1. TMC278 Update, 30th January 2009  C204 data  ECHO and THRIVE - Phase III studies  New TMC278 formulations Peter Williams Tibotec BVBA, Mechelen, Belgium

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

3. Confidential Tibotec Presentation TMC278: high and sustained virological response rate over 96 weeks CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

4. Confidential Tibotec Presentation A limited number of patients experienced virological failure and developed RAMs on TMC278-based therapy CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

5. Confidential Tibotec Presentation Most common grade 2–4 AEs* at least possibly related to TMC278 or EFV CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

6. Confidential Tibotec Presentation Incidences of neurological- and psychiatric-related AEs were lower with TMC278 than with EFV CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

7. Confidential Tibotec Presentation Incidence of rash was lower with TMC278 than with EFV CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

8. Confidential Tibotec Presentation Increases in lipid parameters were lower with TMC278 than with EFV CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

9. Confidential Tibotec Presentation Conclusions CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING

10. Confidential Tibotec Presentation Phase III trial, TMC278-C209 - ARV naïve patients Randomized, double blind, double dummy Non-inferiority, primary efficacy endpoint % of subjects with viral load <50 HIV-1 RNA copies/mL (TLOVR), ARV-naïve subjects, primary NNRTI resistance excluded Backbone fixed to tenofovir + emtricitabine RECRUITMENT START APR 2008 Screening TMC278 25 mg qd + TDF/FTC N=340 Efavirenz 600 mg qd + TDF/FTC N=340 96 weeks  Primary analysis-48 weeks

11. Confidential Tibotec Presentation Phase III trial, TMC278-C215 - ARV naïve patients Randomized, double blind, double dummy Non-inferiority, primary efficacy endpoint % of subjects with viral load <50 HIV-1 RNA copies/mL (TLOVR) ARV-naïve subjects, primary NNRTI resistance excluded Backbone WAS fixed to abacavir + lamivudine Positive test result for HLA-B*5701 excluded RECRUITMENT START MAY 2008 Screening TMC278 25 mg qd + 2 NRTIs N=340 Efavirenz 600 mg qd + 2 NRTIs N=340 96 weeks  Primary analysis-48 weeks

12. Confidential Tibotec Presentation TMC278 new formulations TMC278 for children Oral formulation to allow dosage adjustment by bodyweight in younger children Relative bioavailability study of 3 concept formulations ongoing TMC278 LA Once monthly injectable formulation Maintenance therapy with a companion injectable ARV Pre-exposure prophylaxis

13. Confidential Tibotec Presentation Formulation and clinical methods Innovative nanosuspension* 100mg TMC278 base per mL particles of pure TMC278, average size of 200nm sterile, stable formulation with neutral pH TMC278 LA single doses, given as intramuscular (IM) and subcutaneous (SC) injections PK and injection-site tolerability were evaluated *using NanoCrystal ® technology (under license from Elan Corporation, Ireland) LA = long acting

14. Confidential Tibotec Presentation Single-dose TMC278 LA provided sustained plasma levels for up to 12 weeks in humans Dose proportionality and similar PK profiles after single SC and IM injections 120 100 80 60 0 1234567891211100 40 20 Time (weeks) TMC278 (ng/mL) SC 200mg SC 400mg SC 600mg IM 200mg IM 400mg IM 600mg

15. Confidential Tibotec Presentation Conclusions on TMC278 LA Injectable LA formulations may provide a new paradigm in ARV use and may facilitate long-term compliance TMC278 LA is a promising depot formulation; the concept is viable single 400mg and 600mg doses gave prolonged TMC278 plasma exposure of approximately 20ng/mL after 8 weeks PK exposures were comparable after IM and SC injections favorable safety and tolerability: no serious AEs, grade 3 or 4 AEs or rash injections were well tolerated, particularly when administered IMg; indurations were more frequent after SC than after IM injections placebo injections were better tolerated than injections with TMC278 LA; 600mg IMg injections were better tolerated than 600mg SC and than 400mg IMd injections Next steps: to perform a multiple-dose trial in HIV-negative healthy volunteers; continue with IM and SC (allowing self-administration) injections