M.W. Fried, 1 M. Buti, 2 G.J. Dore, 3 P. Ferenci, 4 I. Jacobson, 5 P. Marcellin, 6 S. Zeuzem, 7 O. Lenz, 8 M. Peeters, 8 V. Sekar, 9 G. De Smedt 8 Efficacy and Safety of TMC435 in Combination With Peginterferon  -2a and Ribavirin in Treatment-naïve Genotype-1 HCV Patients: 24-Week Interim Results from the PILLAR Study 1 University of North Carolina at Chapel Hill, North Carolina, USA ; 2 Hospital Vall d'Hebron and Ciberehd, Barcelona, Spain ; 3 St Vincent's Hospital, Sydney, Australia and National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia ; 4 Allgemeines Krankenhaus der Stadt Wien, Wien, Austria ; 5 Weill Cornell Medical College, New York, USA ; 6 Hopital Beaujon, Clichy, Paris, France ; 7 Klinikum der Johann-Wolfgang-Goethe-Universität - Med. Klinik I, Frankfurt, Germany ; 8 Tibotec, Beerse, Belgium; 9 Tibotec Inc., Titusville, New Jersey, USA

Disclosure Information Michael Fried Grants/Research Support, Consultant (Roche, Merck, Human Genome Sciences, Vertex, Tibotec, Bristol Myers Squibb, Anadys, Conatus, Schering, Pharmasset, Glaxo, Novartis), Stock/Shareholder (Pharmasset) Maria ButiAdvisory Board and Speaker (MSD, Gilead, BMS) Greg Dore Advisory Committee, Grant/Research Support, Teaching and Speaking, Travel Scholarship (Roche, Merck, Bristol-Myer Squibb, Gilead) Peter Ferenci Advisory Committee and Review Panels, Unrestricted Grant/Research Support, Teaching and Speaking, Consulting, Patent Held (Roche, Vertex/Tibotec, Madaus-Rottapharm, Boehringer Ingelheim, MSD/previously SPI) Ira JacobsonGrant/Research Support, Member of Speaker’s Bureau, Consultant/Advisor (Schering/Merck, Tibotec, Roche/Genentech, Pharmasset, Anadys, Boehringer Ingelheim, Novartis, Gilead, Vertex, GlobeImmune, Human Genome Sciences, Bristol Myers Squibb, Pfizer, Zymogenetics, Abbott, sanofi-aventis) Patrick Marcellin Grant, Investigator, Speaker, and Expert (Roche, Schering Plough, Gilead, BMS, Vertex, Novartis, Pharmasset, Tibotec, MSD, Boehringer Ingelheim, Biolex, Intermune, Zymogenetics) Stefan Zeuzem Consultancy, Member of Speaker’s Bureau (Abbott, BMS, Gilead, Merck, Pfizer, Roche, Tibotec, Vertex) Oliver Lenz Employed by Tibotec Monika Peeters Employed by Tibotec Vanitha Sekar Employed by Tibotec Goedele De Smedt Employed by Tibotec

*PegIFN/RBV, peginterferon  -2a (180  g/wk) + ribavirin (1000–1200 mg/day); HCV, hepatitis C virus PILLAR (Study TMC435-C205): Objectives & Endpoints Objective –To assess efficacy and safety of protease inhibitor TMC435 once-daily in combination with PegIFN/RBV* in treatment- naïve patients infected with HCV genotype-1 Study design –Ongoing international, Phase IIb, randomized, double-blind, placebo-controlled clinical trial Primary endpoint –Sustained virologic response at Week 72 Key secondary endpoints –Antiviral activity throughout study –Viral breakthrough and relapse rates –Safety and tolerability –Pharmacokinetics Results of a planned Week 24 interim analysis are reported today

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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks; FU, follow-up; ITT, intent to treat; Pbo, placebo; RNA, ribonucleic acid; TMC, TMC435 Response-guided treatment duration in TMC435 arms End treatment at Week 24, if o HCV RNA <25 IU/mL detectable or undetectable at Week 4, and o HCV RNA <25 IU/mL undetectable at Weeks 12, 16, and 20 All other patients continued Peg/RBV for up to 48 weeks PILLAR: Study Design Planned interim analysis All available data included Week Pbo & PegIFN/RBV TMC mg & PegIFN/RBV TMC mg & PegIFN/RBV Post-therapy FU PegIFN/RBV N=78 N=75 N=79 N=77 N=ITT TMC12/PR24 75 mg TMC24/PR24 75 mg TMC24/PR mg Pbo24/PR48 Pbo & PegIFN/RBV TMC mg & PegIFN/RBV Pbo & PegIFN/RBV N=77 TMC12/PR mg Post-therapy FU

