This enduring activity is supported by educational grants from AbbVie & Gilead Sciences, Inc.

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1 This enduring activity is supported by educational grants from AbbVie & Gilead Sciences, Inc. This webcast is not sanctioned by the AASLD conference organizers, nor is it an official part of the conference proceedings. 1

2 Abstract #74 C-ISLE: Grazoprevir/Elbasvir plus Sofosbuvir in Treatment-naïve and Treatment-experienced HCV GT3 Cirrhotic Patients Treated for 8, 12 or 16 weeks Graham R. Foster 1, Kosh Agarwal 2, Matthew Cramp 3, Sulleman Moreea 4, Stephen T. Barclay 5, Jane Collier 6, Ashley S. Brown 7, Stephen D. Ryder 8, Andrew Ustianowski 9, Daniel M. Forton 1, Ray Fox 11, Fiona Gordon 12, William M. Rosenberg 13, David J. Mutimer 14, Jiejun Du 15, Christopher L. Gilbert 15, Janice Wahl 15, Eliav Barr 15, Barbara Haber 15 ; 1. The Royal London Hospital, London, United Kingdom; 2. Institute of Liver Studies, Kings College Hospital, London, United Kingdom; 3. South West Liver Unit, Derriford Hospital and Peninsula School of Medicine and Dentistry, Plymouth, United Kingdom; 4. Bradford Teaching Hospitals Foundation Trust, Bradford, United Kingdom; 5. Glasgow Royal Campus, Glasgow, United Kingdom; 6. John Radcliffe Hospital, Oxford, United Kingdom; 7. Imperial College Healthcare, London, United Kingdom; 8. NIHR Biomedical Unit in Gastrointestinal and Liver Diseases at Nottingham University Hopsitals NHS Trust and The University of Nottingham, Nottingham, United Kingdom; 9. North Manchester General Hospital, Manchester, United Kingdom; 1. St. Georges University of London, London, United Kingdom; 11. Gartnavel General Hospital, Glasgow, United Kingdom; 12. Hepatology Joint Clinical Research Unit, Bristol, United Kingdom; 13. University College London, London, United Kingdom; 14. QE Hospital, Birmingham, United Kingdom; 15. Merck & Co., Inc., Kenilworth, NJ 2

3 Treatmentexperience d Treatmentnaive EBR/GZR + SOF + RBV SVR12 EBR/GZR + SOF SVR12 EBR/GZR + SOF SVR12 EBR/GZR + SOF + RBV SVR12 EBR/GZR + SOF SVR12 TW TW4 TW8 TW12 TW16 FW12 3

4 Cirrhotic GT3-Infected Patients (n=1) Male, n (%) 68 (68) Race, n (%) Asian White Other Cirrhosis diagnosis method Liver biopsy, n (%) FibroScan, n (%) Mean FibroScan score, kpa (SD) Prior treatment history, n (%) Naïve PR-Experienced 29 (29) 69 (69) 2 (2) 16 (16) 84 (84) 25.4 (12.1) 47 (47) 53 (53) Albumin, g/dl, mean (SD) 3.6 (1.2) Total bilirubin, mg/dl, mean (SD).7 (.4) Platelets x 1 3 cells/μl, mean (range) Platelet count <1 x 1 3 cells/μl, n (%) 148 (46-396) 24 (24) 4

5 SVR, % Treatment-naive Treatment-experienced EBR/GZR + SOF + RBV (8 weeks) EBR/GZR + SOF (12 weeks) EBR/GZR + SOF (12 weeks) EBR/GZR + SOF + RBV (12 weeks) EBR/GZR + SOF (16 weeks) Relapse 2 mfas excluded patients who discontinued treatment for reasons unrelated to study medication. 5

