Background: A Phase I randomized, double-blind, placebo (PLB) controlled study was conducted to assess safety, pharmacokinetics, and antiviral activity of ALS-2200 (a novel nucleotide analog HCV polymerase inhibitor) in healthy volunteers (HV) and treatment-naı¨ve patients with GT1 chronic hepatitis C (CHC). Methods: HV received doses up to 800 mg. CHC patients received multiple doses (ALS–2200 15 mg, 50 mg, 100 mg, 200 mg QD) or PLB (8:2) for 7 days (n = 10 per cohort). An additional cohort received ALS-2200 200 mg with ribavirin (1000 mg or 1200 mg/day). Results: 48 HV and 50 GT1 CHC patients were enrolled of which 35 were male and 48 GT-1b. Plasma PK of ALS-2200 and its metabolites confirmed rapid uptake in the liver. ALS-2200 was well tolerated in HV up to 800 mg and with multiple dosing in GT1 CHC patients. AEs reported in CHC patients receiving ALS-2200 were of mild or moderate severity; all AEs resolved without intervention. Most common AEs: headache (4/50),rash with pruritus (3/50) (2 in RBV arm). No SAEs or discontinuations due to AEs were reported. Median reduction in HCV RNA concentrations following 7-days treatment are shown below. No virologic breakthrough occurred during treatment. Data from 2 additional cohorts, patients with cirrhosis and GT2-6 CHC, will be included in the presentation (Table 1). Conclusions: ALS-2200 has the potential to be a component of oncedaily, all-oral, interferon–free CHC treatment regimens.