Parameter TMC12/ PR24 75 mg N=78 TMC24/ PR24 75 mg N=75 TMC12/ PR mg N=77 TMC24/ PR mg N=79 Pbo24/ PR48 N=77 All subjects N=386 Patient demographics Male, % White, % Age, years, median Body mass index, median Disease characteristics HCV subtype 1a, %* HCV subtype 1b, %* HCV RNA, log 10 ≥800,000 IU/mL at baseline, median, % Metavir score F3, % † IL28B at baseline, CC, % ‡ 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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks; no. of subjects completing therapy at Week 24 was according to response-guided treatment algorithm *As determined by NS5B sequence-based assay † Patients with cirrhosis (F4) were not eligible ‡ Polymorphism on chromosome 19 s , data available for patients who consented only (67.9%) PILLAR: Demographics and Baseline Disease Characteristics

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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks; SE, standard error PILLAR Week 24 Analysis: Mean Change in Plasma HCV RNA From Baseline TMC12/PR24 75 mg TMC24/PR24 75 mg TMC12/PR mg TMC24/PR mg Pbo24/PR Mean (+/- SE) change in plasma HCV RNA (log 10 IU/mL) from baseline Week

TMC12/ PR24 75 mg (n=77) TMC24/ PR24 75 mg (n=75) TMC12/ PR mg (n=76) TMC24/ PR mg (n=75) Pbo24/ PR48 (n=75) TMC12/ PR24 75 mg (n=78) TMC24/ PR24 75 mg (n=73) TMC12/ PR mg (n=77) TMC24/ PR mg (n=77) Pbo24/ PR48 (n=74) <25 IU/mL undetectable<25 IU/mL detectable >25 IU/mL Week 4 Week 12 Proportion of patients (%) HCV RNA ***TMC435 vs placebo: p≤0.001; TMC12/PR24, TMC435 for 12 weeks in addition to Peg/RBV for 24 weeks; TMC24/PR24, TMC435 for 24 weeks in addition to Peg/RBV for 24 weeks; HCV RNA determined using Roche TaqMan v2 PILLAR Week 24 Analysis: Proportion of Patients Achieving Virologic Response at Weeks 4 and 12 ***

Week 24 Proportion of patients (%) TMC12/PR24, TMC435 for 12 weeks in addition to Peg/RBV for 24 weeks; TMC24/PR24, TMC435 for 24 weeks in addition to Peg/RBV for 24 weeks; HCV RNA determined using Roche TaqMan v TMC12/ PR24 75 mg (n=77) TMC24/ PR24 75 mg (n=72) TMC12/ PR mg (n=69) TMC24/ PR mg (n=73) Pbo24/ PR48 (n=73) PILLAR Week 24 Analysis: Proportion of Patients Achieving Virologic Response at Week 24 <25 IU/mL undetectable<25 IU/mL detectable >25 IU/mL HCV RNA

Between 79% and 86% of patients in TMC435 arms ended therapy at Week 24 as per protocol-defined response criteria TMC12/PR24, TMC435 for 12 weeks in addition to PegIFN/RBV for 24 weeks; TMC24/PR24, TMC435 for 24 weeks in addition to PegIFN/RBV for 24 weeks; SVR, sustained virologic response; † not yet defined in the placebo group in this Week 24 analysis as planned end of treatment has not been reached PILLAR Week 24 Analysis: Proportion of Patients Achieving Undetectable HCV RNA After Planned End of Treatment Follow-up after planned end of treatment † TMC12/ PR24 75 mg N=78 TMC24/ PR24 75 mg N=75 TMC12/ PR mg N=77 TMC24/ PR mg N=79 SVR4 (4 weeks after planned end of treatment) SVR12 (12 weeks after planned end of treatment) 91% (59/65*) 97% (32/33*) 93% (56/60*) 93% (27/29*) 93% (57/61*) 89% (32/36*) 91% (62/68*) 88% (28/32*) * Denominator based on number of patients that stopped treatment for any reason by Week 24 and reached specified timepoint