6 6

7 Abstract #11 Safety and Efficacy of the Fixed-Dose Combination Regimen of MK-3682/Grazoprevir/MK-848 With or Without Ribavirin in Non-cirrhotic or Cirrhotic Patients with Chronic HCV GT1, 2 or 3 Infection (Part B of C-CREST-1& 2) Eric Lawitz 2, Eric M. Yoshida 3, Maria Buti 4, John M. Vierling 5, Piero L. Almasio 6, Savino Bruno 12, Peter J. Ruane 7, Tarek I. Hassanein 8, Jacob P. Lalezari 9, Beat Mullhaupt 11, Brian Pearlman 1,13, Wei Gao 1, Hsueh-cheng Huang 1, Aimee Shepherd 1, Brynne Tannenbaum 1, Doreen Fernsler 1, Jerry J. Li 1, Anjana Grandhi 1, Shuyan Wan 1, Frank Dutko 1, Wendy W. Yeh 1, Rebeca Plank 1, Bach-Yen T. Nguyen 1, Janice Wahl 1, Eliav Barr 1, Joan R. Butterton 1 ; 1. Merck & Co., Inc., Kenilworth, NJ; 2. Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; 3. University of British Columbia, Vancouver, BC, Canada; 4. Hospital Vall D Hebron, Barcelona, Spain; 5. Baylor College of Medicine, Advanced Liver Therapies, Houston, TX; 6. U. O. di Gastroenterologia, Palermo, Italy; 7. Ruane Medical and Liver Health Institute, Los Angeles, CA; 8. Southern California GI and Liver Centers, Coronado, CA; 9. Quest Clinical Research, San Francisco, CA; 1. Atlanta Medical Center, Atlanta, GA; 11. University Hospital Zurich, Zurich, Switzerland; 12. IRCCS Istituto Clinico Humanitas and Humanitas University, Rozzano, Italy; 13. Emory School of Medicine, Atlanta, GA 7

8 MK3 is a three-drug regimen formulated into a fixed-dose combination tablet. The regimen is given as two tablets, once-daily, without regard to food. Triplet also called MK-3682B HCV NS5B polymerase nucleotide inhibitor 225 mg per tablet HCV NS3/4A protease inhibitor 5 mg per tablet HCV NS5A nextgeneration inhibitor 3 mg per tablet MK-3682 Grazoprevir (MK-5172) Ruzasvir (MK-848) 8

9 GT1 (n = 88) GT2 (n = 32) GT3 (n = 53) GT2 (n = 31) GT3 (n = 5) GT1 (n = 88) GT2 (n = 46) GT3 (n = 79) GT2 (n = 16) GT3 (n = 8) MK3 MK3 + RBV MK3 MK3 + RBV SVR12 1 Endpoint GT2 (n = 26) GT3 (n = 5) GT3 (n = 25) MK3 MK3 + RBV D1 TW4 TW8 TW12 TW16 FW12 9

10 GT1, n=176 GT2, n=151 GT3, n=337 Overall GT1, GT2 and GT3, (N=664) Male, n (%) 17 (61) 86 (57) 199 (59) 392 (59) Race, White, n (%) 156 (89) 135 (89) 34 (9) 595 (9) Race, Black (or African American), n (%) 18 (1) 8 (5) 4 (1) 3 (5) Ethnicity: Hispanic or Latino, n (%) 33 (19) 37 (25) 13 (4) 83 (13) Cirrhosis (Metavir F4), n (%) 75 (43) 57 (38) 117 (35) 249 (38) HCV GT/subtype, n (%) GT1a 9 (51) (14) GT1b 86 (49) (13) Treatment-naïve, n (%) 176 (1) 151 (1) 189 (56) 516 (78) Treatment (PR)-experienced, n (%) (44) 148 (22) HCV/HIV Co-infected, n (%) 9 (5) 4 (3) 1 (3) 23 (3) Geographic Region, n (%) North America European Union Asian Pacific Middle East 87 (49) 78 (44) 4(2) 7 (4) 87 (58) 56 (37) 4 (3) 4 (3) 125 (37) 128 (38) 45 (13) 39 (12) 299 (45) 262 (39) 53 (8) 5(8) 1

11 SVR12% Weeks 12 Weeks 16 weeks GT1a GT1b GT2 GT Relapse Discontinuation (DR-AE)* 1 Reinfection* 1 Non-virologic failure*

12 SVR12% No cirrhosis Cirrhosis Subgenotype Duration a 1b 1a 1b Weeks 8 Weeks 12 Weeks 12 Weeks Relapses

13 SVR12, % Without RBV With RBV Genotype Duration 8 GT2 Weeks 12 GT2 Weeks 8 Weeks GT3 12 Weeks GT3 16 Weeks GT3 Genotype Duration 8 Weeks 12 Weeks 8 Weeks 12 Weeks Relapse Discontinuation (DR-AE) 16 Weeks 1 13

