Efficacy and Safety of Maraviroc in Antiretroviral- Experienced Patients Infected With CCR5-Tropic HIV-1: 48-Week Results of MOTIVATE 1 J Lalezari 1, J Goodrich 2, E DeJesus 3, R Gulick 4, H Lampiris 5, M Saag 6, N Bellos 7, J Nadler 8, P Tebas 9, B Trottier 10, M Wohlfeiler 11, C Ridgeway 12, M McHale 12, E van der Ryst 12, H Mayer 2, on behalf of the MOTIVATE 1 Study Team 47th ICAAC Chicago, USA, September 17–20, Quest Clinical Research, UCSF, San Francisco, CA, USA 2 Pfizer Global Research and Development, New London, CT, USA 3 Orlando Immunology Center, Orlando, FL, USA 4 Weill Medical College of Cornell University, New York, NY, USA 5 San Francisco Veterans Affairs Medical Center, UCSF, San Francisco, CA, US 6 University of Alabama at Birmingham, Birmingham, AL, USA 7 Southwest Infectious Disease Associates, Dallas, TX, USA 8 University of South Florida, Tampa, FL, USA 9 University of Pennsylvania, Philadelphia, PA, USA 10 Clinique Medicale L'Actuel, Montreal, QC, CANADA 11 Wohlfeiler, Piperato & Associates, North Miami Beach, FL, USA 12 Pfizer Global Research and Development, Sandwich, UK

2 Background ● MOTIVATE 1 is one of two randomized, double-blind, placebo-controlled, Phase 3 studies investigating the safety and efficacy of the CCR5 antagonist maraviroc, in treatment-experienced patients with R5 HIV-1 ● In a planned interim analysis at 24 weeks 1, maraviroc (QD and BID) + OBT vs OBT alone demonstrated – significantly greater virologic suppression rates – significantly greater increases in CD4+ count – no clinically relevant differences in safety profile ● The MOTIVATE 1 primary efficacy endpoint is the change from baseline in HIV-1 RNA at 48 weeks 1. Lalezari J et al. 14th CROI 2007; Presentation 104bLB

3 Randomization 1:2:2 N=601 MOTIVATE 1 Trial Design OBT* + maraviroc (150 mg † BID) OBT* + maraviroc (150 mg † QD) OBT* + placebo 0 24w * OBT = optimized background therapy of 3–6 ARVs (PK boosting doses of RTV not counted as an ARV) † Patients receiving a PI (except TPV) and/or delavirdine in their OBT received 150 mg dose of MVC, all other patients received 300 mg dose of MVC Screening (6 weeks) 48w Patients stratified by: Enfuvirtide use in OBT HIV-1 RNA < and ≥100,000 copies/mL at screening Patient eligibility criteria: R5 HIV-1 infection HIV-1 RNA ≥5,000 copies/mL Stable pre-study ARV regimen, or no ARVs for ≥ 4 weeks Resistance to and/or ≥ 6 months’ experience with ≥ one ARV from three classes (≥ two for PIs)

4 Demographics and Baseline Characteristics Treated N=585 § OBT alone N=118 MVC QD + OBT N=232 MVC BID + OBT N=235 Mean age, yrs (range) 46 (31–71)46 (19–75)46 (25–69) Male, n (%) 106 (90)210 (91)212 (90) White, n (%) 99 (84)187 (81)197 (84) Median CD4+ count*, cells/mm 3 (range) 160 (1  675) 168 (1  812) 150 (2  678) Mean HIV-1 RNA*, log 10 copies/mL (range) 4.84 (3.46  6.02) 4.85 (3.20  6.75) 4.86 (3.26  6.88) Enfuvirtide in OBT, % ≤2 active drugs in OBT †, % Tipranavir use in OBT, % Darunavir use in OBTNot Permitted MOTIVATE 1-Week 48 Includes all patients who received at least one dose of study medication (full analysis set) § Two patients (1 MVC QD, 1 OBT alone) were assigned to the wrong treatment group due to a transcription error * Calculated for each patient as the mean of up to three pre-dose assessments (screening, randomization, and baseline) † According to overall susceptibility score

