Single- and Multi-Dose Data Shows Excellent Safety and Pharmacokinetic Profiles
GENEVA & ARCHAMPS, France--(BUSINESS WIRE)-- Genkyotex, the leading developer of NOX inhibitors to treat oxygen-radical mediated diseases, announced today that Phase I studies have demonstrated excellent safety and tolerability following single and multiple oral doses of GKT137831, the first in class NOX 1 and 4 inhibitor. In addition, GKT137831 demonstrated a favourable pharmacokinetic profile in these subjects. Data were presented today at Kidney Week 2012, the annual meeting of the American Society of Nephrology.
GKT137831 was found to be safe and well tolerated when administered orally to a total of 72 healthy adult males, at single doses of up to1800 mg OD, and at multiple doses of up to 900 mg OD for 10 days. No safety signals were identified, and dose limiting toxicities were not reached. Orally administered GKT137831 is rapidly absorbed and has a broadly dose proportional PK over the 10-900 mg dose range. Multiple dose administration does not modify the PK of GKT137831 and there is no accumulation.
“The recently completed multiple ascending dose study has confirmed the excellent safety and pharmacokinetic profile of GKT137831 in healthy subjects, initially shown in the single ascending dose study completed earlier this year. We are now planning the initiation of Phase II clinical studies, including the evaluation of oral GKT137831 in patients with diabetic nephropathy, the lead indication,” said Ursula Ney, Chief Executive Officer at Genkyotex.
About NOX and its Role in Diabetic Nephropathy
NOX enzymes exist in seven isoforms and produce reactive oxygen species (ROS). ROS can cause tissue damage and modify biological pathways that may be important in a number of pathologies, including metabolic, cardiovascular, pulmonary and neurological diseases. In the kidney, NOX4 is the most abundantly expressed NOX enzyme and is upregulated in diabetic nephropathy. This upregulation is due to a number of parameters that are present in the diabetic milieu, including hyperglycemia, an activated renin angiotensin aldosterone system, advanced glycation endproducts, and oxidized lipids. The participation of NOX enzymes in multiple diabetic complications is well recognised. NOX4 plays a key role in glomerular damage and kidney fibrosis, which lead to albuminuria and end-stage renal disease, respectively. NOX1 is also involved in angiogenesis, atherosclerosis and other diabetic co-morbidities, making the inhibition of both the NOX1 and NOX4 enzymes by GKT137831, an attractive therapeutic option for this hard to treat and growing global disease. This competitive therapeutic profile of GKT137831 has been extensively validated in several animal models of diabetes induced nephropathy and atherosclerosis. The in vitro and in vivo pharmacology of GKT137831 was recently published (Hepatology DOI: 10.1002/hep.25938)) and preclinical studies conducted in multiple in vivo models suggest that GKT137831 may have application in a broad range of indications, including fibrotic diseases such as NASH and IPF.
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 novelNOX inhibitors with the potential to treat disease areas with a high clinical need andlarge market potential. Genkyotex was founded in 2006 by scientists from Switzerland, the USA and Japan, with backing from Geneva incubator Eclosion. A CHF25 million extension of the Series C investment was closed in July 2012, with existing investors, Eclosion, Edmond de Rothschild Investment Partners, Vesalius BioCapital and MP Healthcare Venture Management all reinvesting. Further information can be found at:www.genkyotex.com.