Update on the Treatment of HCV

Update on the Treatment of HCV K. Rajender Reddy, MD Professor of Medicine Director of Hepatology Director, Viral Hepatitis Center University of Pennsylvania Philadelphia, USA 1 K. Rajender Reddy, MD Disclosure Statement Consultant/Advisory Board: AbbVie Inc; Bristol-Myers Squibb; Genentech, Inc; Gilead Sciences, Inc; Janssen Pharmaceuticals, Inc; Merck & Co, Inc; Vertex Pharmaceuticals Investigator: AbbVie Inc; Bristol-Myers Squibb; Genentech, Inc; Gilead Sciences, Inc; Janssen Pharmaceuticals, Inc; Merck & Co, Inc; Vertex Pharmaceuticals (funds are paid to University of Pennsylvania) 1

HCV is a Viral Disease that Affects the Liver, with ~170M Infected Individuals Worldwide Epidemiology and distribution of HCV genotypes in the world Of the 170M HCV-infected, approximately 95 million live in the Asia-Pacific Region 4M 12M 5M 43M 2M 6 different HCV genotypes WW with genotypes 1, 2 and 3 comprising the majority of patients 7M Brazil Current DAA combinations primarily address genotype 1 Pan-genotypic treatments can be used widely in both developed and emerging countries - Roughly half of WW HCVinfected are non-gt1 Despite High Prevalence and Increasing Disease Burden, Most Americans With Chronic HCV Have Not Been Diagnosed and Few Have Been Treated 60% 50% 40% 30% Overall: 3.2 million of U.S. population with chronic HCV 50% (1.6M) 32-38% (1.0-1.2M) 20% 10% 7-11% (220,000-360,000) 000) 5-6% (170,000-200,000) 0% Diagnosed Referred to Care Treated Successfully Treated Holmberg SD et al. New Engl J Med. 2013;368:1859-1861. 2

Who Should Be Tested for HCV CDC Recommendations Everyone born from 1945 through 1965 (one-time) Persons who ever injected illegal l drugs Persons who received clotting factor concentrates produced before 1987 Chronic (long-term) hemodialysis Persons with persistently abnormal ALT levels Recipients of transfusions or organ transplants prior to 1992 Persons with recognized occupational exposures Children born to HCV-positive women HIV-positive persons USPSTF Grade B Recs* Everyone born from 1945 through 1965 (one-time) Past or present injection i drug use Sex with an IDU; other high-risk sex Blood transfusion prior to 1992 Persons with hemophilia Long-term hemodialysis Born to an HCV-infected mother Incarceration Intranasal drug use Receiving an unregulated tattoo Occupational percutaneous exposure Surgery before implementation of universal precautions *Only pertains to persons with normal liver enzymes; if elevated liver enzymes need HBV and HCV testing Smith BD et al. Ann Intern Med. 2012;157:817-822. (C) Moyer VA et al. Ann Intern Med. 2013 Sep 3;159(5):349-357. (C) Direct Acting Antivirals Against HCV asvirs NS5A Inhibitors previrs Protease Inhibitors Nucs Non-Nucs Polymerase Inhibitors buvirs Manns, von Hahn, Nat Rev Drug Discov 2013 3

Asunaprevir Danoprevir ABT-450/r MK-5172 Sovaprevir Direct Acting Antivirals Against HCV.. Daclatasvir Ledipasvir ABT-267 asvirs NS5A Inhibitors Simeprevir Faldaprevir Boceprevir Telaprevir previrs Protease Inhibitors ABT-333 ABT-072 Deleobuvir BMS-731225 Setrobuvir Filibuvir VX-222. Nucs Non-Nucs Polymerase Inhibitors buvirs Sofosbuvir Mericitabine ALS-2200 Manns, von Hahn, Nat Rev Drug Discov 2013 Regimen PEG + RBV Antiviral Therapies for Genotype 1 Currently Available PEG + RBV + boceprevir PEG + RBV + telaprevir PEG + RBV + simeprevir PEG + RBV + sofosbuvir RBV + sofosbuvir* (Extended duration) Sofosbuvir + simeprevir DAA Class None Protease inhibitor (PI) Protease inhibitor Protease inhibitor Nucleotide analogue NS5B polymerase inhibitor Nucleotide analogue NS5B polymerase inhibitor NUC + PI (off-label) *Sofosbuvir + ribavirin for 24 wks can be considered in patients with genotype 1 HCV who are ineligible for interferon. RBV, ribavirin AASLD/IDSA treatment recommendations. www.hcvguidelines.org. Accessed June 18, 2014. 4

