ArQule and the National Human Genome Research Institute of the National Institutes of Health Announce Enrollment of First Patient in the Phase 1 Proteus Syndrome Trial With ARQ 092

ArQule receives orphan drug designation for ARQ 092 in Proteus syndrome

BURLINGTON, Mass., Nov. 17, 2015 (GLOBE NEWSWIRE) -- ArQule, Inc. (NASDAQ:ARQL) and the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) today announced enrollment of the first patient in the phase 1 clinical trial for Proteus syndrome. This trial, with ARQ 092, an orally available, selective pan-AKT inhibitor, marks the first clinical trial in this rare disease. Proteus syndrome is characterized by overgrowth of the skeleton, skin, adipose tissue and central nervous system.

Additionally, ArQule received orphan drug designation from the Federal Drug Administration (FDA) for ARQ 092 in Proteus syndrome. This marks an important regulatory milestone and the first orphan drug designation for this population. Proteus syndrome impacts fewer than one in a million people worldwide.

In 2011, an NHGRI team led by Dr. Leslie G. Biesecker discovered that the somatic single (point) mutation in the AKT1 oncogene causes Proteus syndrome1. Subsequently the NHGRI team presented at the 2014 meeting of the American Society of Human Genetics (ASHG, Abstract # 2180M2) data that demonstrate that treatment with ARQ 092 caused a rapid shutdown of AKT signaling and a reduction in the viability of Proteus syndrome cells taken from patients compared to untreated diseased cells. These findings provided pre-clinical proof-of-concept for advancement of ARQ 092 into clinical testing for Proteus syndrome.

“The collaboration with ArQule has provided an opportunity to initiate a phase 1 trial to investigate the therapeutic impact of ARQ 092 in a rare, genetic disorder that has no approved therapy and for which the only current treatment is surgery,” said Dr. Leslie G. Biesecker, M.D., Chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute. “The goal of the trial is to identify a safe and effective dose to treat Proteus syndrome patients soon after diagnosis. It is hoped the drug, if shown to be safe and effective and approved by the FDA to treat Proteus syndrome in the future, could potentially be administered over many years in order to mitigate the abnormal cell signaling initiated by the point mutation.”

“We are excited to continue our collaboration with Dr. Biesecker and the NHGRI team on the first therapeutic drug clinical trial launched for Proteus syndrome,” said Brian Schwartz, M.D., Head of Research and Development and Chief Medical Officer at ArQule. “Proteus syndrome is the first rare disease indication to enter phase 1 for ARQ 092, and we are pleased to have received orphan drug designation from the FDA. We are also making progress with ARQ 092 in oncology where we have observed five partial responses in the phase 1b trial in patients harboring AKT1/PI3K mutations. We hope Proteus syndrome patients, with the same mutation, will achieve comparable clinical benefit once a therapeutic dose is established.”

The phase 1 trial for ARQ 092 in Proteus syndrome, being conducted by the NHGRI, is a biodynamic dose finding study. ArQule will be providing ARQ 092 for the trial.

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 ARQ 092 and the AKT Pathway

ARQ 092 is an orally available, selective small molecule inhibitor of the AKT kinase. 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.

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 an early leader in precision medicine. ArQule’s lead product, in Phase 2 and Phase 3 clinical development, is tivantinib (ARQ 197), an oral, selective inhibitor of the c-MET receptor tyrosine kinase. The Company’s pipeline includes: ARQ 092, designed to inhibit the AKT serine/threonine kinase; ARQ 087, a multi-kinase inhibitor designed to preferentially inhibit the fibroblast growth factor receptor (FGFR) family; and ARQ 761, a Beta lapachone analog being evaluated as a promoter of NQ01-mediated programmed cancer cell necrosis. ArQule’s current discovery efforts are focused on the identification 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. 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 may not demonstrate promising therapeutic effect; in addition, it 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.

1 N Engl J Med 2011; 365:611-619, August 18, 2011
2 Sci Reports, In Press

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

Source:ArQule, Inc.