5 Mean Change from Baseline in HIV-1 RNA Includes all patients who received at least one dose of study medication HIV-1 RNA value imputed as baseline if patient discontinued before 48 weeks *Treatment difference vs OBT alone MOTIVATE 1-Week 48 Mean change in HIV-1 RNA from baseline (log 10 copies/mL) Difference: -0.85* (97.5% CI: -1.22, -0.49) Difference: -1.02* (97.5% CI: -1.39, -0.66) MVC QD + OBT (N=232) MVC BID + OBT (N=235) OBT alone (N=118) Study week Difference: -0.79* (97.5% CI: -1.14, -0.44) Difference: -0.92* (97.5% CI: -1.28, -0.57) 2448

6 <400 copies/mL Percentage of Patients with Undetectable HIV-1 RNA 57.5%* 50.9%* 22.0% Time (weeks) <50 copies/mL 46.8%* 41.8%* 16.1% Time (weeks) OBT alone (N=118) MVC QD + OBT (N=232) MVC BID + OBT (N=235) Patients (%) 24.6% 48.5%* 42.2% # MOTIVATE 1-Week 48 HIV-1 RNA value imputed as baseline if missing or if patient discontinued before 48 weeks *P< vs OBT alone # P< vs OBT alone Includes all patients who received at least one dose of study medication Number of patients remaining on study treatment at Week 48: OBT alone, 27 (30%); MVC QD + OBT, 109 (60%); MVC BID + OBT, 127 (66%) 60.4%* 54.7%* 31.4%

7 MOTIVATE 1-Week 48 Last observation carried forward * P< vs OBT alone Mean Change from Baseline in CD4+ Count Includes all patients who received at least one dose of study medication Mean change from baseline in CD4+ count (cells/mm 3 ) 2448 Difference: +59 * (95% CI: +34, +84) Difference: +69 * (95% CI: +44, +93) MVC QD + OBT (N=227) MVC BID + OBT (N=233) OBT alone (N=116) Difference: +55 * (95% CI: +30, +79) Difference: +59 * (95% CI: +35, +83) Study week

8 Percentage of Patients With HIV-1 RNA <50 copies/mL at Week 48 According to Screening HIV-1 RNA* Includes all patients who received at least one dose of study medication and had a post-baseline observation Patients (%) MOTIVATE 1-Week 48 <100,000 copies/mL ≥100,000 copies/mL Total population N = Last observation carried forward * Protocol-defined randomization stratum MVC QD + OBT MVC BID + OBT OBT alone

9 Patients (%) N= Maraviroc QD + OBT Maraviroc BID + OBT OBT alone MOTIVATE 1 and 2: Proportion of Patients Receiving ENF With Undetectable HIV-1 RNA at Week 48 According to ENF First Use <400 copies/mL<50 copies/mL MOTIVATE 1 & 2-Week 48 Last observation carried forward ENF first useENF experienced/ resistance ENF first useENF experienced/ resistance

10 Safety Analyses Unadjusted for Duration of Exposure All causalities and severitiesOBT alone N=118 MVC QD + OBT N=232 MVC BID + OBT N=235 Total exposure, patient-years Patients with AEs86%90%92% Patients discontinuing due to AEs6% 5% Patients with grade 3 AEs25%17%23% Patients with grade 4 AEs7%9%10% Patients with SAEs16%14%17% Patients with Category C events5% Deaths*1% 2% AEs = adverse events; SAEs = serious adverse events *Includes deaths reported up to 28 days after stopping study drug No deaths were related to study drug according to the investigator MOTIVATE 1-Week 48 Includes all patients who received at least one dose of study medication

