1. The Endeavor Zotarolimus-Eluting Stent: Device Description and Comprehensive Update of the Clinical Trial Program

2. Endeavor DES - 2008 Device Technology Overview Clinical Trial Perspectives

3. Endeavor DES - 2008 Device Technology Overview

4. ENDEAVOR Safety Considerations Design Features Histopathology Rapid drug elution Stent design = reduced injury (rounded thin struts) % Drug Eluted Time (Days) 65 87 98 99 PC Basecoat (≈ 1μm) Drug Layer 90% Zotarolimus 10% PC (≈ 2-4μm) Stent Strut Biocompatible PC Safeformulation

5. % Endotheliazation Endothelial Coverage Histopathology Porcine coronaries @180 days 7 9028 180 Days Endeavor eNOS Staining BaselineAch (10 -5M ) mm 90days Vaso-reactivity ENDEAVOR Safety Considerations Animal Studies (rabbits and pigs)

6. OCT Angioscopy Endothelial Function Proximal Distal ENDEAVOR Safety Considerations Human Results IVUS ZES (n=14) vs. SES (n=16) @ 8 mos FU ZES improved neointimal coverage (P=0.0004) and fewer thrombi Awata et al; J Am Coll Cardiol 2008;52;789-90 44 overlapped ZES in 17 pts @ 6 mos FU (24,076 struts analyzed) ZES no malapposed or uncovered struts; no intraluminal thrombus Guagliumi et al; ESC 2008 541 ZES pts @ 8 mos FU 0.4% late incomplete apposition; no positive remodeling; homogeneous neointimal distribution Fitzgerald et al; Stanford IVUS core lab ZES (n=20) vs. SES (n=20) vs. BMS (n=10); Ach infusions @ 6 mos; ZES improved endothelial function cw SES (P<0.001) and similar to BMS Kim et al; ACC 2008

7. Endeavor DES - 2008 Clinical Trial Perspectives

8. Endeavor Clinical Program Overview 1yr 2yr 3yr 4yr 5yr Continued Access Single Arm (n = 296) 4yr ENDEAVOR II CA ENDEAVOR I Single Arm First-in-Man (n = 100) 5yr ENDEAVOR II 1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 4yr ENDEAVOR III 3:1 RCT vs. Cypher ® (E = 323,C = 113) 3yr ENDEAVOR IV 1:1 RCT vs.Taxus ® (E = 773,T = 775) 2yr ENDEAVOR PK Pharmacokinetic Study (n = 43) 2yr Single Arm (n = 99) 1yr ENDEAVOR Japan E-FIVE Open Label Single Arm (n = 8000) 1yr PROTECT 1:1 RCT vs. Cypher (E = 4400,C = 4400) Post Approval Premarket Safety and Efficacy Package

9. 1yr 2yr 3yr 4yr 5yr Continued Access Single Arm (n = 296) 4yr ENDEAVOR II CA ENDEAVOR I Single Arm First-in-Man (n = 100) 5yr ENDEAVOR II 1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 4yr ENDEAVOR III 3:1 RCT vs. Cypher ® (E = 323,C = 113) 3yr ENDEAVOR IV 1:1 RCT vs.Taxus ® (E = 773,T = 775) 2yr ENDEAVOR PK Pharmacokinetic Study (n = 43) 2yr Single Arm (n = 99) 1yr ENDEAVOR Japan E-FIVE Open Label Single Arm (n = 8000) 1yr PROTECT 1:1 RCT vs. Cypher (E = 4400,C = 4400) Ongoing Premarket Safety and Efficacy Package 20,519 Patients Endeavor Clinical Program Overview

10. D eliverabilit y E fficacy S afety Endeavor DES - 2008

11. D eliverabilit y Endeavor DES - 2008

12. 100 95 90 85 80 (%) (%) p = 0.02 100 95 90 85 80 (%) (%) ENDEAVOR III 99.4% 95.6% Procedural Success Endeavor (n = 323) Cypher (n = 113) ENDEAVOR IV p = 0.02 98.7% 96.8% Procedural Success Endeavor (n = 774) Taxus (n = 775) ENDEAVOR Deliverability Procedural Success vs. Cypher and Taxus

13. TCTMD Physician Survey on DES Use Patterns % Physicians US (n=143) OUS (n=347) Deliverability EndeavorCypherXience/PromusTaxus TCTMD 10.03.08

