Slides Presented During Q

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Slides Presented During Q A
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Expected Events in Untreated PatientsOver 5 Years
Events / 1000 Patients
Non-skinNon-HCC cancersa
HCCb
Cirrhosisc
a Taiwan Observational Cohort Study and Safety
Cohort b Chen CJ et al. EASL 2005, abstract
1256c Iloeje UH. EASL 2005, abstract 1265
15-20
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Pregnancies in ETV Clinical Program Outcome (N
41)
Outcome ETVN 21 LVDN 16 ETV / LVDN 2 PlaceboN 2
Elective Termination 13 12 0 1
Spontaneous Abortion 1 3 0 1
Live Birth 3 1 2 0
Outcome Unknown 4 0 0 0
Safety Update
5-79
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Substitutions Selected by ETV
Study Patient Population Residues with Novel Emerging Substitutions ETV EC50
022 Nucleoside naïve, eAg E8G, E8Q, R18K, V23A, N33S, G52R, S57P, A62T, S75P, N76K, S78T, R110G, N118S, R120K, H124Q, L132R, L147P, Y148H, G152E, K154R, K154T, H156Y, R167Q, P170S, F178S, A181T, I187V, K212R, K212T, S219P, T222S, L229S, S230A, G232D, G232S, H234Q, K241E, W243G, S246C, G251E, C256G, P261S, I265S, R274G, K275E, I278M, V278L, I282L, K285N, K285T, I290L, C303Y, I315V, N337I, V341I WT levels 0.6-18 nM
027 Nucleoside naïve, eAg- D2N, H9R, R18S, N33T, N71D, S78Y, S78T, D83G, V84M, S117Y, I121S, Q125K, M129T, R153L, A194S, T222S, H234R, R270E, K275N, R280K, W284Stop, R289Q, G292D, F296L, I315L, K318R, A320T, M336I, A342T WT levels 0.8 12 nM
014 LVD Refractory L80I, L229W LVDR levels 22 45 nM
026 LVD Refractory V27A, I53F, S78T, L80V, K168E, A181T, C188S, V191A, A200V, V224A, D263G, G295S, M309L LVDR levels 2.4 31 nM
13-15
5
ETV Virologic Rebounds Year Two
Study 022 eAg pos
Percent of Subjects
Study 022 eAg pos 027 eAg neg
YR 1 Treated 354 325
YR 2 Treated 267 127
YR 1 Rebounds 6 (2) 5 (2)
YR 2 Rebounds 6 (2) 1 (lt1)
Genotypic Resistance 0 (0) 0 (0)
1011
1010
109
108
107
HBV DNA (Copies/mL)
106
105
104
103
300-999
38
65
81
24
37
38
lt300
Wk 0 24 48 96 0 24 48
96
ETV
LVD
n 352 331 341 228 354 322 324 212
Study 022
13-6
6
Knodell Necroinflammatory Mean Score
Naïve eAg Naïve eAg Naïve eAg- Naïve eAg- LVD-Ref eAg LVD-Ref eAg
ETV N 292 LVD N 269 ETV N 265 LVD N 250 ETV N 110 LVD N 98

Baseline 8.2 8.1 8.1 7.8 7.2 7.4
Week 48 4.4 4.6 4.2 4.6 4.2 6.7
Week 48 change from baseline -3.7 -3.5 -4.0 -3.2 -2.9 0.6
Analyses were based on patients with baseline
Knodell necroinflammatory score 2and adequate
Week 48 biopsy p lt 0.01 (ETV vs. LVD)
Studies 022, 027 and 026
2-66
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Sustained Response Through 24 Weeks Off
Treatmentfor Responders at Week 48 Naïve
Patients
Naïve eAg
Naïve eAg-
Percent
n 61
n 49
n 124
n 78
N 74 67
259 220

Studies 022 and 027
2-380
8
Histologic Improvement, HBV DNA, and ALTat Week
48
Number of patients ()
Naïve eAg Naïve eAg Naïve eAg- Naïve eAg- LVD-Ref eAg LVD-Ref eAg
ETVN 314 LVDN 314 ETVN 296 LVDN 287 ETVN 124 LVDN 116
Histologic Improvement, ALT 1 x ULN and HBV DNA lt 400 copies/mL 138 ( 44) 80 ( 25) 170 ( 57) 112 ( 39) 16 ( 13) 0 (  0)
Histologic Improvement, ALT 1 x ULN and HBV DNA lt 105 copies/mL 169 ( 54) 122 ( 39) 179 ( 60) 130 ( 45) 29 ( 23) 1 (  1)
Evaluable Baseline Histology
Studies 022, 027 and 026
17-1
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Growth Rates of HCC
14
Median doubling time 117 days (range 29-398)
12
10
8
Number of Cases
6
4
2
0
lt30
30-90
90-150
150-210
gt210
Doubling Time (days)
Sheu J-C et al, Gastro 198589259
10
Six cases of HCC Origin
Relative to Start of Therapy Doubling Time 29 d
10000
3E
1000
1L
4E
5E
2L
100
6L
Tumor Volume (cc)
10
1
0.1
0.01
-15.0
-10.0
-5.0
0.0
5.0
10.0
15.0
20.0
Months
Months
Start of Therapy
11
Six cases of HCC Origin Relative to
Start of Therapy
6L
doubling time 117 d
doubling time 29 d
-15.0
-10.0
-5.0
0.0
5.0
10.0
15.0
20.0
-20.0
Months
Months
Start of Therapy