Efficacy and Safety of Maraviroc in Treatment- Experienced (TE) Patients Infected with R5 HIV-1: 96-week Combined Analysis of the MOTIVATE 1 & 2 Studies WD Hardy 1, R Gulick 2, H Mayer 3, G Fätkenheuer 4, M Nelson 5, J Heera 3, N Rajicic 6, J Goodrich 3 1 Cedars-Sinai Medical Center/Geffen School of Medicine, UCLA, Los Angeles, CA, USA; 2 Weill Medical College of Cornell University, New York, CA, USA; 3 Pfizer Global Research and Development, New London, CT, USA; 4 University of Cologne, Köln, Germany; 5 Chelsea & Westminster Hospital, London, UK; 6 Pfizer Inc., New York, NY, USA 9TH INTERNATIONAL CONGRESS ON DRUG THERAPY IN HIV INFECTION November 9–13, 2008 Glasgow, UK

Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 MOTIVATE 1 & 2: Trial Design OBT* + maraviroc (150 mg † BID) OBT* + maraviroc (150 mg † QD) OBT* + placebo 0 Week 48 Week 96 * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC Screening 6 weeks Patients were stratified by enfuvirtide use and HIV-1 RNA < and ≥100,000 copies/mL Patient eligibility criteria: R5 HIV-1 infection HIV-1-RNA ≥5,000 copies/mL Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors[PIs]) MOTIVATE 1 and 2 Week 96 Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Percentage of Patients with HIV-1 RNA <50 copies/mL at Week 48 Adapted from Hardy et al. CROI Abstract Patients (%) % 43.2%* 45.5%* *P< vs placebo Time (weeks) MOTIVATE 1 and 2 Week 48 Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426)

MOTIVATE 1 & 2: Week-96 Analyses Two analyses were conducted to characterize the Week-96 combined MOTIVATE 1 and 2 populations: ● Efficacy Analysis This analysis includes patients receiving MVC QD and BID who had undetectable viral load (HIV-1 RNA <50 copies/mL ) at Week 48 and were followed until Week 96 ● Safety Analysis This analysis includes all blinded data for study participants according to their original randomization and includes data from patients who continued to receive blinded therapy beyond Week 48. It does not include any open-label treatment data. This results in a distribution of patients in the study with different exposures to blinded study drug. The study was unblinded when the last patient to be randomized reached Week 48 MOTIVATE 1 and 2 Week 96 Efficacy Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Trial Design OBT* + placebo 0 Week 48 Week 96 Efficacy data include all patients who reached Week 48 with HIV-1RNA <50 copies/mL and continued on blinded therapy or open-label MVC BID MOTIVATE 1 and 2 Week 96 Efficacy * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC Screening 6 weeks Patients were stratified by enfuvirtide use and HIV-1 RNA < and ≥100,000 copies/mL Patient eligibility criteria: R5 HIV-1 infection HIV-1-RNA ≥5,000 copies/mL Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors [PIs]) Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 OBT* + maraviroc (150 mg † BID) OBT* + maraviroc (150 mg † QD) Adapted from Hardy et al. HIV Presentation 0425.

Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 OBT* + maraviroc (150 mg † BID) OBT* + maraviroc (150 mg † QD) 0 Week 48 Week /426 (60.8%) open-label MVC BID 239/414 (57.7%) open-label MVC BID MOTIVATE 1 and 2 Week 96 Efficacy MOTIVATE 1 & 2: Trial Design * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC. Screening 6 weeks Patients were stratified by enfuvirtide use and HIV-1 RNA < and ≥100,000 copies/mL Patient eligibility criteria: R5 HIV-1 infection HIV-1-RNA ≥5,000 copies/mL Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors [PIs]) Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Percentage of Patients with HIV-1 RNA <50 copies/mL at Week 96 Includes all patients who received at least one dose of study medication Placebo + OBT (N=209) MVC QD + OBT (N=414) MVC BID + OBT (N=426) Patients (%) Option to switch to open-label MVC BID 43.7% 45.1% 23.0% 43.5% 46.5% 16.7% 38.9% 41.3% 7.2% Time (weeks) MOTIVATE 1 and 2 Week 96 Efficacy In this analysis, non-completers were categorized as failures Adapted from Hardy et al. HIV Presentation 0425.

81.4% 10.5% 7.0% MOTIVATE 1 & 2: Clinical Outcome At Week 96 of Patients with HIV-1 RNA <50 copies/mL at Week 48 Maraviroc groups include patients on blinded therapy and open-label MVC BID Does not include patients who discontinued for non-efficacy reasons: adverse events (n=4); withdrew/lost to follow up (n=8); other reasons (n=4); no discontinuation and no data at 96 weeks (N=4) 1.2% 2.8% 0.6% N=172N=181 Lack of efficacy = HIV-1 RNA levels of at least three times the baseline HIV-1 RNA level 86.7% 9.9% MVC QD + OBTMVC BID + OBT Patients (%) Discontinuation due to lack of efficacy On study, not failed HIV-1 RNA 50  400 copies/mL HIV-1 RNA <50 copies/mL MOTIVATE 1 and 2 Week 96 Efficacy Adapted from Hardy et al. HIV Presentation 0425.

