SAN DIEGO, Nov. 5 Conatus Pharmaceuticals Inc. todayreported positive preclinical results on its lead compound, CTS-1027 inmultiple models of hepatitis, an inflammatory liver disease. The results werepresented in a poster session today at the American Association for the Studyof Liver Diseases (AASLD) in Boston, MA.
CTS-1027 significantly reduced liver damage following oral administrationin four different preclinical models of liver injury. CTS-1027 markedlyreduced aminotransferase (ALT) activity and improved survival and liverhistology in the TNFalpha/Gln model. CTS-1027 was equally effective dosed atthe same time as the insult or post-insult in the LPS/Gln model. CTS-1027significantly reduced ALT activity in the Fas and Con A models. Dosing waswell below or equivalent to exposure levels previously tolerated in humanclinical studies.
"CTS-1027 represents a potential new and exciting approach to treatpatients infected with Hepatitis C Virus (HCV), and in the treatment of otherliver diseases. Our initial goal for the development of CTS-1027 is toestablish safety and efficacy in patients infected with HCV who have failed orcan not tolerate standard of care," stated Alfred Spada, Ph.D., SVP Researchand Development. "We plan to initiate a Phase 2 clinical trial within thenext few months."
CTS-1027 is an oral, small molecule, matrix metalloproteinase (MMP)inhibitor under development for chronic use to protect the liver from damagedue to a variety of insults including virus infection, obesity, alcohol use,and autoimmune diseases. Preclinical studies demonstrate strong efficacy inmultiple models of liver disease. In previous clinical trials in othertherapeutic areas, CTS-1027 was chronically administered to over 500 people,some for over 18 months.
Matrix metalloproteinases (MMPs) are a well studied family of proteolyticenzymes. In the liver, as in other solid organs, MMPs play a key role inmaintaining the integrity of the extracellular matrix. Excessive MMP activityhas been demonstrated to occur in the liver in response to a variety of acuteand chronic insults. This results in the loss of scaffolding that maintainsthe normal architecture of the liver and the recruitment and activation ofinflammatory cells that perpetuate liver damage. In addition, importantcytokines in the progression of liver damage, such as TGF-beta, stimulate theexpression of MMPs from hepatic stellate cells, the main cell type involved inthe pathology of fibrosis. MMPs are also well recognized to play an importantand direct role in regulating inflammation. These dual activities of tissueremodeling and modulating inflammatory networks make MMPs an attractive targetin the setting of acute and chronic liver disease.
Conatus Pharmaceuticals Inc. is a privately-held specialty pharmaceuticalcompany engaged in the development of innovative human therapeutics to treatliver disease. Chronic liver disease affects millions of people worldwide andcan be caused by many different conditions or "insults" to the liver includingHepatitis C and other viral infections, obesity, chronic alcohol abuse orautoimmune diseases. Conatus was founded by the executive management team ofIdun Pharmaceuticals in July 2005 following the successful sale of Idun toPfizer.
SOURCE Conatus Pharmaceuticals Inc.