ArQule’s Novel AKT Pathway Inhibitor, ARQ 092, Demonstrates Safety, Target Inhibition in Phase 1 Trial

  ArQule’s Novel AKT Pathway Inhibitor, ARQ 092, Demonstrates Safety, Target
  Inhibition in Phase 1 Trial

                    Data presented at AACR Annual Meeting

Business Wire

WOBURN, Mass. -- April 9, 2013

Researchers presented data today on ARQ 092, an AKT inhibitor in Phase 1
clinical development by ArQule, Inc. (NASDAQ: ARQL) at the AACR (American
Association for Cancer Research) Annual Meeting held in Washington, D.C.,
April 6-10, showing that this novel, oral agent inhibits the AKT pathway and
has a manageable safety profile in an ongoing Phase 1 clinical trial.

“AKT is a signal transduction pathway crucially involved in the growth,
survival and metabolism of cancer cells,” said Mansoor N. Saleh, M.D.,
professor of medicine at the University of Alabama Comprehensive Cancer Center
in Birmingham and director of research at Georgia Cancer Specialists in
Atlanta. “Many of the signaling pathways disrupted by commonly seen
cancer-causing mutations merge into the AKT pathway. In addition, the AKT
pathway is often amplified and mutated in patients who relapse following
initial therapy. This means that the AKT pathway is a potential treatment
target for numerous cancer types, either at diagnosis or when they become
resistant to initial therapies.”

Saleh and his colleagues tested the safety and activity of ARQ 092 in patients
with a broad range of advanced or metastatic solid tumors, including
colorectal, endometrial and neuroendocrine cancers. They assigned patients in
the first cohort to a dose of 10 mg every other day and enrolled subsequent
patients into cohorts of three to six patients who were assigned to a dose
escalation schedule with the drug.

“This class of agents has two common toxicities, namely skin toxicity and
hyperglycemia, a rise in blood sugar levels,” Saleh said. “Based on data
presented with other AKT inhibitors, skin toxicity has been the dose-limiting
side effect and often resulted in drug discontinuation.”

To date, Saleh and colleagues have observed no dose-limiting skin toxicity. In
addition, they have observed that with ARQ 092, blood sugar levels rise before
patients experience skin toxicity, and they have been able to treat the
hyperglycemia, thus allowing the patients to continue on the experimental
drug.

“When we see hyperglycemia, we know that the drug is active in patients,”
Saleh said. “We can ameliorate the high blood sugar, potentially allowing us
to achieve drug levels that will be therapeutically active.”

Currently, the maximum tolerated dose has not been declared in this ongoing
trial. Of twenty evaluable patients, seven patients have remained stable on
the drug for more than four months. Four of these seven patients with advanced
and refractory solid tumors have had stable disease for longer than six
months, according to Saleh. Once the maximum tolerated dose is identified,
Saleh and colleagues plan to test the drug for efficacy.

“We will also explore the drug’s activity in patients with a high level of AKT
in the tumor to identify the patient populations that can robustly benefit
from our treatment,” he said.

ArQule recently regained worldwide rights to its AKT program, including ARQ
092, from Daiichi Sankyo Co., Ltd. ARQ 092 is a selective AKT inhibitor that
was discovered through technology from the ArQule Kinase Inhibitor Platform
(AKIP™) and optimized through a structure-based drug design methodology. The
AKT signaling pathway, which plays a role in regulating cell growth, survival,
migration and angiogenesis, is frequently dysregulated in cancer.

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 092, designed to inhibit AKT, 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 ARQ 092, which is in Phase 1 clinical development. 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, ARQ 092 may not demonstrate
promising therapeutic effects; 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 ARQ 092 that could lead the Company 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, and 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 ARQ 092 are subject to the ability of the
Company to enroll patients, enter into agreements with clinical trial sites
and investigators, and overcome other technical hurdles and issues related to
the conduct of the trials for which each of them is responsible that may not
be resolved. Drug development involves a high degree of risk. Only a small
number of research and development programs results 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. 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