14 SVR12, % Weeks, No RBV Weeks + RBV Weeks, No RBV Weeks + RBV Relapses 1 14

15 Abstract #253 ENDURANCE-1: Efficacy and Safety of 8- versus 12-week Treatment with ABT-493/ABT-53 in Patients with Chronic HCV Genotype 1 Infection Stefan Zeuzem 1, Jordan J. Feld 2, Stanley Wang 3, Marc Bourli.re 4, Heiner Wedemeyer 5, Edward J. Gane 6, Robert Flisiak 7, Wan-Long Chuang 8, Steven L. Flamm 9, Paul Y. Kwo 1, Gladys Sepulveda 11, Ruth Soto-Malave 12, Massimo Puoti 13, Edward Tam 14, Rafael Bruck 15, Francisco Fuster 16, Seung Woon Paik 17, Franco Felizarta 18, Bo Fu 3, Teresa Ng 3, Chih-Wei Lin 3, Federico Mensa 3 ; 1. J.W. Goethe University, Frankfurt, Germany; 2. Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada; 3. Abb-Vie, North Chicago, IL; 4. H.pital Saint Joseph, Marseille, France; 5. Medizinische Hochschule Hannover, Hannover, Germany; 6. Liver Unit, Auckland City Hospital, Auckland, New Zealand; 7. Klinika Chor.b Zakaznych i Hepatologii UM w Bialymstoku, Bialystok, Poland; 8. Kaohsiung Medical University, Kaohsiung City, Taiwan; 9. Northwestern Feinberg School of Medicine, Chicago, IL; 1. Indiana University, Indianapolis, IN; 11. Instituto de Investigaci.n Cient.fica del Sur, Ponce, PR; 12. University of Puerto Rico, San Juan, PR; 13. AO Ospedale Niguarda Ca Granda, Milan, Italy; 14. LAIR Centre, Vancouver, BC, Canada; 15. Tel Aviv Medical Center, Tel Aviv, Israel; 16. Centro de Investigaciones Clinicas Vi.a del Mar, Vina del Mar, Chile; 17. Samsung Medical Center, Seoul, Korea (the Republic of); 18. Private practice, Bakersfield, CA 15

16 SVR12 assesment Arm A N = 352 G/P 8 weeks Arm B N = 351 G/P 12 weeks Day Wk 8 Wk 12 Wk 2 Wk 24 Post-treatment Wk 24 Open-label Treatment GT1 non-cirrhotics (n=73) Treatment naïve or treatment-experienced with IFN or PEG +/- RBV or SOF + RBV +/- PEG (excluded any prior experience with HCV DAA other than SOF) HCV monoinfected or HCV/HIV coinfected (ART naïve or on stable ART regimen) 16

17 G/P 8 Weeks N = 352 G/P 12 Weeks N = 351 Characteristic Male, n (%) 176 (5) 167 (48) White race, n (%) 32 (86) 289 (82) GT1a 148 (42) 152 (43) Baseline Fibrosis Stage F-F1 298 (85) 297 (85) F2 24 (7) 22 (6) F3 29 (8) 3 (9) 17

18 Characteristic, n (%) G/P 8 Weeks N = 352 G/P 12 Weeks N = 351 Treatment-naïve 217 (62) 219 (62) Treatment experienced 135 (38) 132 (38) IFN-based, n/n (%) 133/135 (99) 131/132 (99) SOF-based, n/n (%) 2/135 (1) 1/351 (.8) HIV co-infected 18 (5) 15 (4) Raltegravir-containing ART, n/n (%) 3/18 (17) 7/15 (47) Dolutegravir-containing ART, n/n (%) 12/18 (67) 5/15 (33) Rilpivirine-containing ART, n/n (%) 3/18 (17) 3 (2) ART-naive CD4+ cell count, median (range), /µl 81 ( ) 644 ( ) PPI use 35 (1) 2 (6) 18

19 % Patients with SVR % Primary endpoint threshold: 91% ITT-PS: ITT population, excluding HIV co-infected and SOF-experienced patients ITT-PS ITT-PS ITT-PS-PP 12 Week G/P 8 Week G/P ITT-PS-PP: ITT-PS population excluding patients with premature D/C or virologic failure prior to week 8, and missing data in the SVR12 window 19