TREATMENT OF CHRONIC HEPATITIS C: GENOTYPE 1 Treatment-Naïve and Prior Relapsers AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Initial Therapy for Patients with Genotype 1 Chronic HCV Patients with GT 1 HCV: Initial Treatment & Retreatment of Relapsers* Recommended Therapy Interferon Eligible Sofosbuvir + Peginterferon + Ribavirin x 12 weeks Not Interferon Eligible Sofosbuvir + Simeprevir +/- Ribavirin x 12 weeks *Patients who experienced relapse after Peginterferon plus Ribavirin therapy Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 22, 2014 5

AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Initial Therapy for Patients with Genotype 1 Chronic HCV Patients with GT 1 HCV: Initial Treatment & Retreatment of Relapsers* Alternative Therapy Interferon Eligible ^Simeprevir x 12 weeks + [Peginterferon + Ribavirin] x 24 weeks Not Interferon Eligible + Sofosbuvir + Ribavirin x 24 weeks *Patients who experienced relapse after Peginterferon plus Ribavirin therapy ^Acceptable regimen for persons with genotype 1b or genotype 1a in whom Q80K polymorphism not detected prior to treatment + Preliminary data suggest this regimen may be less effective than sofosbuvir + simeprevir, particularly for patients with cirrhosis Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 22, 2014 TREATMENT OF CHRONIC HEPATITIS C: GENOTYPE 1 Retreatment of Prior Nonresponders 6

AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Retreatment of Patients with Genotype 1 Chronic HCV Patients with GT 1 HCV: Retreatment of Prior Nonresponders* Recommended Therapy Sofosbuvir + Simeprevir +/- Ribavirin x 12 weeks *Patients who experienced nonresponse (partial or null) with Peginterferon plus Ribavirin therapy Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 8, 2014 AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Retreatment of Patients with Genotype 1 Chronic HCV Patients with GT 1 HCV: Retreatment of Prior Nonresponders* Alternative Therapy Sofosbuvir x 12 weeks + [Peginterferon + Ribavirin] x 12-24 weeks Sofosbuvir + Ribavirin x 24 weeks ^Simeprevir x 12 weeks + [Peginterferon + Ribavirin] x 48 weeks *Patients who experienced nonresponse (partial or null) with Peginterferon plus Ribavirin therapy ^For genotype 1a, baseline resistance testing for Q80K should be performed and alternative treatments considered if this mutation is present Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 8, 2014 7

AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Retreatment of Patients with Genotype 1 Chronic HCV Patients with GT 1 HCV: Retreatment of Prior Nonresponders* Not Recommended Peginterferon + Ribavirin +/- [Boceprevir or Telaprevir] Monotherapy with Peginterferon, Ribavirin, or a Direct Acting Antiviral Agent Treatment of Decompensated Cirrhosis with Peginterferon or Simeprevir *Patients who experienced nonresponse (partial or null) with Peginterferon plus Ribavirin therapy Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 8, 2014 AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Initial Therapy for Patients with Genotype 2 Chronic HCV Patients with GT 2 HCV: Initial Treatment & Retreatment of Relapsers* Recommended Therapy, Regardless of Eligibility for Interferon Therapy Sofosbuvir + Ribavirin x 12 weeks Alternative Therapy, Regardless of Eligibility for Interferon Therapy None Not Recommended Peginterferon + Ribavirin x 24 weeks Monotherapy with Peginterferon, Ribavirin, or a Direct Acting Antiviral Agent Any Regimen with Telaprevir, Boceprevir, or Simeprevir *Patients who experienced relapse after Peginterferon plus Ribavirin therapy Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 22, 2014 Hepatitis web study 8

AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Retreatment of Patients with Genotype 2 Chronic HCV Patients with GT 2 HCV: Retreatment of Prior Nonresponders* Recommended Therapy Sofosbuvir + Ribavirin x 12 weeks^ Alternative Therapy Sofosbuvir + Peginterferon + Ribavirin x 12 weeks Not Recommended Peginterferon+Ribavirin+/ +/- [Telaprevir, Boceprevir, or Simeprevir] Monotherapy with Peginterferon, Ribavirin, or a Direct Acting Antiviral Agent Treatment of Decompensated Cirrhosis with Peginterferon *Patients who experienced nonresponse (partial or null) with Peginterferon plus Ribavirin therapy ^Patients with cirrhosis may benefit by extension of therapy to 16 weeks Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 22, 2014 Hepatitis web study TREATMENT OF CHRONIC HEPATITIS C: GENOTYPE 3 Treatment-Naïve, Prior Relapsers and Non- Responders 9

AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Initial Therapy for Patients with Genotype 3 Chronic HCV Patients with GT 3 HCV: Initial Treatment & Retreatment of Relapsers* Recommended Therapy, Regardless of Eligibility for Interferon Therapy Sofosbuvir + Ribavirin x 24 weeks Alternative Therapy, Eligible for Interferon Therapy Sofosbuvir + Peginterferon + Ribavirin x 12 weeks Not Recommended Peginterferon+Ribavirinx24-48 48 weeks Monotherapy with Peginterferon, Ribavirin, or a Direct Acting Antiviral Agent Any Regimen with Telaprevir, Boceprevir, or Simeprevir *Patients who experienced relapse after Peginterferon plus Ribavirin therapy Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 22, 2014 AASLD/IDSA/IAS-USA 2014 HCV Treatment Recommendations Retreatment of Patients with Genotype 3 Chronic HCV Patients with GT 3 HCV: Retreatment of Prior Nonresponders* Recommended Therapy Sofosbuvir + Ribavirin x 24 weeks Alternative Therapy Sofosbuvir + Peginterferon + Ribavirin x 12 weeks Not Recommended Peginterferon + Ribavirin i i +/- [Boceprevir or Simeprevir i or Telaprevir] Monotherapy with Peginterferon, Ribavirin, or a Direct Acting Antiviral Agent Treatment of Decompensated Cirrhosis with Peginterferon *Patients who experienced nonresponse (partial or null) with Peginterferon plus Ribavirin therapy Source: AASLD/IDSA/IAS-USA (www.hcvguidelines.org). Viewed April 22, 2014 10

GT2 and GT 3: SVR by Genotype FISSION (TN) S VR12 (%) 67 67 97 78 63 56 170/ 162/ 68/ 52/ 102/ 110/ 253 243 70 67 183 176 SVR12 (%) P <0.001 73 50 50/ 100 69/ 95 86 94 31/ 36 30 30/ 32 19/64 P <0.001 62 39/ 63 SVR12 (%) 93 78 61 161/207 101/109 60/98 SOF + RBV 12 weeks Jacobson et al. N Engl J Med 2013, 368: 1867-1877, Lawitz et al., N Engl J Med 2013, 368: 1878-1887, Sofosbuvir + Ribavirin for Genotype 3 VALENCE: 24 weeks, n=250 93 92 87 SVR 12 (%) 62 86/92 12/13 87/100 28/45 No cirrhosis Cirrhosis No cirrhosis Cirrhosis Naïve Treatment-experienced Zeuzem S, et al. N Engl J Med. 2014;370:1993-2001 11

Novel HCV Treatment Regimens in HCV treatment naïve and experienced patients Sofosbuvir + Simeprevir Daclastasvir+Sofosbuvir Sofosbuvir/Ledipasvir ABT450/r + Ombitasvir + Dasabuvir ± RBV MK-5172 + MK8742 Daclatasvir + Asunaprevir Pill Burden in HCV Therapy Fixed Dose Combination Ledipasvir/Sofosbuvir MK-5172 and MK-8742 3 DAA Regimens 450r/Ombitasvir +Dasabuvir Simeprevir plus Sofosbuvir Daclatasvir and Sofosbuvir Asunaprevir+ Daclatasvir+BMS-791325 Ribavirin 5-6 pills a day 12

