ArQule, a Woburn, Mass.-based biotech company engaged in the R&D of next-generation, small-molecule cancer therapeutics, has formed an agreement with the National Human Genome Research Institute (NHGRI) of the NIH, providing for the clinical development of ARQ 092, an orally available, selective small molecule inhibitor of AKT, in Proteus syndrome, a rare disease characterized by overgrowth of the skeleton, skin, adipose tissue and central nervous system.

The NIH Proteus syndrome team is led by researchers who originally discovered the somatic single (point) mutation in the AKT 1 oncogene that causes Proteus syndrome. On that basis, the NIH entered a collaboration with ArQule focused on preclinical testing of ARQ 092. Results from that preclinical research demonstrate 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 represent preclinical proof-of-concept for advancement of ARQ 092 into clinical testing in this indication.

"This collaboration provides the opportunity to clinically 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 Leslie G. Biesecker, M.D., chief of the medical genomics and metabolic genetics branch at the NHGRI. "We believe the goal of treatment for Proteus syndrome will be early diagnosis and administration of therapy over years to mitigate the abnormal cell signaling initiated by the point mutation."

"The need for medical treatment of Proteus syndrome is high," said Brian Schwartz, M.D., chief medical officer of ArQule. "Characterized by non-cancerous overgrowths of tissue, Proteus syndrome is the first non-oncology rare indication to enter clinical testing for ARQ 092. We are hopeful that intervention in a single aberrant pathway responsible for this disease may hold potential for a therapeutic advance."

The NIH currently is developing a protocol for a phase I trial with ARQ 092 in this indication, with input from ArQule. The company also will be providing compound for the planned NIH clinical trial, which currently is expected to begin in 2015.