RAPAMUNE ® TM I-1 RAPAMUNE ® WYETH-AYERST RESEARCH January 24, 2002 Subcommittee of the Antiviral Drugs Advisory Committee on Immunosuppressive Drugs January 24, 2002 Subcommittee of the Antiviral Drugs Advisory Committee on Immunosuppressive Drugs

RAPAMUNE ® TM I-2 RAPAMUNE ® Introduction Randy Brenner, MS Senior Manager, Worldwide Regulatory Affairs Wyeth-Ayerst Research Randy Brenner, MS Senior Manager, Worldwide Regulatory Affairs Wyeth-Ayerst Research

RAPAMUNE ® TM I-3 Randy Brenner, MS Introduction John Neylan, MD Overview Design of Clinical Studies Efficacy Review Safety Review James Zimmerman, PhDPharmacokinetics Concentration-Controlled Trials Therapeutic Drug Monitoring John Neylan, MDConcluding Remarks Randy Brenner, MS Introduction John Neylan, MD Overview Design of Clinical Studies Efficacy Review Safety Review James Zimmerman, PhDPharmacokinetics Concentration-Controlled Trials Therapeutic Drug Monitoring John Neylan, MDConcluding Remarks Agenda

RAPAMUNE ® TM I-4 RAPAMUNE Approved Formulations  Oral Solution –Dec 98:NDA priority review –Jul 99:FDA Advisory Committee recommendation –Sep 99:FDA approval  Dosing Recommendations - in combination with cyclosporine and corticosteroids –2 mg fixed daily dose RAPAMUNE –5 mg fixed daily dose RAPAMUNE  Tablets –Oct 99:NDA submitted –Aug 00:FDA approval of RAPAMUNE 1 mg Tablets  Oral Solution –Dec 98:NDA priority review –Jul 99:FDA Advisory Committee recommendation –Sep 99:FDA approval  Dosing Recommendations - in combination with cyclosporine and corticosteroids –2 mg fixed daily dose RAPAMUNE –5 mg fixed daily dose RAPAMUNE  Tablets –Oct 99:NDA submitted –Aug 00:FDA approval of RAPAMUNE 1 mg Tablets

RAPAMUNE ® TM I Advisory Committee Meeting  Protocols 301 and 302 determined that the combination of RAPAMUNE + CsA was safe and well-tolerated  Significantly lower rates of acute rejection RAPA + CsA: < 18%  Excellent survival Patient: > 95% Graft: > 90%  Unanimous recommendation Recommendation to further evaluate the impact of RAPAMUNE on renal function  Protocols 301 and 302 determined that the combination of RAPAMUNE + CsA was safe and well-tolerated  Significantly lower rates of acute rejection RAPA + CsA: < 18%  Excellent survival Patient: > 95% Graft: > 90%  Unanimous recommendation Recommendation to further evaluate the impact of RAPAMUNE on renal function

RAPAMUNE ® TM I-6 RAPAMUNE + CsA (Studies 301, 302) Fixed Dose RAPA + CsA RAPAMUNE + CsA (Studies 301, 302) Fixed Dose RAPA + CsA RAPAMUNE Base Therapy (Studies 207, 210) Concentration- Controlled RAPA (without CsA) Key Concepts in Clinical Development CsA Elimination Trials Study 212 Study 310 Animal Data Effective agent when evaluated alone Non-nephrotoxic

RAPAMUNE ® TM I-7 RAPAMUNE CsA Elimination Studies  Equivalent patient and graft survival at 12 months –> 97% and > 95%, respectively, in all groups  Significantly better renal function  Significantly better blood pressure  No difference in biopsy-confirmed acute rejection at 12 months  Equivalent patient and graft survival at 12 months –> 97% and > 95%, respectively, in all groups  Significantly better renal function  Significantly better blood pressure  No difference in biopsy-confirmed acute rejection at 12 months

RAPAMUNE ® TM I-8 RAPAMUNE Current Application  CsA Elimination –Apr 01: sNDA submitted  Dosing Recommendations –6 mg loading dose of RAPAMUNE followed by 2 mg/day in combination with CsA and corticosteroids –2 to 4 months after transplantation, CsA elimination should be considered and RAPAMUNE dose selection based on trough levels with a recommended range  Therapeutic Drug Monitoring  CsA Elimination –Apr 01: sNDA submitted  Dosing Recommendations –6 mg loading dose of RAPAMUNE followed by 2 mg/day in combination with CsA and corticosteroids –2 to 4 months after transplantation, CsA elimination should be considered and RAPAMUNE dose selection based on trough levels with a recommended range  Therapeutic Drug Monitoring

RAPAMUNE ® TM I-9 RAPAMUNE Current Indication  RAPAMUNE is indicated for the prophylaxis of organ rejection in patients receiving renal transplants. It is recommended that RAPAMUNE be used in a regimen with cyclosporine and corticosteroids.

RAPAMUNE ® TM I-10 RAPAMUNE Proposed Indication Cyclosporine withdrawal should be considered 2 to 4 months after transplantation.  RAPAMUNE is indicated for the prophylaxis of organ rejection in patients receiving renal transplants. It is recommended that RAPAMUNE be used initially in a regimen with cyclosporine and corticosteroids.