COSMOS: Simeprevir + Sofosbuvir ± RBV in Genotype 1 HCV: Phase 2a Study Design Week 0 4 12 24 36 48 Arm 1 SMV + SOF + RBV Post-treatment follow-up Enrolment ratio 2:1:2:1 Arm 2 Arm 3 SMV + SOF + RBV SMV + SOF Post-treatment follow-up Post-treatment follow-up Arm 4 SMV + SOF Post-treatment follow-up Cohort 1: Prior null responders (METAVIR F0-F2) F2) Cohort 2: Treatment-naive and prior null responders (METAVIR F3-F4) SMV 150 mg QD + SOF 400 mg QD +/- RBV 1000/1200 mg/day QD, once daily; RBV, ribavirin; SMV, simeprevir; SOF, sofosbuvir; SVR, sustained virologic response; SVR4, sustained virologic response 4 weeks after planned treatment end; SVR12, sustained virologic response 12 weeks after planned treatment end. Jacobson I, et al. AASLD 2013. Abstract LB-3; Lawitz, et al. EASL 2014. Abstract 165. Combination of Sofosbuvir (NUC) and Simeprevir (Protease Inhibitor): COSMOS SVR12 (%) SMV + SOF + RBV Cohort 1 (F0-F2 Nulls): SVR12 SMV + SOF Cohort 2 (F3-F4 Naives/Nulls): SVR12 (N = 80, all arms) (N = 87, all arms) 100 100 96.3 93.3 100 92.9 93 93 93 80 79.2 80 60 40 20 0 SVR12 (%) 20 19/24 14/15 26/27 13/14 28/30 16/16 25/27 13/14 0 24-Wk Arms 12-Wk Arms 24-Wk Arms 12-Wk Arms Relapse in 3 pts in Cohort 1 and 3 pts in Cohort 2; all with GT 1a and 2 with Q80K polymorphism at BL AEs (anemia and indirect bilirubin increases) largely confined to RBV arms SVR in patients with GT 1a and Q80K+ = 88%-100% Jacobson I, et al. AASLD 2013. Abstract LB-3. Lawitz, et al. EASL 2014. Abstract 165. 60 40 13

Combination of Daclatasvir ( NS5A inhibitor) and Sofosbuvir (NS5B Nucleotide Inhibitor) Patients Achieving SVR12 HCV RNA <LLOQ Patients, % 100% 100% 100% 100% a 100 95% 80 60 40 20 0 15 15 A LI SOF, DCV SOF 14 14 C DCV + SOF 15 15 E DCV + SOF + RBV 41 41 G DCV + SOF 39 41 H DCV + SOF RBV 100% 21 21 I DCV + SOF 95% b 19 20 J DCV + SOF + SOF + RBV + RBV 24 Weeks Treatment Naïve 12 Weeks Treatment Naïve 24 Weeks PI Failures GT1a - 98% (129/132) GT1b - 100% (35/35) BMS Confidential For Internal Use Only Sulkowski et al. N Engl J Med. 2014;370:211. 27 Combination of Daclatasvir ( NS5A inhibitor) and Sofosbuvir (NS5B Nucleotide Inhibitor) Patients Achieving SVR12 GT 2 and 3 Combined GT 2 and 3 Analyzed Separately HCV RNA <LLOQ Patients, % 100 80 60 40 20 0 88% 14 16 B LI SOF, DCV + SOF 100% 14 14 D DCV + SOF a 86% 12 14 F DCV + SOF + RBV HCV RNA <LLOQ Patients, % 100 80 60 40 20 0 92% a 89% 24 16 26 18 GT2 DCV + SOF ± RBV GT3 DCV + SOF ± RBV 24 Weeks Treatment Naïve 24 Weeks Treatment Naïve BMS Confidential For Internal Use Only Sulkowski et al. N Engl J Med. 2014;370:211. 28 14

