1. clinicaloptions.com/hepatitis Highlights From AASLD 2010 October 29 - November 2, 2010 Boston, Massachusetts Highlights From AASLD 2010 CCO Official Conference Coverage of the 61st Annual Meeting of the American Association for the Study of Liver Diseases This program is supported by an educational grant from This program is supported by educational grants from

2. clinicaloptions.com/hepatitis Highlights From AASLD 2010 About These Slides  Our thanks to the presenters who gave permission to include their original data  Users are encouraged to use these slides in their own noncommercial presentations, but we ask that content and attribution not be changed. Users are asked to honor this intent  These slides may not be published or posted online without permission from Clinical Care Options (email permissions@clinicaloptions.com) Disclaimer The materials published on the Clinical Care Options Web site reflect the views of the authors of the CCO material, not those of Clinical Care Options, LLC, the CME providers, or the companies providing educational grants. The materials may discuss uses and dosages for therapeutic products that have not been approved by the United States Food and Drug Administration. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or using any therapies described in these materials.

3. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Faculty and Disclosures Robert G. Gish, MD Chief of Hepatology Professor of Clinical Medicine Medical Director Center for Hepatobiliary Disease and Abdominal Transplantation University of California, San Diego San Diego, California Robert G. Gish, MD, has disclosed that he has received grant or research support from Bayer- Onyx, Bristol-Myers Squibb, Genentech, Gilead Sciences, Hoffmann-La Roche, Pharmasset, and Zymogenetics; has served as a consultant to Abbott, Anadys, Bayer AG, Bristol-Myers Squibb, Durect, Genentech, Gilead Sciences, GlaxoSmithKline, GlobeImmune, Hepahope, Hoffmann-La Roche, Human Genome Sciences, Merck, Metabasis Therapeutics, OSI/Astellas, Pharmasset, Schering-Plough, Three Rivers Pharmaceuticals, Vital Therapies, and Zymogenetics; has served on speaker bureaus for Bayer, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Hoffmann-La Roche, Merck, Onyx, Roche, Salix, Schering-Plough, SciClone Pharmaceuticals, and Three Rivers Pharmaceuticals; and holds stock in Hepahope. Stephen A. Harrison, MD, FACP, has disclosed that he has served as a consultant for and has received fees for non-CME services from Bristol-Myers Squibb and Onyx. Stephen A. Harrison, MD, FACP Clinical Associate Professor of Medicine University of Texas Health Science Center San Antonio, Texas

4. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Outline  Investigational Agents for the Treatment of HCV  Advances in HBV Therapy

5. Investigational Agents for the Treatment of HCV

6. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Boceprevir and Telaprevir  Boceprevir, a potent inhibitor of HCV NS3 protease  Telaprevir, a potent inhibitor of HCV NS3/4A protease  Both being tested in combination with standard- of-care peginterferon alfa-2/ ribavirin in phase III studies in chronic HCV infection Trials reported at AASLD 2010  Boceprevir –SPRINT-III: naive GT1 patients –RESPOND-2: nonresponder GT1 patients  Telaprevir –ADVANCE: naive GT1 patients –ILLUMINATE: response- guided therapy in naive GT1 patients

7. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Phase III SPRINT-2: Boceprevir + PegIFN/RBV in GT1 Tx-Naive Patients Treatment-naive patients with genotype 1 HCV (2 cohorts: N = 938 nonblack and 159 black) PR* (n = 316, 52) PR* (n = 311 nonblack, 52 black) Wk 72 Wk 48 Follow-up Wk 28 Follow-up Wk 4 BOC + PR* (n = 316 nonblack, 52 black) BOC + PR* (n = 311 nonblack, 55 black) PR* (n = 311, 55) PR* *BOC 800 mg q8h; pegIFN alfa-2b 1.5 µg/kg/wk; weight-based RBV 600-1400 mg/day. † Undetectable HCV RNA at Wk 4 of BOC treatment (ie, at Wk 8) and at all subsequent assays. Poordad F, et al. AASLD 2010. Abstract LB-4. Follow-up RVR † No RVR  Randomized, placebo-controlled trial

