25 February 2019 - - US-based ArQule, Inc. (NASDAQ: ARQL) has published clinical pharmacodynamic, safety and efficacy data in patients with Proteus syndrome, the company said.

These data, together with data already presented at ASHG last year, support miransertib's further development as a potential first systemic treatment for patients suffering from overgrowth diseases, such as Proteus syndrome.

The study, published in the American Journal of Human Genetics, and led by the National Institutes of Health, demonstrated good target engagement, tolerability and reductions in lesion size and pain, especially in children.

ArQule is a biopharmaceutical company engaged in the research and development of targeted therapeutics to treat cancers and rare diseases.

ArQule's 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.

Its clinical-stage pipeline consists of five 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 current discovery efforts are focused on the identification and development of novel kinase inhibitors, leveraging the company's proprietary library of compounds.

Miransertib (ARQ 092) is an orally available, selective, pan-AKT (protein kinase B) inhibitor that potently inhibits AKT1, 2 and 3 isoforms.

Dysregulation of AKT has been implicated in a variety of rare overgrowth diseases and cancers; however, there are currently no approved inhibitors of AKT.

AKT inhibitors, either as single agent or combination therapy, show significant promise in molecularly defined patient populations.

Miransertib is currently in a Phase 1/2 company-sponsored study for PIK3CA-Related Overgrowth Spectrum, a Phase 1 study for ultra-rare Proteus syndrome conducted by the National Institutes of Health (NIH/NHGRI), and a Phase 1b study in combination with the hormonal therapy, anastrozole, in patients with advanced endometrial cancer with AKT and PI3K mutations.

Miransertib has been granted Rare Pediatric Disease Designation and Fast Track Designation by the US Food and Drug Administration, as well as Orphan Designation by the FDA and European Medicines Agency in the rare overgrowth disease, Proteus syndrome.

Proteus syndrome is an ultra-rare condition characterized by the aberrant overgrowth of multiple tissues of the body.

Patients with Proteus syndrome 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.

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 10 years of life.

There are currently no approved medicinal treatments for Proteus syndrome, leaving patients with minimal treatment options to manage the disease and a mortality of 25% by age 22.