20 Abstract #113 SURVEYOR-II, Part 3: Efficacy and Safety of ABT- 493/ABT-53 in Patients with Hepatitis C Virus Genotype 3 Infection with Prior Treatment Experience and/or Cirrhosis David L. Wyles 2, Fred Poordad 3, Stanley Wang 1, Laurent Alric 4, Franco Felizarta 5, Paul Y. Kwo 6, Benedict Maliakkal 2, Kosh Agarwal 7, Tarek I. Hassanein 8, Frank Weilert 9, Samuel S. Lee 1, Ran Liu 1, Chih-Wei Lin 1, Teresa Ng 1, Federico Mensa 1 ; 1. AbbVie, Inc, North Chicago, IL; 2. University of California San Diego, La Jolla, CA; 3. The Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; 4. Department of Internal Medicine and Digestive Diseases, IRD Toulouse 3 University, Toulouse, France; 5. Private Practice, Bakersfield, CA; 6. Indiana University School of Medicine, Indianapolis, IN; 7. Institute of Liver Studies, Kings College Hospital, London, United Kingdom; 8. Southern California GI and Liver Centers and Southern California Research Center, Coronado, CA; 9. Tawa Street Specialist Clinic, Hamilton, New Zealand; 1. University of Calgary, Calgary, AB, Canada 2

21 1 : 1 Randomized Treatment Period G/P N = 22 TE without cirrhosis G/P TE without cirrhosis G/P N = 4 TN with cirrhosis G/P TE with cirrhosis N = 22 N = 47 Post-Treatment Period SVR12 SVR12 SVR12 SVR Weeks Included GT3 Patients without cirrhosis or with compensated cirrhosis Excluded prior treatment with HCV DAA other than SOF Excluded HBV or HIV coinfection 21

22 SVR12, % Patients Weeks Cirrhosis T-Experience Breakthrough Relapse LTFU :1 Randomized

23 LB-15 Glecaprevir/Pibrentasvir Demonstrates High SVR Rates in Patients with HCV Genotype 2, 4, 5, or 6 Infection without Cirrhosis Following an 8-Week Treatment Duration (SURVEYOR-II, Part 4) Tarek I. Hassanein 1, David L. Wyles 2, Stanley Wang 3, Paul Y. Kwo 4, Mitchell L. Shiffman 5, Ziad Younes 6, Susan Greenbloom 7, Catherine A. Stedman 8, Joe Sasadeusz 9, Humberto I. Aguilar 1, Jeong Heo 11, Ran Liu 3, Teresa Ng 3, Chih-Wei Lin 3, Federico J. Mensa 3 ; 1. Southern California GI and Liver Centers and Southern California Research Center, Coronado, CA; 2. University of California San Diego, La Jolla, CA; 3. AbbVie, North Chicago, IL; 4. Indiana University School of Medicine, Indianapolis, IN; 5. Liver Institute of Virginia, Bon Secours Health System, Newport News, VA; 6. GastroOne, Germantown, TN; 7. Toronto Digestive Disease Associates, Toronto, ON, Canada; 8. Christchurch Hospital, Christchurch, New Zealand; 9. Island Health Authority, Victoria, BC, Canada; 1. Louisiana Research Center, Shreveport, LA; 11. Pusan National University and Medical Research Institute, Busan, Korea (the Republic of) 23

24 <1% prevalence GT2 GT4 GT5 GT6 >1% prevalence of more than one (GT2, 4-6) GT 24

25 SVR12 assesment GT 2,4,5,6 N=23 G/P 3 mg/12 mg* Day Wk 8 Wk 2 Wk 4 Open-label Treatment *G/P is co-formulated and dosed once daily as three 1 gm/4 mg pills for a total dose of 3 mg/12 mg. Included GT2 (n=123), GT4 (n=41), GT5 (n=1) or GT6 (n=6) Excluded cirrhotics Excluded prior treatment with HCV DAA other than SOF Excluded HBV or HIV coinfection 48% Male 76% White, 1% Black, 11% Asian 87% Treatment-naïve, 1% IFNexperienced, 3% SOF-experienced 84% F-F1, 6% F2, 1% F3 25

26 % Patients With SVR Overall GT2 GT4 GT5 GT6 Breakthrough Relapse Discontinuation Missing SVR12 data : 2: 2: 3: 2 1* *Patient discontinuedon Day 15 due to loss to follow-up. Patient discontinued on Day 36 due to non-compliance. Of the 3 with missing SVR12 data, 2 had achieved SVR4 and 1 had achieved SVR

27 Background SOF Nucleotide Polymerase inhibitor VEL NS5A inhibitor Sofosbuvir (SOF)/Velpatasvir (VEL) SOF: Nucleoside polymerase inhibator with activity against HCV GT 1-6 VEL: Potent pangenotypic NS5A inhibitor F F H H H F H F H VOX NS3/4A Protease inhibitor Voxilaprevir (VOX) HCV NS3/4A PI with potent antiviral activity against GT 1-6, including most RASs SOF Nucleotide Polymerase inhibitor VEL NS5A inhibitor VOX NS3/4A Protease inhibitor SOF/VEL/VOX Once daily, oral, fixed-dose combination (4/1/1 mg) for GT

