ArQule Summarizes Abstracts Presented at AACR

ArQule, Inc. (NASDAQ: ARQL) today announced that four abstracts submitted by the Company will be presented in poster sessions at the 2008 Annual Meeting of the American Association for Cancer Research (AACR), April 12-16, 2008 in San Diego.

These AACR abstracts are based on pre-clinical studies that support the Company’s approaches to molecularly targeted cancer therapy embodied in ongoing Phase 2 clinical trials with ARQ 197, a selective inhibitor of the c-Met receptor tyrosine kinase, and in pre-clinical development programs with ARQ 621, a product candidate designed to inhibit the Kinesin Spindle Protein (KSP) (kinesin-5 or Eg5), and ARQ 218, the prototype of a novel class of BRAF kinase inhibitors with potential clinical utility for human cancers harboring mutant BRAF genes.

Summaries of these studies are presented below.

Summaries of AACR abstracts

ARQ 197 / c-Met inhibition

1.

In Vitro ADME Properties of ARQ 197 (Abstract Number 1291, Poster Session on April 13, 2008, 1:00 p.m. – 5:00 p.m.)

Initial metabolism studies with ARQ 197 demonstrated favorable ADME (Absorption, Distribution, Metabolism and Excretion) properties and predicted good oral bioavailability in patients, which has been confirmed by clinical pharmacokinetic data with ARQ 197. Currently, ARQ 197 is in Phase 2 clinical trials in MiT-driven tumors and pancreatic cancer and in a Phase 1 trial in combination with erlotinib in non-small cell lung cancer.

2.

Validation of IHC Staining on Phosphorylation of c-Met Receptor and Preclinical and Clinical Specimens of ARQ 197 Biomarker Study (Abstract Number 2803, Poster Session on April 14,2008, 1:00 p.m. – 5:00 p.m. )

The inhibition c-Met phosphorylation by ARQ 197 in animals and humans has been demonstrated by a number of antibodies against phospho-c-Met in tumor tissues. Data presented demonstrate further validation of the immunohistochemistry (IHC) staining procedure that recognizes the docking site pY1349 of p-c-Met. This antibody is currently being applied to human tissue biopsies to collect pharmacodynamic data on ARQ 197.

ArQule Pre-Clinical Programs

3.

Discovery of Novel Eg5 Kinesin Inhibitor, ARQ 621, With Potent Anti-Tumor Activity While Sparing Bone Marrow-Derived Cells (Abstract Number 656, Poster Session on April 13, 2008, 8:00 a.m. – 12:00 p.m.)

A compound designated as ARQ 621 has been discovered to inhibit the human Eg5 microtubule-based kinesin potently and selectively. In cell proliferation assays, ARQ 621 showed broad spectrum cytotoxicity against a panel of human cancer cell lines, with significantly less cytotoxicity against hematopoietic cells. In a human pancreatic tumor xenograft model in nude mice, ARQ 621 treatment resulted in complete tumor stasis, with no evidence of bone marrow toxicity. Furthermore, initial toxicology studies in rats showed no hematological abnormalities in either bone marrow or peripheral blood. ARQ 621 has been advanced into full pre-clinical development as a broad-spectrum anti-cancer agent with the promise of an improved safety profile over the first generation Eg5 inhibitors.

4.

Discovery and Biological Characterization of a Novel Class of BRAF Inhibitors That Spare KDR (VEGFR2) Kinase (Abstract Number 2308, Poster Session on April 14, 2008, 8:00 a.m. – 12:00 p.m.)

Mutant BRAF containing the V600E mutation represents an attractive therapeutic target in several types of cancer, including melanoma. Inhibition of mutated BRAF in human melanoma cells inhibits the MAPK pathway, causing growth arrest and apoptosis. ARQ 218, a novel BRAF kinase inhibitor, shows marked selectivity against mutant BRAF while sparing cells with wild-type BRAF. ARQ 218 also inhibits the MAPK pathway potently, rapidly and in a durable fashion. Additionally, in biochemical screens, ARQ 218 does not inhibit vascular endothelial growth factor receptor 2 (VEGFR2 or KDR), a profile distinct from sorafenib and other reported BRAF inhibitors. Lack of such inhibition may circumvent adverse events such as hypertension and stroke. These data demonstrate that ARQ 218 is the prototype of a novel class of BRAF kinase inhibitors with potential clinical utility in treating human cancers harboring mutant BRAF.

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, an activator 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 ARQ 761, a second-generation E2F-1 product candidate, as well as compounds that inhibit the Eg5 kinesin spindle protein and the BRAF 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 clinical-stage product, ARQ 197, and its pre-clinical product candidates, ARQ 621 and ARQ 218. 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 studies or early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, ARQ 197, ARQ 621and ARQ 218 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 with ARQ 197, ARQ 621 and ARQ 218 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.