1. The new Treatments Dr John F Dillon

2. Curing one person Curing a population one person at a time

3. Cirrhosis prevented from antiviral therapy* Living IDUs with cirrhosis 201020202030 0 1,000 2,000 3,000 201020202030 0 1,000 2,000 3,000 201020202030 0 1,000 2,000 3,000 Decompensated cirrhosis HCC * Excludes those prevented from antiviral therapy prior to 2008 Compensated cirrhosis Uptake of therapy by 225 IDUs per year Uptake of therapy by 1,000 IDUs per year Uptake of therapy by (up to) 2,000 IDUs per year Curing one person Curing a population one person at a time

4. SVR = Cure SVR rate of 70% Means 7 out of 10 people are cured 100% SVR 3 out of 10 are not cured 0% SVR If we have prediction tools

7. 1985-1989-1991 HCV Therapy 0% 25% 50% 75% 100% Cure rate IFN-α 48 weeks 9% IFN-α 24 weeks 4% IFN/RBV 48 weeks 27% PEG/RBV 48 weeks 45% Triple Rx Protease inhibitor + PEG/RBV 24 weeks 75%2003-2011 PEG/RBV + 2 nd DAA 12 weeks 90%2014 1998 Combo DAA 8-12 weeks No IFN No RGT 95%2015

8. Genotype 1

9. Error bars represent 95% confidence intervals GT 1, 4, 5, 6 Treatment-Naïve: SOF+PEG-IFN+RBV x 12 Weeks NEUTRINO Primary Endpoint and Virologic Response  Study met primary endpoint of superiority over historical control rate of 60% ( P <0.001) On treatment 299/327321/325326/327 Week 2Week 4 Week 12/EOT Patients with HCV RNA <LLOQ (%) 90 Post-treatment Week 12 295/327 Lawitz E, et al. EASL 2013. Amsterdam, The Netherlands. Oral #1411 Lawitz E, et al. N Engl J Med. 2013 Apr 23 [Epub ahead of print]  Relapse accounted for all virologic failures  No S282T mutations observed by population or deep sequencing (1% cutoff) > HCV1/UK/13-05/ABAR/1201c

10. QUEST-1: Phase 3 trial of Simeprevir + PR in G1 treatment-naive patients 10 Jacobson IM et al, EASL 2013, Amsterdam, #1425 A NS3a PI a replacement for Boceprevir or telaprevir Response Guided Therapy criteria met by 85% SVR in 91% of RGT patients No incremental rash/anemia Hyperbilrubinemia

11. Sulkowski M, et al. J Hepatol 2012; 56: S1422 NUC NS5B inhibitor sofosbuvir & Daclatasvir ± Ribavirin (geno 1, n =45)

12. AbbVie Phase III Clinical Program Results fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ABT-267 (25mg), dosed once daily, and ABT-333 (250mg) twice daily StudyPatientsTreatment RegimenSVR 12 PEARL-II (12 weeks) GT1b treatment- experienced (N=179) AbbVie regimen + RBV (n=88) 97% (85/88) AbbVie regimen only (n=91) 100% (91/91) PEARL-III (12 weeks) GT1b treatment-naive (N=419) AbbVie regimen + RBV (n=210) 99% (209/210) AbbVie regimen only (n=209) 99% (207/209) PEARL-IV (12 weeks) GT1a treatment-naive (N=305) AbbVie regimen + RBV (n=100) 97% (97/100) AbbVie regimen only (n=205) 90% (185/205) TURQUOISE-II (12 & 24 weeks) GT1 treatment-naive and treatment-experienced with compensated cirrhosis (N=380) AbbVie regimen + RBV, 12 weeks (n=208) 92% (191/208) AbbVie regimen + RBV, 24 weeks (n=172) 96% (165/172) SAPPHIRE-I (12 weeks) GT1 treatment-naive (N=631) AbbVie regimen + RBV (n=473) 96% (455/473) SAPPHIRE-II (12 weeks) GT1 treatment-experienced (N=394) AbbVie regimen + RBV (n=297) 96% (286/297)

13. Genotype 3 The new tough kid on the block

14. SVR12 Rates Across SOF-Based Studies HCV GT 3 Patients Treatment-Naïve Treatment-Experienced Lawitz E, et al. N Engl J Med. 2013 May 16;368(20):1878-87. Zeuzem S, et al. AASLD 2013. Washington, DC. #1085. Jacobson IM, et al. N Engl J Med. 2013 May 16;368(20):1867-77. Lawitz E, et al. AASLD 2013. Washington, DC. Oral #LB-4. Noncirrhotic Cirrhotic 61% 87% 60% SVR12 (%) 89/145 86/92 FUSION SOF RBV 16 wk VALENCE SOF + RBV 24 wk LONESTAR-2 SOF + PegIFN + RBV 12 wk 87/100 14/23 83% 10/12 92% 94% 12/13 25/40 63% 27/45 83% 10/12 68% 21% 61% 34% 0% 20% 40% 60% 80% 100% FISSION SOF + RBV 12 wk VALENCE SOF + RBV 24 wk 13/38 POSITRON SOF + RBV 12 wk 57/84 3/14 HCV GT 3 patients treated with SOF + RBV for 24 weeks or SOF + RBV + PegIFN for 12 weeks achieved high SVR rates regardless of presence of cirrhosis or treatment experience

15. NS3/NS4A PROTEASE INHIBITORS  BOCEPREVIR  TELAPREVIR  SIMEPREVIR  FALDAPREVIR  VANIPREVIR (MK-7009)  DANOPREVIR  ASUNAPREVIR  ABT-450  MK-5172  SOLAPREVIR  GS-9451

16. POLYMERASE INHIBITORS (NS5b) NUCLEOSIDE –MERICITABINE NUCLEOTIDE –SOFOSBUVIR –VX-135 NON-NUC’s –ABT-072 –ABT-333 –BI-207127

17. NS5A COMPLEX INHIBITORS DACLATASVIR ABT-267 LEDIPASVIR MK-8742 ACH-3102 PP-1668

18. CYCLOPHILIN INHIBITORS ALISPORIVIR TLR7-INHIBITOR GS-9620 NOVEL INTERFERONS LAMBDA-IFN

19. Future treatment Genotype 1 SVR better than 90% with 2 or 3 oral drugs for 8-12 weeks OR Interferon plus 1 or 2 drugs for 12 weeks Genotype 3 SVR about 90% Interferon plus 2 oral drugs 12 weeks 2 or 3 Oral drugs 24 weeks With Prediction Interferon/ribavirin 16 weeks

20. So back to treating one person The new treatments are much more expensive SO Get a lot more money? In Scotland there will be some new money Treat a lot less people? Use some of the old treatments in some people. Including a bit of Interferon