28 Wk POLARIS-1 NS5A DAA Experienced n=28 n=1 SOF/VEL/GS-9857 Placebo SVR 12 POLARIS-2 DAA Naive, GT 1-6 n=45 n=375 SOF/VEL/GS-9857 SOF/VEL SVR 12 POLARIS-3 DAA Naive, GT 3 with Cirrhosis n=1 n=1 SOF/VEL/GS-9857 SOF/VEL POLARIS-4 Non-NS5A DAA Experienced n=25 n=175 SOF/VEL/GS-9857 SOF/VEL 28

29 LB-12 A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks Compared to Sofosbuvir/Velpatasvir for 12 Weeks in DAA-Naïve Genotype 1-6 HCV-Infected Patients: The POLARIS-2 Study Ira M. Jacobson 1, Tarik Asselah 2, Ronald Nahass 3, Bal R. Bhandari 4, Albert Tran 5, Robert H. Hyland 6, Luisa M. Stamm 6, Hadas Dvory-Sobol 6, Yanni Zhu 6, Diana M. Brainard 6, Mani Subramanian 6, John G. McHutchison 6, Stephen Shafran 7, Mitchell Davis 8, Catherine A. Stedman 9, Eric Lawitz 1, Edward J. Gane 11 ; 1. Department of Medicine, Mount Sinai Beth Israel, New York, NY; 2. Service d Hépatologie, Hôpital Beaujon, AP-HP, INSERM UMR1149, Université Paris Diderot, Clichy, France; 3. ID Care, Hillsborough, NJ; 4. Gastroenterology & Nutritional Medical Services, Bastrop, LA; 5. Digestive Center, Centre Hospitalier Universitaire de Nice, Nice, France; 6. Gilead Sciences, Inc., Foster City, CA; 7. Department of Medicine, University of Alberta, Edmonton, AB, Canada; 8. Digestive Care-South Florida Center of Gastroenterology, Wellington, FL; 9. Gastroenterology Department, Christchurch Hospital, Christchurch, New Zealand; 1. Texas Liver Institute, University of Texas Health Science Center, San Antonio, TX; 11. Auckland Clinical Studies, Auckland, New Zealand 29

30 Genotype 1-4 HCV-infected patients were randomized equally to receive open-label SOF/VEL/VOX (4 mg/1 mg/1 mg daily) FDC for 8 weeks or SOF/VEL (4 mg/1 mg daily) FDC for 12 weeks and stratified according to HCV genotype, prior treatment with an interferonbased regimen, and cirrhosis status. Patients with other genotypes assessed at screening were enrolled in the SOF/VEL/VOX treatment arm. Patients with genotype 3 HCV infection and cirrhosis were excluded from this study but eligible for another Phase 3 trial (POLARIS-3). The primary endpoint is SVR12 with a pre-specified non-inferiority margin of 5%. 3

31 SVR12 (%) % 95% 98% 96% 96% 97% % / 263 % (pbo) 476/ / 44 16/ 11 15/ / / POLARIS-1 (GT1-6) (Placebo control) (NS5A inhibitor experienced; 41% cirrhotic) POLARIS-2 (GT1-6) (DAAnaïve; 18% cirrhotic) POLARIS-3 (GT-3) (DAAnaïve; 1% cirrhotic) POLARIS-4 (GT1-4) (DAAexperienced, no NS5A inhibitor; 46% cirrhotic) SOF/VEL/VOX SOF/VEL 33

