ÿþ<!DOCTYPE HTML PUBLIC "-//W3C//DTD HTML 4.01 Transitional//EN" "http://www.w3.org/TR/html4/loose.dtd"> <html> <head> <meta http-equiv="Content-Type" content="text/html; charset=iso-8859-1"> <title>EASL 2010 - Poster Presentations</title> <link rel="stylesheet" type="text/css" href="style.css"> </head> <body> <table width="750" align="center" border="0" cellspacing="0" cellpadding="0" class="MainTable"> <tr> <td><img src="http://www2.kenes.com/liver-congress/PublishingImages/top_ei.jpg" width="760" height="129" /></td> </tr> <tr> <td class="content"><h1>Poster Presentations</h1> <P><b>Session Title:</b> Category 5b. VIRAL HEPATITIS: b. HEPATITIS C - EXPERIMENTAL (VIROLOGY)<br><b>Presentation Date:</b> Apr 16, 2010</P><h2 align='left'><B>ENHANCED <I>IN VITRO</I> ANTIVIRAL ACTIVITY OF ANA598 IN COMBINATION WITH OTHER ANTI-HCV AGENTS SUPPORT COMBINATION TREATMENT</B></h2> <p align='left'><b>P.A. Thompson</b>*, R.E. Showalter, R.A. Patel, J.R. Appleman<br> <em>Anadys Pharmaceuticals, Inc., San Diego, CA, USA. *pthompson@anadyspharma.com</em></p><br> <p align='justify'><b><b>Background: </b></b> ANA598 is a novel HCV non-nucleoside polymerase inhibitor that is currently in a Phase II trial in combination with current SOC in hepatitis C-infected patients. Future clinical trials in HCV are expected to explore combinations of two or more direct antivirals, which may provide additional benefit in certain populations and may reduce or eliminate the need for interferon or ribavirin. To better understand the potential of combinations utilizing ANA598, co-selection studies of ANA598 with IFN-± and clinically advanced direct antiviral agents were evaluated <i>in vitro. </i>The results provide support for future clinical exploration of combination regimens that include ANA598.<br><b><b>Methods: </b></b> Co-selection studies were conducted using Huh7-Luc/neo wt 1b dicistronic replicon cells. Combinations of ANA598 with IFN-±, the HCV NS3/4 protease inhibitor telaprevir, and the NS5B nucleoside polymerase inhibitor PSI-6130 were evaluated. The direct antiviral agents have distinct mechanisms of action and non-overlapping resistance profiles. The cells were selected with G418 in the absence or presence of either one or two agents at combinations between their EC<sub>50</sub> and EC<sub>99</sub>. After 3 weeks in culture, cells were either fixed and stained or total cellular RNA was extracted. The NS5B and NS3 coding sequences were determined through direct sequencing of PCR products. <br><b><b>Results: </b></b> <i>In vitro</i> combination of ANA598 with IFN-±, telaprevir, and PSI-6130 after 3 days in the replicon system showed that the antiviral interaction between the compounds was additive to synergistic. Treatment of the replicon cells for 21 days with ANA598 or telaprevir alone selected for resistant colonies. The co-selection studies demonstrated that at the EC<sub>95 </sub>of ANA598, which is readily achievable in the clinic, combination with IFN-±, telaprevir or PSI-6130 led to clearance of the replicon from the cells rather than emergence of resistant colonies. <br><b><b>Conclusions: </b></b> The <i>in vitro</i> co-selection studies demonstrate an elimination of resistant variants and additive to synergistic antiviral effects when ANA598 is combined with other anti-HCV agents. Clinical use of such combinations may produce a greater viral load reduction and potentially allow durable clearance of virus prior to the emergence of drug resistance in most patients.</p> <br><a href='Session-P02-5b.htm'>Back</a><br> <p>&nbsp;</p> <p>&nbsp;</p></td> </tr> </table> </body> </html>