1. TMC125 Safety and Tolerability: 24-week Results of the Pooled DUET-1 and -2 Trials R Haubrich, M Schechter, S Walmsley, M Peeters, M Janssens, G De Smedt on behalf of the DUET-1 and DUET-2 study groups TTCA0062-07262-1 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

2. Inclusion criteria plasma viral load >5,000 HIV-1 RNA copies/mL and stable therapy for ≥8 weeks ≥1 NNRTI mutations, ‡ current or documented historical ≥3 primary PI mutations sites: Thailand, Australia, Europe and the Americas DUET: Study Design 24-week primary analysis Randomized *All patients received a background regimen of DRV/r plus NRTIs and optional enfuvirtide TMC125 + BR* Placebo + BR* ‡ From extended list of NNRTI mutations; BR = background regimen; DRV/r = darunavir with low-dose ritonavir; RAM = resistance-associated mutation TTCA0062-07262-2 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

3. Baseline Characteristics and Treatment Duration Parameter, % or median (range) TMC125 group (n=599) Placebo group (n=604) Treatment duration at time of analysis (weeks)30 (1–60)29 (3–55) Patient demographics Male (%) 9089 Caucasian (%)70 Age45 (18–77)45 (18–72) Disease characteristics Viral load (log 10 copies/mL)4.8 (2.7–6.8)4.8 (2.2–6.5) Viral load >100,000 copies/mL3836 CD4 cells (cells/mm 3 )99 (1.0–789)109 (0.0–912) CD4 cells <50 cells/mm 3 3635 CDC category C (%)5859 Hepatitis B/C coinfection1312 Patient historyPsychiatric symptoms (any type)4642 NNRTI-associated rash814 Prior ARV use  10 ARVs (%) 8083 TTCA0062-07262-3 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

4. Overview of Adverse Events Parameter, % TMC125 group (n=599) Placebo group (n=604) Any AE (any cause)9293 Grade 3 AE2225 Grade 4 AE79 Serious AE (SAE)1319 Death (any cause)12 Discontinuation due to AE64 Most common AEs (>10% in either group, regardless of severity and causality)* Rash (any type)179 Diarrhea1520 Nausea1411 Headache912 AEs leading to death were not reported in more than one patient except for pneumonia and sepsis (n=2 each) in the placebo group None of the deaths in the TMC125 group were considered related to TMC125 *excluding injection site reactions; § p=0.0001 vs placebo; AE = adverse event TTCA0062-07262-4 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

5. Grade 3 and 4 Adverse Events AE regardless of causality, n (%) TMC125 group (n=599) Placebo group (n=604) Any grade 3/4 AE2527 Most common grade 3/4 clinical AEs (>0.5% in pooled TMC125 group)* Rash (any type)1.30 Peripheral neuropathy1.00 Pancreatitis0.70 Pneumocystis jiroveci pneumonia0.7 Renal failure0.70.3 *excluding injection site reactions and grade 3/4 laboratory abnormalities reported as AEs TTCA0062-07262-5 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

6. Rash In the TMC125 group: Early onset: median 12 days Limited duration: median 11 days Low severity: most mild to moderate; 1.3% grade 3, none grade 4 mostly maculopapular; no mucosal involvement Infrequently led to discontinuation: 2.2% of patients (0% with placebo) most resolved with continued treatment Clinical associations with rash No association with baseline CD4 cell count No increased risk with prior NNRTI-related rash Investigator assessment of cause of rash, % TMC125 group (n=599) Placebo group (n=604)Significance Any cause179.4p<0.001 Possibly related to study medication124.8 TTCA0062-07262-6 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

7. Incidence of Rash by Gender Patients experiencing rash (any type), % TMC125 group Male (n=539)Female (n=60) Overall incidence1628 Grade 31.13.3 Leading to permanent discontinuation1.95.0 Higher incidence in women: 28% vs 16% in men No clear difference in severity or discontinuations between genders TTCA0062-07262-7 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

8. Incidence and Prevalence of Rash (Any Type) by Treatment Group Incidence Prevalence Placebo group (n=604)TMC125 group (n=599) Incidence (%) 10 8 6 4 2 0 Prevalence (%) 04812162024 Week 04812162024 Week 10 8 6 4 2 0 TTCA0062-07262-8 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

