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Arqule Announces Clinical and Pre-Clinical Data on Anti-Metastatic Potential of ARQ 197, a Selective c-Met Inhibitor

WOBURN, Mass.--(BUSINESS WIRE)--Oct 24, 2007 - ArQule, Inc. (NASDAQ: ARQL) today announced data demonstrating early clinical signs of potential anti-metastatic activity observed with ARQ 197, the Company's selective, small molecule inhibitor of the c-Met receptor tyrosine kinase, as well as data showing a reduction in metastases in animal models treated with this compound.

These data were presented in two posters at the 2007 AACR-NCI-EORTC International Conference in San Francisco. The posters were titled "A Phase 1 dose escalation study of ARQ 197, a specific c-Met inhibitor with anti-metastatic potential" and "ARQ 197, a small molecule inhibitor of c-Met, prevents bone metastasis in a humanized mouse model of breast cancer."

"The effects observed in both of these studies are consistent with the mechanism of action of a molecularly targeted c-Met inhibitor and the demonstrated role of dysregulated c-Met in metastatic disease," said Dr. Stephen A. Hill, president and chief executive officer of ArQule. "The clinical effects were noted earlier this year by investigators in the Phase 1 trial with ARQ 197, and since then, further analyses have been conducted based on independently read scans of patients in this trial.

"We believe these findings support a viable hypothesis of anti-metastatic effect that requires additional investigation," said Dr. Hill. "Toward that end, we are planning certain Phase 2 trials with ARQ 197 that will explore and better characterize that effect."

Summary of Clinical Findings Presented

Safety and Anti-Cancer Activity

To date, 60 patients have been enrolled in the Phase 1 trial with ARQ 197, and 56 of these have been treated at doses of up to 180 milligrams (mg) administered twice daily on two schedules. On the first dosing schedule, 37 patients were treated twice daily for two weeks, followed by one week of rest, and on the second dosing schedule, 19 patients were treated twice daily continually. No dose-limiting toxicity was observed, and a recommended Phase 2 dose of 120 mg twice daily was established based on pharmacokinetic data. No drug-related serious adverse events were reported, and the most commonly reported drug-related adverse events were fatigue and nausea.

As of October 14, 2007, a total of 49 patients were evaluable for efficacy analysis as defined by study protocol. These patients have completed at least one cycle of treatment with ARQ 197 and have had baseline measurements and at least one post-treatment tumor measurement. Three (6.1 percent) had partial responses. Thirty-one (63.2 percent) had stable disease for more than eight weeks, and 18 (36.7 percent) had prolonged stable disease for periods ranging from 16 to 74 weeks.

Anti-Metastatic Analysis

Following initial observations of potential anti-metastatic activity made by clinical investigators, patients' original tumor scans were independently reviewed to better define this activity. Forty-five patients who were evaluable and whose tumor image files were available for the independent evaluation were included in an anti-metastatic analysis.

Eighteen of 19 (94.7 percent) of patients treated with ARQ 197 for 12 weeks or longer did not develop detectable new metastatic lesions. Five of 7 (71.4 percent) patients treated for 7 to 12 weeks did not develop detectable new metastatic lesions. In contrast, eleven of 19 (57.9 percent) patients treated for 6 weeks or less developed new metastatic lesions. All new metastatic lesions occurred only in organs with documented pre-existing metastatic disease, except in two patients.

Based on these observations, further clinical evaluation of the potential anti-metastatic activity of ARQ 197 is planned as part of a Phase 2 clinical trial program.

Summary of Pre-Clinical Findings Presented

The dysregulation of c-Met-related cell signaling pathways has been shown to correlate with the appearance of metastases in a number of human cancers, including breast cancer. In more than 70 percent of human breast cancer cases that spread beyond the primary tumor, skeletal metastasis remains an incurable complication. This study employed a novel mouse model that recapitulated each step in the metastatic cascade of breast cancer to bone tissue.

To test the efficacy of ARQ 197 at preventing bone metastases, mice were implanted with human bone grafts and subsequently injected with breast cancer cells. Approximately 20 percent of mice treated with ARQ 197 showed metastases of these cells to the bone grafts, a marked reduction compared to the nearly 50 percent of mice in two other groups that showed metastases, one group treated with paclitaxel and one a control group. These findings demonstrate the potential of ARQ 197 as an anti-osteotropic, anti-metastasis drug.

About ArQule

ArQule, Inc. 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 Roche. For more information, please visit www.arqule.com.

This press release contains forward-looking statements regarding the Company's Phase 1 and 2 clinical trials with ARQ197. 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, early signals of anti-metastatic effects could prove to not be clinically significant, and ARQ 197 may not demonstrate promising therapeutic effect; in addition, they 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 ongoing or 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. 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

Corp. Communications
William B. Boni, 781-994-0300
VP, Investor Relations

Posted: October 2007

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