ArQule Provides Proprietary Pipeline Update for AKT Inhibitors

First cohort dosed in phase 1 trial with ARQ 092 in Proteus syndrome
ArQule receives Investigational New Drug approval for ARQ 751

BURLINGTON, Mass., Jan. 28, 2016 (GLOBE NEWSWIRE) -- ArQule, Inc. (NASDAQ:ARQL) today announced a pipeline update for its AKT inhibitors, including ARQ 092 and ARQ 751, both orally available, selective pan-AKT inhibitors.

ARQ 092 – Lead AKT Inhibitor

The phase 1 trial for ARQ 092 in Proteus syndrome, which was opened for enrollment in November 2015, has completed dosing of its first cohort. The first cohort, consisting of three patients, is being observed for safety. The phase 1 trial is being conducted by our collaborators at the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH). Proteus syndrome is a rare disease that is characterized by overgrowth of the skeleton, skin, adipose tissue and central nervous system. ARQ 092 was recently granted orphan drug designation by the Food and Drug Administration (FDA) in this indication which impacts less than one in a million people worldwide.

Recently, a manuscript was published by the NHGRI of the NIH in Scientific Reports (available on-line at discussing pre-clinical research with ARQ 092 in Proteus syndrome. This pre-clinical study tested the efficacy of ARQ 092 in suppressing AKT signaling in cells and tissues from patients with Proteus syndrome. Reduced phosphorylation of AKT and downstream targets of AKT in a concentration-dependent manner were observed in as little as two hours without reduction in cell viability.

ArQule continues to enroll patients harboring AKT1 or PI3K mutations in the company sponsored phase 1b expansion cohort of its oncology trial. Cohorts for lymphoma and endometrial are fully enrolled. Thus far the company has observed five partial responses in the phase 1b portion of the trial, three of which occurred in patients whose tumors have AKT1 or PI3K mutations and two of which occurred in patients where the mutational status is unknown.

ARQ 751 – Next Generation AKT Inhibitor

ArQule received FDA approval of its investigational new drug (IND) application for ARQ 751, a next generation AKT inhibitor, in oncology. As published in PLOS ONE, (available on-line at, ARQ 751 has demonstrated signal abrogation and efficacy in pre-clinical in vitro and in vivo models harboring AKT1 and PI3K mutations. The company expects to commence a phase 1 trial in oncology during the first half of 2016 targeting AKT1 and PI3K mutations.

“We are pleased with the two recent publications on our AKT program, and we look forward to further advancing our AKT pipeline in 2016 with ARQ 092 and our next generation AKT inhibitor, ARQ 751,” said Brian Schwartz, Chief Medical Officer and Head of Research and Development at ArQule. “The understanding accumulated by us and our collaborators on our AKT program in oncology and rare diseases positions us for leadership in this class. We plan to explore opportunities to advance our trials in oncology as well as in rare over-growth indications beyond Proteus syndrome.”

“2015 was an exciting year for ArQule as we were able to bring forward clinical results from our proprietary pipeline which now includes two orphan drug designations from the FDA,” said Paolo Pucci, Chief Executive Officer at ArQule. “Looking ahead into 2016, we expect the interim analysis for the tivantinib phase 3 METIV-HCC trial to occur early in the second quarter, and we also expect to be able to make decisions on next steps in clinical development for ARQ 092 in oncology and Proteus syndrome, as well as for ARQ 087 in intrahepatic cholangiocarcinoma (iCCA).”  

About Proteus Syndrome

According to the patient advocacy and support group, the Proteus syndrome Foundation (, the condition was named for Proteus, the Greek god who could transform his shape. Patients experience changes in the shapes of certain body structures over time, including abnormal, often asymmetric, massive growth (overgrowth) of the skeleton, skin, adipose tissue and central nervous system out of proportion to the rest of the body, which may appear normal. Although patients may have minimal or no manifestations at birth, the disease develops and becomes apparent in early childhood (6-18 months) and rapidly progresses with intense growth in the first ten years of life. It is primarily a childhood-onset disease but there are very few living affected adults. 

Proteus syndrome is a rare condition with an incidence of less than 1 in 1 million people worldwide. Only a few hundred individuals have been reported in the medical literature.  At this time, there are more than 120 documented cases worldwide, but because not all cases are documented, it is not known how many individuals have this syndrome. The incidence of Proteus syndrome classifies it as a rare disorder, defined by the National Organization of Rare Diseases (NORD) as any disease affecting fewer than 200,000 Americans.

About the AKT Pathway, ARQ 092 and ARQ 751

ARQ 092 and ARQ 751 are orally bioavailable, selective small molecule inhibitors of the AKT kinases.  The AKT pathway when abnormally activated is implicated in multiple oncogenic processes such as cell proliferation and apoptosis.  This pathway has emerged as a target of potential therapeutic relevance for compounds that inhibit its activity, which has been linked to a variety of cancers as well as to select non-oncology indications.

ARQ 092, the lead compound in ArQule’s AKT program, has completed phase 1a clinical testing and has advanced into phase 1b expansion testing in cohorts of patients with endometrial cancer, lymphoma and tumors harboring either AKT or PI3K mutations. A number of next-generation compounds in the Company’s AKT program are in early to late stages of pre-clinical development. The company plans to initiate a phase 1 clinical trial in the first half of 2016 for ARQ 751, a next generation AKT inhibitor.

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 b-lapachone analog being evaluated as a promoter of NQO1-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 ARQ 092 and ARQ 751. 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, including in Proteus syndrome, does not ensure that later stage or larger scale clinical trials will be successful. For example, ARQ 092 and ARQ 751 may not demonstrate promising therapeutic effect; in addition, neither drug candidate may not demonstrate 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 during clinical trials or in the course of developing, testing or manufacturing these compounds that could lead the Company or its partners, including the National Institutes of Health, 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 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.  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