BERKELEY, Calif.--(BUSINESS WIRE)--Plexxikon Inc. today announced data from preclinical studies of Polycystic Kidney Disease (PKD) demonstrating significantly reduced kidney disease following treatment with Plexxikon’s novel drug candidate. Plexxikon’s novel small molecule kinase inhibitor is a highly selective and potent inhibitor of Raf kinase, a critical mediator of PKD pathology. These data were recently presented at the ISN Forefronts Symposium on Polycystic Kidney Disease in Montreal, Canada by Stefan Somlo, M.D., CNH Long Professor of Internal Medicine and Genetics and Chief of Nephrology at the Yale University School of Medicine.
“The degree to which this compound slowed progression of the kidney disease in preclinical models with early onset aggressive polycystic kidney disease was very dramatic, demonstrating the promise of this agent as a candidate therapy for patients with this disease,” stated Dr. Somlo. “There are currently no treatments for PKD, which is an inherited disease of the kidneys and other organs that often becomes manifest between the ages of 30 and 40 and eventually leads to kidney failure in a significant proportion of affected individuals.”
“Plexxikon’s PKD drug candidate is another example of the highly selective kinase inhibitors we are developing at Plexxikon, a prerequisite for a compound to be useful in treating a chronic disease such as PKD, and we are pleased to see such strong preclinical data in polycystic kidney disease and safety in GLP toxicology studies,” stated K. Peter Hirth, Ph.D., chief executive officer of Plexxikon. “We look forward to initiating a Phase 1 clinical trial for this novel drug candidate in 2008.”
In the preclinical study of Plexxikon’s PKD drug candidate, doses of the drug candidate were administered orally daily for 14 days. A marked reduction in kidney cyst burden was observed in the treatment group compared to vehicle treated mice. Levels of blood urea nitrogen (BUN), an indicator of kidney function, were also significantly improved in the drug-treated groups compared with the vehicle-treated group, suggesting that improved renal function accompanied reduced cyst growth in treated animals.
Using its proprietary Scaffold-Based Drug Discovery™ platform, Plexxikon has identified a portfolio of unique compounds that selectively block Raf-dependent cells, leaving healthy cells unharmed since Raf activity is differentially regulated in those cells. The co-crystallography platform enabled scientists at Plexxikon to determine the exact location where such inhibitors selectively bind to the kinase active site.
Plexxikon’s family of Raf kinase inhibitors selectively target a unique binding site of the protein, minimizing the common side effects seen from other less selective kinase inhibitors. In several different systems, Plexxikon’s Raf inhibitor blocks proliferation of dysfunctional cells, without detectable affects on healthy cells. Interestingly, our drug candidate is highly selective for the PKD indication, with no detectable inhibition of cancer cell line growth – including no activity in cancers bearing the important B-RafV600E oncogene.
About Polycystic Kidney Disease
PKD is a genetic disease characterized by the development of many fluid filled cysts in the kidneys. The cysts can profoundly increase the size of the kidneys while damaging much of the normal tissue resulting in impaired function of the kidneys and ultimately kidney failure. Approximately 600,000 people in the U.S. and 12.5 million people worldwide suffer from PKD, which is the fourth leading cause of kidney failure. Patients whose kidneys fail require either dialysis or kidney transplantation to survive. There are currently no treatments available to alter the progression of PKD.
Edward T. Mathers Appointed to Plexxikon Board of Directors
In other news, Plexxikon today announced the appointment of Edward T. Mathers to its board of directors. Mr. Mathers currently serves as executive vice president, corporate development and venture at MedImmune, where he has been since 2002. He is responsible for the company’s licensing and business development activities and is also a key leader of the company’s MedImmune Ventures, Inc. team evaluating investment opportunities.
“We are pleased to welcome Ed to our board of directors. His depth of experience in corporate development will be invaluable as we further develop and execute on our business strategies and position our product candidates for partnering. While Plexxikon has been very successful to date in securing industry leading partnerships, our discovery platform has continued to prove prolific in producing a broad portfolio of unpartnered assets. We are pleased to bring in Ed’s expertise as our business grows and additional strategic opportunities are explored,” stated Dr. Hirth.
Prior to joining MedImmune, Mr. Mathers was vice president of marketing and corporate licensing and acquisitions at Inhale Therapeutic Systems. He was with Glaxo Wellcome, Inc. (GlaxoSmithKline) for 15 years prior to that holding a number of increasingly responsible positions in sales and marketing. Mr. Mathers started his career at Ortho Pharmaceuticals Corporation (a division of Johnson & Johnson) as a researcher. In addition to Plexxikon, he currently serves on the boards of directors of both Metastatix, Inc. and Kémia, Inc. He holds a bachelor’s degree in chemistry from North Carolina State University.
Plexxikon is a leader in structure-guided discovery and development of novel small molecule pharmaceuticals to treat human disease. The company’s clinical stage programs include PLX204 for the treatment of diabetes, and PLX4032 for the treatment of melanoma and colorectal cancer. Preclinical development programs include a kinase inhibitor for the treatment of pain, and a portfolio of kinase inhibitors for the treatment of kidney disease, rheumatoid arthritis and metastatic breast cancer.
Plexxikon’s proprietary Scaffold-Based Drug Discovery™ platform is being applied to build a pipeline of diverse product opportunities for the treatment of metabolic and cardiovascular disease, inflammation, oncology and CNS disorders. This discovery process integrates a number of state-of-the-art technologies, including structural screening as one key component that provides a significant competitive advantage over other drug discovery approaches. To date, the company has discovered a portfolio of clinical and preclinical stage compounds in multiple disease areas addressing significant unmet needs in each therapeutic category.
Plexxikon is seeking pharmaceutical and biotechnology partners for select collaboration opportunities. For more information, please visit www.plexxikon.com.