1. Adefovir Dipivoxil 10 mg for the Treatment of Chronic Hepatitis B NDA 21-449 August 6, 2002 Gilead Sciences, Inc.

9. In Vitro Activity of Adefovir Wild-type and Lamivudine-resistant HBV Xiong et al. Hepatology, 1998, 28:1669-1673

13. Chronic Hepatitis B Exposure to Adefovir Dipivoxil Total 2084 ADV 10 mg 1647 Other ADV doses 437 Phase 2, Supportive Studies, Early Access 831 Pivotal studies and transplantation 816  48 Weeks 578  72 Weeks 420  96 Weeks 256 As of NDA Safety update

14. Clinical Efficacy and Safety Carol Brosgart, MD Vice President, Clinical Research Gilead Sciences

15. Adefovir Dipivoxil Pivotal Studies 96 48 Liver Histology Study 438 HBeAg– Week 0 Liver Histology ADV 10 mg (n=171) Study 437 HBeAg+ ADV 30 mg (n=173) Placebo (n=167) Placebo (n=142) ADV 10 mg (n=138) ADV 10 mg (n=123) ADV 10 mg (n=79) Placebo (n=40) Placebo (n=71) ADV 10 mg (n=85) Placebo (n=61) ADV 10 mg (n=60)

17. Studies 437 and 438 Baseline Characteristics (ITT)

18. Studies 437 and 438 Baseline HBV Characteristics (ITT)

20. Studies 437 and 438 (ITT) 48 Weeks Primary Endpoint: Improvement in Liver Histology p<0.001 a Patients (%) PLB ADV 10 PLB ADV 10 HBeAg+ HBeAg– p<0.001 a Missing/unevaluable week 48 biopsy = no improvement a Cochran-Mantel-Haenszel Test

21. Studies 437 and 438 Integrated 48 Weeks (ITT) Histological Improvement by Demographic Characteristics 0% 10% 20% 30% 40% 50% 60% 70% Placebo ADV 10 Gender Ethnicity Age Patients (%) Male Female Caucasian Asian  40 < 40 (n =) (388) (119) (238) (249) (261) (246)

22. Studies 437 and 438 Integrated 48 Weeks (ITT) Histological Improvement by Baseline HBV Characteristics  2xULN < 2xULN < 7.6  7.6 No Prior Prior  10 < 10 0% 10% 20% 30% 40% 50% 60% 70% 80% Patients (%) IFN Knodell HBV DNA ALT n = (358) (149) (177) (230) (282) (225) (322) (185) Placebo ADV 10

24. Studies 437 and 438 (ITT) 48 Weeks Necroinflammation – Ranked Assessment p<0.001 a p<0.001 a HBeAg+ HBeAg– Improved Worsened Patients (%) 42% 80% 51% 3% ADV 10 PLB PLB ADV 10 41% 71% 34% 13% 40% 20% 0% 20% 40% 60% 80% 60% a Cochran-Mantel-Haenszel Test

25. p<0.001 a p<0.001 a Studies 437 and 438 (ITT) 48 Weeks Fibrosis – Ranked Assessment 24% 41% 26% 14% 30% 20% 10% 0% 10% 20% 30% 40% 50% PLB ADV 10 Improved Worsened 25% 48% 38% 4% PLB ADV 10 Patients (%) 40% a Cochran-Mantel-Haenszel Test HBeAg+ HBeAg–

26. Studies 437 and 438 Median Change from Baseline in HBV DNA a Wilcoxon Rank-Sum Test p<0.001 a HBeAg- p<0.001 a HBeAg+ PLB ADV 10 -4 -3 -2 -1 0 PLB ADV 10 Weeks 0 4 8 12 16 20 24 28 32 36 40 44 48 -4 -3 -2 -1 0 0 4 8 12 16 20 24 28 32 36 40 44 48 log 10 copies/mL

