ArQule Presents Clinical Biomarker Data From Phase 2 Study and Ongoing Phase 3 METIV-HCC Study of Tivantinib in Second-Line Hepatocellular Carcinoma at the 2016 Gastrointestinal Cancers Symposium

Preliminary analysis of baseline MET incidence in METIV-HCC trial confirms results observed in phase 2 trial

BURLINGTON, Mass., Jan. 25, 2016 (GLOBE NEWSWIRE) -- ArQule, Inc. (NASDAQ:ARQL) today announced that an analysis of preliminary baseline tumor MET status of patients screened in the phase 3 METIV-HCC trial for tivantinib in second-line hepatocellular carcinoma (HCC) confirms previously presented data from the company’s phase 2 trial in the same patient population. In both trials MET status, as determined by immunohistochemistry, was more frequently high after first-line therapy and was a predictive and prognostic biomarker in the phase 2 trial. The data was presented in an oral presentation and poster at the 2016 Gastrointestinal Cancers Symposium (ASCO GI) on January 22, 2016.

The METIV-HCC trial screened patient tumor biopsies for MET status as an inclusion criteria for Met-high patients. Approximately half of the more than 1,000 samples tested were MET-high. A higher MET-high rate (73%) was observed in those samples from patients analyzed following first-line treatment with sorafenib while a lower MET-high rate (39%) was observed in those samples analyzed prior to sorafenib treatment.

An additional analysis found that 70% (50 out of 71) of patients who tested MET-low before sorafenib treatment became MET-high after receiving sorafenib. The presentations can be accessed in the “Publications and Presentations” section of our website,

“The totality of the biomarker data presented further enforces our confidence in the design and target patient population that we have chosen for the METIV-HCC trial,” said Dr. Brian Schwartz, Chief Medical Officer and Head of Research and Development at ArQule. “Having recently completed enrollment, we look forward to the planned interim analysis early in the second quarter.”

The METIV-HCC trial, being conducted in western countries in partnership with Daiichi Sankyo, has completed enrollment and a planned interim analysis, which is triggered when 60% of events occur, is expected to take place early in the second quarter of 2016. The trial enrolled over 300 patients, is randomized 2:1 treatment to best supportive care, and has overall survival as its primary end-point.

The phase 2 study, completed in the third quarter of 2011 and published in The Lancet Oncology medical journal in November 2012, enrolled 107 HCC patients who progressed or were intolerant to one prior systemic therapy. Multiple biomarkers were evaluated as part of the study, and tumor MET status as determined by immunohistochemistry emerged as the strongest predictor of tivantinib response.

About Hepatocellular Carcinoma (HCC)

Liver cancer is the sixth most common cancer globally with about 782,000 new cases in 2012 and is the second most common cause of cancer-related death with 746,000 deaths in 2012.i HCC accounts for about 90 percent of primary liver cancers.ii Cirrhosis, chronic hepatitis B and C and smoking are recognized worldwide as factors increasing the risk of HCC.ii

About MET and Tivantinib (ARQ 197)

Tivantinib is an orally administered, selective inhibitor of MET, a receptor tyrosine kinase, which is currently in two phase 3 clinical trials. In healthy adult cells, MET can be present in normal levels to support natural cellular function, but in cancer cells, MET can be inappropriately and continuously activated. When abnormally activated, MET plays multiple roles in aspects of human cancer, including cancer cell growth, survival, angiogenesis, invasion and metastasis. The activation of certain cell signaling pathways, including MET, has also been associated with the development of resistance to anti-EGFR (epidermal growth factor receptor) antibodies such as cetuximab and panitumumab.

Pre-clinical data have demonstrated that tivantinib inhibits MET activation in a range of human tumor cell lines and shows anti-tumor activity against several human tumor xenografts. In clinical trials to date, treatment with tivantinib has been generally well tolerated and has shown clinical activity in a number of tumors studied. Tivantinib has not yet been approved for any indication in any country.