Sofosbuvir (NUC) + Ledipasvir (NS5A) in G1 Insights on Treatment Duration and Role of Ribavirin ION-1 Treatment Naïve ~16% w/cirrhosis 0 Weeks 12 24 N=214 SOF + LDV N=217 N=217 SOF + LDV + RBV SOF + LDV SVR 99% 97% 98% N=217 SOF + LDV + RBV 99% ION-2 Treatment Experienced ~20% w/cirrhosis N=109 N=111 N=109 SOF + LDV SOF + LDV + RBV SOF + LDV 94% 96% 99% N=111 SOF + LDV + RBV 99% Afdhal N et al. N Engl J Med. 2014;370:1483-1493; Afdhal N et al. N Engl J Med. 2014;370:1889-1898. Sofosbuvir (NUC) + Ledipasvir (NS5A) in Genotype 1: ION-2 Special Subgroups ION-2 N=22 SOF + LDV 86% Treatment Experienced Cirrhosis N=22 N=22 SOF + LDV + RBV SOF + LDV 82% 100% N=22 SOF + LDV + RBV 100% ION-2 Treatment Experienced PI Failures N=66 SOF + LDV 94% N=64 N=50 SOF + LDV + RBV SOF + LDV 97% 98% N=51 Afdhal N et al. N Engl J Med. 2014;370:1483-1493. SOF + LDV + RBV 100% 15

Sofosbuvir (NUC) + Ledipasvir (NS5A) in Genotype 1: Shorter Duration Is Possible 0 Weeks 6 8 12 SVR ION-3 1 N=215 SOF + LDV 94% Treatment Naïve N=216 SOF + LDV + RBV 93% No cirrhosis N=216 SOF + LDV 95% ELECTRON* 2 Treatment Naïve No cirrhosis N=25 SOF+LDV+RBV 68% Treatment Duration >6 weeks is needed for this combination *The addition of third DAA could allow for shorter therapy 1. Kowdley KV et al. N Engl J Med. 2014;370(20):1879-1888; 2. Gane EJ et al. Gastroenterology. 2014;146:736-743. Results: Reasons For Not Achieving SVR GT 1 Treatment-Naïve (ION-3) 8 Weeks 12 Weeks Patients, n (%) LDV/SOF n=215 LDV/SOF + RBV n=216 LDV/SOF n=216 SVR12 202 (94) 201 (93) 206 (95) Breakthrough 0 0 0 Relapse 11 (5) 9 (4) 3 (1) Lost to Follow-Up 2 (<1) 6 (3) 7 (3) Kowdley K, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O56. 32 16

Study Design-Synergy Trial Sofosbuvir (nucleotide NS5B inhibitor) 400 mg / ledipasvir (NS5A inhibitor) 90 mg once daily GS-9669 (non-nucleoside NS5B inhibitor) 500 mg once daily GS-9451 (a protease/ NS3/4 inhibitor) 80 mg once daily Week 0 6 12 Treatment naïve All stages fibrosis Sofosbuvir + Ledipasvir (n=20) SVR12 Treatment naïve Cirrhosis excluded Sofosbuvir + Ledipasvir i + GS- 9669 (n=20) SVR12 Treatment naïve Cirrhosis excluded Sofosbuvir + Ledipasvir + GS- 9451 (n=20) SVR12 48 weeks Treatment Response (ITT) 17

