1. EASL 2011 31 March 2011 - Berlin, Germany Impact of IL28B Genotype and Pre-treatment Serum IP-10 in Treatment-Naïve Genotype 1 HCV Patients Treated with TMC435 in Combination with Peginterferon  -2a and Ribavirin in the PILLAR Study Jeroen AERSSENS, 1 Greg FANNING, 2 Annick SCHOLLIERS, 3 Oliver LENZ, 4 Monika PEETERS, 5 Goedele DE SMEDT, 6 Michael W FRIED 7 1 Department of Translational Genomics & Genetics; 2 Department of Infectious Disease and Vaccines; 3 Department of Enabling Biology; 4 Department of Clinical Virology; 5 Department of Statistics; 6 Department of Clinical Development, Tibotec, Beerse, Belgium; 7 University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

2. Disclosures Jeroen Aerssens Greg Fanning Annick Scholliers Oliver Lenz Monika Peeters Goedele De Smedt Michael W Fried TMC435 is an investigational product for hepatitis C virus (HCV) treatment, under development by Tibotec (part of the Janssen Pharmaceutical Companies of Johnson & Johnson) Employed by Tibotec, stock/shareholder J&J Employed by Tibotec Employed by Tibotec, stock/shareholder J&J Grants/Research Support, Consultant (Roche, Merck, Human Genome Sciences, Vertex, Tibotec, Bristol-Myers Squibb, Anadys, Conatus, Schering, Pharmasset, Glaxo, Novartis), Stock/Shareholder (Pharmasset)

3. Background: IL28B genotype and virologic response during treatment with PegIFN/RBV Proportion of patients achieving virologic response (%) cEVR, complete early virologic response; IL28B CC/CT/TT, rs12979860 polymorphism; PegIFN, pegylated interferon α-2a; RBV, ribavirin; RVR, rapid virologic response; SVR, sustained virologic response Thompson et al. Gastroenterology 2010; 139:120-129 RVR (week 4) Treatment-naïve, HCV genotype 1, Caucasian patients (n=1171) PegIFN/RBV treatment cEVR (week 12) SVR p<0.0001 5% 28% 38% 87% 27% 33% 69% TTCTCC TT CT CC TT CT CC

4. Background: Pre-treatment serum IP-10 and virologic response during treatment with PegIFN/RBV n=47n=102n=24 68% 55% 21% IP-10 at baseline (pg/ml) p=0.003 p=0.0002 Proportion of patients achieving virologic response (%): SVR IP-10 (pg/mL) at baseline Lagging et al. Hepatology 2006; 44:1617-1625 IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin; SVR, sustained virologic response, HCV RNA <25 IU/mL (undetectable) Treatment-naïve, HCV genotype 1, European patients (n=173) PegIFN/RBV treatment

5. Background: Pre-treatment serum IP-10 improves predictive value of IL28B for PegIFN/RBV treatment response IL28B genotype and pre-treatment serum IP-10 are independent and additive factors to predict sustained virologic response (SVR) IL28B TT/CT/CC, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin Serum IP-10 concentration IL28B genotype % patients with SVR 20% 89% 79% 64% 24% 48% ViraHepC cohort (n=210) HCV genotype 1 Overall SVR = 59% Likelihood ratio Chi 2 = 55 p<0.0001 Darling et al. Hepatology 2011; 53:14-22

6. Evaluate the relationship of IL28B genotype and/or pre- treatment serum IP-10 level with on-treatment virologic response up to Week 24 in the TMC435 PILLAR study – TMC435 is a once-daily oral HCV NS3/4A protease inhibitor – PILLAR (TMC435-C205; NCT00882908) is a Phase IIb, randomised, double-blind, placebo-controlled study in treatment-naïve genotype 1 HCV patients treated with TMC435 in combination with PegIFN/RBV IL28B and IP-10 analyses: Objective Fried et al. AASLD 2010 IL28B, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin.

7. PILLAR study design Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks; TMC12/PR24, TMC435 + PegIFN/RBV for 12 weeks followed by PegIFN/RBV for 24 weeks (PegIFN/RBV, peginterferon  -2a [180  g/wk] + ribavirin [1000–1200 mg/day]); TMC24/PR24, TMC435 + PegIFN/RBV for 24 weeks; all TMC435 doses administered once-daily; FU, follow-up; IL28B, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; ITT, intent to treat; Pbo, placebo; TMC, TMC435. Week 012 24 72 48 Pbo & PegIFN/RBV TMC435 75 mg & PegIFN/RBV TMC435 150 mg & PegIFN/RBV PegIFN/RBV N=78 N=75 N=79 N=77 N=ITT TMC12/PR24 75 mg TMC24/PR24 75 mg TMC24/PR24 150 mg Pbo24 / PR48 Pbo & PegIFN/RBV TMC435 150 mg & PegIFN/RBV Pbo & PegIFN/RBV N=77 TMC12/PR24 150 mg Post-therapy FU 4 N=58 N=51 N=52 N=46 N=55 For IL28B and IP-10 analyses, dose groups were pooled 68% of patients (262 out of 386) consented for DNA research (including IL28B genotyping) Consented for DNA research Post-therapy FU PegIFN/RBV Post-therapy FU PegIFN/RBV Post-therapy FU PegIFN/RBV Post-therapy FU PegIFN/RBV Post-therapy FU * RGT: Response-guided treatment duration in TMC435 arms RGT*

