The National Human Genome Research Institute (NHGRI), a branch of the NIH, has made an agreement with ArQule to support the clinical development of ARQ 092 for the rare disease Proteus syndrome. The NIH says it is currently developing a protocol for a Phase I trial with ARQ 092 in this indication, with input from ArQule, which will also be providing compound for the NIH clinical trial.

ARQ 092 is a small molecule inhibitor of AKT, and NIH says its Proteus syndrome team is being led by researchers who originally discovered in 2011 the somatic single (point) mutation in the AKT 1 oncogene that causes Proteus syndrome. Preclinical tests conducted by the NIH and ArQule showed 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—results strong enough to advance the candidate into clinical testing, which NIH and ArQule anticipate will begin in 2015.

Proteus syndrome is characterized by overgrowth of the skeleton, skin, adipose tissue, and central nervous system. Joseph Merrick, the “Elephant Man,” may have suffered from this condition. Leslie G. Biesecker, M.D., chief of the Medical Genomics and Metabolic Genetics branch at NHGRI, said in a statement that Proteus syndrome has no approved therapy and the only treatment currently available is surgery.

“The need for medical treatment of Proteus syndrome is high,” ArQule CMO Brian Schwartz, M.D., commented. “Characterized by noncancerous overgrowths of tissue, Proteus syndrome is the first nononcology 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.”

ArQule regained worldwide rights to develop and commercialize ARQ 092 from Daiichi Sankyo back in April of 2013 after Daiichi Sankyo terminated a license and co-commercialization agreement made between the two firms in November 2011. ARQ 092 was discovered through technology from the ArQule Kinase Inhibitor Platform (AKIP™) and, up until the agreement's termination, Daiichi Sankyo had global exclusive rights for development, manufacturing, and marketing of ARQ 092 and other compounds discovered via AKIP.