27. Studies 437 and 438 (ITT) 48 Weeks Serum HBV DNA < 400 copies/mL p<0.001 a p<0.001 a PLB ADV 10 PLB ADV 10 HBeAg+ HBeAg– Patients (%) a Cochran-Mantel-Haenszel Test Missing = Failure

28. Studies 437 and 438 (ITT) 48 Weeks ALT Normalization PLB ADV 10 PLB ADV 10 HBeAg+ HBeAg– p<0.001 a p<0.001 a Patients (%) a Cochran-Mantel-Haenszel Test Missing = Failure

29. Study 437 (ITT) 48 Weeks HBeAg Loss and Seroconversion PLB ADV 10 PLB ADV 10 p=0.001 a p<0.05 a Patients (%) a Cochran-Mantel-Haenszel Test Missing = Failure

30. Study 437 and 438 Efficacy Beyond 48 Weeks

31. Study 437 and 438 All ADV 10 mg (n=492) Efficacy Beyond 48 weeks a K-M estimates

33. Studies 437 and 438 Safety of Adefovir Dipivoxil 10 mg

34. Studies 437 and 438 0-48 Weeks Adverse Events and Discontinuations

37. Studies 437 and 438 Integrated 0-48 Weeks Grade 1-4 Renal Laboratory Parameters

39. Studies 437 and 438 0-48 Weeks Renal Laboratory Abnormalities a Confirmed (two consecutive laboratory abnormalities)

40. Studies 437 and 438 Integrated ADV 10 mg Renal Laboratory Abnormalities 0-96 Weeks a Confirmed (two consecutive laboratory abnormalities)

41. Study 437 and 438 All ADV 10 mg Resolution of  0.3 mg/dL Increases in Serum Creatinine 0-96 Weeks (n=29) Resolved on drug n=20 Stable on drug n=8 Resolved on discontinuation n=1

45. Adefovir Dipivoxil 30 mg Efficacy and Safety

46. Study 437 (ITT) Efficacy Results 48 Weeks

47. Study 437 Renal Laboratory Abnormalities 48 Weeks a Confirmed (two consecutive laboratory abnormalities)

49. Resistance Surveillance

52. Supportive Studies

54. Study 435 Compassionate Access Adefovir Dipivoxil 10 mg for the Treatment of Patients Pre- and Post-Liver Transplantation with Lamivudine-Resistant HBV

56. Study 435 Baseline Characteristics a Median

57. Study 435 Baseline HBV Disease Characteristics

58. Study 435 Median Change from Baseline in HBV DNA 169 Post- transplant 161 156 149 116 88 57 43 27 24 15 103 Pre- transplant 98 91 84 52 28 13 2 2 2 0 -5.0 -4.0 -3.0 -2.0 -1.0 0.0 0 4 8 12 24 36 48 60 72 84 96 4 8 12 24 36 48 60 72 84 96 Pre-transplant Post-transplant log 10 copies/mL

59. Study 435 Week 48 Secondary Efficacy Endpoints Through NDA Safety Update

60. Study 435 Survival Post- transplant 185 170 155 135 127 117 0.0 0.2 0.4 0.6 0.8 1.0 0 8 16 24 32 40 48 56 64 72 80 88 96 Week 109 94 84 69 55 42 28 Pre- transplant 96 69 50 37 24 11 5 3 2 Post-transplant Pre-transplant

61. Study 435 Patient Disposition Through NDA Safety Update

67. Lamivudine-Resistant HBV Other Supportive Studies

68. a Data through primary endpoint Week 16 reported in NDA p<0.001 compared to LAM ADV+LAM (n=19) ADV (n= 19) LAM (n=19) Study 461 Median Change from Baseline in HBV DNA a Weeks 0 8 16 24 32 40 48 log 10 copies/mL

69. Study 461 ALT Normalization Week 48 ADV + LAM ADV LAM Patients (%) (n=19) (n=19) (n=19)

70. Further Studies