In December 2008, ArQule and Daiichi Sankyo signed a license, co-development and co-commercialization agreement for tivantinib in the U.S., Europe, South America and the rest of the world, excluding Japan, China (including Hong Kong), South Korea and Taiwan.

In November 2015, ArQule exercised its co-commercialization option for tivantinib in the U.S. A co-commercialization agreement is expected to be finalized in the first quarter of 2016.

About ArQule

ArQule is a biopharmaceutical company engaged in the research and development of targeted therapeutics to treat cancers and rare diseases. Our mission is to discover, develop and commercialize novel small molecule drugs in areas of high unmet need that will dramatically extend and improve the lives of our patients. Our prioritized clinical-stage pipeline consists of four drug candidates, all of which are in targeted, biomarker-defined patient populations, making ArQule a potential early leader in precision medicine. ArQule’s lead product, in phase 3 clinical development, is tivantinib (ARQ 197), an oral, selective inhibitor of the c-MET receptor tyrosine kinase, for second-line treatment of hepatocellular carcinoma in partnership with Daiichi Sankyo in the West and Kyowa Hakko Kirin in Asia. ArQule’s proprietary pipeline includes: ARQ 092, designed to inhibit the AKT serine/threonine kinase, in phase 1 for multiple oncology indications as well as ultra-rare Proteus syndrome, in partnership with the National Institutes of Health (NIH); ARQ 087, a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family, is in phase 2 for iCCA and in phase 1b for multiple oncology indications; and ARQ 761, a Beta lapachone analog being evaluated as a promoter of NQ01-mediated programmed cancer cell necrosis, is in phase 1/2 in multiple oncology indications in partnership with the University of Texas Southwestern Medical Center. ArQule’s current discovery efforts are focused on the identification and development of novel kinase inhibitors, leveraging the Company’s proprietary library of compounds.

This press release contains forward-looking statements regarding the Company’s clinical trials with tivantinib (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 pre-clinical and early stage clinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, tivantinib may not demonstrate promising therapeutic effect or appropriate safety profiles 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 or to justify further development. Problems or delays may arise prior to the initiation of planned clinical trials, during clinical trials or in the course of developing, testing or manufacturing that could lead the Company or its partners and collaborators to fail to initiate or to discontinue development. Even if later stage clinical trials are successful, unexpected concerns may arise from subsequent 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. 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 as well as Daiichi Sankyo, Inc., our development partner for tivantinib, and Kyowa Hakko Kirin, a licensee of tivantinib, to enroll patients, enter into agreements with clinical trial sites and investigators, and overcome technical hurdles and other issues related to the conduct of the trials for which each of them is responsible. There is a risk that these issues may not be successfully resolved. In addition, we and our partners are utilizing companion diagnostic tests to identify MET-high patients in the METIV-HCC, JET-HCC and other trials. We may encounter difficulties in developing and obtaining approval for companion diagnostics, including issues relating to selectivity/specificity, analytical validation, reproducibility, or clinical validation. Any delay or failure by our collaborators or us to develop or obtain regulatory approval of the companion diagnostics could delay or prevent approval of our product candidates. 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, with respect to partnered programs, even if certain compounds show initial promise, Daiichi Sankyo or Kyowa Hakko Kirin may decide not to license or continue to develop them, as the case may be. In addition, Daiichi Sankyo and Kyowa Hakko Kirin have certain rights to unilaterally terminate their agreements with ArQule. If either company were to do so, the Company might not be able to complete development and commercialization of the applicable licensed products 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.

i Ferlay J, et al. GLOBOCAN 2012 v1.0. Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. 2013.

ii Llovet JM, et al. J Hepatol. 2012;56(4):908-43.

Dawn Schottlandt
Sr. Director, Investor Relations/
Corp. Communications
(781) 994-0300

Source:ArQule, Inc.