8. clinicaloptions.com/hepatitis Highlights From AASLD 2010 SPRINT-2: Response Rates According to Race 0 20 40 60 80 100 Patients (%) SVR Relapse 4-wk PR + 44 weeks BOC + PR4-wk PR + response-guided BOC + PR48-wk PR 67 68 40 8 23 9 0 20 40 60 80 100 Patients (%) SVRRelapse 42 53 23 17 14 12 Nonblack Patients Black Patients P <.0001 P =.044 P =.004 Poordad F, et al. AASLD 2010. Abstract LB-4. n =211 213125 21 183722 2912 362

9. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Phase III ADVANCE: Telaprevir + PegIFN/RBV in GT1 Tx-Naive Patients Treatment-naive patients with genotype1 HCV (N = 1088) Wk 12 TVR + PR* (n = 364) TVR + PR* (n = 363) PR* (n = 361) eRVR † : PR* Wk 72 Wk 48 Wk 8 Follow-up *TVR 750 mg q8h; pegIFN alfa-2a 180 µg/wk; weight-based RBV 1000-1200 mg/day. † eRVR: extended rapid virologic response = undetectable HCV RNA at Wks 4 and 12. Jacobson IM, et al. AASLD 2010. Abstract 211. Wk 24 PR* eRVR † : PR* PR* Follow-up  Randomized, placebo-controlled trial

10. clinicaloptions.com/hepatitis Highlights From AASLD 2010 ADVANCE: Overall SVR and Relapse Rates 0 20 40 60 80 100 Patients (%) 69 SVR 75 44 P <.0001 for both treatment arms vs control 12-wk TVR + PR + 12/36-wk PR (n = 363) 48-wk PR (n = 361) 8-wk TVR + PR + 16/40-wk PR (n = 364) n = 250 271 158 Relapse 99 28 n =28 27 64 Jacobson IM, et al. AASLD 2010. Abstract 211.

11. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Phase III ILLUMINATE: Response-Guided Telaprevir + PegIFN/RBV in GT1 Naive Pts Treatment- naive patients with GT1 HCV (N = 540) PR* (n = 162) PR* (n = 160) Wk 72Wk 48Wk 24 Follow-up *TVR 750 mg q8h; pegIFN alfa-2a 180 µg/wk; weight-based RBV 1000-1200 mg/day. † eRVR: extended rapid virologic response = undetectable HCV RNA at Wks 4 and 12. Sherman KE, et al. AASLD 2010. Abstract LB-2. Follow-up  Open-label, randomized trial Wk 20 eRVR † No eRVR † PR* (n = 218) TVR + PR* Wk 12 PR*

12. clinicaloptions.com/hepatitis Highlights From AASLD 2010 ILLUMINATE: Overall SVR Rates 0 20 40 60 80 100 24-wk therapy SVR (%) 92 48-wk therapy 88 Overall 72 Patients With eRVR n/N =388/540149/162 140/160 Sherman KE, et al. AASLD 2010. Abstract LB-2.

13. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Similarities and Differences in Phase III Studies of TVR and BOC in GT1 Naive Pts ParameterTVR [1] BOC [2] PR lead-in?NoYes: 4 wks Peginterferon alfa formulation2a2b PI dosing requirements TID; administer with fatty meal TID Duration of PI triple therapy 8-12 wks followed by 12-40 wks PR 24-44 wks after 4 wks PR lead-in Qualification for shortened therapy (response guided) eRVR RVR (Wk 4 after addition of BOC; Wk 8 of total therapy) Qualified for shortened therapy, %58 (24 wks)44 (28 wks) SVR, %69-7563-66 Relapse, %99 Adverse events more frequent in PI arms Rash, anemia, pruritus, nausea Anemia, dysgeusia 1. Jacobson IM, et al. AASLD 2010. Abstract 211. 2. Poordad F, et al. AASLD 2010. Abstract LB-4.

14. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Phase III RESPOND-2: Boceprevir in GT1 Prior Nonresponders to PegIFN/RBV PR* (n = 80) PR* (n = 161) BOC + PR* PR* (n = 162) BOC + PR* If detectable at Wk 8 PR* Bacon BR, et al. AASLD 2010. Abstract 216. Treatment- experienced patients with GT1 HCV (N = 403) Wk 48 Wk 8 Wk 36 Follow-up † *BOC 800 mg TID; pegIFN alfa-2b 1.5 µg/kg/wk; weight-based RBV 600-1400 mg/day. † Follow-up for 24 wks after completion of therapy.

15. clinicaloptions.com/hepatitis Highlights From AASLD 2010 RESPOND-2: SVR Rates According to Treatment Arm and Prior Response 0 20 40 60 80 100 Overall SVR (%) 4-wk PR + 44-wk BOC + PR (n = 161) 59* Previous Nonresponders Previous Relapsers 48-wk PR (n = 80) 4-wk PR + response-guided BOC + PR (n = 162) 66 21 40 52 7 75 29 69 P <.0001 vs control (both arms) Bacon BR, et al. AASLD 2010. Abstract 216. 95/ 162 107/ 161 17/ 80 23/ 57 30/ 58 2/29 72/ 105 77/ 103 15/ 51

16. clinicaloptions.com/hepatitis Highlights From AASLD 2010 GS-9256 + Tegobuvir Alone, With RBV, or With PegIFN/RBV in GT1 Tx-Naive Patients  Phase II study of tegobuvir (GS-9190), an NS5B nonnucleoside polymerase inhibitor, and GS-9256, an NS3 protease inhibitor as part of HCV therapy Zeuzem S, et al. AASLD 2010. Abstract LB-1. GS-9256 75 mg BID + Tegobuvir 40 mg BID (n = 16) † Wk 48 Wk 4 GS-9256 75 mg BID + Tegobuvir 40 mg BID + RBV* † (n = 15) PR* (n = 16) PR* (n = 15) GS-9256 75 mg BID + Tegobuvir 40 mg BID + PR* (n = 15) PR* (n = 15) Part A Part B (nonrandomized) Treatment-naive patients with GT1 HCV *PegIFN alfa-2a 180 µg/wk; weight-based RBV 1000-1200 mg/day. † PegIFN/RBV started early if virologic breakthrough.

17. clinicaloptions.com/hepatitis Highlights From AASLD 2010 GS-9256 + Tegobuvir Alone, With RBV, or With PegIFN/RBV: Virologic Response Zeuzem S, et al. AASLD 2010. Abstract LB-1. HCV RNA ResponseGS-9256 + Tegobuvir (n = 15) GS-9256 + Tegobuvir + RBV (n = 13) GS-9256 + Tegobuvir + PegIFN/RBV (n = 14) Median maximal change from baseline, log 10 IU/mL -4.1-5.1-5.7 Achieved nadir ≤ 25 IU/mL, % 1362100 Day 14 HCV RNA ≤ 25 IU/mL, % 74671 Day 28 HCV RNA ≤ 25 IU/mL (RVR), % 738100

18. clinicaloptions.com/hepatitis Highlights From AASLD 2010 BMS-790052 + BMS-650032 Alone or With PegIFN/RBV in GT1 Null Responders Lok A, et al. AASLD 2010. Abstract LB-8. Prior null responders with GT1 HCV (N = 21) BMS-790052 60 mg QD + BMS-650032 600 mg BID (n = 11) Wk 72 Wk 24 Follow-up BMS-790052 60 mg QD + BMS-650032 600 mg BID + PR* (n = 10)  Open-label, randomized, placebo-controlled phase IIa trial  BMS-790052: NS5A polymerase inhibitor  BMS-650032: NS3 protease inhibitor Follow-up *PegIFN alfa-2a 180 µg/wk; weight-based RBV 1000-1200 mg/day.

