WOBURN, Mass.–(BUSINESS WIRE)–Mar 29, 2012 – ArQule, Inc. (Nasdaq: ARQL) today announced eight presentations of clinical and pre-clinical data for tivantinib (ARQ 197) at the Annual Meeting of the American Association for Cancer Research (AACR), held from March 31 – April 4 in Chicago, Illinois. Tivantinib is an oral inhibitor of c-MET, a receptor tyrosine kinase, which is currently in Phase 3 clinical trials for non-squamous non-small cell lung cancer (NSCLC). Several other studies related to the Company’s earlier-stage product candidates and discovery platform will also be presented at AACR.
Tivantinib highlights
An exploratory biomarker analysis evaluating the effect of the c-MET inhibitor tivantinib (ARQ 197) and erlotinib in NSCLC patients in a randomized, double-blinded phase 2 study: Abstract number 1729.
An exploratory immunohistochemistry (IHC) analysis was conducted of archival tissue from a concluded Phase 2 clinical trial with tivantinib and erlotinib in NSCLC. Findings confirmed that in this trial non-squamous NSCLC tumors were more often positive for c-MET expression than squamous NSCLC tumors. In this study, 76 percent of evaluable patients with non-squamous tumors were c-MET positive, and 12 percent of evaluable patients with squamous tumors were c-MET-positive, a percentage that is consistent with existing literature.
Data analysis showed that treatment with the combination of tivantinib and erlotinib improved progression-free survival (HR = 0.58, p = 0.28) and overall survival (HR = 0.46, p = 0.21) in patients with non-squamous histology and c-MET-positive tumors, as measured by IHC, compared with patients who received with erlotinib plus placebo.
Targeted inhibition of c-MET receptor by a selective c-MET inhibitor, Tivantinib, and a specific shRNA reduces breast cancer-derived bone metastases: Abstract number 846.
A pre-clinical study with tivantinib explored dual c-MET inhibition with both tivantinib and RNA interference in an experimental bone metastatic model of human breast cancer. C-MET inhibition with the combined therapeutic interventions induced pronounced tumor growth suppression with marked decreases in tumor size and an improvement in survival.
Findings highlighted the efficacy of c-MET inhibition in delaying the onset and progression of bone metastases and suggest that targeting the c-MET receptor may have promise in the prevention and treatment of bone metastases from breast cancer.
The titles and times of ArQule’s and alliance partner Daiichi Sankyo’s data presentations for tivantinib at AACR are as follows:
An exploratory biomarker analysis evaluating the effect of the c-MET inhibitor tivantinib (ARQ 197) and erlotinib in NSCLC patients in a randomized, double-blinded phase 2 study
Abstract Number 1729
Poster Section 26
Poster Board 19
Monday, April 2, 2012, 8:00 AM – 12:00 PMTargeted inhibition of c-MET receptor by a selective c-MET inhibitor, Tivantinib, and a specific shRNA reduces breast cancer-derived bone metastases
Abstract Number 846
Poster Section 32
Poster Board 3
Sunday, April 1, 2012, 1:00 PM – 5:00 PMTargeting the pro-survival protein c-MET with ARQ 197 inhibits growth of multiple myeloma cells
Abstract Number 844
Poster Section 32
Poster Board 1
Sunday, April 1, 2012, 1:00 PM – 5:00 PMPreclinical assessment of MET modulation by a VEGFR inhibitor/MET inhibitor combination that shows additive antitumor efficacy
Abstract Number 3672
Poster Section 25
Poster Board 14
Tuesday, April 3, 2012, 8:00 AM – 12:00 PMP53 is potential predictive biomarker for combination therapy of epidermal growth factor receptor (EGFR) and MET inhibitors in non-small cell lung cancer (NSCLC) with wild-type EGFR
Abstract Number 2476
Poster Section 18
Poster Board 1
Monday, April 2, 2012, 1:00 PM – 5:00 PMA randomized, crossover, phase 1 study to evaluate the effect of a strong CYP3A4 inhibitor on tivantinib (ARQ 197) pharmacokinetics in healthy subjects
Abstract Number 760
Poster Section 28
Poster Board 14
Sunday, April 1, 2012, 1:00 PM – 5:00 PMA randomized, open-label, phase 1 study to evaluate the effect of food on tivantinib (ARQ 197) pharmacokinetics
Abstract Number 755
Poster Section 28
Poster Board 9
Sunday, April 1, 2012, 1:00 PM – 5:00 PMAbsorption, distribution, metabolism and excretion of 14C-Labeled tivantinib (ARQ 197) in healthy male subjects
Abstract Number 747
Poster Section 28
Poster Board 1
Sunday, April 1, 2012, 1:00 PM – 5:00 PM
Additional ArQule data presentations include:
Discovery and optimization of orally bioavailable, selective and potent ATP-independent Akt inhibitors
Abstract Number LB-1
Sunday, April 1, 2012, 1:00 PM – 5:00 PM
Poster Section 40Synthesis and structure activity relationship of substituted N,6-diphenyl-5,6-dihydrobenzo(h)quinazolin-2-amine as inhibitors of fibroblast growth factor receptors (FGFR)
Abstract Number 3905
Tuesday, April 3, 2012, 8:00 AM – 12:00 PM
Poster Section 35
Poster Board 18Creation of a novel biochemical and biophysical assay suite to enable the identification of inhibitors targeting inactive kinases
Abstract Number 2914
Monday, April 2, 2012, 3:50 PM – 4:05 PM
Location: McCormick Place West (Level1), Room W187
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 human cancers. ArQule’s lead product, in Phase 2 and Phase 3 clinical development, is tivantinib, an oral, selective inhibitor of the c-MET receptor tyrosine kinase. The Company’s pipeline consists of ARQ 621, designed to inhibit the Eg5 kinesin motor protein, and ARQ 736, designed to inhibit the RAF kinases. ArQule’s current discovery efforts, which are based on the ArQule Kinase Inhibitor Platform (AKIP™), are focused on the identification of novel kinase inhibitors that are potent, selective and do not compete with ATP (adenosine triphosphate) for binding to the kinase.
This press release contains statements regarding the Company’s pre-clinical and clinical development of tivantinib (ARQ 197), as well as pre-clinical activities related to its Akt inhibitor program, its fibroblast growth factor inhibitor program, and its discovery platform. 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 and early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, these products and programs 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 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 partners 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. Obstacles may arise or issues may be identified in connection with review of clinical data with regulatory authorities, or 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 tivantinib is subject to the ability of the Company or Daiichi Sankyo, Inc., its partner, and Kyowa Hakko Kirin, a licensee of tivantinib, to enroll patients, enter into agreements with clinical trial sites and investigators, and overcome other technical hurdles and issues related to the conduct of the trials 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. Positive pre-clinical data may not be supported in later stages of development. Furthermore, ArQule may not have the financial or human resources to successfully pursue drug discovery in the future. Moreover, Daiichi Sankyo has certain rights to unilaterally terminate its tivantinib license, co-development and co-commercialization agreement with the Company. If it were to do so, the Company might not be able to complete development and commercialization of tivantinib on its own. 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: ArQule, Inc.
William B. Boni, 781-994-0300
VP, Investor Relations/
Corp. Communications
http://www.ArQule.com
Posted: March 2012
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