AllOral Treatment With Daclatasvir Plus Sofosbuvir Plus Ribavirin

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All-Oral Treatment With Daclatasvir Plus Sofosbuvir Plus Ribavirin for 12 or 16 Weeks in

All-Oral Treatment With Daclatasvir Plus Sofosbuvir Plus Ribavirin for 12 or 16 Weeks in HCV Genotype 3 -Infected Patients With Advanced Fibrosis or Cirrhosis: The ALLY-3+ Phase 3 Study Leroy V, 1 Angus P, 2 Bronowicki JP, 3 Dore G, 4 Hézode C, 5 Pianko S, 6 Pol S, 7 Stuart K, 8 Tse E, 9 Mc. Phee F, 10 Bhore R, 11 Jimenez-Exposito MJ, 11 Thompson A 4 1 CHU de Grenoble, La Tronche, France; 2 Austin Hospital, Heidelberg, Australia; 3 CHU Nancy & Lorraine University, Nancy, France; 4 St. Vincent’s Hospital and Kirby Institute, Sydney, Australia; 5 CHU Henri Mondor, Créteil, France; 6 Monash Medical Centre, Clayton, Australia; 7 Hôpital Cochin, Paris, France; 8 Gallipoli Medical Research Foundation, Greenslopes, Australia; 9 Royal Adelaide Hospital, Adelaide, Australia; 10 Bristol-Myers Squibb Research & Development, Wallingford, CT; 11 Bristol-Myers Squibb Research & Development, Princeton, NJ. The Liver Meeting 2015® San Francisco, CA, 13– 17 November 2015 Oral LB-3 Mercury-Nr: 1392 DE 15 NP 07880 -04 Date of preparation: Nov-2015

ALLY-3+ Background ■ HCV GT 3 infection is associated with rapid fibrosis progression, a

ALLY-3+ Background ■ HCV GT 3 infection is associated with rapid fibrosis progression, a high prevalence of steatosis, and a high risk of hepatocellular carcinoma 1 ■ HCV GT 3 -infected patients with advanced fibrosis, especially those with cirrhosis, remain a population in urgent need of optimally effective therapies ■ In ALLY-3 (AI 444218), the pangenotypic, all-oral, RBV-free regimen of DCV + SOF for 12 weeks achieved 96% SVR 12 in non-cirrhotic patients; 63% SVR 12 was achieved in cirrhotic patients 2 ■ ALLY-3+ (AI 444326) investigated DCV + SOF + RBV for 12 or 16 weeks in GT 3 -infected patients with advanced fibrosis (F 3) or compensated cirrhosis (F 4) 1. Probst A, et al. J Viral Hepat 2011; 18: 745 -759. 2. Nelson DR, et al. Hepatology 2015; 61: 1127– 1135. 2

ALLY-3+ Study Design Phase 3 b, open-label, randomized study DCV + SOF + RBV

ALLY-3+ Study Design Phase 3 b, open-label, randomized study DCV + SOF + RBV 12 weeks 1: 1 randomization (N = 50) Stratified by fibrosis stage (F 3 or F 4) 24 -week follow-up DCV + SOF + RBV 16 weeks 0 DCV 60 mg daily N = 50 SOF 400 mg daily RBV (weight-based 1200 or 1000 mg/day) 4 8 12 24 -week follow-up 16 20 24 28 32 36 40 Week Primary efficacy endpoint: SVR 12 ■ HCV RNA <LLOQTD/TND (next observation carried backward) by Roche COBAS Taq. Man v 2. 0 assay (LLOQ 25 IU/m. L) Safety endpoints ■ Frequencies of serious AEs, discontinuations due to AEs, grade 3/4 AEs, and laboratory abnormalities 3

ALLY-3+ Inclusion / Exclusion Criteria Key inclusion criteria ■ Adults (≥ 18 years) with

ALLY-3+ Inclusion / Exclusion Criteria Key inclusion criteria ■ Adults (≥ 18 years) with HCV GT 3 infection ■ HCV treatment-naive or -experienced – Excluding patients with prior exposure to NS 5 A inhibitors ■ Advanced fibrosis (F 3) or compensated cirrhosis (F 4) – Assessed by liver biopsy > Fibro. Scan (advanced fibrosis: 9. 6 to < 14. 6 k. Pa; cirrhosis: 14. 6 k. Pa) > Fibro. Test + APRI above 2 Key exclusion criteria ■ Evidence of hepatic decompensation – Albumin < 35 g/L and platelets < 50 x 109 cells/L ■ Pregnancy or not using contraception 4

