1. Frequencies of Resistance-Associated Amino Acid Variants Following Combination Treatment with Boceprevir (BOC) Plus PEGINTRON (PegInterferon Alfa-2b) and Ribavirin (P/R) in Patients With Chronic Hepatitis C (CHC), Genotype 1 (G1) Richard J.O. Barnard, Lisa D. Pedicone, Eirum Chaudhri, Xiao Tong, Ping Qiu, Clifford A. Brass, Janice K. Albrecht, Patricia Mendez, and Robert Ralston

2. SPRINT-1 Methods Phase 2 study of previously untreated adults with genotype 1 HCV Part 1 - 520 patients randomized to receive Peg-interferon (P)/Ribavirin (R) for 48 weeks (control) or one of four boceprevir regimens – Arms 3 and 5 of Part 1 received a 4 week lead-in with P/R prior to the addition of boceprevir to: o Achieve steady state of P/R prior to adding 3rd drug o Up-regulate immune response elements o Decrease viral load and quasispecies, thereby decreasing resistance Part 2 - 75 patients randomized to receive P/R and low- dose ribavirin

3. Definitions Sustained Virologic Response (SVR): Plasma HCV-RNA level below the lower limit of detection at follow-up week 12 Incomplete Virologic Response (IVR): A 2 log 10 increase in HCV-RNA viral load compared with the previous two visits and HCV viral load 50,000 IU/mL Viral Breakthrough (BT): Undetectable HCV-RNA and subsequent HCV-RNA 2 log 10 elevation during therapy Relapse (RL): Undetectable HCV-RNA at end of treatment and detectable HCV RNA at follow-up week 24 Nonresponder (NR) (treatment failure): o Subjects in Arm 1 with detectable HCV-RNA at treatment week 24 who crossed over to boceprevir o Subjects in any of the seven treatment arms with detectable HCV-RNA at end of therapy and at follow-up week 24 o Subjects in any of the seven treatment arms with missing HCV-RNA values at follow-up week 24 and do not have an undetectable HCV-RNA at follow-up week 12 Resistance Associated Amino Acid Variant (RAV)

4. SPRINT-1 Study Design and Sustained Virologic Response

5. Table 1. Subjects with Baseline RAVs Previously Demonstrated to Confer Reduced Susceptibility to Boceprevir in vitro

6. Number of RAVs Detected by HCV Genotype 49% 52%

7. Number of Subjects Having RAVs Detected Post- baseline, Including All Patients Treated with Boceprevir 3 0 1 5 53 0 11 3 29 5 1 60 1 13 8 1 4 1 0 0 10 20 30 40 50 60 70 V36A V36G V36I V36L V36M Q41H T54A T54C T54S V55A R155I R155K R155M R155TA156S A156T V158I V158M I170A Patients, n 0 1 00 11 11 0 17 5 0000 13 3 4 0 0 2 4 6 8 10 12 14 16 18 V36A V36G V36I V36L V36M Q41H T54A T54C T54S V55A R155I R155K R155M R155TA156S A156T V158I V158M I170A Patients, n

8. Frequency of RAVs for Different Treatment Response Categories IVR = Incomplete Virologic Response, BT = Breakthrough RL = Relapse, NR = Non-responder 0 10 20 30 40 50 60 70 80 IVRBTRLNR Patients, n Subjects with Variants Detected Subjects with no Variants Detected

9. RAVs Detected in BOC 28 and 48 Week Treatment Arms Lead-in - + - + - - 0 20 40 60 80 100 120 Arm 2Arm 3Arm 4Arm 5Arm 6Arm 7 Patients, n Subjects Subjects with RAVs Subjects without RAVs

10. RAVs Detected with No Lead-in (Arm 2) vs. Lead- in (Arm 3) Study Arms (i.e. Arms where Patients Received a Shorter Duration of Treatment with Boceprevir) 0 1 0 1 12 0 3 1 2 0 14 0 3 2 0 1 0000 5 0 5 0 2 4 6 8 10 12 14 16 V36AV36G V36I V36L V36M Q41H T54A T54C T54S V55A R155I R155K R155M R155T A156S A156T V158I V158M I170A I170T V36Apct V36Gpct V36Ipct V36Lpct Patients, n Lead-in No Lead-in

11. RAVs Detected with No Lead-in (Arms 4) vs. Lead-in (Arm 5) Study Arms (i.e. Arms where Patients Received a Longer Duration of Treatment with Boceprevir) Lead-in No Lead-in 1 00 1 8 0 2 1 7 00 10 0 11 0 1 000 0 2 4 6 8 12 V36A V36G V36I V36L V36MQ41H T54AT54CT54S V55A R155I R155K R155M R155TA156S A156T V158I V158M I170A I170T Patients, n 0000 5 0 3 0 22 0 7 0 11111 00 0 2 4 6 8 10 12 V36A V36G V36I V36L V36MQ41H T54AT54CT54S V55A R155I R155K R155M R155TA156S A156T V158I V158M I170A I170T Patients, n

12. Conclusions In SPRINT-1, combination therapy with boceprevir and peginterferon plus ribavirin increased SVR rates with shorter treatment durations In Non-SVR patients, most frequent RAVs were; o Genotype 1a; V36M, T54S, and R155K o Genotype 1b; T54A, T54S, A156S, and V170A In subjects with detectable RAVs at baseline, the majority achieved SVR The use of lead-in period led to increased SVR rates and reduced the frequency of T54S variant