14. D eliverabilit y more user-friendly (esp. Rx platform) very deliverable in complex lesions and challenging anatomy excellent sidebranch access Endeavor is… Endeavor DES - 2008

15. E fficacy Endeavor DES - 2008

16. SIRIUS (n=501/525) TAXUS IV (n=618/650) 4.9 6.8 7.9 9.4 6.3 4.4 5.6 6.9 7.8 9.1 Pivotal Trials TLR - DES Arms ENDEAVOR II, SIRIUS, and TAXUS IV NA EII (n=581/598) 5.9 6.5 7.2 0 2 4 6 8 10 12345 Years of Follow-up TLR (%) 0 2 4 6 8 10 12345 Years of Follow-up TLR (%) 0 2 4 6 8 10 12345 Years of Follow-up TLR (%)

17. Primary Endpoint: TVF at 9 months Secondary Endpoints: In-segment % DS at 8 months; TLR and TVR at 9 months Drug Therapy: ASA and Clopidogrel/Ticlid >6 months Zotarolimus Dose: 10  g per mm stent length Endeavor IV Single Blind RCT vs. Taxus DES PI: Martin B. Leon Single De Novo Native Coronary Lesion Vessel Diameter: 2.5–3.5 mm Lesion Length: ≤ 27 mm Pre-dilatation required 1:1 randomization N = 1,548 patients 80 sites US Endeavor Stent n=774 Taxus Stent n=774 30d 6mo 4yr 3yr 2yr 9mo 12mo 8mo 5yr Clinical/MACE Angiography/IVUS QCA and IVUS Subset (328 total = 21.2%)

18. Endeavor IV TLR and TVR at 12 months Endeavor (34/749) Taxus (24/741) Endeavor (47/749) Taxus (50/741) P = 0.228 TLRTVR Rate P = 0.753 4.5% 3.2% 6.3% 6.7%

19. Endeavor IV TLR by Angio FU at 12 mos TLR Rate 12/141 4/133 22/60820/608 EndeavorTaxusEndeavorTaxus Angiographic Follow-up Clinical Follow-up P =0.070 P =0.875 18% of pts 82% of pts

20. Endeavor In-Stent Late Loss Endeavor II, II CA, III and IV % of Patients TLR Probability In-Stent LL (mm) 800 pts with angio FU at 8 mos

21. Primary Endpoint: MACE at 12 months Secondary Endpoints: MACE at 30 days and 6 mo, Stent thrombosis, procedure success rate; device success rate; lesion success rate Drug Therapy: ASA and Clopidogrel ≥ 3 months Zotarolimus Dose: 10  g per mm stent length Primary Endpoint: MACE at 12 months Secondary Endpoints: MACE at 30 days and 6 mo, Stent thrombosis, procedure success rate; device success rate; lesion success rate Drug Therapy: ASA and Clopidogrel ≥ 3 months Zotarolimus Dose: 10  g per mm stent length Single and Multiple Coronary Artery Lesions Stent Diameters: 2.25-4.0 mm Stent Length: 8/9-30 mm Single and Multiple Coronary Artery Lesions Stent Diameters: 2.25-4.0 mm Stent Length: 8/9-30 mm N = 8,000 patients followed for 1 yr N = 2,000 patients followed for 2 yrs N = 2,000 patients followed for 2 yrs 200 sites Europe, Asia Pacific, Israel, New Zealand, South America Clinical/MACE 30d 6mo 2yr 12mo E-Five Registry Prospective Multicenter Registry PIs: Chaim Lotan, Ian Meredith, and Martin Rothman

22. Cardiac Death MI e-Five (n = 7832) TVRMACETLRTVFDeathARC ST Def ARC ST Def/Prob E-Five Registry Clinical Events to 12 mos

23. E-Five Registry High Risk Patients and Lesions High Risk included patients with: AMI (<72 hrs) 13.9% AMI (<72 hrs) 13.9% Multivessel stenting 10.9% Multivessel stenting 10.9% Long lesion (>27 mm) 16.6% Long lesion (>27 mm) 16.6% Ostial lesion 5.8% Ostial lesion 5.8% Bifurcated lesion 18.9% Bifurcated lesion 18.9% In-stent restenosis 4.8% In-stent restenosis 4.8% Graft stenting 1.8% Graft stenting 1.8% Severe tortuosity 3.3% Severe tortuosity 3.3% Small vessel (RVD<2.5 mm)OR Small vessel (RVD<2.5 mm)OR Large vessel (RVD>3.5 mm) 18.3% Large vessel (RVD>3.5 mm) 18.3% Left main stenting 2.4% Left main stenting 2.4% Moderate/severe Calcification 31.6% Moderate/severe Calcification 31.6% Moderate/severe renal impairment 5.3% Moderate/severe renal impairment 5.3%8314Patients6189 High Risk 2125SimpleSimple