ALLY-3+ Baseline Demographics and Disease Characteristics Age, median (range) yrs Male, n (%) Race,

ALLY-3+ Baseline Demographics and Disease Characteristics Age, median (range) yrs Male, n (%) Race, n (%) White Asian IL 28 B non-CC, n (%) HCV RNA, median (range) log 10 IU/m. L HCV RNA category (IU/m. L), n (%) 2 million 6 million Fibrosis stage, n (%) Advanced fibrosis (F 3) Cirrhosis (F 4) Albumin, median (range) g/L Platelets, median (range) 109 cells/L Prior HCV treatment experience, n (%) Naive Experienceda IFN-based regimens SOF-based regimensb a Includes DCV+SOF+RBV Overall DCV+SOF+RBV 12 Weeks DCV+SOF+RBV 16 Weeks N = 50 53. 5 (36– 73) 40 (80) N = 24 53. 0 (36– 73) 18 (75) N = 26 56. 0 (42– 62) 22 (85) 49 (98) 1 (2) 28 (56) 6. 87 (4. 6– 7. 8) 23 (96) 1 (4) 13 (54) 6. 70 (4. 6– 7. 6) 26 (100) 0 15 (58) 6. 91 (4. 7– 7. 8) 38 (76) 26 (52) 18 (75) 11 (46) 20 (77) 15 (58) 14 (28) 36 (72) 43 (33– 48) 161 (63– 324) 6 (25) 18 (75) 43. 0 (33– 47) 161 (63– 299) 8 (31) 18 (69) 42. 5 (34– 48) 155 (84– 324) 13 (26) 37 (74) 31 (62) 6 (12) 6 (25) 18 (75) 15 (63) 3 (13) 7 (27) 19 (73) 16 (62) 3 (12) 30 patients with cirrhosis (F 4); 7 patients with advanced fibrosis (F 3); b Includes 5 patients (12 -week, n = 2; 16 -week, n = 3) who relapsed after a previous SOF + RBV regimen, and 1 patient (12 -week) who relapsed after SOF + IFN/RBV. 5

ALLY-3+ SVR 12: All Treated Patients HCV RNA < LLOQTD/TND (%) ITT ANALYSIS (Primary

ALLY-3+ SVR 12: All Treated Patients HCV RNA < LLOQTD/TND (%) ITT ANALYSIS (Primary Endpoint) 100 90 80 70 60 50 40 30 20 10 0 90 88 92 45 50 21 24 24 26 Overall 12 Weeks 16 Weeks VBTa 0 0 0 Relapseb 4 2 2 Deathc 1 1 0 (virologic breakthrough}: confirmed HCV RNA 1 log 10 IU/m. L above nadir, or LLOQ if previously < LLOQ TD or TND; confirmed HCV RNA LLOQ at any posttreatment visit following < LLOQ TND at end of treatment; c Dilated cardiomyopathy on Day 72, not related to treatment. a VBT b Relapse: 6

ALLY-3+ SVR 12: All Treated Patients 100 90 80 70 60 50 40 30

ALLY-3+ SVR 12: All Treated Patients 100 90 80 70 60 50 40 30 20 10 0 90 88 92 45 50 21 24 24 26 Overall 12 Weeks 16 Weeks OBSERVED ANALYSIS 100 90 80 70 60 50 40 30 20 10 0 HCV RNA < LLOQTD/TND (%) ITT ANALYSIS (Primary Endpoint) 92 91 92 45 49 21 23 24 26 Overall 12 Weeks 16 Weeks VBTa 0 0 0 Relapseb 4 2 2 Deathc 1 1 0 (virologic breakthrough}: confirmed HCV RNA 1 log 10 IU/m. L above nadir, or LLOQ if previously < LLOQ TD or TND; confirmed HCV RNA LLOQ at any posttreatment visit following < LLOQ TND at end of treatment; c Dilated cardiomyopathy on Day 72, not related to treatment. a VBT b Relapse: 7

ALLY-3+ HCV RNA < LLOQTD/TND (%) SVR 12: Patients with Advanced Fibrosisa a Diagnosed

