ArQule Announces Data from Phase 1B Trial with ARQ 501 and Docetaxel.

WOBURN, Mass. -- ArQule, Inc. (Nasdaq: ARQL) today announced data from a Phase 1b combination therapy trial with ARQ 501 and docetaxel that support previously announced findings demonstrating clinical tolerability and promising signs of anti-tumor activity in cancer patients with a range of advanced solid tumors who had failed prior treatments with a range of anti-cancer therapies.

These data were presented as a poster at the 18th EORTC-NCI-AACR International Conference on Molecular Targets and Cancer Therapeutics in Prague (A Phase 1b Trial of ARQ 501, a Checkpoint Pathway Activator, in Combination with Docetaxel in Patients with Advanced Solid Tumors - Poster Number 387). Initial data from this trial were disclosed in a June 2006 publication in the 2006 Proceedings of the American Society of Clinical Oncology (ASCO).

"These data confirm the potential of ARQ 501 when used as combination therapy with chemotherapeutic agents," said Dr. Stephen A. Hill, president and chief executive officer of ArQule. "They are part of a broader set of data from a series of monotherapy and combination therapy trials with ARQ 501 that support our Phase 2 program, initiated earlier this year. That program consists of two monotherapy trials, in leiomyosarcoma and head and neck cancer, and one combination therapy trial, with gemcitabine in pancreatic cancer, into which patients are being actively recruited."

Combination trial with ARQ 501 and docetaxel

Summary

The following data were collected as of October 9, 2006. A total of 43 patients have received the combination therapy of ARQ 501 and docetaxel in this trial, with doses of ARQ 501 ranging from 140 milligrams (mg) / square meter (m2) to 550 mg / m2, infused over one or three hours. Promising anti-tumor activity has been observed over the range of doses administered. Of 36 patients evaluable for efficacy, 20 have achieved disease stabilization, and evidence of tumor regression was observed in 4 of these patients, 3 of whom had a partial response and 1 of whom had a minor response.

The data demonstrated the clinical tolerability and favorable pharmacokinetics of ARQ 501 in combination with docetaxel. The most common adverse events were anemia, fatigue, hyperbilirubinemia and leucopenia.

Trial details

The objectives of this study were to determine the maximum tolerated dose, dose-limiting toxicity, safety, tolerability and preliminary anti-tumor activity of the combination of ARQ 501 and docetaxel. All patients enrolled in the study except for one had received and failed prior courses of therapy.

Two dosing schedules were investigated in this combination therapy protocol. In the first, ARQ 501 was administered for five consecutive days, with a single docetaxel infusion administered on day three. In the second, a single dose of ARQ 501 was administered in combination with a single docetaxel infusion on day one. Once tolerated, additional weekly infusions of ARQ 501 were administered. Both schedules were repeated every three weeks. Dose escalation of ARQ 501 was conducted to explore and evaluate the effects of both doses and infusion regimens.

A total of 11 patients were enrolled and received the first dosing schedule. Of these, 9 patients were evaluable for efficacy, defined as having completed 6 weeks of the study and at least one post-baseline tumor assessment. Of these, 5 patients (56 percent) achieved a best response of stable disease or better, ranging from 9.4 to 23.6 weeks. Two patients with ovarian cancer achieved a partial response based on reduction in the levels of the tumor marker CA-125. One of these also showed an unconfirmed 42 percent reduction in tumor burden according to RECIST (Response Evaluation Criteria in Solid Tumors) guidelines.

A total of 32 patients were enrolled and received the second dosing schedule. Twenty-seven of these were evaluable for efficacy, as defined above. Of the 27 patients, 15 (55 percent) achieved a response of stable disease or better, ranging from 12 to more than 41 weeks. Two patients achieved a partial response (one unconfirmed), including one with head and neck cancer and one with melanoma. In addition, a minor response was seen in a pancreatic cancer patient.

About ARQ 501

ARQ 501, the Company's lead product generated from its Activated Checkpoint Therapy(SM) (ACT) platform, is being developed under an alliance with Roche. ACT compounds are designed to selectively and broadly target cancer cells through activation of checkpoint pathways. ARQ 501 activates E2F1-mediated checkpoint pathways, resulting in apoptosis (cell suicide) in cancer cells selectively.

The Company's Phase 2 clinical program with ARQ 501 consists of three separate trials, including two monotherapy trials, in leiomyosarcoma and head and neck cancer, and one combination therapy trial, with gemcitabine in pancreatic cancer.

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 designed to affect key biological processes that are central to cancer. ArQule's lead clinical-stage products have been generated from two scientific platforms. The first of these, Activated Checkpoint Therapy(SM) (ACT), 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 E2F1 pathway, is partnered with Roche. ArQule's second cancer platform, Cancer Survival Protein modulation, has generated a clinical-stage product designed to inhibit a molecule known as c-Met, which plays multiple roles in cancer cell growth, survival, invasion, angiogenesis and metastasis. For more information, please visit www.arqule.com.

This press release contains forward-looking statements regarding the Company's Phase 1b combination therapy clinical trials with ARQ 501 and docetaxel. 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 501 may not demonstrate promising therapeutic effect; in addition, it may not demonstrate an appropriate safety profile in 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 ARQ 501 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 of clinical trials for ARQ 501 is 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.