administered, selective inhibitor of MET, a receptor
tyrosine kinase. Tivantinib is currently in Phase 3 development and has not
been approved in any market. In healthy adult cells, MET is present in normal
levels to support natural cellular function, but in cancer cells MET is
inappropriately and continuously activated for unknown reasons. When
abnormally activated, MET plays multiple roles in aspects of human cancer,
including cancer cell growth, survival, angiogenesis, invasion and metastasis.

About ArQule and Daiichi Sankyo Co., Ltd.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development
and co-commercialization agreement for tivantinib (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.

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 www.daiichisankyo.com.

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
consists of ARQ 621, designed to inhibit the Eg5 kinesin motor protein, ARQ
736, designed to inhibit the RAF kinases, and ARQ 087, designed to inhibit
fibroblast growth factor receptor (FGFR). ArQule’s current discovery efforts,
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 statements regarding clinical trials with
tivantinib (ARQ 197) by ArQule and its business partner, Daiichi Sankyo,
including the Phase 3 METIV-HCC trial in second-line hepatocellular carcinoma
(HCC) conducted under a Special Protocol Assessment (SPA). These statements
are based on the current beliefs and expectations of both companies, 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 a 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 during clinical
trials or in the course of developing, testing or manufacturing these
compounds that could lead ArQule or its partners to discontinue development.
Even if later stage clinical trials are successful, unexpected concerns may
arise from 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 ArQule’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 are subject to the ability of ArQule, Daiichi Sankyo,
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,
ArQule 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 ArQule’s drug development and other
activities, see ArQule’s periodic reports filed with the Securities and
Exchange Commission. Neither ArQule nor Daiichi Sankyo undertakes any
obligation to publicly update any forward-looking statements

^1 EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular
carcinoma. Journal of Hepatology. 2012;56: 908-943

^2 EASL–EORTC Clinical Practice Guidelines: Management of hepatocellular
carcinoma. Journal of Hepatology. 2012;56: 908-943

^3 Chiaramonte M, Stroffolini T, Vian A, et al.: Rate of incidence of
hepatocellular carcinoma in patients with compensated viral cirrhosis. Cancer
85 (10): 2132-37, 1999.

Contact:

ArQule, Inc.
William B. Boni, 781-994-0300
or
Daiichi Sankyo, Inc. (US)
Tara Camp, 973-944-2393
or
Daiichi Sankyo Europe GmbH
Lydia Worms, +49 89-7808-751
or
Daiichi Sankyo Co., Ltd. (Japan)
Michaela Paudler-Debus, PhD, +81-3-6225-1338