Safety and Efficacy of Biolimus A9 Eluting Stent with Biodegradable Polymer in Real Life NOBORI 2 Trial: Primary Endpoi

1. Safety and Efficacy of Biolimus A9 Eluting Stent with Biodegradable Polymer in Real LifeNOBORI 2 Trial: Primary Endpoint DataDr. Gian Battista Danzi Ospedale Maggiore Policlinico, Milan, Italy M. Wiemer, R. Koning, A. Serra, K. E. Hauptmann, P. Kala, D. Carrie, F. Fath-Ordoubadhi, J. Goicolea, W. Wijns, J.J. Koolen, B. Chevalier on behalf of NOBORI 2 investigators

2. Speakers’s name: ❒ I have the following potential conflicts of interest to report: ❒ Consulting ❒ Employment in industry ❒ Stockholder of a healthcare company ❒ Owner of a healthcare company ❒ Other(s) ❒ I do not have any potential conflict of interest

3. INTRODUCTION • Pivotal DES trials enrolled selected patients population, not truly representative of every day practice • The use of drug eluting stents (DES) in contemporary PCI practice is not restricted to approved indications and the safety of this approach is not fully established • Therefore, we initiated a large study to assess in a real life setting, the usage pattern and outcomes of patients treated with Nobori DES

4. Nobori DES Components Excellent Flexibility and Scaffolding Optimal Side Branch Access Delivery System with Hydrophilic M-coating Biolimus A9™ (rapamycin derivative) Prevents Smooth Muscle Cell Proliferation • Highly Lipophilic with Optimal Local Tissue Uptake • Biodegradable polymer Abluminal Coating • Precise Drug Release Kinetics

5. Patient is ≥ 18 years old; Patient is, according to routine hospital practice, eligible for percutaneous coronary intervention using DES (and RVD matches available Nobori® DES sizes); Patient or the patient’s legal representative has been informed of the nature of the study and agrees to its provisions and has provided written informed consent as approved by the Institutional Review Board/Ethics Committee of the respective clinical site, wherever such requirement exists. NOBORI 2Eligibility criteria

6. NOBORI 2 Study Patient population • 3068 consecutive patients treated with, Nobori DES in 125 centres in Europe and Asia are included. • Patients are automatically allocated to 2 prespecified groups based on baseline lesions/patients characteristics : • On-label group included patients with characteristics similar to patients enrolled in pivotal clinical trials • Off-label group included all patients not fulfilling eligibility criteria for those trials

7. Clinical Follow-Up 1m 6m 12m 2y 3y 4y 5y NOBORI 2 Study Design 12 Months FUP = 97% • Primary Endpoint: Target Lesion Failure at 12 months post-procedure • Cardiac death, • Myocardial infarction (Q-wave and non-Q-wave not clearly • attributable to non-target vessel), • Clinically driven target lesion revascularization

8. NOBORI 2 Study Study Organization • PI: Dr. G.B. Danzi • Executive Operational Committee: • B. Chevalier • P. Urban • W. Wijns • M. Wiemer • J. Goicolea • A. Serra • Monitoring • 100% monitoring on-line, 30% on-site • EMCD and independent monitors • Study management: Terumo • Data management • Electronic data collection KIKA Medical • Steering Committee: • E. Stabile • K. E. Hauptmann • P. Kala • J. Koolen • R. Koning • F. Fath-Ordoubadi • D. Carrie • CEC: • C. Hanet • G. Stankovic • J. Vos • A. Vogt • B. Rensing • C. J. Royaards • Angiographic Corelab: • MCR – Milan • CorExperts - Belgrade • Sponsor: Terumo

9. AMI 18.6 % LM 2.0 % Chronic renal failure 3.0 % Bifurcation 21.9 % Calcification 38.0 % Diabetes 28.9 % Direct stenting 40.3 % Graft 2.4 % Multi-vessel 53.3 % Multi-stenting/lesion 26.4 % Ostial/aorto-ostial 14.3 % Thrombus 9.8 % CTO 3.2 % NOBORI 2 Trial “REAL WORLD” Occlusion 10.1%

10. NOBORI 2 StudyBaseline Demographics

11. NOBORI 2 StudyClinical Presentation

12. NOBORI 2 StudyProcedural Characteristics

13. NOBORI 2 StudyLesion Location P-value <0.001

14. NOBORI 2 Study Lesion Characteristics

15. NOBORI 2 Study QCA Quantitative Data

16. NOBORI 2 Study1 Year Clinical Outcomes TLF: Cardiac death, MI target vessel related, TLR; MACE: Cardiac death, MI, TVR;

17. NOBORI 2 Study 1 Year TLF in Pre-specified Patient/Lesions Subgroups N = 675 N = 889 N = 1153 N = 846 N = 249 N = 98 N = 671 N=838 TLF = Target Lesion Failure (Cardiac death, MI target vessel related, TLR)

18. NOBORI 2 StudyStent Thrombosis p=NS Early = acute +subacute Definite and Probable ST, ARC definitions

19. NOBORI 2 StudyConclusions Despite inclusion of 71% of patients treated for Off-Label indications, results were similar to pivotal trials Across subsets of challenging lesions and high-risk patient subgroups excellent acute results and low rates of TLF and particularly late stent thrombosis have been observed at one year follow-up The results of this largest so far series of consecutive patients give further indication of potential benefit of Nobori DES with biodegradable polymer and abluminal coating for treatment of patients with CAD

20. ATLAS* e-FIVE e-CYPHER SPIRIT V NOBORI 2 vs. Other DES Registries MACE Rate (%) and 95% Confidence Interval 3.7 NOBORI 2 5.1 7.5 5.8 11.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Confidence Interval (%) MACE for this analysis = Cardiac Death, MI and TLR * Half of the patients had angiographic FU

21. Complexity of the patients *NOBORI 2 and ATLAS by QCA, others by investigators judgment ** Treated

22. NOBORI 2 StudyPredefined Patient/Lesions subgroups

23. NOBORI 2 Study1 Year Clinical Outcomes TLF = Target Lesion Failure (Cardiac death, MI target vessel related, TLR)