Conclusions: MK-8742 exhibits potent antiviral activity during 5-day monotherapy in patients with chronic GT-1 and GT-3 HCV infection. Robust antiviral response was observed in the presence of baseline RAVs in 2 GT1 patients. RAVs at resistance loci common to other NS5A inhibitors were selected under antiviral pressure. The antiviral data support the continued clinical investigation of MK-8742 as a once-daily component of an all-oral, interferon-free regimen for the treatment of chronic HCV-infec-tion. Disclosures: Stephanie Curry – Employment: Merck Patricia McMonagle – Employment: Merck and Co. Robert B. Nachbar – Employment: Merck Sharp &

Dohme Corp.; Stock Shareholder: Merck Sharp & Dohme Corp. Patricia Jumes – Employment: Merck; Stock Shareholder: Merck Steve Ludmerer – Employment: Merch & Co Ernest Asante-Appiah – Employment: Merck Daria Hazuda GDC-0068 ic50 – Employment: Merck & Co.; Stock Shareholder: Merck & Co Wendy W. Yeh – Employment: Merck & Co. Anita Y. Howe – Employment:

Merck Research Laboratory The following people have Selleckchem SCH727965 nothing to disclose: Rong Liu, Irene Pak SB 9200 is a novel, first-in-class anti-HCV drug which acts by enhancing the function of host cytosolic sensor proteins RIG-I and NOD2 that detect RNA viruses. It has shown potent activity against HCV G1a and G1 b replicons in vitro and is synergistic with other anti-HCV drugs such as telaprevir (NS3 protease inhibitor), NM283 (NS5B inhibitor), interferon and ribavirin. MCE To explore the genotypic range of SB 9200, sensitivity of patient-derived HCV of different genotypes was tested in the recently developed capture-fusion assay, a novel HCV replication model that is highly predictive of clinical outcome of potential antivirals. Prestimulated THP-1 cells were infected with serum from donors with chronic HCV G1, 2, 3, 4 or 6, then fused with Huh7.5 cells

and treated once with varying concentrations of SB 9200. For comparison, fused cells infected with G1 and G3 sera were treated with telaprevir or alisporivir. Hybrid cells were cultured for 5 days, before quantification of HCV RNA by PCR. Dose-response curves were used to calculate IC50 values. Results are given as mean ± s.d. and p values were calculated using the Mann-Whitney U test. SB 9200 inhibited replication of G1, 2, 3, 4 and 6 HCV strains in the fused cells. G3 isolates were significantly more sensitive to SB 9200 than to telaprevir (SB 9200 IC500.04 ± 0.01 μM, telaprevir IC500.12 ± 0.03 μM, p = 0.016). In G1 isolates, anti-viral potency of SB 9200 was comparable to that of alisporivir in this replication model (SB 9200 IC500.16 ± 0.12 μM, alisporivir IC500.14 ± 0.03 μM; p = 1.0). A similar pattern was seen in G3 isolates (SB 9200 IC500.04 ± 0.01 μM, alisporivir IC500.04 ± 0.02 μM; p = 0.4) (Figure 1).