19. clinicaloptions.com/hepatitis Highlights From AASLD 2010 BMS-790052 + BMS-650032 Alone or With PegIFN/RBV: Wk 12 Interim Analysis  All viral breakthroughs occurred in patients with GT1a Lok A, et al. AASLD 2010. Abstract LB-8. 64 36 46 60 90 0 20 40 60 80 100 RVReRVRcEVR BMS-790052 + BMS-650032 BMS-790052 + BMS-650032 + PR Patients (%) 7/116/10 4/115/119/10

20. clinicaloptions.com/hepatitis Highlights From AASLD 2010 PILLAR: TMC435 + PegIFN/RBV in GT1 Tx-Naive Patients: 24-Wk Interim Analysis Fried M, et al. AASLD 2010. Abstract LB-5. Treatment- naive patients with GT1HCV (N = 386) Wk 12 TMC435 75 mg + PR (n = 78) TMC435 150 mg + PR (n = 77) PR (n = 77) Wk 72 Wk 48Wk 24 TMC435 75 mg + PR (n = 75) TMC435 150 mg + PR (n = 79) PR (n = 78) PR (n = 77) Follow-up *Treatment ended at Wk 24 if HCV RNA < 25 IU/mL at Wks 4, 12, 16, and 20; all others continued on PR.  Randomized, double-blind, placebo-controlled phase IIb trial  TMC435: NS3/4A protease inhibitor administered once daily Follow-up* or PR (n = 79) Follow-up* or PR (n = 77) Follow-up* or PR (n = 75) Follow-up* or PR (n = 78)

21. clinicaloptions.com/hepatitis Highlights From AASLD 2010 PILLAR: Undetectable HCV RNA at Wks 4 and 12 After EOT at Wk 24 Fried M, et al. AASLD 2010. Abstract LB-5.  79% to 86% of patients able to stop therapy at Wk 24  Adverse events leading to discontinuation observed in < 10% of all study arms TMC24 + PR24 75 mg (n = 75) TMC12 + PR24 150 mg (n = 77)TMC12 + PR24 75 mg (n = 78) 0 20 40 60 80 100 Patients (%) 91 SVR4 93 n/N =59/6556/6057/61 91 62/68 97 93 89 32/33 27/29 32/36 88 28/32 SVR12 TMC24 + PR24 150 mg (n = 79)  TMC435 75 mg did not totally abrogate graded response due to IL28B genotype

22. clinicaloptions.com/hepatitis Highlights From AASLD 2010 New Data on Other HCV Protease Inhibitors in Development  Danoprevir (RG7227): phase II study (ATLAS) in GT1 naive patients [1] –88% to 92% of patients achieved cEVR when combined with pegIFN/RBV vs 43% with SOC  Vaniprevir (MK-7009): phase IIa study (Protocol 007) in GT1 naive patients without cirrhosis [2] –Significantly higher early response rates when combined with pegIFN/RBV vs SOC –RVR: 67% to 84% vs 5%; cEVR: 74% to 85% vs 47% –SVR rates in higher-dose arms numerically, but not significantly, higher vs control –SVR: 61% to 84% vs 63% –Highest 2 doses allow for once-daily dosing  MK-5172: phase I study in GT1 and GT3 patients without cirrhosis [3] –Potent activity against GT1 and GT3 over 7-day dosing period –Active against known resistance mutants in healthy persons [4] 1. Terrault N, et al. AASLD 2010. Abstract 32. 2. Manns MP, et al. AASLD 2010. Abstract 82. 3. Petry A, et al. AASLD 2010. Abstract 807. 4. Brainard DM, et al. AASLD 2010. Abstract 1885.

23. clinicaloptions.com/hepatitis Highlights From AASLD 2010 New Data on Other HCV Polymerase Inhibitors in Development  ANA598 (nonnucleoside): phase II study in GT1 naive patients [1] –ANA598 200 or 400 mg BID + pegIFN/RBV given for 12 wks before response-guided pegIFN/RBV –73% to 75% of patients achieved cEVR when combined with pegIFN/RBV vs 63% with SOC  RG7128 (nucleoside): phase IIb PROPEL study in GT1 and GT4 naive patients [2] –RG7128 500 or 1000 mg + pegIFN/RBV given for 8 or 12 wks before response-guided pegIFN/RBV –80% to 88% of patients in arms receiving 12 wks of RG7128 combined with pegIFN/RBV achieved cEVR vs 49% with SOC 1. Lawitz E, et al. AASLD 2010. Abstract 31. 2. Jensen DM, et al. AASLD 2010. Abstract 81.