24. 0% 3% 6% 9% 12% 15% 03090180270360390 Time after Initial Procedure (days) Cumulative Incidence of TLR 2.8% 5.0% 4.5% Simple (n = 2,125 pts) High Risk (n = 6,189 pts) Overall (n = 8,314 pts) TLR030180270360Standard21252122208820571982 Overall83148299806678777549 High Risk 61896177597858205567 E-Five Registry – “High Risk” Cumulative TLR to 12 mos

25. Endeavor 在 “ 真实世界 ” 研究中一致的 TLR ESTROFA-2 TLR rates not available. 1 E-Five 12-month data: Rothman et al., EuroPCR 2008. 2 Lassen F et al., TCT 2008. 3 9 months 12 months E-Five 1 n = 7832 SORT-OUT III 2 n = 1162

26. E fficacy Endeavor DES - 2008 associated with higher angio late loss but, similar TLR/TVR, even in some high restenosis subgroups angio FU magnifies the visual “oculostenotic reflex” when late loss is relatively higher Endeavor is…

27. S afety Endeavor DES - 2008

28. Time after Initial Procedure (days) Cumulative Incidence of Def/Prob ST (ARC) 360450540630720 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 0.9% 0.1% Endeavor Taxus 1-2year HR 0.17 [0.20, 1.39]P=0.059 Endeavor 726 726 709 705 699 Taxus 725 725 706 703 699 ENDEAVOR IV – 2yr FU ARC Def/Prob ST 12-24 mos (VLST)

29. 0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 3.0% 036072010801440 ARC (Def/Prob) Endeavor 2058 2036 16501037 No. at Risk Cypher 863 848 824789 Taxus 1351 1300 1117715 1 Year2 Years3 Years Pooled Data Xience V /Promus 892 865 NA NA 4 Years Days Endeavor Stent: 确保长期安全性 ARC 定义 ( 肯定 / 可能 ) 累积 4 年支架血栓 Results come from separate clinical trials. Data may differ in a head-to-head comparison. 1. Leon et al. TCT. 2008. 2. Mauri L et al. N Engl J Med. 2007;356:1020-1029. 3. Serruys PW et al. ACC 2008 3. Stone GW et al. PCR 2008.

30. Endeavor 在 “ 真实世界 ” 的 研究一致的血栓发生率 n=1162 ARC 定义 1 E-Five 12-month data: Rothman et al., EuroPCR 2008. 2 Hernandez et al., TCT 2008. 3 Lassen F et al., TCT 2008. 2 3 4 9 months 12 months E-Five 1 n = 7832 ESTROFA-2 2 n = 967 SORT-OUT III 3 n = 1162

31. % Physicians US (n=143) OUS (n=347) EndeavorCypherXience/PromusTaxus TCTMD Physician Survey on DES Use Patterns Safety (esp. stent thrombosis)

32. S afety Endeavor DES - 2008 associated with improved pre-clinical safety evaluations AND very low clinical safety endpoints (death and MI) AND very low stent thrombosis (esp. very late) – “BMS-like” IVUS without late incomplete apposition or aneurysms Endeavor is…

33. All Comers Dual APT >3 to <12 months N = 8800 >200 International Sites Randomization 1:1 Endeavor N=4400 Clinical Follow-up 30d6mo 4 yr 3yr 30mo24mo5 yr Primary Endpoint: ARC Definite or Probable Stent Thrombosis at 3 years Principle Secondary Endpoints: Death/Non-Fatal MI, Cardiac death/Non-Fatal MI Additional Endpoints: MACCE, TLR, TVR, Procedural Success Clinical Follow up and Dual Antiplatelet Monitoring: At 30 days, and every 6 months until 3 years, than each year until 5 years Cypher N=4400 12mo18mo PROTECT Worldwide RCT (Endeavor vs. Cypher) >8500 pts enrolled

34. Endeavor Experience 1 case from Fu Wai 1 case from Fu Wai