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Initiates IDX184 Phase I Clinical Study and Advances HCV Protease Inhibitor and Non-Nucleoside Polymerase Inhibitor Clinical Candidates into IND-Enabling Preclinical Studies
CAMBRIDGE, MA, USA | July 29, 2008| Idenix Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases, today announced that it has initiated a first-in-man study of IDX184 under a United States investigational new drug (IND) application. IDX184 is a once-daily, oral nucleotide prodrug polymerase inhibitor for the treatment of chronic hepatitis C. Today, Idenix also announced that is has selected a lead clinical candidate (IDX375) from its HCV non-nucleoside polymerase inhibitor discovery program and has advanced IDX375 into IND-enabling pharmacokinetic and toxicology studies. Idenix has also advanced two protease inhibitor drug candidates (IDX136 and IDX316) into IND-enabling pharmacokinetic and toxicology studies.
"We are pleased with the progress we have made in our hepatitis C discovery program in the past few months," said Jean-Pierre Sommadossi, Ph.D., chief executive officer of Idenix. "With IDX184 entering human testing and clinical candidates undergoing late-stage preclinical testing from our HCV non-nucleoside and protease inhibitor programs, we are progressing toward our ultimate goal of developing a proprietary combination of direct-acting antivirals for the treatment of hepatitis C."
IDX184 Nucleotide Prodrug Polymerase Inhibitor
IDX184 is a once-daily, oral nucleotide prodrug candidate based on Idenix's proprietary liver-targeting technology that has demonstrated HCV antiviral activity in both in vitro and in vivo preclinical models. Pre-clinical testing suggests that this technology enables the delivery of high levels of active nucleoside triphosphate into the liver, the site of primary HCV infection. In HCV genotype-1 infected chimpanzees, once-daily oral administration of 10 mg/kg of IDX184 produced a mean viral load reduction of 2.3 log10 after four days of dosing.
"The in vitro antiviral activity of IDX184 combined with the marked viral load reductions observed in HCV-infected chimpanzees support the potential for once-a-day, low milligram dosing of IDX184 in HCV-infected patients," said David Standring, Ph.D., executive vice president of biology for Idenix.
The company has initiated a first-in-man study of IDX184 under a U.S. IND. The study design is a double-blind, placebo-controlled, single dose-escalation study to evaluate the safety and pharmacokinetic activity of IDX184 in healthy volunteers. This study will evaluate six single rising doses of IDX184, ranging from 5 mg to 100 mg once-per-day. Each cohort of the study will evaluate eight volunteers randomized six to IDX184 and two to placebo. This study will be followed by a phase I/II proof-of-concept study in treatment/naive, HCV genotype-1 infected patients.
IDX375 Non-Nucleoside Polymerase Inhibitor
Idenix has selected IDX375 as its lead clinical candidate from its HCV non-nucleoside polymerase inhibitor discovery program. Preclinical testing demonstrated that IDX375 targets the palm non-nucleoside pocket of HCV polymerase. IDX375 has exhibited single nanomolar in vitro potency against HCV genotype 1b replicon (EC50 = 2 nM) and against HCV genotype 1a and 1b polymerases. Additionally, cellular cytotoxicity testing in Huh-7 cells demonstrated that IDX375 is not cytotoxic (CC50 >100 micrometers), resulting in a selectivity index >33,000 for IDX375. In preclinical in vitro studies, IDX375 did not inhibit human cellular DNA polymerases alpha, beta and gamma (IC50 >100 micrometers), demonstrating selectivity for the HCV 1a and 1b polymerases. After oral administration in monkeys, bioavailability of IDX375 was approximately 30%. Based on monkey plasma drug exposure levels, IDX375 has the potential for once-daily dosing in man.
IDX136 and IDX316 Macrocyclic Protease Inhibitors
Idenix has scaled up manufacturing of two clinical candidates, IDX136 and IDX316, from its HCV protease inhibitor discovery program to support IND-enabling pharmacology and toxicology studies. Both IDX136 and IDX316 are based on Idenix's proprietary scaffold B and were developed through SAR (structural activity relationship) approaches aided by high-resolution co-crystal structures with the HCV protease. IDX136 and IDX316 have demonstrated single nanomolar potency against HCV genotype 1a and 1b purified proteases and nanomolar potency against HCV genotype 1b replicon (EC50 = 4 to 10 nM). Additionally, these compounds are highly selective, binding tightly to the HCV protease and demonstrating no activity against eight human cellular proteases. Both drug candidates appear to have a differentiated resistance profile when compared to other macrocyclic protease inhibitors in development. Favorable pharmacokinetic properties of IDX136 and IDX316 in non-human primates suggest the potential for once- or twice-daily dosing in man.
About Idenix
Idenix Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts, is a biopharmaceutical company engaged in the discovery and development of drugs for the treatment of human viral and other infectious diseases. Idenix's current focus is on the treatment of infections caused by hepatitis C virus and HIV. For further information about Idenix, please refer to www.idenix.com.
SOURCE: Idenix Pharmaceuticals, Inc. |
