Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a Pote

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Idenix Pharmaceuticals Reports Favorable Pharmacokinetic Data for IDX320, a

Potent, Multi-Genotypic Protease Inhibitor for the Treatment of Hepatitis C

press announcement

- IDX320 pharmacokinetic data in healthy volunteers suggest potential for

once-daily dosing in HCV-infected patients - Triple combinations of

direct-acting antiviral agents demonstrate strong in vitro synergy against

hepatitis C virus (HCV) - Data were presented in three posters at the 45th

Annual Meeting of the European Association for the Study of the Liver (EASL)

CAMBRIDGE, Mass., April 16, 2010 /PRNewswire via COMTEX/ --Idenix

Pharmaceuticals, Inc. (Nasdaq: IDIX), a biopharmaceutical company engaged in the

discovery and development of drugs for the treatment of human viral diseases,

today reported promising in vitro data for IDX320, an HCV protease inhibitor,

demonstrating potent and selective antiviral activity in multiple genotypes, or

strains, of the virus. The favorable pharmacokinetic profile defined in

preclinical studies was confirmed by interim Phase I clinical data in healthy

volunteers. Additional data presented demonstrated that a combination of three

Idenix drug candidates, including IDX320, with different mechanisms of action

produced strong synergy in vitro. These data support the evaluation of

direct-acting antiviral (DAA) combination regimens for the treatment of HCV.

" We are excited about the preclinical and first-in-man data presented today from

the IDX320 program. With the in vitro potency and favorable pharmacokinetic

profile seen to date combined with the potential for once-daily dosing and

multi-genotypic coverage, we believe IDX320 could offer improvements over other

protease inhibitors currently in development, " said Standring, Ph.D.,

Idenix's executive vice president, biology. " The Phase I single and multiple

ascending dose clinical study in healthy volunteers is now complete, and we look

forward to advancing IDX320 into a three-day proof-of-concept study expected to

begin in the second quarter. "

" The in vitro combination data presented today continue to support our belief

that the future of HCV treatment will be a combination of direct-acting

antivirals from different drug classes. We are pursuing a drug development

strategy to achieve that goal, " said Jean-Pierre Sommadossi, Ph.D., chief

executive officer of Idenix.

IDX320 is a potent inhibitor of NS3/4A proteases from genotypes 1a, 1b, 2a and

4a (IC(50) values from 0.8 to 1.9 nM), as well as from genotype 3a (IC(50)=23

nM). IDX320 did not inhibit nine tested cellular proteases (IC(50) > 10

micromolars) in vitro, suggesting high selectivity. IDX320 bound tightly to the

HCV protease enzyme with a long dissociation half-life (> 9 hours). The

signature mutation observed in vitro was D168V, consistent with other

macrocyclic inhibitors. This mutation had reduced replication fitness and was

susceptible to treatment with interferon as well as other classes of DAAs.

Additionally, IDX320 retained activity against mutations that produce resistance

to other protease inhibitors in clinical development. (Lallos, et al, " In Vitro

Antiviral Activity of IDX320, a Novel and Potent Macrocyclic HCV Protease

Inhibitor " , Poster #768.)

After single 2 mg/kg oral doses of IDX320 in two animal species, favorable

bioavailability and a long plasma half-life were observed, with substantial

plasma concentrations 24 hours post dose. These preclinical data were confirmed

in orally-dosed healthy volunteers (n=6) receiving a single 200 mg tablet.

Further, no significant in vitro inhibition of human drug metabolizing enzymes,

CYP450s and UGT1A1, by IDX320 suggests low potential for drug-drug interactions

in patients. (Good, et al, " Preclinical Pharmacokinetic Profile of IDX320, a

Novel and Potent HCV Protease Inhibitor " , Poster #750).

Double and triple combination in vitro studies of Idenix's HCV direct-acting

antiviral drug candidates from different HCV drug classes, including IDX184 (a

nucleotide inhibitor), IDX320 (a protease inhibitor), IDX375 (a non-nucleoside

inhibitor) and a prototype Idenix NS5A inhibitor, were reported. Data

demonstrated that double combinations (IDX320 with IDX184, IDX375 or NS5A

inhibitor) resulted in additive to mildly synergistic effects after 3 days of

treatment in vitro. Furthermore, triple combinations, especially those including

agents from three different HCV drug classes (IDX184/IDX320/IDX375 or

IDX184/IDX320/NS5A inhibitor), demonstrated the strongest synergy in vitro.

Similar results were observed over 14-days of treatment with no evidence of

viral breakthrough or cellular cytotoxicity. (La Colla, et al, " A Triple

Combination of Direct-Acting Antiviral Agents Demonstrates Robust Anti-HCV

Activity In Vitro " , Poster #769.)