ArQule Presents Preclinical Data for ARQ 531, a Proprietary Reversible Inhibitor of Wild Type and Mutant BTK, at the 2016 Pan Pacific Lymphoma Conference

Burlington, Massachusetts, UNITED STATES

Data supports further preclinical and clinical research in BTK sensitive and ibrutinib resistant malignancies

BURLINGTON, Mass., July 18, 2016 (GLOBE NEWSWIRE) -- ArQule, Inc. (Nasdaq:ARQL) today announced the first public presentation of data on its novel BTK inhibitor, ARQ 531, at the 2016 Pan Pacific Lymphoma Conference in Koloa, Hawaii. ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor.

In preclinical testing, ARQ 531 demonstrated biochemical inhibition of both wild type and C481S-mutant BTK at sub-nanomolar levels and potent cellular inhibition in C481S-mutant BTK cells that are resistant to ibrutinib. This molecule also exhibits a distinct kinase selectivity profile with inhibitory activity against several key oncogenic drivers related to ibrutinib resistance. It is currently estimated that about 10% of patients treated with ibrutinib develop resistance with over 80% presenting the C481S mutation. This incidence rate is expected to increase.

Additionally, the compound potently suppresses cell proliferation of hematological malignancies in vitro, with B-cell receptor signaling inhibition. ARQ 531 also demonstrates strong in vivo target and pathway inhibition of phospho-BTK with potent and durable growth suppression.

“We are beginning to see increasing resistance to ibrutinib which is creating the need for a BTK inhibitor, like ARQ 531, that targets the C481S mutation,” said Dr. Brian Schwartz, Head of Research and Development and Chief Medical Officer at ArQule. “The preclinical profile of ARQ 531 as a potent and reversible inhibitor of wild type and mutant BTK presents the potential for a first-in-class and best-in-class molecule. We are working toward completing GLP toxicology studies and filing an IND in early 2017.”

The poster titled “ARQ 531, a Novel, Oral, Non-Covalent Inhibitor of Wild Type and C481S Mutant BTK with Potent Anti-Tumor Activity” can be viewed at

About BTK and ARQ 531

ARQ 531 is an investigational, orally bioavailable, potent and reversible Bruton’s tyrosine kinase (BTK) inhibitor. Biochemical and cellular studies have shown that ARQ 531 inhibits both the wild type and C481S-mutant forms of BTK. The C481S mutation is a known emerging resistance mechanism for first generation irreversible BTK inhibitors.  ARQ 531 has high oral bioavailability as well as good ADME, pharmacokinetic and metabolic properties. The company plans to file an IND for ARQ 531 in early 2017. BTK is a therapeutic target that has been clinically proven to inhibit B-cell receptor signaling in blood cancers.

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 proprietary clinical-stage pipeline consists of four drug candidates, all of which are in targeted, biomarker-defined patient populations, making ArQule a leader among companies our size 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, in phase 2 for iCCA and in phase 1b for multiple oncology indications; and ARQ 761, a β-lapachone analog being evaluated as a promoter of NQO1-mediated programmed cancer cell necrosis, 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 preclinical trials and planned clinical trials with ARQ 531. 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 preclinical trial results does not ensure that later stage or larger scale clinical trials will be successful. For example, ARQ 531 may not demonstrate promising therapeutic effect; in addition, ARQ 531 may not demonstrate appropriate safety profiles in current or later stage or larger scale preclinical or 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 during clinical trials or in the course of developing, testing or manufacturing these compounds that could lead the Company 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. 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 preclinical 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. 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.

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