*Viral breakthrough: confirmed increase of >1 log from nadir or >100 IU/mL if undetectable; 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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks PILLAR Week 24 Analysis: Viral Breakthrough TMC12/PR24 75 mg TMC24/PR24 75 mg TMC12/PR mg TMC24/PR mg Pbo24/PR48 Proportion of patients with viral breakthrough,* cumulative (%) Weeks 1-4 Weeks 1-12 Weeks % 2.7% 7.8% 2.5% 3.9%

*Data shown for patients who consented only (67.9%); CC/TT/CT, polymorphism on chromosome 19 s PILLAR Week 24 Analysis: Mean Change in HCV RNA from Baseline According to IL28B Genotype* Mean (+/- SE) change in plasma HCV RNA (log 10 IU/mL) from baseline Placebo All TMC mg Week All TMC mg Week CC CT TT

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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks *Reported in ≥25% of subjects in the ‘All TMC435’ group (all dose groups combined) † Rash (any type) combines all reported types of rash ‡ Reported as an adverse event by study investigator if laboratory abnormalities considered clinically relevant PILLAR Week 24 Analysis: Adverse Events Preferred term, % TMC12/ PR24 75 mg N=78 TMC24/ PR24 75 mg N=75 TMC12/ PR mg N=77 TMC24/ PR mg N=79 All TMC435 N=309 Pbo24/ PR48 N=77 Adverse events leading to permanent discontinuation of TMC435/Pbo Discontinuation Most common adverse events* Headache Fatigue Influenza-like illness Pruritus Nausea Adverse events of interest Rash (any type) † Anemia ‡

Mild and reversible increases in bilirubin (direct and indirect) were noted in TMC mg dose arms 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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks; SE, standard error; to convert from bilirubin  mol/L to mg/dL, divide by 17.1 PILLAR Week 24 Analysis: Laboratory Parameters, Bilirubin Over Time Mean (+/- SE) values of bilirubin (μmol/L) Week Pbo24/PR48 TMC 75 mg TMC 150 mg Upper limit of normal Lower limit of normal

Mild and reversible increases in bilirubin (direct and indirect) were noted in TMC mg dose arms 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 were administered once-daily; Pbo24/PR48, placebo and PegIFN/RBV for 24 weeks followed by PegIFN/RBV for 24 weeks; SE, standard error; to convert from bilirubin  mol/L to mg/dL, divide by 17.1 PILLAR Week 24 Analysis: Laboratory Parameters, Bilirubin Over Time Mean (+/- SE) values of bilirubin (μmol/L) Week TMC12/PR24 75 mg TMC24/PR24 75 mg TMC12/PR mg TMC24/PR mg Pbo24/PR48 TMC 75 mg TMC 150 mg Upper limit of normal Lower limit of normal

PILLAR Week 24 Analysis: Laboratory Parameters, Bilirubin, ALT, and ALP Over Time (TMC12/PR mg) Mean (+/- SE) values of ALT (IU/mL) 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]); ALT, alanine aminotransferase; ALP, alkaline phosphatase ; SE, standard error; to convert from bilirubin  mol/L to mg/dL, divide by Mean (+/- SE) values of ALP (IU/mL) Week Upper limit of normal Mean (+/- SE) values of bilirubin (μmol/L) Upper limit of normal

TMC435 administered once-daily with PegIFN/RBV over 12 or 24 weeks demonstrated potent antiviral activity At Weeks 4 and 12, HCV RNA was <25 IU/mL (undetectable) for the majority of patients in TMC435 groups The majority of patients in TMC435 groups met the criteria to stop treatment at Week 24 In patients who completed therapy at or before Week 24, response rates remained high 12 weeks after planned end of therapy Addition of TMC435 to PegIFN/RBV increased response rates in all IL28B genotypes PILLAR Week 24 Analysis: Efficacy Summary

No clinically relevant difference in safety and tolerability between TMC435 and placebo groups Frequency of rash, gastrointestinal events, and anemia were similar to placebo group Mild and reversible increases in bilirubin concentration observed with 150 mg dose ALT concentration decreased in all treatment groups Discontinuation in TMC435 groups was low and similar to placebo group Planning of Phase III studies of TMC435 is underway PILLAR Week 24 Analysis: Safety Summary

The patients and their families The PILLAR investigators and their study staff 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 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 Gregory Fanning, Richard Hoetelmans, Ronald Kalmeijer, Eric Lefebvre, Karen Manson, Gaston Picchio, Setareh Seyedkazemi, and Brian Woodfall (Tibotec) have also contributed to development of the presentation, and editorial assistance was provided by Bethan Lowder at Complete Medical Communications. Acknowledgements