9 MOTIVATE 1 & 2: Week 96 Analyses Two analyses were conducted to characterize the Week 96 combined MOTIVATE 1 and 2 populations: ● Efficacy Analysis This analysis includes patients receiving MVC QD and BID, who had undetectable viral load (HIV-1 RNA <50 copies/mL ) at Week 48 and were followed until Week 96. ● Safety Analysis This analysis includes all blinded data for study participants according to their original randomization and includes data from patients who continued to receive blinded therapy beyond Week 48. It does not include any open-label treatment data. This results in a distribution of patients in the study with different exposures to blinded study drug. The study was unblinded when the last patient to be randomized reached Week 48. MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV Presentation 0425.

Randomization 1:2:2 MOTIVATE 1 N=601 MOTIVATE 2 N=474 MOTIVATE 1 & 2: Trial Design OBT* + maraviroc (150 mg † BID) OBT* + maraviroc (150 mg † QD) OBT* + placebo 0 Week 48 Week /426 (60.8%) open-label MVC BID 239/414 (57.7%) open-label MVC BID 98/209 (46.9%) open-label MVC BID MOTIVATE 1 and 2 Week 96 Safety * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of ritonavir not counted as an ARV) † Patients receiving a PI (except tipranavir) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC. Screening 6 weeks Patients were stratified by enfuvirtide use and HIV-1 RNA < and ≥100,000 copies/mL Patient eligibility criteria: R5 HIV-1 infection HIV-1-RNA ≥5,000 copies/mL Stable pre-study antiretroviral (ARV) regimen, or no ARVs for ≥4 weeks Resistance to and/or ≥6 months’ experience with ≥one ARV from three classes (≥two for protease inhibitors [PIs]) Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Duration of Exposure to Study Drug Median (bars) and range (lines) of study treatment duration at indicated study time point 0 Week 48 End of Blinded Therapy Time (weeks) MVC QD + OBT (N=414) MVC BID + OBT (N=426) Placebo + OBT (N=209) MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Incidence of Malignancies at Week 48 and End of Blinded Therapy Includes all patients who received at least one dose of study medication MVC QD + OBT (N=414) MVC BID + OBT (N=426) Placebo + OBT (N=209) Total patient-years Rate per 100 patient-years Week 48End of blinded therapy Adjusted incidence 0 Patients (%) Unadjusted incidence Week 48End of blinded therapy N= If the same patient in a given treatment arm had more than one occurrence in the same event category, only the most severe occurrence was taken MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Incidence of Category C (AIDS-defining) Events at Week 48 and End of Blinded Therapy Includes all patients who received at least one dose of study medication MVC QD + OBT (N=414) MVC BID + OBT (N=426) Placebo + OBT (N=209) Total patient-years Rate per 100 patient-years 10.0 Week 48End of blinded therapy N= Patients (%) Unadjusted incidence Adjusted incidence Week 48End of blinded therapy MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Incidence of LFT Abnormalities (Without Regard to Baseline) at Week 48 and End of Blinded Therapy ULN, upper limit of normal Total patient-years of exposure to study drug at Week 48: Placebo + OBT 111; MVC QD + OBT 300; MVC BID + OBT 309 Total patient-years of exposure to study drug at at end of blinded therapy: Placebo + OBT 160; MVC QD + OBT 522; MVC BID + OBT 551 Incidence (unadjusted) n (%) Incidence (adjusted) Event counts adjusted to 100 years of patient exposure Placebo + OBT MVC QD + OBT MVC BID + OBT Placebo + OBT MVC QD + OBT MVC BID + OBT Week 48 AST: >3.0 x ULN17 (8)39 (10)45 (11) ALT: >3.0 x ULN13 (6)29 (7)37 (9) Total bilirubin: >1.5 x ULN 30 (14)66 (16)51 (12) End of blinded therapy AST: >3.0 x ULN19 (9)45 (11)46 (11) ALT: >3.0 x ULN15 (7)37 (9)39 (9) Total bilirubin: >1.5 x ULN 31 (15)68 (17)54 (13) MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2: Adverse Events Occurring in ≥5% Patients at End of Blinded Therapy MVC QD + OBT (N=414) MVC BID + OBT (N=426) Placebo + OBT (N=209) Includes all patients who received at least one dose of study medication Patients (%) Unadjusted incidence RTI, respiratory tract infection If the same patient in a given treatment had more than one occurrence in the same preferred term event category, only the most severe occurrence is taken. Event counts are adjusted to 100 years of patient exposure. Includes data up to 7 days after last dose of study drug. Rate per 100 patient-years NauseaVomitingFatigueNaso- pharyngitis Upper RTIDizzinessHeadacheRash Exposure adjusted incidence NauseaVomitingFatigueNaso- pharyngitis Upper RTIDizzinessHeadacheRash MOTIVATE 1 and 2 Week 96 Safety Adapted from Hardy et al. HIV Presentation 0425.

MOTIVATE 1 & 2 Week 96: Summary Efficacy Analysis ● Maraviroc + OBT results in durable viral suppression through 96 weeks in treatment-experienced patients with R5 HIV-1. – 87% of patients in the BID arm who were fully suppressed at Week 48 remained suppressed at Week 96. Safety Analysis ● Pooled analyses revealed no new or unique safety signals between Week 48 and end of blinded therapy. – Category C events, malignancies, and LFT abnormalities occurred with similar frequency among treatment groups when not adjusted for the longer duration of exposure in the maraviroc groups. – The incidence of these events decreased between Week 48 and end of blinded therapy. – After adjusting for exposure, the incidence of Category C events and malignancies was lower in the maraviroc groups compared to placebo. MOTIVATE 1 and 2 Week 96 Adapted from Hardy et al. HIV Presentation 0425.