ArQule Enrolls First Patient in Phase 1/2 Clinical Trial Program of ARQ 197 in Non-Small Cell Lung Cancer

WOBURN, Mass.--(BUSINESS WIRE)--ArQule, Inc. (NASDAQ: ARQL) today announced the commencement of patient dosing in a Phase 1/2 clinical trial program of ARQ 197 administered in combination with erlotinib in patients with advanced non-small cell lung cancer (NSCLC). ARQ 197 is an orally available, small molecule inhibitor of the c-Met receptor tyrosine kinase. Erlotinib, marketed as Tarceva®, is an inhibitor of the EGFR (epidermal growth factor receptor) tyrosine kinase.

“The tumor types we have selected for this program reflect the multiple roles of c-Met as a driver of the onset and progress of certain cancers.”

The NSCLC program consists of two trials. The first is a Phase 1 trial in which investigators will determine the safety, tolerability and a recommended Phase 2 dose of ARQ 197 when administered in combination with erlotinib in this patient population. Secondarily, investigators will evaluate the pharmacokinetic profile and assess the preliminary anti-tumor activity of this combination therapy.

Pending the completion of Phase 1, the Company plans to initiate a Phase 2 trial, designed as a multi-center, placebo controlled, randomized trial comparing ARQ 197 plus Tarceva against placebo plus Tarceva.

“Non-small cell lung cancer is the third indication within our Phase 2 clinical program with ARQ 197,” said Peter S. Lawrence, chief operating officer of ArQule. “The tumor types we have selected for this program reflect the multiple roles of c-Met as a driver of the onset and progress of certain cancers.

“The high level of interest in this particular indication within the oncology community has been generated by scientific data showing that the development of resistance in NSCLC tumors to therapy with EGFR inhibitors may be linked to an increase in c-Met signaling. Overcoming such resistance has been a challenge, and we believe the inhibition of c-Met may offer a new strategy in treating these tumors and extending the lives of patients.”

In addition to published scientific literature supporting the role of c-Met in the onset of resistance to EGFR therapy, pre-clinical efficacy studies in NSCLC cells conducted by ArQule have demonstrated synergy between ARQ 197 and erlotinib in halting cancer cell proliferation.

According to the American Cancer Society, lung cancer (both small cell and non-small cell) is the leading cause of cancer death for both men and women. About 85 percent to 90 percent of all lung cancers are of the non-small cell type. In 2008, the American Cancer Society estimates that there will be about 215,000 new cases of lung cancer in the U.S. and that 162,000 people will die of this disease.

ARQ 197 is also currently being evaluated in Phase 2 clinical trials in MiT (Microphthalmia Transcription Factor)-driven tumors, which include clear cell sarcoma (CCS), alveolar soft parts sarcoma (ASPS) and translocation-associated renal cell carcinoma (RCC), and in pancreatic cancer.

Patients, physicians and other healthcare professionals seeking additional information regarding this trial and others involving ARQ 197 may call 1-800-373-7827.

About ARQ 197 and c-Met

ARQ 197 is a selective inhibitor of c-Met, a receptor tyrosine kinase that, when abnormally activated, plays multiple roles in 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 wide range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical studies 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.

ArQule 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.

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 products, which are in clinical-stage development, consist of ARQ 197, an inhibitor of the c-Met receptor tyrosine kinase, and ARQ 501 and ARQ 171, activators of the cell’s DNA damage response mechanism mediated by the E2F-1 transcription factor. The Company’s most advanced pre-clinical development programs are focused on the inhibition of the Eg5 kinesin spindle protein and the B-RAF kinase. ArQule’s discovery efforts are focused on the identification of novel kinase inhibitors that are potent, selective and do not compete with ATP (adenosine triphosphate), an energy source for cells.

This press release contains forward-looking statements regarding the Company’s Phase 1 and 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.