32 Abstract #258 A Randomized Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir for 8 Weeks and Sofosbuvir/Velpatasvir for 12 Weeks for Patients with Genotype 3 HCV Infection and Cirrhosis: The POLARIS-3 Study Graham R. Foster 1, Alex J. Thompson 2, Peter J. Ruane 3, Sergio M. Borgia 4, Gregory Dore 5, Kimberly Workowski 6, Robert H. Hyland 7, Jing Wang 7, Evguenia S. Svarovskaia 7, Luisa M. Stamm 7, Diana M. Brainard 7, Mani Subramanian 7, John G. McHutchison 7, Thomas Berg 8, Kosh Agarwal 9, Brian Conway 1, Jordan J. Feld 11, Bernard E. Willems 12, Stuart K. Roberts 13 ; 1. Royal London Hospital, London, United Kingdom; 2. Department of Gastroenterology, St. Vincent s Hospital, Melbourne, VIC, Australia; 3. Ruane Medical and Liver Health Institute, Los Angeles, CA; 4. William Osler Health System, Brampton Civic Hospital, Brampton, ON, Canada; 5. St Vincent s Public Hospital, Sydney, NSW, Australia; 6. Emory University, Atlanta, GA; 7. Gilead Sciences, Inc, Foster City, CA; 8. Medical Department of Hepatology and Gastroenterology, Charit. Universit.tsmedizin Berlin, Berlin, Germany; 9. Institute of Liver Studies, Kings College Hospital, London, United Kingdom; 1. Vancouver Infectious Disease Research and Care Centre, Vancouver, BC, Canada; 11. Toronto Western Hospital Liver Centre, Toronto, ON, Canada; 12. Centre Hospitalier de l Universit. de Montr.al, Montr.al, QC, Canada; 13. Alfred Hospital, Melbourne, VIC, Australia 34

33 Patients at 84 sites in North America, Europe, Australia, and New Zealand were randomized 1:1 to receive open-label SOF/VEL (4 mg/1 mg daily) FDC for 12 weeks or SOF/VEL/VOX (4 mg /1 mg/1 mg daily) FDC for 8 weeks. Patients were stratified according to their prior treatment with an interferonbased regimen. Patients had cirrhosis defined by liver biopsy, Fibroscan >12.5 kpa, or combined Fibrotest >.74 and APRI >2.. HCV RNA was measured with the CAP/CTM HCV 2. assay with LLOQ =15 IU/mL. The primary endpoint compares the sustained virologic response 12 weeks after treatment (SVR12) of each treatment, to a pre-specified historic control rate of 83%. Secondary endpoints included safety and tolerability, viral resistance, and additional efficacy outcomes. 35

34 Of 219 patients randomized and treated, 72% were male, 89% were white, 42% had the IL28B CC genotype, and 3% had previously failed treatment with an interferon-based regimen. Patients from the US (44%) and other regions (56%) were well represented. Most (9%) patients with treatment experience had received a Peg-IFN+RBV regimen. All patients had cirrhosis; the median platelet count was 139x13 cells/ml with 24% of patients having a platelet count of <1 x13 cells/ml. Treatment was well tolerated; at the time of abstract submission, one patient has discontinued therapy due to an unrelated adverse event. No serious adverse events attributed to either study medication had been reported. 36

35 SVR12 (%) % 95% 98% 96% 96% 97% % / 263 % (pbo) 476/ / 44 16/ 11 15/ / / POLARIS-1 (GT1-6) (Placebo control) (NS5A inhibitor experienced; 41% cirrhotic) POLARIS-2 (GT1-6) (DAAnaïve; 18% cirrhotic) POLARIS-3 (GT-3) (DAAnaïve; 1% cirrhotic) POLARIS-4 (GT1-4) (DAAexperienced, no NS5A inhibitor; 46% cirrhotic) SOF/VEL/VOX SOF/VEL 37

36 38

37 Abstract #19 A Randomized, Controlled, Phase 3 Trial of Sofosbuvir/Velpatasvir/Voxilaprevir or Sofosbuvir/Velpatasvir for 12 Weeks in Direct Acting Antiviral-Experienced Patients with Genotype 1-6 HCV Infection: The POLARIS-4 Study Stefan Zeuzem 1, Steven L. Flamm 2, Myron J. Tong 3, John M. Vierling 4, Stephen Pianko 5, Peter Buggisch 6, Victor de Ledinghen 7, Robert H. Hyland 8, Xiaoru Wu 8, Evguenia S. Svarovskaia 8, Luisa M. Stamm 8, Diana M. Brainard 8, Mani Subramanian 8, John G. McHutchison 8, Elizabeth C. Verna 9, Meena B. Bansal 1, Charles S. Landis 11, Simone I. Strasser 12, Curtis Cooper 13, Kris V. Kowdley 14 ; 1. Johann Wolfgang Goethe University Medical Center, Frankfurt, Germany; 2. Northwestern University, Chicago, IL; 3. Huntington Medical Research Institutes, Pasadena, CA; 4. Baylor College of Medicine, Houston, TX; 5. Monash University, Clayton, VIC, Australia; 6. ifi-institute for Interdisciplinary Medicine, Hamburg, Germany; 7. University Hospital of Bordeaux, Pessac, France; 8. Gilead Sciences, Inc, Foster City, CA; 9. Columbia University Medical Center, New York, NY; 1. Ichan School of Medicine at Mount Sinai, New York, NY; 11. University of Washington, Seattle, WA; 12. Royal Prince Alfred Hospital, Sydney, NSW, Australia; 13. Ottawa Hospital, Ottawa, ON, Canada; 14. Swedish Medical Center, Seattle, WA 39

