Overview of Phase 1 and 2a Safety and Efficacy Data of Maraviroc (UK-427,857)

1. Overview of Phase 1 and 2aSafety and Efficacy Dataof Maraviroc (UK-427,857) Mary McHale, Sam Abel, Deborah Russell, James Gallagher, Elna van der Ryst Pfizer Global Research and Development, Sandwich Laboratories, Kent, UK

2. Maraviroc (MVC) • Maraviroc (UK-427,857, MVC) is a CCR5 antagonist with potent anti-HIV activity in vitro • An extensive Phase 1/2a program has been carried out • Here we present a summary of the data from the five double-blinded, placebo-controlled, multiple-dose studies with MVC alone, and one drug–drug interaction study with oral contraceptives (expected not to affect exposure to MVC in plasma) • Studies included a total of 259 healthy volunteers and HIV+ positive patients who received MVC at QD and BID doses ranging from 3 mg BID to 1200 mg QD or placebo • Some volunteers received more than one dose of MVC/placebo and are therefore included in more than one dose group in tables and figures. • Total dosing events for MVC = 220 (154 healthy volunteers, 66 HIV+) • Total dosing events for placebo = 111 (95 healthy volunteers, 16 HIV+)

3. Study Details *Unit dose refers to actual dose taken at any time point and not total daily dose, several studies included BID doses 1. Abel S et al. 10th CROI 2003; Paper 547. 2. Russell D et al. 43rd ICAAC 2003; Paper 3080. 3. Abel S et al. 43rd ICAAC 2003; Paper 3066. 4. Fätkenheuer G et al. 15th IAC 2004; Abstract TuPeB4489.

4. Demographic Data

5. Most Frequent Adverse Events – Treatment Related

6. Postural Hypotension • Postural hypotension was the dose-limiting AE in phase 1 • Occurred at rates in excess of placebo only at doses of 600 mg 6/9 Incidence ofpostural hypotension (%) 5/17 3/35 2/111 0/36 0/57 0/16 0/50

7. SAEs and Discontinuations • No SAEs reported • 11 discontinuations on MVC • 9 in 154 healthy volunteers in four Phase 1 studies(3 related) • 2 in 66 HIV+ patients in two Phase 2a studies (not related) • “no longer willing to participate” (25 mg QD) • “headache” (100 mg QD fasted) • 8 discontinuations on placebo • 8 in 95 healthy volunteers in four Phase 1 studies (2 related) • 0 in 16 HIV+ patients in two Phase 2a studies

8. Discontinuations *Investigator assessment

9. Laboratory Abnormalities • Changes in s-creatinine • Elevations in creatinine (<2ULN) in one studyat 1200 mg QD and placebo • Not seen in other studies where similar exposures to MVC were achieved • Liver-enzyme abnormalities • Sporadic transaminase elevations with no dose relationship • No associated bilirubin elevations

10. Laboratory Abnormalities ULN = Upper Limit of Normal

11. Max Increase in QTcF From Baseline (msec) • No evidence of dose-related changes in QTcF at dosesof  1200 mg QD QTcF, Fridericia’s correction

12. MVC Safety Profile Summary • At doses of 300 mg BID, AE profile was similar to placebo • Postural hypotension was the dose-limiting AE – only seen at rates higher than placebo for doses of 600 mg • Clinically relevant elevations in transaminases occurred sporadically, with no dose relationship and no associated elevation in bilirubin • No evidence of clinically relevant prolongation of QTcF

13. Last day of dosing 0.5 0.0 Maraviroc dose n –0.5 Placebo 1015 4 Change from baseline (log10 HIV-1 copies/mL) Placebo 1007 12 25 mg QD 8 –1.0 50 mg BID 8 100 mg QD 8 100 mg BID 7 150 mg BID Fast 8 –1.5 150 mg BID Fed 8 300 mg QD 8 300 mg BID 8 –2.0 Baseline 5 10 15 20 25 30 35 40 Time (day) Fätkenheuer G et al. 15th IAC 2004; Abstract TuPeB4489 MVC Efficacy Results:Mean Reduction in Viral Load over Time

14. MVC Reduces Viral Load in All Patients Receiving Therapeutic Doses

15. Emergence of CXCR4-Tropic Virus (1) • 61/63 patients (97%) with CCR5-tropic virus at baseline remained CCR5-tropic after 10 days of MVC monotherapy • 2 patients showed emergence of CXCR4-using variants during treatment with MVC 100 mg QDfor 10 days • R5 variants remained the predominant virus species post-treatment Lewis M et al. 44th ICAAC 2004; Poster H-584b

16. Emergence of CXCR4-Tropic Virus (2) • Patient 1 • HIV RNA decline: –0.71 log10 copies/mL • Transient emergence of dual-/mixed-tropic virus at day 11 • Reverted to CCR5-tropic at day 40. • Patient 2 • HIV RNA decline: –1.26 log10 copies/mL • Dual-/mixed-tropic virus detected from day 11 onwards • R5 variants constituted ~80% of the circulating virus after one year’s follow-up. • Phylogenetic analysis suggested that R5/X4 variants which emerged post-treatment in each patient most likely expanded from a pre-treatment R5/X4 virus reservoir, rather thanco-receptor switching of an R5 clone Lewis M et al. 44th ICAAC 2004; Poster H-584b

17. Conclusions • MVC was safe and well tolerated in doses up toand including 300 mg BID in this population • Doses of 100 mg BID resulted in viral load reductions of >1 log10 copies/mL • Dosing with food had no significant effect onviral load reduction • Dosing of 150 mg BID and 300 mg QD resulted in similar viral load reductions • Currently in Phase 2b/3 development in both naive and treatment-experienced patients using doses equivalent to 300 mg QD and 300 mg BID

18. Acknowledgements • The maraviroc development team • All the investigators and study-site staff • The patients and volunteers for their participation in these studies