ATLANTA & GENEVA & ARCHAMPS, France--(BUSINESS WIRE)--Genkyotex, the leading developer of selective NOX enzyme inhibitors, announced today that data from a group of academic collaborators demonstrated that NOX4 is an important driver of kidney injury in diabetes and that its novel, first in class NOX 1 and 4 inhibitor, GKT137831, has the potential to prevent or delay the development of diabetic nephropathy. Data were presented at the American Society of Nephrology’s Kidney Week 2013 in Atlanta and have been accepted for publication in the Journal of the American Society of Nephrology (JASN).
Increased production of reactive oxygen species (ROS) plays a key role in the development of diabetic nephropathy, a major diabetic complication responsible for more than 40 percent of cases of chronic kidney disease. In diabetes, many factors including hyperglycemia drive the expression and activity of NADPH oxidases (NOX enzymes). This in turn activates and/or amplifies pathogenic pathways which lead to kidney injury and progressive fibrosis.
“In a model of diabetic nephropathy, our studies showed that NOX4 in particular was a key driver of reactive oxygen species production and hence kidney damage. We found that inhibiting NOX4 with GKT137831 appeared to reduce oxidative stress, and attenuate critical disease processes, resulting in marked kidney protection,” explained Dr. Karin Jandeleit-Dahm of the Baker IDI Heart & Diabetes Institute in Melbourne, Australia, who co-led the study with Prof. Harald Schmidt from Maastricht University.
“These excellent data support growing evidence of the role of NOX in complications of diabetes. Earlier work from Karin’s and Harald’s teams demonstrated that NOX1 was important for the accelerated development of atherosclerosis in diabetes. This latest data, showing the role of NOX4 in diabetic nephropathy and the protection conferred by GKT137831, supports the development of this NOX1 and 4 inhibitor for diabetic complications.” stated Dr. Ursula Ney, CEO of Genkyotex. “We have recently started an international Phase II clinical study with GKT137831 in centers throughout North America, Europe and Australia with the aim of confirming these data in patients with diabetic nephropathy.”
In a mouse diabetes model, deletion of the NOX4 gene, but not NOX1 gene, resulted in protection from kidney damage. A similar renoprotection was seen in these mice when GKT137831 was administered.
In vitro, in human podocytes (a key cellular component of the glomerular filtration barrier) exposed to high levels of glucose, silencing of the NOX4 gene resulted in reduced reactive oxygen species production and a down-regulation of profibrotic markers that are implicated in diabetic nephropathy.
The data has been accepted for publication in the JASN and an abstract was selected as a Top Oral Abstract by trainees of the American Society of Nephrology (ASN), and was presented at Kidney Week 2013 by Dr. Jay Jha from the Baker IDI Heart & Diabetes Institute. Scientists from the Cardiovascular Research Institute Maastricht (CARIM), Maastricht, Netherlands; Ottawa Hospital Research Institute, Ottawa, Canada; and Monash University, Melbourne, Australia also contributed to the research, which had support from the Juvenile Diabetes Research Foundation.
Genkyotex is developing first in class, small molecule therapeutics that specifically and selectively inhibit the NOX family of enzymes. Using a unique screening platform, Genkyotex has identified novel NOX inhibitors with the potential to treat disease areas with a high clinical need and large market potential. The company’s lead product, GKT137831, has started Phase II clinical studies in patients with diabetic nephropathy and has shown promise in several other disease models, including atherosclerosis, idiopathic pulmonary fibrosis, liver fibrosis and models of angiogenesis. Genkyotex was founded in 2006 by scientists from Switzerland, the USA and Japan, with backing from Geneva incubator Eclosion. Leading global investors Edmond de Rothschild Investment Partners, Vesalius BioCapital and MP Healthcare Venture Management have joined Eclosion in providing significant investment to Genkyotex. Further information can be found at: www.genkyotex.com.