1. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 1 SAFETY AND ANTIVIRAL ACTIVITY OF SCH 900518 ADMINISTERED AS MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2B TO NAIVE AND TREATMENT-EXPERIENCED HCV-1 INFECTED PATIENTS H. W. Reesink, J. F. Bergmann, J. de Bruijne, C. J. Weegink, J. van Lier, A. van Vliet, A. Keung, J. Li, E. O’Mara, M. A. Treitel, E. A. Hughes, H. L. A. Janssen, R. J. de Knegt 44th European Association for the Study of the Liver (EASL) Meeting Copenhagen, Denmark, April 24, 2009

2. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 2 Background: SCH 900518   Mechanism-based inhibitor of the HCV NS3 serine protease   Replicon assay activity (HCV genotype 1b)   EC 50 = 20 nM, EC 90 = 40 nM   IFN-alfa–enhanced antiviral activity   Resistance profile of SCH 900518   Similar to other protease inhibitors   Decreased resistance in combination with IFN- alfa in vitro   Primarily CYP3A4-mediated metabolism

3. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 3 Study Design   Treatment-naive and treatment-experienced patients with HCV genotype 1 infection   Two treatment periods in a fixed-sequence   Period 1 → Monotherapy for 7 days   Period 2 → Combination therapy with PEG-IFN alfa-2b for 14 days   Two doses explored (placebo-controlled)   800 mg TID SCH 900518   400 mg BID SCH 900518 with ritonavir 200 mg BID (metabolic inhibition)

4. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 4 Study Design and Treatment Regimens 800 mg SCH 900518 TID Tx-Naive [n = 10] Tx-Experienced [ n = 10] 400 mg SCH 900518 BID + 200 mg RTV BID Tx-Naive [ n = 10] Tx-Experienced [ n = 11] >28-Day Washout 800 mg SCH 900518 TID + PEG-IFN alfa-2b (1.5  g/kg) >28-Day Washout 400 mg SCH 900518 BID + 200 mg RTV BID + PEG-IFN alfa-2b (1.5  g/kg) SOC Period 1Period 2 7 days14 days SOC = Standard of care, began after period 2 Serum HCV-RNA was determined using Roche COBAS TaqMan (v.2.0; LLQ = 25 IU/mL, LLD = 9.3 IU/mL) Randomized 4:1 (Active: Placebo) SCH 900518 dosed as amorphous suspension with food RTV = ritonavir

5. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 5 Baseline Characteristics Tx-Naive 800 mg TID (n = 10) Tx-Experienced 800 mg TID (n = 10) Tx-Naive 400 mg BID + RTV (n = 10) Tx-Experienced 400 mg BID + RTV (n = 11) Male, n (%)6 (60)7 (70)8 (80)10 (91) Race, n (%) Caucasian9 (90)8 (80) 7 (64) Black1 (10) 0 Other01 (10) 4 (36) Age, mean (SD), y51.1 (3.9)47.9 (7.4)43.6 (9.2)51.1 (7.2) Weight, mean (SD), kg73.5 (11.5)82.2 (12.5)79.4 (14.8)84.4 (13.2) BMI, mean (SD), kg/m 2 24.1 (2.1) 27.8 (4.4) 25.3 (4.1) 26.3 (5.2) Patients receiving methadone, n (%) 1 (10)0 1 (9) Patients with hemophilia, n (%)001 (10)1 (9) Baseline HCV RNA, mean (SD) 4.8 x 10 6 (3.2 x 10 6 ) 6.3 x 10 6 (4.4 x 10 6 ) 3.8 x 10 6 (2.9 x 10 6 ) 4.3 x 10 6 (4.6 x 10 6 )

6. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 6 Safety AEs ≥10% During 7 Days of Monotherapy with SCH 900518 (± Ritonavir) Tx-Naive 800 mg TID (n = 8) Tx-Exper 800 mg TID (n = 8) Tx-Naive 400 mg BID+ RTV (n = 8) Tx-Exper 400 mg BID+ RTV (n = 9) Placebo (n = 4) Placebo+ RTV (n = 4) SUBJECTS REPORTING ANY AE, n 7*8*7*8*3* Headache304*400 Diarrhea213400 Anorectal Discomfort4*21200 Nausea5*12010 Dizziness221101 Somnolence4*20010 Abdominal Discomfort111003* Influenza-like Illness013000 Abdominal Distension011101 *Reported by ≥50% of patients

7. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 7 Safety AEs ≥10% During 14 Days of Combination Therapy SCH 900518 + PEG-IFN alfa-2b (± Ritonavir) Tx-Naive 800 mg TID (n = 8) Tx-Exper 800 mg TID (n = 8) Tx-Naive 400 mg BID + RTV (n = 8) Tx-Exper 400 mg BID + RTV (n = 8) Placebo (n = 4) Placebo + RTV (n = 4) SUBJECTS REPORTING ANY AE, n 8* 3*4* Influenza-like Illness 8* 7* 3* Diarrhea2114*00 Headache301201 Dyspepsia110200 Injection Site Erythema 120100 Nausea012100 *reported by ≥50% of patients *Reported by ≥50% of patients

8. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 8 SCH 900518 Overall Safety   Safe and well tolerated   No clinically significant changes in laboratory values, ECG recordings, or vital signs   Most AEs were mild or moderate in severity   One subject discontinued immediately after first dose because of intolerance to drug suspension   No SCH 900518-related SAEs   No deaths

9. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 9 Pharmacokinetics of SCH 900518 (± Ritonavir) at Steady-State in Combination With PEG-IFN alfa-2b Trough 11 x EC 90 Trough 61 x EC 90 t ½ ≈ 16 hours (+ RTV) t ½ ≈ 5 hours (alone) 0 500 1000 1500 2000 2500 3000 3500 00.5246812 Hours After SCH 900518 Dose Plasma Concentration SCH 900518 (ng/mL) 400 mg BID + RTV 800 mg TID

10. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 10 SCH 900518 Monotherapy (± Ritonavir) Mean Change From Baseline in HCV RNA (Log 10 IU/mL) Morning Day 8 -5 -4 -3 -2 0 024487296120144168 Hours Mean Change in HCV RNA (Log 10 IU/mL) Placebo (n = 8) 800 mg TID Tx-Naive (n = 8) 800 mg TID Tx-Exper (n = 8) 400 mg BID/RTV Tx-Naive (n = 8) 400 mg BID/RTV Tx-Exper (n = 8)

11. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 11 SCH 900518 (± Ritonavir) + PEG-IFN alfa-2b Mean Change From Baseline in HCV RNA (Log 10 IU/mL) = PEG-IFN alfa-2b Dose -5 -4 -3 -2 0 024487296120144168192216240264288312336 Mean Change in HCV RNA (Log 10 IU/mL) Hours Placebo (n = 8) 800 mg TID Tx-Naive (n = 8) 800 mg TID Tx-Exper (n = 8) 400 mg BID/RTV Tx-Naive (n = 8) 400 mg BID/RTV Tx-Exper (n = 8) Morning Day 15

12. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 12 Resistance Analysis Individual Patient Plots of Treatment-Experienced Subjects Receiving SCH 900518 400 mg BID + Ritonavir -6 -5 -4 -3 -2 0 Plasma HCV RNA (Log 10 IU/mL) = PEG-IFN alfa-2b Dose Hours Morning Day 15 024487296120144168192216240264288312336 Resistant variants detected in these subjects at loci: V36, R155, A156

13. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 13 SCH 900518: Antiviral Activity in Combination With PEG-IFN alfa-2b at Day 15 SCH 900518 (± RTV) + PEG-IFN alfa-2b Percent of Subjects With HCV RNA <LLQ (<25 IU/mL) Percent of Subjects With HCV RNA <LLD (<9.3 IU/mL) ExperiencedNaiveExperiencedNaive 800 mg TID SCH 900518 50% (4/8) 75% (6/8) 0% (0/8) 38% (3/8) 400 mg BID SCH 900518 + RTV 50% (4/8) 63% (5/8) 25% (2/8) 25% (2/8) Placebo 0% (0/4) 0% (0/4) 0% (0/4) 0% (0/4)

14. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 14 SCH 900518 Pharmacokinetic/Pharmacodynamic Relationship (Monotherapy ± Ritonavir) (6 × EC 90 ) (11 × EC 90 ) (41 × EC 90 ) (62 × EC 90 ) n = 7n = 8 -5 -4 -3 -2 0 17029611501725 Median C min (ng/mL) by Quartile Mean Change in HCV-RNA Log 10 (lU/mL) on Day 7

15. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 15 Modeled SCH 900518 Tablet + Ritonavir Pharmacokinetics for Phase 2 Study ~12 x EC 90 ~16 x EC 90 Trough Values 0 500 1000 1500 2000 2500 3000 3500 0510152025 Time (hr) SCH 900518 200 mg QD/RTV SCH 900518 400 mg QD/RTV SCH 900518 100 mg BID/RTV ~8 x EC 90 Plasma Concentration SCH 900518 (ng/mL) Doses Tested in Phase 2

16. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 16 Preliminary Phase 2 Data in Naïve Patients SCH 900518/Ritonavir + PEG-IFN alfa-2b/RBV (n=25) Once-Daily Dosing = PEG-IFN alfa-2b/RBV = 200 mg SCH 900518 QD + 100 mg RTV + PEG-IFN alfa-2b/RBV *Excludes one subject because of noncompliance with study medications Treatment Week 4 <LLQ = 19/20 (95%) <LLD = 15/20 (75%) 10 100 1000 10,000 100,000 1,000,000 10,000,000 100,000,000 051015202530 Days HCV RNA (Log 10 IU/mL) LLQ <25 IU/mL

17. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 17 Conclusions   SCH 900518 (± ritonavir ± PEG-IFN alfa-2b) was safe and well tolerated   No SCH900518-related SAEs   SCH 900518 exhibited potent antiviral activity in both treatment-naive and treatment- experienced patients   Pharmacokinetic and pharmacodynamic modeling, as well as preliminary in-treatment antiviral data, support once-daily dosing of SCH 900518 with metabolic inhibition

18. Reesink H, et al. Presented at the 44 th Annual Meeting of the European Association for the Study of the Liver (EASL), April 23, 2009, Copenhagen, Denmark.04/28/09 18 Study Investigators and Colleagues AMC:SPRI: H. W. ReesinkE. A. Hughes J. de BruijneM. A. Treitel C. J. WeeginkE. O’Mara J. Li A. Keung EMC:PRA: H. L. A. JanssenJ. van Lier R. J. de KnegtA. van Vliet J. F. BergmannM. Ypey