24. clinicaloptions.com/hepatitis Highlights From AASLD 2010 PegIFN Lambda for Treatment-Naive GT1, 2, 3, or 4 HCV Patients  Phase IIa study  High rates of HCV RNA undetectability at 3 highest pegIFN lambda levels, comparable to pegIFN alfa-2a controls [1] –RVR: 80% to 100% –cEVR: 80% to 100%  HCV RNA response rates lower with genotype 1/4 vs 2/3  Response rates numerically higher with IL28B CC vs non-CC genotype [1]  Fewer hematologic AEs at Wk 12 with pegIFN lambda than pegIFN alfa-2a 1. Muir AJ, et al. AASLD 2010. Abstract 821. 2. Thompson AJ, et al. Gastroenterology. 2010;139:120-129. Virologic Response According to IL28B Genotype (ITT), % PegIFN alfa- 2a/RBV (HCV GT1 † ; Published Data) [2] PegIFN Lambda/RBV 120-180 µg (Genotype 1/4* HCV) CC (n = 7)  RVR 2871  cEVR 8486 Non-CC (n = 12)  RVR 525  cEVR 3350

25. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Regional Distribution of IL28B rs12979860 CC Genotype Thomas DL, et al. Nature. 2009;461:798-801. Reprinted by permission from Macmillan Publishers Ltd:

26. clinicaloptions.com/hepatitis Highlights From AASLD 2010 IL28B Associations in Patients With Chronic Hepatitis C  IL28B polymorphisms associated with –Higher SVR rates [1] –Higher RVR rates [2] –Higher HCV RNA [3] –Higher LDL levels [4] –Higher baseline ALT levels [5] –Higher rate of spontaneous viral clearance [6]  Modeling study supports IL28B genotype stratification (CC vs non-CC) in HCV clinical trials of pegIFN/RBV + DAAs [7] 1. Ge D, et al. Nature. 2009;461:399-401. 2. Mangia A, et al. AASLD 2010. Abstract 897. 3. Liu L, et al. AASLD 2010. Abstract 231. 4. Saito H, et al. AASLD 2010. Abstract 732. 5. Thompson AJ, et al. AASLD 2010. Abstract 1893. 6. Thomas DL, et al. Nature. 2009;461:798-801. 7. Thompson AJ, et al. AASLD 2010. Abstract 810.

27. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Predictors of Response to Hepatitis C Treatment 1. Ge D, et al. Nature. 2009;461:399-401. 2. Freedman ND, et al. AASLD 2010. Abstract 224. 3. Harrison SA, et al. Hepatology. 2010;52:864-874. 4. Mouch AS, et al. AASLD 2010. Abstract 809. 5. Sulkowski MS, et al. AASLD 2010. Abstract 816. Pretreatment ParameterOn-Treatment Parameter  Race  Cirrhosis  Genotype  HCV RNA  IL28B polymorphisms [1]  Coffee use [2]  Baseline LDL levels [3]  Statin use [3]  Diabetes [4]  Vitamin D levels [5]  RVR  eRVR

28. Advances in HBV Therapy

29. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Vertical HBV Transmission in Mothers Treated With Telbivudine in Late Pregnancy HBsAg-Positive Infants With or Without Detectable HBV DNA, n (%) Infants in Telbivudine 600 mg/day Group (n = 95) Infants in Untreated Control Group (n = 92) P Value  At birth6 (6.3)28 (30.4)<.001  At 28 wks (sensitivity analysis) 08 (8.7).003  At 28 wks (ITT [M = F] analysis) 2 (2.1)12 (13.0).004  Prospective, nonrandomized, case-controlled, open-label study Pan C, et al. AASLD 2010. Abstract 212.

30. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Mode of Delivery and Risk of Perinatal HBV Transmission in HBeAg+ Mothers Zou H, et al. AASLD 2010. Abstract 235. Vaginal delivery (n = 286) Elective cesarean (n = 189) Emergency cesarean (n = 94) 0 5 10 15 20 25 HBV Infection in Infant (%) At Birth*At 7-12 Mos of Age † P =.384 13 14 19 6 2 9 P =.028P =.047  Retrospective, observational study  556 mothers; 569 infants  Immunoprophylaxis schedule (standard of care) –200 IU HBIG and HB vaccine 10 µg within 6 hrs after birth –200 IU HBIG 2 wks postpartum –HB vaccine 10 µg at 1 and 6 mos *HBsAg+ or HBV DNA detectable in umbilical cord blood. † HBsAg+.

31. clinicaloptions.com/hepatitis Highlights From AASLD 2010 NEPTUNE: PegIFN alfa-2a Dosed at 90 vs 180 µg/wk in HBeAg+ Patients  PegIFN alfa-2a 90 µg/wk inferior to 180 µg/wk, regardless of treatment duration, in randomized, double-blind phase IV study Liaw Y-F, et al. AASLD 2010. Abstract 215. HBeAg Seroconversion 6 Mos After Rx, % 90 µg/wk (n = 274) 180 µg/wk (n = 270) OR (95% CI)P Value* Overall19.729.3 1.79 (1.18-2.72).410  Genotype B2738 1.89 (0.98-3.67).508  Genotype C1727 2.00 (1.09-3.69).581  ALT > 1-2 x ULN1317NR--  ALT > 2-5 x ULN2035NR--  ALT > 5-10 x ULN4046NR-- *For noninferiority; ie, nonsignificance = not noninferior.

32. clinicaloptions.com/hepatitis Highlights From AASLD 2010 NEPTUNE: PegIFN alfa-2a Administered for 24 vs 48 Wks in HBeAg+ Patients  24 wks inferior to 48 wks of pegIFN alfa-2a therapy, regardless of dose, in randomized, double-blind phase IV study Liaw Y-F, et al. AASLD 2010. Abstract 215. HBeAg Seroconversion 6 Mos After Rx, % 24 Wks (n = 282) 48 Wks (n = 262) OR (95% CI)P Value Overall18.430.9 2.17 (1.43-3.31).749  Genotype B2936 1.44 (0.75-2.78).215  Genotype C1331 3.29 (1.76-6.15).960  ALT > 1-2 x ULN1119NR--  ALT > 2-5 x ULN2036NR--  ALT > 5-10 x ULN3453NR-- *For noninferiority; ie, nonsignificance = not noninferior.

33. clinicaloptions.com/hepatitis Highlights From AASLD 2010 PegIFN alfa-2b Administered for 24 vs 48 Wks in HBeAg+ Patients  Patients recruited from 25 centers in China, Malaysia, Taiwan, and Singapore in prospective, randomized phase IV trial Fan X, et al. AASLD 2010. Abstract 133. EOT 24 Wks After EOT PegIFN alfa-2b 1.0 µg/kg/wk for 24 wks PegIFN alfa-2b 1.5 µg/kg/wk for 24 wks PegIFN alfa-2b 1.5 µg/kg/wk for 48 wks 0 20 40 60 80 100 HBeAg Seroconversion (%) P =.001 13.8 12.2 17.9 16.9 16.3 29.9

34. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Safety of Extending PegIFN alfa-2a From 48 to 96 Wks in Genotype D HBeAg- Pts  PegBeLiver: higher virologic/serologic response rates observed 1 yr posttreatment in HBeAg-negative pts (94% genotype D) treated with pegIFN alfa-2a for 96 vs 48 wks [1] 1. Lampertico P, et al. EASL 2010. Abstract 98. 2. Lampertico P, et al. AASLD 2010. Abstract 135. Safety Outcome [2] PegIFN Alfa-2a 48 Wks (n = 51) PegIFN Alfa-2a 96 Wks (n = 77) P Value Treatment discontinuation, %2026.52 Any treatment-related adverse event, %8279.82 Any serious adverse event, %1412.79 Treatment-related serious AE %431.00 Dose modification, %2921.30 Death, n101.00 Laboratory abnormalities, %  Increased ALT431.00  Neutropenia2416.36  Thrombocytopenia1210.77  Anemia85.71

35. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Entecavir in Previously NA-Naive HBV Patients With Partial Virologic Response  PVR: HBV DNA > 80 IU/mL at Wk 48 of therapy but > 1 log IU/mL decrease from baseline  Majority of previously NA-naive pts with PVR and HBV DNA < 1000 IU/mL achieved HBV DNA < 80 IU/mL at Wk 96 without modifying treatment  However, pts with HBV DNA ≥ 1000 IU/mL at Wk 48 did not achieve HBV DNA < 80 IU/mL at Wk 96 except when treatment modified –1 added tenofovir, 2 switched to tenofovir/emtricitabine Zoutendijk R, et al. AASLD 2010. Abstract 448. Table used with permission. HBV DNA at Wk 48 Pts With PVR, n Switch/Add-on, n (%) Response at Wk 72, n (%) Response at Wk 96, n (%) < 1000 IU/mL22013 (59)16 (72) ≥ 1000 IU/mL143 (21)1 (7)2 (14)

36. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Rates of HBsAg Loss With Longer Duration of Tenofovir  192-wk results of Study 103: randomized, double-blind phase III trial Heathcote EJ, et al. AASLD 2010. Abstract 477. Graphic used with permission. 0 0.12 Cumulative Probability of HBsAg Loss TDF-TDF ADV-TDF Wks on Study 10.8% 8.5% 0.10 0.08 0.06 0.04 0.02 192180168156144132120108928064483624120 Switch to open- label TDF

37. clinicaloptions.com/hepatitis Highlights From AASLD 2010 TDF Monotherapy vs TDF/FTC for HBV Patients Viremic After Adefovir Therapy  At Wk 48, 81% of patients initially given TDF or TDF/FTC had HBV DNA < 400 copies/mL [1]  13/13 patients with baseline LAM resistance and 9/10 with baseline ADV resistance had HBV DNA < 400 copies/mL at Wk 168 1. Berg T, et al. Gastroenterology. 2010;139:1207-1217. 2. Berg T, et al. AASLD 2010. Abstract 136. Chronic HBV patients with incomplete suppression on ≥ 6 mos adefovir (N = 105) TDF 300 mg (n = 53) TDF/FTC 300/200 mg (n = 52) Wk 168Wk 48 Wk 96 Wk 24* *After Wk 24, patients with detectable HBV DNA on TDF could receive open-label TDF/FTC. Outcomes at Wk 168 [2] TDFTDF/FTC HBV DNA < 400 copies/mL (69 IU/mL), % (ITT, NC = F)82 HBeAg loss (LOCF)2123 HBeAg seroconversion (LOCF)13 HBsAg loss or seroconversion (LOCF)60

38. clinicaloptions.com/hepatitis Highlights From AASLD 2010 Correlates of Severe Liver Disease Outcomes in HBV Patients Parameter Adjusted Risk Ratios for Chronic HBV Outcomes HCCDecompensated Cirrhosis Younger than 50 yrs of age0.160.25 Male3.873.42 Non-Asian race0.65*1.47* Diagnosed alcohol abuse2.843.96 Diabetes1.09*2.67 Manos MM, et al. AASLD 2010. Abstract 175.  Retrospective, longitudinal cohort study of the Kaiser Permanente Medical Care Program of Northern California Viral Hepatitis Registry *Nonsignificant correlations.

39. Go Online for More CCO Coverage of AASLD 2010! Capsule Summaries of key studies plus Expert Analyses panel discussions exploring the clinical implications Expert Highlights: download mp3 files and listen to our experts review the highlights of this conference clinicaloptions.com/Boston2010