ALLY-3+ HCV RNA < LLOQTD/TND (%) SVR 12: Patients with Advanced Fibrosisa a Diagnosed 100 90 80 70 60 50 40 30 20 100 100 14 14 6 6 8 8 Overall 12 Weeks 16 Weeks by Fibro. Scan 9. 6 to < 12. 5 k. Pa (n = 9), Fibro. Scan ≥ 12. 5 – 14. 6 k. Pa (n = 4), liver biopsy, (n = 1). 8

ALLY-3+ SVR 12: Patients with Cirrhosis HCV RNA < LLOQTD/TND (%) ITT ANALYSIS 100

ALLY-3+ SVR 12: Patients with Cirrhosis HCV RNA < LLOQTD/TND (%) ITT ANALYSIS 100 90 80 70 60 50 40 30 20 10 0 VBTa Relapseb Deathc 86 83 89 31 36 15 18 16 18 Overall 12 Weeks 16 Weeks 0 2 1 0 2 0 0 4 1 (virologic breakthrough): confirmed HCV RNA 1 log 10 IU/m. L above nadir, or LLOQ if previously < LLOQ TD or TND; confirmed HCV RNA LLOQ at any posttreatment visit following < LLOQ TND at end of treatment; c Dilated cardiomyopathy on Day 72, not related to treatment; cirrhosis status diagnosed by liver biopsy (F 4) n = 9; Fibro. Scan ≥ 14. 6, n = 27. a VBT b Relapse: 9

ALLY-3+ SVR 12: Patients with Cirrhosis 100 90 80 70 60 50 40 30

ALLY-3+ SVR 12: Patients with Cirrhosis 100 90 80 70 60 50 40 30 20 10 0 VBTa Relapseb Deathc OBSERVED ANALYSIS 86 83 89 31 36 15 18 16 18 Overall 12 Weeks 16 Weeks 0 2 1 0 2 0 0 4 1 89 88 89 31 35 15 17 16 18 Overall 12 Weeks 16 Weeks VBT 0 0 0 Relapse 4 2 2 HCV RNA < LLOQTD/TND (%) ITT ANALYSIS 100 90 80 70 60 50 40 30 20 10 0 (virologic breakthrough): confirmed HCV RNA 1 log 10 IU/m. L above nadir, or LLOQ if previously < LLOQ TD or TND; confirmed HCV RNA LLOQ at any posttreatment visit following < LLOQ TND at end of treatment; c Dilated cardiomyopathy on Day 72, not related to treatment; cirrhosis status diagnosed by liver biopsy (F 4) n = 9; Fibro. Scan ≥ 14. 6, n = 27. a VBT b Relapse: 10

ALLY-3+ SVR 12 (ITT) by Prior Treatment TREATMENT HISTORY TREATMENT-EXPERIENCED 100 90 80 70

ALLY-3+ SVR 12 (ITT) by Prior Treatment TREATMENT HISTORY TREATMENT-EXPERIENCED 100 90 80 70 60 50 40 30 20 10 0 92 89 26 26 12 30 30 13 14 14 33 16 16 37 Naive Experienced Cirrhotic Patients HCV RNA < LLOQTD/TND (%) All Patients 100 90 80 70 60 50 40 30 20 10 0 87 261 301 Overall 4 4 88 86 14 16 20 12 20 22 14 22 12 Weeks 16 Weeks 11

Baseline Characteristics of Patients Experiencing Relapse Treatment Prior Patient Group Treatment ALLY-3+ IL 28

Baseline Characteristics of Patients Experiencing Relapse Treatment Prior Patient Group Treatment ALLY-3+ IL 28 B Genotype HCV RNA (log 10 IU/m. L) Fibro. Scan (k. Pa) Albumin (g/L) Platelets ( 109/L) 1 (51/M) 12 wks None CC 6. 7 66. 5 33 83 2 (53/M) 12 wks IFN-based (VBT) CT 7. 0 19. 0 43 157 3 (61/M) 4 (57/M) 16 wks SOF + RBV (relapse) CT 5. 3 NA (biopsy) 41 188 CT 6. 8 14. 6 46 201 ■ All patients had cirrhosis VBT, virologic breakthrough; No patients had RBV dose reductions. 13

Resistance-associated Variants (RAVs) at Baseline and Failure Y 93 Y/H (n = 1) Y

Resistance-associated Variants (RAVs) at Baseline and Failure Y 93 Y/H (n = 1) Y 93 H (n = 1) SVR 12 93% (38/41) No BL NS 5 A RAVs n = 41 BL NS 5 A RAVs n=8 A 30 K (n = 5) A 30 A/K (n = 1) Relapse SVR 12 88% (7/8) 45 50 ■ At failure, all 4 patients who relapsed had NS 5 A-Y 93 H ■ No SOF-associated RAVs in NS 5 B were observed at baseline or relapse (sensitivity 1%) – S 282 T or any substitution at L 159, L 320, or V 321 Resistance assessed by population sequencing (sensitivity ≥ 10%) Assessment of baseline RAVs on SVR 12 excludes 1 patient without RAVs who died of dilated cardiomyopathy on Day 72, unrelated to treatment. One relapse without A 30 K or Y 93 H had baseline M 28 I polymorphism not present at failure. M 28 I does not affect DCV susceptibility in vitro. 14

ALLY-3+ On-Treatment Safety Summary n (%) DCV + SOF + RBV Overall 12 weeks

ALLY-3+ On-Treatment Safety Summary n (%) DCV + SOF + RBV Overall 12 weeks 16 weeks N = 50 N = 24 N = 26 Any AE 47 (94) 23 (96) 24 (92) Serious AEsa 5 (10) 2 (8) 3 (12) Deathsb 1 (2) 1 (4) 0 0 Grade 3– 4 AEs 4 (8) 2 (8) RBV dose reduction 6 (12) 2 (8) 4 (15) 1 (2) 2 (4) 0 0 0 1 (4) 0 0 Discontinuations for AEs Treatment-emergent grade 3– 4 laboratory abnormalitiesc Hemoglobin < 9. 0 g/d. L or decrease ≥ 4. 5 g/d. L Total bilirubin 2. 5 x ULN Platelet count < 50 x 109/L ALT 5 x ULN AST > 5 x ULN Creatinine > 1. 9 x ULN AE, adverse event; ULN, upper limit of normal. a No serious AE was related to treatment. 12 -week: dilated cardiomyopathy (n = 1) and somnolence (n = 1); 16 -week: pneumonia (n = 1), arteriosclerosis (n = 1), and basal cell carcinoma (n = 1); b Not related to treatment (dilated cardiomyopathy on Day 72). c All listed events were of grade 3 intensity. No grade 4 laboratory abnormalities. 14

ALLY-3+ Common AEs on Treatment ( 10% Overall) DCV + SOF + RBV Overall

ALLY-3+ Common AEs on Treatment ( 10% Overall) DCV + SOF + RBV Overall N = 50 DCV + SOF + RBV 12 weeks N = 24 DCV + SOF + RBV 16 weeks N = 26 Insomnia 15 (30) 8 (33) 7 (27) Fatigue 13 (26) 6 (25) 7 (27) Headache 12 (24) 7 (29) 5 (19) Irritability 7 (14) 5 (21) 2 (8) Asthenia 7 (14) 2 (8) 5 (19) Diarrhea 5 (10) 1 (4) 4 (15) Dyspnea 5 (10) 2 (8) 3 (12) n (%) Grades 1– 4 regardless of causality. 15

ALLY-3+ Summary & Conclusions ■ Overall, 90% SVR 12 was achieved in HCV GT

ALLY-3+ Summary & Conclusions ■ Overall, 90% SVR 12 was achieved in HCV GT 3 -infected patients with advanced fibrosis or compensated cirrhosis treated with DCV + SOF + RBV – SVR 12 was comparable for the 12 -week (88%) and 16 -week (92%) groups – No on-treatment virologic failures; two relapses in each treatment arm ■ 100% SVR 12 among patients with advanced fibrosis ■ 86% SVR 12 among patients with cirrhosis (mostly treatment experienced) ■ Treatment was safe and well tolerated; no patient discontinued for AEs ■ DCV + SOF + RBV for 12 or 16 weeks is a highly efficacious therapy for GT 3 -infected patients with advanced fibrosis or compensated cirrhosis, a population in urgent need of treatment 16

ALLY-3+ Acknowledgments ■ The authors thank the patients and their families for their support

ALLY-3+ Acknowledgments ■ The authors thank the patients and their families for their support and dedication, and investigators and research staff at all study sites ■ The authors acknowledge Bristol-Myers Squibb personnel: Kimberly Brown, Patricia Mendez, and Eric Y Wong ■ Editorial support was provided by Nick Fitch of Articulate Science and funded by Bristol-Myers Squibb ■ Clinical. Trials. gov registration number NCT 02319031 (Study AI 444326) 18