9. Nervous System * Similar incidence to placebo: 15% in TMC125 group versus 18% in placebo group (p=0.09) Low severity: mostly grade 1 and 2 Did not lead to discontinuation: none in TMC125 group and 1.0% of placebo group Patients experiencing nervous system-related AEs, % TMC125 group (n=599) Placebo group (n=604) Grade 30.31.6 Grade 400 Most common (reported in ≥1.0% of patients in the TMC125 group) Headache912 Dizziness34 Somnolence22 *Includes only nervous system events associated with the use of approved NNRTIs TTCA0062-07262-9 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

10. Psychiatric Disorders Patients experiencing psychiatric-related AEs, % TMC125 group (n=599) Placebo group (n=604) Grade 30.21.3 Grade 400.2 Most common (reported in ≥1.0% of patients in the TMC125 group) Insomnia67 Depression35 Anxiety33 Sleep disorder11 Similar incidence to placebo: 13% in TMC125 group versus 15% in placebo group (p=0.3) Low severity: mostly grade 1 and 2 Infrequently lead to discontinuation: 1 patient (0.2%) in each group No increased risk in patients with a history of psychiatric disorders Abnormal dreams/nightmares in 5 patients (0.8%) in each group and no episodes of hallucinations, suicidal ideation or manic symptoms with TMC125 TTCA0062-07262-10 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

11. Hepatic AEs and Laboratory Abnormalities 20 0 –20 –40 081624324048 ALT Change from baseline (U/L) Week 20 0 –20 –40 081624324048 AST Week TMC125 group Placebo group ALT = alanine aminotransferase; AST = aspartate aminotransferase Hepatic AEs, % TMC125 group (n=599) Placebo group (n=604) Any cause or severity5.35.1 Grade 3/43.83.1 Grade 3/4 in hepatitis coinfected patients4.24.4 Leading to discontinuation0.7 Laboratory abnormalities ALT elevated (grade 3 or 4)1.9 and 0.71.3 and 0.3 AST elevated (grade 3 or 4)2.0 and 0.51.3 and 0.3 TTCA0062-07262-11 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

12. Treatment-emergent Laboratory Abnormalities Parameter, % TMC125 group (n=599) Placebo group (n=604) At least one laboratory abnormality98100 Grade 1/293 Grade 3/432 Most common (>2% in TMC125 group) grade 3/4 laboratory abnormalities Amylase (>2x ULN)7.57.9 Triglycerides (>750mg/dL)7.04.3 Total cholesterol (>300mg/dL)5.84.1 Increased LDL-cholesterol (  190mg/dL) 5.25.4 Decreased neutrophils (<750mg/dL)3.76.3 Increased glucose (>250mg/dL)2.52.0 Increased ALT (>5x ULN)2.51.7 Increased AST (>5x ULN)2.51.7 Abstract 1210 ALT = alanine aminotransferase; AST = aspartate aminotransferase; ULN = upper limit of normal TTCA0062-07262-12 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

13. HDL LDL calculated Lipid Changes over Time Total cholesterol/HDL Triglycerides TMC125 group Placebo group HDL = high density lipoprotein; LDL = low density lipoprotein Change from baseline (mg/dL) Week TTCA0062-07262-13 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

14. Hospitalizations Patients hospitalized at least once by 24 weeks (%) 16% 11% Placebo groupTMC125 group p=0.0031 1700 1105 Cumulative days hospitalized by 24 weeks TTCA0062-07262-14 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.

15. Safety Conclusions from DUET Assessing safety/ tolerability of this new agent in a complex background was facilitated by the placebo-controlled design Safety and tolerability of TMC125 was similar to placebo Rash, the only AE to occur more frequently with TMC125 generally mild to moderate often resolved with continued treatment associated with low discontinuation (2% versus 0% with placebo) Overall, most AEs were of low severity and infrequently led to discontinuation 6% vs 4% in the TMC125 vs placebo groups TMC125 was not associated with any increase in laboratory abnormalities, including hepatic and lipid parameters TMC125 provides a tolerable new option for treatment-experienced patients not associated with common NNRTI side effects TTCA0062-07262-15 Haubrich R, et al. Oral presentation presented at IDSA 2007. Abst 1210.