8. PILLAR study: Demographics and baseline disease characteristics for patients who consented to DNA research TMC435 75 mg/PR N=109 TMC435 150 mg/PR N=107 Pbo/PR N=46 Patient demographics Male, % White, % Age, >40 years, % Body mass index, median 53.2 94.5 62.4 25.4 55.1 95.3 68.2 24.7 56.5 95.6 65.2 25.9 IL28B rs12979860 genotype, CC, % ‡ CT TT 28.4 58.7 12.8 32.7 56.1 11.2 26.1 60.9 13.0 Baseline serum IP-10, ≥600 pg/ml at baseline, %9.4 22.3*9.0 Disease characteristics HCV subtype 1a, % # HCV subtype 1b, % # 44.9 55.1 46.2 53.8 39.1 60.9 HCV RNA, ≥800,000 IU/mL at baseline, % 83.588.880.4 Metavir fibrosis score F3, % † 17.414.08.7 IL28B TT/CT/CC, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10. #As determined by NS5B sequence-based assay; †patients with cirrhosis (F4) were not eligible; ‡no significant differences between treatment groups; *higher frequency of patients with high IP-10 in TMC435 150 mg group vs other groups (p<0.02)

9. PILLAR: On-treatment virologic response up to Week 24 by IL28B genotype The data analysis excluded missing values. CC/CT/TT, rs12979860 polymorphism; N.S., not significant; PegIFN, pegylated interferon α-2a; RBV, ribavirin. n=28 Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) Pearson Chi 2 test Proportion of patients (%) p<0.04p<0.01N.S. n=6 n=12 Placebo + PegIFN/RBV

10. PILLAR: On-treatment virologic response up to Week 24 by IL28B genotype Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) n=64 n=6 n=28 n=12 n=60 n=35 n=14 n=31 TMC435 75 mg + PegIFN/RBV TMC435 150 mg + PegIFN/RBV Proportion of patients (%) N.S.p<0.003 N.S. Pearson Chi 2 test N.S.p<0.04p<0.01 The data analysis excluded missing values. CC/CT/TT, rs12979860 polymorphism; N.S., not significant; PegIFN, pegylated interferon α-2a; RBV, ribavirin. Placebo + PegIFN/RBV

11. PILLAR: On-treatment virologic response up to Week 24 by baseline serum IP-10 n=4 n=40 N.S. Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) Low (<600 pg/mL) High (≥600 pg/mL) Baseline IP-10 Proportion of patients (%) The data analysed excluded missing values. IP-10, interferon-  inducible protein 10; N.S., not significant; PegIFN, pegylated interferon α-2a; RBV, ribavirin. Placebo + PegIFN/RBV Pearson Chi 2 test

12. PILLAR: On-treatment virologic response up to Week 24 by baseline serum IP-10 n=96 n=4 n=40 n=23 n=80 n=10 N.S. Pearson Chi 2 test Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) Low (<600 pg/mL) High (≥600 pg/mL) Baseline IP-10 Proportion of patients (%) The data analysed excluded missing values. IP-10, interferon-  inducible protein 10; N.S., not significant; PegIFN, pegylated interferon α-2a; RBV, ribavirin. Placebo + PegIFN/RBV TMC435 75 mg + PegIFN/RBV TMC435 150 mg + PegIFN/RBV

13. PILLAR: On-treatment virologic response up to Week 24 by IL28B genotype/baseline serum IP-10 combined: Placebo + PegIFN/RBV IL28B CC/CT/TT, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) 20% 5% 17% 0% 40% 57% 100% 25% 40% 77% 100% 50% Week 4Week 12Week 24 IL28B IP-10 IL28B IP-10 Proportion of patients (%) n IL28B TTCTCC IP-10 Low52312 IP-10 High040

14. PILLAR: On-treatment virologic response up to Week 24 by IL28B genotype/baseline serum IP-10 combined: TMC435 75 mg + PegIFN/RBV Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) 67% 96% 100% IL28B IP-10 67% 100% 67% 96% 100% 86% 93% 100% IL28B IP-10 Week 4Week 12Week 24 Proportion of patients (%) n IL28B TTCTCC IP-10 Low125628 IP-10 High163 n=1 IL28B CC/CT/TT, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin

15. PILLAR: On-treatment virologic response up to Week 24 by IL28B genotype/baseline serum IP-10 combined: TMC435 150 mg + PegIFN/RBV 83% 95% 100% 90% 100% 95% 100% 77% 100% 77% 100% 95% 96% Week 4Week 12Week 24 Virologic response: HCV RNA <25 IU/ml (detectable or undetectable) IL28B IP-10 IL28B IP-10 Proportion of patients (%) n IL28B TTCTCC IP-10 Low1910055 IP-10 High5199 IL28B CC/CT/TT, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin

16. Summary During the first 24 weeks of treatment in the PILLAR study: – In the control group, treated with placebo and PegIFN/RBV, IL28B CC genotype and low baseline serum IP-10 levels were associated with the highest virologic response – In patients treated with TMC435 in combination with PegIFN/RBV, high virologic response rates were observed, regardless of IL28B genotype and/or baseline serum IP-10 – The highest response for IL28B TT genotype was observed in TMC435 150 mg group IL28B, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin

17. Conclusions The addition of TMC435 to PegIFN/RBV reduces the impact of IL28B genotype and/or baseline serum IP-10 on virologic response up to 24 weeks of treatment Evaluation of the potential impact of these markers on sustained virologic response (SVR) in triple combination therapy will be assessed in the Phase IIb and Phase III trials IL28B, rs12979860 polymorphism; IP-10, interferon-  inducible protein 10; PegIFN, pegylated interferon α-2a; RBV, ribavirin

18. Acknowledgements New Zealand Ed Gane, Auckland Catherine Stedman, Christchurch Graeme Dickson, Hamilton Norway Trond Bruun, Bergen Bent von der Lippe, Kirkeveien Zbigniev Konopski, Trondheimsveien Kjell Block Hellum, Sykehusveien Jon Florholmen, Tromso Poland Robert Flisiak, Bialystok Andrzej Horban, Warszawa Waldemar Halota, Bydgoszcz Wieslaw Kryczka, Kielce Maciej Jablkowski, Lodz Ewa Janczewska-Kazek, Czeladz Russia Alexey A. Yakovlev, Saint Petersburg Vladimir V. Rafalskiy, Smolensk Evgeny E. Voronin, Saint Petersburg N Zakharova, Saint Petersburg Igor G. Nikitin, Moscow Pavel O. Bogomolov, Moscow Vladimir T. Ivashkin, Moscow Vyacheslav G. Morozov, Samara The patients and their families The PILLAR investigators and their study staff Olga V. Korochkina, Nizhny Novgorod Spain Maria Buti, Barcelona Moises Diago, Valencia Ricardo Moreno-Otero, Madrid Manuel Romero, Sevilla Jose Luis Calleja, Madrid Germany Keikawus Arasteh, Berlin Thomas Berg, Berlin Peter Buggisch, Hamburg Hartwig Klinker, Würzburg Andreas Trein, Stuttgart Tobias Goeser, Köln Stefan Mauss, Düsseldorf Dr Jens Rasenack, Freiburg Stefan Zeuzem, Frankfurt Hans-Jürgen Stellbrink, Hamburg USA Daniel Pambianco, Charlottesville Edwin DeJesus, Orlando Kyle Etzkron, Jacksonville Michael Fried, Chapel Hill Andrei Gasic, Longview Nigel Girgrah, New Orleans Ira M. Jacobson, New York Donald M. Jensen, Chicago Mark E. Jonas, Cincinnati Fred Poordad, Los Angeles Coleman Smith, Plymouth Jawahar Taunk, Palm Harbor Lawrence Wruble, Germantown Ziad Younes, Germantown Canada Pierre Cote, Montreal Gideon Hirschfield, Toronto Maged Peter Ghali, Montreal Sam Lee, Calgary Morris Sherman, Toronto Australia Greg Dore, Darlinghurst Paul Desmond, Fitzroy Stuart Roberts, Melbourne Jacob George, Westmead Graeme Macdonald, Woolloongabba Alice Lee, Concord Austria Peter Ferenci, Wien Hermann Laferl, Wien Michael Gschwantler, Wien Belgium F. Nevens, Leuven Y. Horsmans, Bruxelles C. Moreno, Bruxelles H. Van Vlierberghe, Ghent P. Michielsen, Edegem H. Orlent, Brugge H. Reynaert, Bruxelles J. Decaestecker, Roeselare Denmark Jan Gerstoft, Copenhagen Alex Lund Laursen, Aarhus Lars Mathiesen, Hvidovre Axel Møller, Kolding Peer Brehm Christensen, Odense France Yves Benhamou, Paris Christian Trepo, Lyon Jean Pierre Bronowicki, Vandoeuvre Les Nancy Christophe Hezode, Creteil Patrick Marcellin, Clichy Jean-Didier Grange, Paris Jean Pierre Zarski, Grenoble Albert Tran, Nice Editorial support was provided by Dr. Bethan Lowder at Complete Medical Communications, funded by Tibotec. Maria Beumont-Mauviel, Joan Cannon, Ronald Kalmeijer, Eric Lefebvre, Karen Lindsay, Karen Manson, Gaston Picchio and Vanitha Sekar contributed to development of the presentation.