38 Patients at 11 sites in North America, Europe, Australia and New Zealand were enrolled and those with genotypes 1, 2 or 3 were randomized 1:1 to receive open-label SOF/VEL/VOX or SOF/VEL for 12 weeks, stratified according to genotype and cirrhosis status. Patients of all other genotypes were assigned to receive SOF/VEL/VOX for 12 weeks. DAA-experienced patients who previously were treated with an NS5A inhibitor or with an NS3/4A protease inhibitor in combination with ribavirin and Peg-IFN were excluded. The primary endpoint evaluates the superiority of the sustained virologic response 12 weeks after treatment (SVR12) of each treatment to a prespecified performance goal of 85%. 4

39 Of the 333 patients who were randomized and treated, 77% were male, 86% were white, 18% had the IL28B CC genotype, 46% had compensated cirrhosis, 57% were from the United States and 4% had genotype 1 HCV infection. Most patients had prior DAA experience with either an NS5B inhibitor alone (73%) or an N5SB inhibitor and an NS3/4A protease inhibitor (25%); the most common prior treatment regimens were SOF with ribavirin with or without Peg-IFN and SOF combined with simeprevir. Treatment was well tolerated; No serious adverse events attributed to either study medication had been reported. Diarrea in group VOX 41

40 SVR12 (%) % 95% 98% 96% 96% 97% 9% / 263 % (pbo) 476/ / 44 16/ 11 15/ / / POLARIS-1 (GT1-6) (Placebo control) (NS5A inhibitor experienced; 41% cirrhotic) POLARIS-2 (GT1-6) (DAAnaïve; 18% cirrhotic) POLARIS-3 (GT-3) (DAAnaïve; 1% cirrhotic) POLARIS-4 (GT1-4) (DAAexperienced, no NS5A inhibitor; 46% cirrhotic) SOF/VEL/VOX SOF/VEL 42

41 Abstract #194 Sofosbuvir/Velpatasvir/Voxilaprevir for 12 Weeks as a Salvage Regimen in NS5A Inhibitor Experienced Patients with Genotype 1-6 Infection: The Phase 3 POLARIS-1 Study Marc Bourli.re 1, Stuart C. Gordon 2, Alnoor Ramji 3, Natarajan Ravendhran 4, Tram T. Tran 5, Robert H. Hyland 6, Jie Zhang 6, Hadas Dvory-Sobol 6, Luisa M. Stamm 6, Diana M. Brainard 6, Mani Subramanian 6, John G. McHutchison 6, Ziad Younes 7, Michael P. Curry 8, Eugene R. Schiff 9, K. Rajender Reddy 1, Michael P. Manns 11 ; 1. Hospital Saint Joseph, Marseille, France; 2. Henry Ford Health System, Detroit, MI; 3. St Paul s Hospital, Vancouver, BC, Canada; 4. Digestive Disease Associates, Cantonsville, MD; 5. Cedars-Sinai Medical Center, Los Angeles, CA; 6. Gilead Sciences, Inc, Foster City, CA; 7. Gastro One, Germantown, TN; 8. Beth Israel Deaconess Medical Center, Boston, MA; 9. University of Miami, Miami, FL; 1. University of Pennsylvania Hospital, Philadelphia, PA; 11. Hannover Medical School, Hannover, Germany 43

42 Patients at 18 sites in North America, Europe, Australia and New Zealand were enrolled. Eligible patients received at least 4 weeks of a prior NS5A inhibitorcontaining regimen which was not discontinued due to an adverse event or unsuccessful due to non-compliance. Those with HCV genotype (GT) 1 were randomized 1:1 to receive SOF/VEL/VOX (4mg/1mg/1mg) or matching placebo daily for 12 weeks, stratified by the presence or absence of cirrhosis. Patients of all other GTs were assigned to receive SOF/VEL/VOX for 12 weeks. Those patients assigned to receive placebo will be offered deferred treatment with SOF/VEL/VOX for 12 weeks. The primary endpoint evaluates the superiority of the sustained virologic response 12 weeks after treatment (SVR12) to a pre-specified performance goal of 85%. 44

