GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a Design Single arm Open label W12 ≥ 18 years HCV genotype 1a HCV RNA ≥ 1000 IU/mL Treatment-naïve or treatment-experienced with IFN/PEG-IFN + RBV No cirrhosis No HBV or HIV co-infection N = 105 OBV/PTV/r + DSV + RBV 600 mg QD SVR12 Objectives SVR12 (HCV RNA < 15 IU/ml), by ITT : non-inferiority if lower margin of the 95% CI > 92% (PEARL-IV study) Comparison of SVR12 in the presence or absence of baseline polymorphisms in NS3 or NS5A (comparison by Fisher’s exact test) On-treatment virologic failure and post-treatment relapse GEODE-II Poordad F. AASLD 2016, Abs. 872 1

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a Baseline characteristics and disposition of patients OBV/PTV/r + DSV + RBV 600 mg QD, N = 105 Median age, years 54 Female, % 48 Race : White / Black, % 86 / 14 Mean BMI, kg/m2 28 Mean HCV RNA, log10 IU/mL 6.01 ± 0.85 IL28B CC, % 27 Fibrosis stage : F0-F1 / F2 / F3, % 81 / 11 / 9 IFN/PEG-IFN + RBV-experienced, % Null response Relapse Intolerance Unknown 11 50 25 17 8 Discontinuation, N Lost to follow-up Adverse event Other 2 2 (1 related to study drugs) 4 GEODE-II Poordad F. AASLD 2016, Abs. 872 2

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a SVR12, % Reasons not achieving SVR12 100 N = 105 Virologic failure Breakthrough Relapse 5 1 4 Non-virologic failure Drug discontinuation Missing data 6 4 2 90% 95% % of patients 50 94 105 94 99 ITT mITT Non-inferiority to 3-DAA + full dose RBV (PEARL-IV) was not achieved GEODE-II Poordad F. AASLD 2016, Abs. 872

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a Resistance analysis : polymorphisms (alone or as components of double variants) that confer ≥ 5-fold increase in EC50 were considered PTV specific RAVs: F43L, Y56H, R155G/K/S/T/W, A156S/T/V, or D168A/E/F/H/N/V/Y. Q80K (3-fold increase in EC50) was evaluated separately based on the significance of this polymorphism for simeprevir (SMV) OBV specific RAVs: M28T/V, Q30E/K/R/Y, L31V, P32L, H58D, or Y93C/F/H/L/N/S DSV specific RAVs: L314H, C316Y, M414I/T/V, E446K/Q, Y448C/H, C451R, A553T, G554S, Y555 GEODE-II Poordad F. AASLD 2016, Abs. 872 4

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a Prevalence and Impact of Naseline Polymorphisms on GT1a-infected Patients No BP With BP 0.02 1.0 0.01 1,0 100 100 100 94.7 97.6 94.7 100 88.9 80 72.7 SVR12 % 60 40 20 Q80K PTV-specific OBV-specific DBV-specific 1,0 11,5 2,1 46,9 Prevalence, % 99,0 53,1 88,5 97,9 Baseline polymorphisms (BP) Prevalence % (n/N) SVR12 rate with BP % (n/N) SVR12 rate without either BP, % (n/N) Q80K + OBV-specific 7.3 (7/96) 57.1 (4/7) OBV-specific alone 4.2 (4/96) 100 (4/4) 100 (47/47) Q80K alone 39.6 (38/96) 94.7 (36/38) GEODE-II Poordad F. AASLD 2016, Abs. 872

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a Adverse events and laboratory abnormalities, % GLE/PIB , N = 105 Any adverse event 73.3 Serious adverse event 2.9 * Adverse event leading to discontinuation 1.9 Adverse event leading to RBV dose reduction (haemoglobin decrease) Death Adverse events in > 10% of patients Fatigue Headache Insomnia Nausea 27.6 13.3 11.4 10.5 Laboratory abnormalities Hemoglobin grade 2 (8-10 g/dL) / grade ≥ 3 (6.5-8 g/dL) ALT grade 2 (3-5 x ULN) / grade ≥ 3 (> 5 x ULN) AST grade 2 (3-5 x ULN) / grade ≥ 3 (> 5 x ULN) Total bilirubin grade 2 (1.5-3 x ULN) / grade ≥ 3 (> 3 x ULN) 1 / 0 1 / 1 0 / 1 5 / 0 * 1 possibly related to study drug (bipolar disorder), the 2 others not related to study drugs ** 1 possibly related to study drug (chest pain, heart rate increased, and dyspnea) GEODE-II Poordad F. AASLD 2016, Abs. 872 6

GEODE-II Study: OBV/PTV/r + DSV + low dose RBV in genotype 1a Summary OBV/PTV/r + DSV + 600 mg RBV QD achieved a SVR12 of 90% in patients with genotype 1a in the ITT analysis and 95% in the mITT analysis Non-inferiority was not established for the primary study end point The regimen was well tolerated with mostly mild or moderate AEs. Laboratory abnormalities were lower compared to historical controls: Grade ≥ 2 hemoglobin occurred in 1% of patients (compares favorably to 6.2% in historical controls who received full dose RBV) No Grade ≥ 3 total bilirubin occurred (compares favorably to 5.7% in historical controls who received full dose RBV) Patients with baseline polymorphisms showed numerically lower SVR12 Several patients failed to achieve SVR12 due to loss to follow-up, incarceration, and other underlying behavioral disorders (high rate of history of IV drug abuse, alcohol abuse, and cognitive or psychiatric disorders in the study population) GEODE-II Poordad F. AASLD 2016, Abs. 872 7