1.  Treatment regimens –Co-formulated ombitasvir (OBV)/paritaprevir (PTV)/rironavir (r) : 25/150/100 mg QD = 2 tablets –Dasabuvir (DSV) : 250 mg BID –RBV : 1000 or 1200 mg/day (bid dosing) according to body weight (< or ≥ 75 kg) OBV/PTV/r + DSV + RBV Open-label 18-70 years HCV genotype 1 HCV RNA > 10,000 IU/ml Naïve or pre-treated with PEG-IFN + RBV No cirrhosis ≥ 6 months opioid replacement* No HBV or HIV co-infection * Methadone or buprenorphine (± naloxone) N = 38 W12W24 SVR 12  Objective –Primary endpoint : SVR 12 (HCV RNA < 25 IU/ml), with 95% CI –Intensive 24 hours steady-state PK analysis  Design M14-103 Lalezari J. J Hepatology 2015;63:364-9 M14-103 Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for genotype 1 on opioid replacement therapy

2. N = 38 Mean age, years60 Female34% Race : white95% Body mass index, mean27.0% IL28B non-CC genotype68% HCV RNA log 10 IU/ml, mean (SD)6.58 ± 0.7 Fibrosis stage F0-F1 / F2 / F3, N30 / 6 / 2 Genotype 1a84.2% Treatment-naïve94.7% Opioid replacement therapy Methadone Buprenorphine 50% Discontinued study drug (for adverse event), N1 SVR 12 37/38 (97.4%) No virologic breakthrough, no relapse Baseline characteristics and outcome M14-103 Lalezari J. J Hepatology 2015;63:364-9 M14-103 Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for genotype 1 on opioid replacement therapy

3. N = 38 Any adverse event35 (92) AE leading to treatment discontinuation1 Serious adverse event2 (5) Common adverse events, % Nausea50% Fatigue47% Headache32% Insomnia18% Rash16% Anxiety13% Arthralgia13% Anemia11% Irritability11% Vomiting11% Hemoglobin < 10 g/dl / < 8 g/dl, N8* / 2 (*RBV dose reduction in 6/8) Grade 3 bilirubin elevation, N1 M14-103 Adverse events, n (%) Lalezari J. J Hepatology 2015;63:364-9 M14-103 Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for genotype 1 on opioid replacement therapy

4. DrugGeometric mean (% CV) C max (ng/ml)T max (h) *AUC (ng/ml)** Dasabuvir666 (44%) 4.1 (4.2 ± 2.2) 4797 (45%) Dasabuvir M1 metabolite374 (58%) 4.1 (4.5 ± 0.95) 2435 (63%) Ombitasvir95 (31%) 4.3 (4.9 ± 1.0) 1438 (31%) Paritaprevir1353 (124%) 4.3 (5.5 ± 4.3) 14,066 (129%) Ritonavir947 (53%) 4.3 (5.5 ± 4.3) 10,977 (56%) Ribavirin3180 (30%)3.6 (4.7 ± 3.7)31,984 (31%) * Median (arithmetic mean ± SD) ; ** AUC 24 for drugs qd, AUC 12 for drugs BID  The steady-state exposures for OBV, PTV, and RTV were comparable to exposures in phase I studies of adults receiving similar formulations of OBV/PTV/r + DSV without methadone or buprenorphine, while exposures of DSV and DSV M1 were slightly lower M14-103 Steady-stade pharmacokinetic parameters (N = 22) Lalezari J. J Hepatology 2015;63:364-9 M14-103 Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for genotype 1 on opioid replacement therapy

5.  Summary –The 3D + RBV regimen achieved an SVR 12 rate of 97.4% among these 38 genotype 1-infected patients receiving opioid replacement therapy –No viral breakthroughs or relapses were observed –The regimen was well tolerated, with low rate of discontinuation –Adverse events were generally mild –Drug-drug interactions did not impact HCV treatment or opioid maintenance No patient required a change in the dosage of methadone or buprenorphine during study treatment –12 weeks all-oral regimen of OBV/PTV/r + DSV + RBV is well- tolerated and may be an attractive treatment option for genotype 1 infected patients receiving opioid replacement therapy M14-103 Lalezari J. J Hepatology 2015;63:364-9 M14-103 Study: ombitasvir/paritaprevir/ritonavir + dasabuvir + RBV for genotype 1 on opioid replacement therapy