icon-folder.gif   Conference Reports for NATAP  
 
  Digestive Disease Week 2007
Washington DC
May 19-24, 2007
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InterMune Presents Research on ITMN-191 in Hepatitis C at Digestive Disease Week Meeting
 
 
  Reports 'Picomolar' Potency and Slow Dissociation from HCV Protease
 
WASHINGTON, May 21 /PRNewswire-FirstCall/ -- InterMune, Inc. (Nasdaq: ITMN) today presented new preclinical data on the company's Hepatitis C virus (HCV) NS3/4A protease inhibitor, ITMN-191, during a scientific session of the Digestive Disease Week (DDW) meeting being held May 19-24 in Washington, D.C. The reported study (DDW abstract #M1816) examined ITMN-191 potency and binding kinetics in biochemical assays.
 
The new InterMune study represents an in-depth characterization of the mechanism of inhibition of the HCV NS3/4A serine protease by ITMN-191. Full characterization of the inhibition mechanism indicated that ITMN-191's true biochemical potency of 36 picomolar (pM) was approximately ten-fold better than previously inferred (~ 250 pM reported at DDW 2006). The presented data also suggest that ITMN-191 binds to the NS3/4A protease target in a two-step binding mechanism in which ITMN-191 initially associates with NS3/4A in a collision complex that isomerizes to a long-lived but non-covalent drug-target complex. The half life of the complex between ITMN-191 and NS3/4A was estimated to be five hours or more, and inhibition of protease activity of NS3/4A was stable over this same time period. Slow dissociation of ITMN-191 from the NS3/4A protease may have a relevant in vivo consequence, as a two-hour exposure of ITMN-191 to tissue culture cells that harbor an HCV replicon resulted in an antiviral effect equal to that delivered by continuous exposure of ITMN-191.
 
Lawrence M. Blatt, Ph.D., Chief Scientific Officer of InterMune, said, "This preclinical study of ITMN-191 provides a better understanding of its attractive potency and binding characteristics. While ITMN-191 is a non-covalent, reversible inhibitor of the protease, the onset of inhibition and slow dissociation compare favorably with those observed with covalent protease inhibitors currently in development. The immediate onset of inhibition and slow dissociation observed with ITMN-191 suggest that liver concentrations may underestimate its antiviral activity, since ITMN-191 will likely remain bound to the protease target after unbound drug is cleared from the liver."
 
About ITMN-191
Preclinical toxicology and pharmacokinetic studies in multiple species suggest that ITMN-191 has attractive characteristics, including significant liver exposure, slow dissociation from the NS3/4 protease, high in vitro potency and specificity, and an advantageous cross-resistance profile, including considerable effectiveness against variants of the NS3/4A protease that are resistant to other HCV protease inhibitors currently in development. The preclinical pharmacokinetic results support the exploration of twice-daily oral dosing. In early May 2007, InterMune reported that it had completed dosing in a Phase 1a single ascending-dose (SAD) trial of ITMN-191 in healthy subjects. No serious adverse events were reported in the SAD trial. Preliminary safety data from the SAD trial suggests that ITMN-191 was well tolerated and safe at the doses intended for the Phase 1b multiple-ascending dose (MAD) trial of ITMN-191. InterMune currently anticipates that the MAD trial will begin in the third quarter of 2007 and initial top-line viral kinetic data reported in the fourth quarter of 2007.
 
InterMune and Roche have a collaboration agreement for the research, development and commercialization of ITMN-191 (referred to as R7227 within the Roche research and development programs) and second-generation HCV protease inhibitor compounds.
 
About HCV and HCV Protease Inhibitors
According to the Centers for Disease Control and Prevention (CDC), an estimated 3.9 million Americans (1.8%) have been infected with HCV, of whom 2.7 million are chronically infected. It is estimated that there are 170 million people worldwide afflicted with this disease. While currently available therapies can cure many patients, there is considerable need for the development of novel therapeutic approaches. The HCV NS3/4 protease is an attractive drug target because of its potential involvement in viral replication and suppressive effects on host response to viral infection. Inhibitors of the HCV protease, such as ITMN-191, represent a promising new class of drugs for HCV.
 
About InterMune
InterMune is a biotechnology company focused on the research, development and commercialization of innovative therapies in pulmonology and hepatology. InterMune has a pipeline portfolio addressing idiopathic pulmonary fibrosis (IPF) and hepatitis C virus (HCV) infections. The pulmonology portfolio includes the Phase 3 program, CAPACITY, which is evaluating pirfenidone as a possible therapeutic candidate for the treatment of patients with IPF and a research program focused on small molecules for pulmonary disease. The hepatology portfolio includes the HCV protease inhibitor compound ITMN-191 in Phase 1a, a second-generation HCV protease inhibitor program, and a research program evaluating a new target in hepatology. For additional information about InterMune and its R&D pipeline, please visit http://www.intermune.com.