ArQule Announces Initiation of Two Phase 2 Trials with c-Met Inhibitor, ARQ 197.

Trials target MiT tumors and pancreatic cancer 

WOBURN, Mass. -- ArQule, Inc. (NASDAQ: ARQL) today announced the initiation of two Phase 2 trials with ARQ 197, an orally administered, small molecule inhibitor of the c-Met receptor tyrosine kinase, in patients with MiT (Microphthalmia Transcription Factor) tumors and pancreatic cancer.

MiT tumors include clear cell sarcoma (CCS), alveolar soft part sarcoma (ASPS) and translocation-associated renal cell carcinoma (RCC). They are linked biologically through a common chromosomal abnormality that drives the over-expression of c-Met and thereby the development of cancer. Tumors with this abnormality tend to spread throughout the body and to resist all known therapies. They strike primarily adolescents and young adults, and are fatal if not resectable at diagnosis.

Pancreatic cancer is the fourth leading cause of cancer death in the U.S. Although advances in understanding the molecular basis of the disease have been made in recent years, treatment of advanced pancreatic cancer remains a clinical challenge. It has been demonstrated that c-Met is over-expressed in 78 to 88 percent of tumor tissue samples from patients with pancreatic cancer, indicating that the c-Met signaling pathway may play a role in the development of this disease and that inhibition of this pathway may represent a viable therapeutic intervention.

"We believe MiT tumors represent an important disease for a potentially rapid proof-of-concept for c-Met inhibition," said Dr. Stephen A. Hill, president and chief executive officer of ArQule. "Clinical investigators have demonstrated that they are able to use siRNA inhibition of c-Met to kill cell lines from these tumors effectively. We have now repeated their study, using ARQ 197 instead, and have demonstrated significant cancer cell-killing activity. We believe therefore that MiT tumors, which are highly dependent on c-Met over-expression, may be an excellent initial target indication for ARQ 197.

"Our second trial with ARQ 197 targets treatment-naive patients with unresectable locally advanced or metastatic pancreatic adenocarcinoma," said Dr. Hill. "The median survival of patients with advanced disease is less than six months, current treatment options are unsatisfactory, and the clinical evaluation of compounds with novel therapeutic targets is urgently needed. Given the abnormal level of c-Met over-expression in pancreatic tumor tissue samples, the demonstrated activity of ARQ 197 in animal models of human pancreatic cancer, and the activity and safety profile of this compound seen in Phase 1 testing, we believe this disease represents another promising indication for ARQ 197.

"These trials mark the first in a series of studies with ARQ 197 that we expect to initiate in the coming months," said Dr. Hill. "They will test therapeutic approaches that are based on the multiple roles of c-Met as a driver of cancer development."

MiT Tumors: Trial Summary

Approximately 45 patients from up to ten clinical study sites in the U.S. and potentially in Europe will be enrolled in a multi-center, single arm, two-stage trial. Eligible patients will receive 120 milligrams (mg) of ARQ 197 orally twice daily.

During the first stage of the trial, approximately 23 patients will be treated. If a partial response or a complete response is observed in more than one patient in this stage, the study will be continued to the second stage, where an additional 22 patients will be enrolled. Otherwise, the study will be stopped.

The primary objective of the trial is to determine the overall response rate in patients treated with ARQ 197. Secondary objectives include the evaluation of progression-free survival time, as well as six-month and one-year overall survival in these patients.

Pancreatic Adenocarcinoma: Trial Summary

Approximately 60 patients from approximately 20 clinical sites in Eastern Europe will be enrolled in an open-label, randomized trial in which patients will be treated with either ARQ 197 or gemcitabine. Eligible patients will receive either 120 mg of 197 orally twice daily or intravenous infusion of gemcitabine at a dose of 1000 mg/m2 (meter squared).

The primary objective of the trial is to evaluate and compare progression-free survival in the two groups of patients. Secondary objectives include the evaluation of overall response rate and one-year overall survival rates in both groups.

Patients, physicians and other healthcare professionals seeking additional information regarding these trials may call 1-800-373-7827.

About ARQ 197 and c-Met

ARQ 197 is the lead product from the Company's Cancer Survival Protein modulation program. The Company has licensed rights to develop and commercialize ARQ 197 in Japan and parts of Asia to Kyowa Hakko Kogyo Co., Ltd. (Kyowa). Other than the rights licensed under the agreement with Kyowa, ArQule retains all worldwide rights to ARQ 197.

ARQ 197 mediates its effects by inhibiting the activity of c-Met, a receptor tyrosine kinase that plays multiple key roles in human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. C-Met is abnormally activated in most cancers and is believed to control multiple signal transduction pathways involved in tumor growth and metastasis. Pre-clinical findings have demonstrated that ARQ 197 inhibits c-Met in a wide range of human tumor cell lines and possesses anti-tumor activity against several types of xenografted human tumors in mice.

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 cancer. ArQule's lead clinical-stage products have been generated from two scientific platforms: Cancer Survival Protein modulation and Activated Checkpoint Therapy([R]) (ACT). The Cancer Survival Protein modulation platform has generated a clinical-stage product that mediates its effects by inhibiting the activity of a molecule known as c-Met, which plays multiple roles in cancer cell growth, survival, invasion, angiogenesis and metastasis. The ACT platform is designed to kill cancer cells selectively while sparing normal cells through direct activation of DNA damage response/checkpoint pathways. The Company's lead ACT program, based on the E2F-1 pathway, is partnered with Hoffman-La Roche. For more information, please visit www.arqule.com.

This press release contains forward-looking statements regarding the Company's Phase 2 clinical trials with ARQ 197. 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 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, 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. 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 or information or additional studies. In addition, the planned timing of initiation and completion of clinical trials for ARQ 197 are subject to the ability of the Company to enroll patients, enter into agreements with clinical trial sites and investigators, and other technical hurdles and issues that may not be 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. 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.