3 Direct Acting Antiviral Regimen The 3D regimen includes: Co-formulated dabt-450/r/ombitasvir /O i with Dasabuvir ABT-450, a NS3/4A protease inhibitor (identified by AbbVie and Enanta) Ritonavir (pharmacokinetic enhancer) Ombitasvir (ABT-267), a NS5A inhibitor Dasabuvir (ABT-333), a non-nucleoside NS5B polymerase inhibitor 1 Feld J, et al. N Engl J Med. 2014; published on-line. 2 Zeuzem S, et al. N Engl J Med. 2014; published on-line. ABT-450/r (PI) + ABT-267 (NS5A) + ABT-333 (NNI) + RBV SAPPHIRE and TURQUOISE SAPPHIRE-1 Treatment Naïve 0% w/cirrhosis 1 N=473 0 Weeks 12 ABT-450/r + ABT-267 + ABT-333 + RBV 24 SVR 96% SAPPHIRE-2 Treatment Experienced 0% w/cirrhosis 2 N=297 ABT-450/r + ABT-267 + ABT-333 + RBV 96% TURQUOISE-II Treatment Naïve/ Experienced 100% w/cirrhosis 3 N=208 N=172 ABT-450/r + ABT-267 + ABT-333 + RBV ABT-450/r + ABT-267 + ABT-333 + RBV 92% 96% ABT-450/r, ABT-450 with ritonavir 1. Feld JJ et al. N Engl J Med. 2014;370(17):1594-1603; 2. Zeuzem S et al. N Engl J Med. 2014:370:1604-1614; 3. Poordad F et al. N Engl J Med. 2014; 370(21):1973-1982. 18

AbbVie Regimen Phase 3 Clinical Development Program Study Patients Treatment Regimen SVR 12 97% AbbVie regimen* + RBV (n=88) PEARL-II GT1b treatment-experienced (85/88) (12 weeks) (N=179) 100% AbbVie regimen* only (n=91) (91/91) 99% AbbVie regimen* + RBV (n=210) PEARL-III GT1b treatment-naive (209/210) (12 weeks) (N=419) 99% AbbVie regimen* only (n=209) (207/209) 97% AbbVie regimen* + RBV (n=100) PEARL-IV GT1a treatment-naive (97/100) (12 weeks) (N=305) 90% AbbVie regimen* only (n=205) (185/205) GT1 treatment-naive 92% AbbVie regimen* + RBV, 12 weeks (n=208) TURQUOISE-II II and treatment-experiencedexperienced (191/208) (12 & 24 weeks) w/compensated cirrhosis 96% AbbVie regimen* + RBV, 24 weeks (n=172) (N=380) (165/172) SAPPHIRE-I GT1 treatment-naive 96% AbbVie regimen* + RBV (n=473) (12 weeks) (N=631) (455/473) SAPPHIRE-II GT1 treatment-experienced 96% AbbVie regimen* + RBV (n=297) (12 weeks) (N=394) (286/297) * AbbVie Regimen = ABT-450/r/Ombitasvir(150/100/25 mg QD) plus Dasabuvir (250 mg BID) SAPPHIRE-I: Placebo-Controlled Design (N=631) Double-Blind Treatment Period 3D + RBV (n=473) Open-Label Treatment Period 48-Week Follow-Up Placebo (n=158) 3D + RBV 48-Week Follow-Up Week 0 Week 12 Week 24 Week 60 Week 72 Pi Primary Analysis: SVR 12 Feld JJ et al. N Engl J Med. 2014;370(17):1594-1603 19

SAPPHIRE-I: Adverse Events Occurring in >10% of Patients in Either Group Event, n (%) 3D + RBV (N=473) Placebo (N=158) P Value Any AE 414 (87.5) 116 (73.4) <0.05 Fatigue 164 (34.7) 45 (28.5) NS Headache 156 (33.0) 42 (26.6) NS Nausea 112 (23.7) 21 (13.3) <0.05 Pruritus 80 (16.9) 6 (3.8) <0.05 Insomnia 66 (14.0) 12 (7.6) <0.05 Diarrhea 65 (13.7) 11 (7.0) <0.05 Ath Asthenia 57 (12.1) 1) 6(38) (3.8) <0.05 005 Rash 51 (10.8) 9 (5.7) NS AEs were generally mild. Feld JJ et al. N Engl J Med. 2014;370(17):1594-1603 HALLMARK-DUAL (AI447-028): Study Design Day 1 Week 12 Week 24 Week 48 Treatment-naive n Randomizatio 2:1 DCV 60 mg QD + ASV 100 mg BID 24 weeks Follow up 24 weeks (N = 203) a DCV-PBO + ASV-PBO 12 Enter another study: STOP weeks (N = 102) DCV + ASV 24 weeks Nonresponder Ineligible/intolerant DCV + ASV 24 weeks (N = 205) DCV + ASV 24 weeks (N = 235) Follow up 24 weeks Follow up 24 weeks Patients infected with HCV genotype 1b Treatment-naive Nonresponders: prior null or partial response to pegifn/rbv Interferon-ineligible/intolerant (treatment-naive or -experienced) due to Depression Anemia/neutropenia Compensated advanced fibrosis/cirrhosis (F3/F4) with thrombocytopenia SVR 12 Kao JH, et al. 49th EASL; London, England; April 9-13, 2014. Abst. P1300. 20

HALLMARK-DUEL: Virologic Response - SVR 12 SVR 12 (Percentage of patients) a a,b Treatment- t Nonresponders Ineligible/ ibl naive intolerant SVR 12 rates documented on or after post-treatment Week 12 Treatment-naive: 91% Nonresponders: 82% Ineligible/intolerant: 83% Kao JH, et al. 49th EASL; London, England; April 9-13, 2014. Abst. P1300. Study Design: MK-5172 (100 mg QD) + MK-8742 (50 mg QD) ± RBV in 253 Patients TN + Cirrho osis n=123 n = 31 n = 29 n = 32 n = 31 + RBV No RBV + RBV No RBV Follow-up Follow-up Follow-up Follow-up PR-Nulls ± Cirrh hosis n=130 n = 32 n = 33 n = 33 n = 32 + RBV No RBV + RBV No RBV Follow-up Follow-up Follow-up Follow-up D1 TW4 TW8 TW12 TW18 FU4 FU8 SVR12 Lawitz E, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O61. SVR24 21

Efficacy of MK-5172 + MK-8742 ± RBV in Treatment-Naïve Patients with Cirrhosis: 12 vs 18 Weeks 2831 29 32 28 30 29 31 31 28 28 30 29 29 32 31 31 29 32 31 31 29 31* 30* Breakthrough Relapse Discontinuation TW4 TW12 FU4/8 *Excludes patients who have not yet reached the FU4 time point 12 week arms include 97% of FU8 results Lawitz E, et al. 49th EASL; London, England; April 9-13, 2014. Abst. O61. Treatment Options in the Future for HCV Other NS5B Nonnucleoside Polymerase Inhibitor ± RBV NS5A Inhibitor ± RBV 1. Treatment duration: 6,8,12 weeks 2. Genotype 1b vs 1a 3. Non-genotype 1 4. Cirrhosis NS5B Nucleotide Polymerase Inhibitor ± RBV Platform Issues that may dictate treatment Pangenotypic Protease Inhibitor ± RBV Interferon ± RBV 5. Race and ethnicity 6. IL28B status 7. Viral resistance 8. Cost 22

Treatment Options in the Future for HCV Other NS5B Nucleotide Polymerase Inhibitor ± RBV NS5A Inhibitor ± RBV Pangenotypic Protease Inhibitor ± RBV NS5B Nonnucleoside Polymerase Inhibitor ± RBV 1. Treatment duration: 6,8,12 weeks 2. Genotype 1b vs 1a 3. Non-genotype 1 4. Cirrhosis Platform Issues that may dictate treatment Interferon ± RBV 5. Race and ethnicity 6. IL28B status 7. Viral resistance 8. Cost Treatment Options in the Future for HCV NS5B Nucleotide Polymerase Inhibitor ± RBV NS5A Inhibitor ± RBV Other NS5B Nonnucleoside Polymerase Inhibitor ± RBV 1. Treatment duration: 6,8,12 weeks 2. Genotype 1b vs 1a 3. Non-genotype 1 4. Cirrhosis Pangenotypic Protease Inhibitor ± RBV Platform Issues that may dictate treatment Interferon ± RBV 5. Race and ethnicity 6. IL28B status 7. Viral resistance 8. Cost 23