43 Of 415 patients treated, 77% were male, 41% had compensated cirrhosis and 73% had GT 1 HCV infection. The majority of patients had DAA experience with an NS5A inhibitor given in combination with an NS5B inhibitor, and the most common prior treatment regimen was ledipasvir/sof (66%). Treatment with SOF/VEL/VOX has been well tolerated; at the time of abstract submission, two patients have discontinued therapy due to adverse events not related to study drug, one due to chest pain, confusion, dizziness and blurred vision and another due to grade 4 elevations in transaminases, present prior to initiation of therapy. No serious adverse events attributed to study medication have been reported. 45

44 SVR12 (%) % 95% 98% 96% 96% 97% % / 263 % (pbo) 476/ / 44 16/ 11 15/ / / POLARIS-1 (GT1-6) (Placebo control) (NS5A inhibitor experienced; 41% cirrhotic) POLARIS-2 (GT1-6) (DAAnaïve; 18% cirrhotic) POLARIS-3 (GT-3) (DAAnaïve; 1% cirrhotic) POLARIS-4 (GT1-4) (DAAexperienced, no NS5A inhibitor; 46% cirrhotic) SOF/VEL/VOX SOF/VEL 46

45 Abstract #193 Safety and Efficacy of the Fixed-Dose Combination Regimen of MK-3682/Grazoprevir/MK-848 in Cirrhotic or Non-cirrhotic Patients with Chronic HCV GT1 Infection who Previously Failed a Direct-acting Antiviral Regimen (C-SURGE) David L. Wyles 2, Heiner Wedemeyer 3, K. Rajender Reddy 4, Anne Luetkemeyer 2, Ira M. Jacobson 5, John M. Vierling 6, Stuart C. Gordon 7, Ronald Nahass 8, Stefan Zeuzem 9, Janice Wahl 1, Eliav Barr 1, Bach-Yen T. Nguyen 1, Michael Robertson 1, Shuyan Wan 1, Patricia Jumes 1, Frank Dutko 1, Elizabeth Martin 1 ; 1. Merck & Co., Inc., Kenilworth, NJ; 2. University of California, San Diego, CA; 3. Hannover Medical School, Hannover, Germany; 4. University of Pennsylvania, Philadelphia, PA; 5. Mount Sinai Beth Israel, New York, NY; 6. Baylor College of Medicine, Houston, TX; 7. Henry Ford Health System, Detroit, MI; 8. ID Care, Hillsborough, NJ; 9. Goethe University Hospital, Frankfurt, Germany 47

46 This multicenter, open-label trial randomized compensated cirrhotic (platelet cutoff=75,μl or non-cirrhotic HCV GT1-infected patients who relapsed after a recommended regimen of LDV/SOF or EBR/GZR to receive a once-daily regimen of MK-3682 (45 mg)/grazoprevir (1 mg)/mk-848 (6 mg) either 16 weeks + ribavirin (RBV) or 24 weeks without RBV. Patients who failed LDV/SOF were stratified by previous 8 or 12 week regimen. Next-generation sequencing (15% sensitivity) was used to test for baseline RAVs. The primary objectives of the trial are to determine the efficacy (the proportion of patients with HCV RNA <15 IU/mL at 12 weeks after the end of study therapy; SVR12), and the safety & tolerability of the regimen. 48

47 94 GT1 patients were randomized in this trial (78 [83%] GT1a; 16 [17% GT1b] Patients had failed 12 or 24 weeks of LDV/SOF (59 [63%]), 8 weeks of LDV/SOF (13 [14%]), or 12 weeks of EBR/GZR (22 [23%]). Forty-two patients (45%) had cirrhosis. More than 75% of patients had at least 1 NS5A RAV at baseline. Treatment was generally well tolerated in both arms. no patient discontinued due to an adverse event. The table shows on-treatment results for the patients who have reached treatment weeks 4 or 8. The SVR4 results and analysis of predictors of outcomes presented at the meeting. 49

48 Preliminary results show that the regimen of MK- 3682/grazoprevir/MK-848 produced robust ontreatment virologic responses and was well-tolerated in cirrhotic and non-cirrhotic GT1 patients who previously failed a direct-acting antiviral regimen. Arm Proportion of Patients with HCV RNA <15 IU/mL [n/m, (%)] Treatment Week 4 Treatment Week 8 16 weeks + RBV 39/42 (93%) 35/35 (1%) 24 weeks without RBV 44/49 (9%) 38/38 (1%) 5

49 This enduring activity is supported by educational grants from AbbVie & Gilead Sciences, Inc. 51