M Santoscoy, 1 P Cahn, 2 C Gonsalez, 3 W Hao, 4 A Pozniak, 5 P Shalit, 6 S Vanveggel, 7 K Boven 8

1. TMC278 (rilpivirine), an investigational next-generation NNRTI, demonstrates long-term efficacy and tolerability in ARV-naïve patients: 96-week results of study C204 M Santoscoy,1 P Cahn,2 C Gonsalez,3 W Hao,4A Pozniak,5 P Shalit,6 S Vanveggel,7 K Boven8 1Hospital Carlos Mac Gregor IMSS, Mexico City, Mexico; 2Hospital Juan A Fernández and Fundación Huesped, Buenos Aires, Argentina; 3Hospital das Clíncias, Pinheiros, Brazil; 4Beijing You’an Hospital, Beijing, China; 5Chelsea and Westminster NHS Foundation Trust and PKR/SSR, London, UK; 6Swedish Medical Center, Seattle, WA, USA; 7Tibotec BVBA, Mechelen, Belgium; 8Tibotec Inc., Yardley, PA, USA.

2. TMC278: a next-generation NNRTI with potent anti-HIV-1 activity • TMC278 has demonstrated potent in-vitro anti-HIV-1 activity against wild-type and NNRTI-resistant isolates1 • Half-life of 45 hours • 48-week results from the global Phase IIb TMC278-C204study showed potent and sustained efficacy at all doses (25, 75 and 150mg qd) in ARV-naïve patients, and was generally well tolerated2,3 • Currently in Phase III trials 1de Bethune M-P, et al. CROI 2005. Abstract 5562Pozniak A, et al. CROI 2007. Abstract 144LB 3Yeni P, et al. EACS 2007. Abstract P7.2/08 ARV = antiretroviral

3. TMC278-C204: study design 96 weeks • Ongoing (extended to 5 years), randomized, active-controlled, dose-ranging Phase IIb study in ARV-naïve patients • Primary objective to evaluate the TMC278 efficacy (ITT-TLOVR) and safety dose-response relationship at Week 48 Primary analysis at 48W Analysis at 96W Screening and randomization1:1:1:1 ARV-naïve patients (N=368) HIV RNA5,000 copies/mL EFV 600mg qd + 2 NRTIs N=89 TMC278 25mg qd + 2 NRTIs N=93 TMC278 75mg qd + 2 NRTIs N=95 TMC278 150mg qd + 2 NRTIs N=91 EFV = efavirenz; ITT = intent to treat; TLOVR = time to loss of virologic response; NRTI backbone chosen by investigator and is either AZT/3TC or TDF/FTC administered as fixed-dose combinations where available

4. Demographic and baseline characteristics *Median values ‡n=88 for EFV 600mg

5. TMC278: high response rate and sustained virologic response over 96 weeks similar to EFV HIV-1 RNA <50 copies/mL to Week 96 (ITT-TLOVR algorithm) TMC278 25mg qd (n=93) TMC278 75mg qd (n=95) TMC278 150mg qd (n=91) EFV 600mg qd (n=89) 100 80 60 40 20 0 76% 72% 71% 71% Virologic responders (%, 95% CI) 0 2 4 8 12 16 20 24 32 40 48 56 64 72 80 88 96 Time (weeks) CI = confidence interval

6. TMC278: potent antiviral efficacy at Week 48 sustained to Week 96 AE = adverse event*Patients with loss of virologic response, patients who never achieved confirmed viral load <50 copies/mL or patients who discontinued before reaching Week 96 due to lack of virologic efficacy

7. TMC278: continued CD4 increases through Week 96 Hatched bars: Week 48 Solid bars: Week 96 122 146 145 172 143 159 127 160 200 150 Mean change in CD4 cell countfrom baseline (cells/mm3, 95% CI) 100 50 0 TMC278 25mg qd (n=93) TMC278 75mg qd (n=95) TMC278 150mg qd (n=91) EFV 600mg qd (n=88) For premature discontinuations, subsequent timepoints were imputed with baseline value up to week 96 (non-completer status equals failure imputation algorithm) Intermediate missing values were imputed using last observation carried forward

8. A limited number of patients experienced virologic failure and developed RAMs on TMC278-based therapy • Very few patients experienced virologic failure with RAMs • 6% (17/279) in the TMC278 arms • 7% (6/89) in the EFV arm • The proportion* of patients in whom treatment-emergent NNRTI RAMs developed was similar across arms • 56% (5/8) in the TMC278 25mg qd group • 60% (3/5) in the TMC278 75mg qd group • 33% (1/3) in the TMC278 150mg qd group • 60% (3/5) in the EFV arm • Resistance findings to be explored further in Phase III trials *Sequence information not available in 2 VF failures (1 in TMC278 75mg arm and 1 in EFV arm)

9. All TMC278 doses were safe and well tolerated, with no consistent association between safety assessments and TMC278 dose Summary of treatment-emergent AEs, regardless of severity and causality *Investigations included laboratory assessments and electrocardiograms

10. Incidences of rash, nervous system- and psychiatric-related AEs were lower with TMC278 than with EFV Summary of NNRTI AEs of interest, regardless of severity and causality* *Well-described AEs associated with current NNRTIs and occurring in ≥5% of TMC278- or EFV-treated patients †All rashes were grade 1 or 2, except for one patient with grade 3 rash in the TMC278 75mg group (associated with fever) probably related to dapsone‡p<0.01 vs EFV; §p<0.05 vs EFV (Fisher’s exact test)

11. Increases in lipid parameters were lower with TMC278 than with EFV • No TMC278 dose relationship for mean changes in lipid parameters Mean change from baseline (SD) at 96 weeks TC = total cholesterol; LDL-C = low-density lipoprotein-cholesterol; HDL-C = high-density lipoprotein-cholesterol; TG = triglycerides*p<0.01, ‡p=0.19 for EFV vs TMC278 (nonparametric Wilcoxon rank sum test, post-hoc analysis)

12. Additional investigations Endocrine • No clinically relevant changes in adrenal and thyroid parameters were observed ECG • Increases in QTc interval were seen with all TMC278 doses and EFV up to 48 weeks, which then stabilizedup to Week 96 • increases were primarily seen with the AZT/3TC backbone • mean increase was lowest with TMC278 25mg

13. Conclusions • Once-daily oral TMC278 at all doses demonstrated a high response rate and sustained virologic response over 96 weeks • TMC278 was generally safe and well tolerated • Incidences of rash, nervous system- and psychiatric-related AEs and increase in lipids were significantly lower with TMC278 than with EFV • There were trends suggesting a favourable profile of TMC278 25mg compared with the higher dose groups • Both efficacy and safety of TMC278 were well maintained between 48 and 96 weeks • TMC278 is being further evaluated in Phase III trials at a dose of 25mg qd

14. Acknowledgements The authors would like to thank the patients who participated in the study, the study centre staff, DSMB members, Tibotec study personnel and the following principal investigators: