1. NOBORI New Generation Drug Eluting Stent Clinical Data Danny Detiege Clinical Manager - Cardiology Terumo Europe N.V. Leuven, Belgium

2. MY CONFLICTS OF INTEREST ARE Employee of Terumo Europe

3. Nobori DES components Highly Flexible BMS Platform Proprietary Hydrophilic Coating for excellent deliverability Drug – Biolimus A9 Lipophilic Specifically developed for local applications Coating Only abluminal Polymer - PLA Biodegradable

4. Mechanism of Action Biolimus A9 mTOR FKBP Biolimus A9 G1G0 S p27 kip FKBP Biolimus A9 p34 CDC2 mTOR Receptor M G2 Growth Factor Everolimus Sirolimus Biolimus A9 mTOR FKBP-12

5. NOBORI – Clinical Program NOBORI 2 – 3000 patients NOBORI PK – 20 Patients Nobori DES Randomized versus Taxus (surrogate endpoint-LL) NOBORI 1 – 363 patients Nobori DES Randomized versus Cypher (clinical endpoint-TVF) NOBORI Japan – 340 patients Real life registry Confirmation of pharmacokinetics Nobori DES NOBORI CORE – 107 patients Nobori DES similarity versus Cypher (surrogate endpoint-LL) COMPARE II 2700 patients Randomized vs Xience V in all Comers population In all Nobori trials treatment of more than one vessel was allowed NOBORI CORE endothelial study 43 patients Comparison endothelial function at 9 months Nobori vs Cypher

6. NOBORI Pharmacokinetics Study TrialSample Size (n) TIME POINTS Pre- Proce- dure Mins / Hours / Days / Months 21530123824487272836 Nobori PK Study 20 * t=0 defined as deployment balloon inflation/ stent implantation BA9 Blood Collection Time Points Biochemistry/Haematology Blood Collection Time Points

7. Biolimus A9 concentration 14mm 28mm LLOQ Ostojic et al. CCI 2008 LLOQ = Lowest level of quantification

8. Systemic concentration of drugs (ng/mL) eluted from DES 1= Ostojic et al. CCI 2008 2=Vetrovec et al. CCI 2006 3=Wiemer et al. AHJ 2008 NR= Not reported Maximum blood concentration of Biolimus A9 is 52 times LOWER than Sirolimus and 87 times lower than Everolimus

9. NOBORI 1 PI: Dr B. Chevalier N = 363 patients 29 sites Europe, Asia, Australia Primary endpoint: In-stent late lumen loss by QCA at 9 months Secondary endpoints: MACE (Death, MI, TVR) TLR, TVF at 9 months and ABR at 9 months, Procedure, Lesion success, In-segment late loss Drug therapy: ASA and clopidogrel 6 months Primary endpoint: In-stent late lumen loss by QCA at 9 months Secondary endpoints: MACE (Death, MI, TVR) TLR, TVF at 9 months and ABR at 9 months, Procedure, Lesion success, In-segment late loss Drug therapy: ASA and clopidogrel 6 months 30d 4mo 4yr 3yr 2yr 9mo 12mo QCAIVUS 5yr Clinical/MACE Angio/IVUS Nobori stent n = 85 phase 1 153 phase 2 153 phase 2 Nobori stent n = 85 phase 1 153 phase 2 153 phase 2 Control Taxus stent n = 35 Express Ph 1 90 Liberte Ph 2 Control Taxus stent n = 35 Express Ph 1 90 Liberte Ph 2 De novo native coronary lesion Vessel diameter: 2.5-3.5 mm Lesion length: <25 mm Predilatation required De novo native coronary lesion Vessel diameter: 2.5-3.5 mm Lesion length: <25 mm Predilatation required Clinicalendpoints 2:1 randomization, non-inferiority design Single blind – two vessel – staging allowed

10. Late Loss result 0.33 ± 0.51 mm Taxus  0.11 ± 0.30 mm Nobori 00.20 Taxus  betterNobori ® Δ LL (mm) - 0.12- 0.21 Assumed in-stent Late Loss (LL) 0.39 mm for Taxus  / 0.34 mm Nobori Assumed SD: 0.50 mm Delta non-inferiority margin: 0.20mm Primary Endpoint Result Result: Nobori = NON-INFERIOR p<0.001 Nobori = SUPERIOR* p=0.001 *The SUPERIORITY was a secondary objective

11. Key Angiographic Results Late Loss mm 64% Reduction p < 0.001 53% Reduction p < 0.05 0.12 0.09 0.33 0.17 0.00 0.10 0.20 0.30 0.40 In-stentIn-segment Nobori N=269Taxus N=139 0% 2% 4% 6% 8% 10% In-stentIn-segment 91% Reduction p = 0.01 91% Reduction p = 0.01 0.4% 4.6% Binary Restenosis

12. Intravascular Ultrasound Results Nobori ® 101 lesions Taxus ® 53 lesions P- value Mean Lumen Area (mm²  SD) Post procedure 9 Month follow-up 7.4  1.6 7.5  1.8 7.9  2.3 7.2  2.3 0.16 0.48 Minimum Lumen Area (mm²  SD) Post procedure 9 Month follow-up 6.1  1.4 5.9  1.7 6.5  2.0 5.6  2.2 0.23 0.40 Mean Plaque Area (mm²  SD) * 0.1  0.50.5  0.6 <0.001 Neointima volume (mm³  SD) * 3.1  8.813.5  20.4 0.003 In-stent Volume Obstruction (%  SD) * 1.9  5.56.8  8.00.001

13. MACE Rate at 1 Year

14. Stent Thrombosis up to 2 years Nobori Stent N=238 Taxus Stent N=125 Acute0.02.4 Subacute0.01.6 Late0.00.8 Total up to 1 year0.03.2 Total up to 2 years** 0.04.0 Nobori Stent N=238 Taxus Stent N=125 Early 0.01.6 Late 0.0 Very Late 0.00.8 Definite and probable 0.02.4 Total up to 2 years** 0.02.4 Stent thrombosis Per Protocol Definite and Probable Stent Thrombosis According to ARC* *ARC = Academic Research Consortium – Procedural MIs not counted as ST ** Only patients from Phase 1 were followed up to 2 Years

15. NOBORI CORE

16. NOBORI CORE Study Design N = 107 patients (6 sites) Co-PI – M. Ostojic W. Wijns Secondary endpoints: Endothelial functionality, MACE (Death, MI, TVR) TLR, TVF at 9 months and restenosis at 9 months, Procedure, Lesion success 30d 4yr 3yr 2yr 9mo 12mo QCA Endothelial Function Assessment 5yr Clinical/MACE Angio/Atrial Pacing Nobori stent n = 54 Control Cypher stent n = 53 Control Cypher stent n = 53 De novo native coronary lesion Vessel diameter: 2.5-3.5 mm Predilatation required Antiplatelet therapy: ASA and clopidogrel 6 months De novo native coronary lesion Vessel diameter: 2.5-3.5 mm Predilatation required Antiplatelet therapy: ASA and clopidogrel 6 months Clinical endpoints Prospective, Multicentre, Comparative Non-randomized Primary endpoint: In-stent late lumen loss by QCA at 9 months

17. QCA Findings at 9 Months Nobori ® 72 Lesions Cypher ® 74 Lesions P Value RVD (mm) MLD – stent (mm) MLD – lesion (mm) DS (%) Late loss – stent (mm) Late loss – lesion (mm) 3.00 ± 0.36 2.59 ± 0.42 2.27 ± 0.48 13 ± 10 0.10 ± 0.26 0.12 ± 0.35 2.84 ± 0.40 2.28 ± 0.49 2.13 ± 0.48 20 ± 12 0.12 ± 0.43 0.18 ± 0.40 0.09 <0.001 0.15 0.001 0.70 0.43 Binary Restenosis % 1.7 (1/60)4.2 (2/48)0.18 Ostojic et all EuroIntervention 2008

18. NOBORI CORE Endotelial Function Assessments

19. HR 90-110 Pacing 2 min Angio 2 min STOP Pacing HR 110-130HR 130-150Ntg IC bolus Protocol of atrial pacing for Endothelial Function Assessment METHODS 1.Baseline conditions were established and angiography performed 2.Rapid Atrial pacing with 20 bpm higher than baseline for 2 min 3.Angiographic images acquisition followed by 2 minutes rest 4.Repeat procedure with increasing pacing rate by 20 bpm up to 150 5.Intra-arterial nitroglycerin injection 6.Angiographic image acquisition 7.Off line QCA analysis of proximal, in-stent, distal segments and reference vessel HR 70-90 Angio

20. Distal vessel: change in diameter after pacing 2,0 2,2 2,4 2,6 2,8 3,0 3,2 BaselineHighest pacing stepNitroglycerin mm X X X Nobori reference Nobori stented vessel Cypher reference Cypher stented vessel *p=0.001 for percentage change * * Hamilos et al JACC 2008 Hamilos et al Circulation CI 2008

21. Proximal vessel: change in diameter after pacing Nobori reference Nobori stented vessel Cypher reference Cypher stented vessel *P=0.03 for percentage change * *

22. NOBORI CLINICAL TRIALS Summary

23. MACE Rate in NOBORI Trials MACE = Cardiac Death, Myocardial Infarction, Clinically Driven TLR 2 Years 1 Year 3 Years

24. Key Angiographic Findings in NOBORI Trials NOBORI 1 Phase 1 N=120 NOBORI CORE N=107 NOBORI Phase 2 N=243 Noborin=85Taxusn=35Noborin=54Cyphern=53Noborin=153 Taxus n=90 Follow-up 9 months Late loss mm 0.15±0.270.33±0.340.10±0.260.12±0.430.11±0.300.32±0.50 Diameter stenosis 14±819±1013±1020±1214±821±15 Restenosis - stent 0.0%0.0%1.7%6.3%0.7%6.2% Restenosis - lesion 0.0%0.0%3.3%6.3%0.7%6.2% TLR0.0%2.90.0%4.1%0.0%1.1% TLR = Clinically driven target lesion revascularization

25. DES Efficacy Clinically Driven TLR Rate in DES Pivotal Trials Holmes et al Circulation 2004; Stone et al Circulation 2004; Leon – ACC 2004; Stone, TCT 2004; Fajadet, Circulation 2006; Fajadet PCR-2006; Chevalier et al; Eurointervention 2007; PCR 2008 *Nobori 2 years N=85 Nobori Upper Limit of 95%CI =1.2%

26. DES Safety Stent Thrombosis in Pivotal DES Trials Holmes et al Circulation 2004; Stone et al Circulations 2004; Leon – ACC 2004; Stone, TCT 2004; Fajadet, Circulation 2006; Fajadet PCR-2006; Chevalier et al; Eurointervention 2007; PCR 2008 Nobori Upper Limit of 95%CI =1.2% 0,0 0,5 0,7 1,0 0,0 0,3 0,0 0,9 0,0 0,2 0,4 0,6 0,8 1,0 1,2 0 Months1 Months1 Year2 Years % Sirius=N=533 Taxus IV-N=662 Endeavor II-N=600 Spirit II-N=225 NOBORI 1=N=363

27. CONCLUSIONS - Nobori DES clinical results Nobori stent showed non-inferiority vs Taxus and Cypher DES with respect to in-stent late loss Endothelial function showed better recovery in Nobori- than in Cypher- treated vessels at 9m  could be related to drug release kinetics, biodegradable polymer or abluminal coating The clinical evidence available to date for Nobori stent shows excellent safety and efficacy confirmed by: Very low rate of MACE, Restenosis and TLR No late stent thrombosis Long term follow-up results awaited to confirm current trends and to further explore the potential positive impact of biodegradable polymer on long term safety of this innovative DES Initial excellent results to be confirmed in ‘real-life’ setting