11 Incidence of Adverse Events Occurring in ≥10% of Patients in Any Group, Unadjusted for Exposure Includes all patients who received at least one dose of study medication Total exposure in patient-years: OBT alone 64, MVC QD + OBT 168, MVC BID + OBT 169 MOTIVATE 1-Week 48 MVC QD + OBT (N=232) MVC BID + OBT (N=235) OBT alone (N=118) Patients (%) RTI = respiratory tract infection; ISR = injection site reaction

12 Number of Category C Events Event, n OBT alone N=118 MVC QD + OBT N=232 MVC BID + OBT N=235 Total exposure, patient-years Cryptosporidial gastroenteritis010 Cytomegalovirus infection*011 Herpes simplex225 Mycobacterium avium001 Esophageal candidiasis061 Pneumocystis jiroveci pneumonia 001 Pneumonia021 Progressive multifocal leukoencephalopathy 001 Kaposi’s sarcoma200 Lymphoma * 211 Total number of events Total number of patients, n (% ) 6 6 patients (5.1%) patients (4.7%) patients (5.1%) * Includes T-cell and diffuse large B-cell lymphomas MOTIVATE 1-Week 48 Includes all patients who received at least one dose of study medication

13 Maximum Liver Function Test Values Over 48 Weeks Without Regard to Baseline All causalities, n (%) Unadjusted for duration of exposure OBT alone N=116* MVC QD + OBT N=228* MVC BID + OBT N=234* AST: Grade 3 (5–10 x ULN † ) Grade 4 (>10 x ULN † ) 4 (3.4) 0 7 (3.1) 3 (1.3) 7 (3.0) 4 (1.7) ALT: Grade 3 (5–10 x ULN † ) Grade 4 (>10 x ULN † ) 2 (1.7) 0 11 (4.8) 1 (0.4) 5 (2.1) 3 (1.3) Total bilirubin: Grade 3 (2.5–5 x ULN † ) Grade 4 (>5 x ULN † ) 4 (3.4) 2 (1.7) 17 (7.4) 2 (0.9) 10 (4.3) 2 (0.9) * Total patients evaluated for each laboratory parameter † Upper limit of normal MOTIVATE 1-Week 48

14 MOTIVATE 1 and 2: Change in CD4+ Cell Count from Baseline by Tropism Result at Time of Failure MOTIVATE 1 & 2-Week 48 Tropism result, Baseline → Treatment Failure Mean change from baseline in CD4+ count in patients with treatment failure (cells/mm 3 ) OBT alone N=271 MVC QD + OBT N=477 MVC BID + OBT N=487 All treatment failures* +24 (n=111) +64 (n=92) +74 (n=96) R5 → R5 +25 (n=89) +77 (n=33) +133 (n=24) R5 → D/M or X4 +61 (n=6) +47 (n=35) +57 (n=41) * Includes patients with non-reportable/non-phenotypable tropism result at baseline and patients with non-reportable/non-phenotypable/missing tropism result at time of failure

15 MOTIVATE 1: Summary of 48-Week Primary Analysis ● Maraviroc (BID or QD) + OBT provided significantly greater virologic suppression rates and increases in CD4+ count compared to OBT alone at 48 weeks in this treatment-experienced population ● No new or unique safety findings emerged – Adverse events, serious adverse events, and lab abnormalities (including grade 3/4 transaminase elevations) occurred with similar frequency between treatment groups – Category C (AIDS-defining events) were balanced across treatment groups ● These results demonstrate that treatment with maraviroc + OBT provides sustained antiretroviral efficacy and tolerability in treatment- experienced patients

16 Acknowledgments ● Investigators and study site staff ● Patients who participated in the study ● Colleagues from Monogram Biosciences: J Whitcomb, E Coakley, C Petropoulos ● R Harrigan, BC Centre for Excellence in HIV ● Colleagues from Quintiles ● Colleagues from Pfizer: S Felstead, A Bullivant, I Oborska, K George, M Westby, K Turner, D Lindell, D Paige, S Nuttall, J Merson, L Kapili, M Dunne