1. EuroSTAR II The European Randomized CoStar Trial: Cobalt-Chromium Paclitaxel-eluting Stent vs. identical BMS EuroSTAR II The European Randomized CoStar ™ Trial: Cobalt-Chromium Paclitaxel-eluting Stent vs. identical BMS Sigmund Silber, MD, FACC, FESC Cardiology Practice and Hospital Munich, Germany sigmund@silber.com

2. Disclosure EuroSTAR II Consulting fees and honoraria from various companies, No stocks or patents, no conflict of interest related to this presentation

3. CoStar ™ Stent Platform UniStar™ Cobalt Chromium stent platform PLGA Bioresorbable polymer Paclitaxel EuroSTAR II

4. No residual polymer following tissue removal at 180 days CoStar ™ Resorbable Polymer- Animal Data Explant In-vivo porcine model EuroSTAR II

5. CoStar™ Stent Design Bridge Elements Reservoirs Ductile Hinges Alternating hexagonal pattern EuroSTAR II

6. CoStar™ Stent Design Bridge Elements Reservoirs Ductile Hinges Alternating hexagonal pattern EuroSTAR II highly deliverable

7. CoStar™ Stent Design Bridge Elements Reservoirs Avoid possible cracking of polymer EuroSTAR II Ductile Hinges

8. The Power of Reservoir Technology Single Drug Structure Multiple Drug Structures Drug Delivery Reservoirs Bi-Directional Uni-Directional SingleAdjacent EuroSTAR II

9. Objective: To compare the the CoStar ™ Paclitaxel- Eluting Coronary Stent System to the same stent without a drug or polymer. Dose: 10 µg / 30 days (in-vitro) EuroSTAR II Trial Prospective, Multi-Center, Randomized, Study of the CoStar™ Paclitaxel- eluting Coronary Stent System in Patients with De Novo Lesions of Native Coronary Arteries EuroSTAR II

10. Study Administration EuroSTAR II Principal Investigator: Prof. Dr. S. Silber, Munich, Germany Data Coordinating Center: DATATRAK Deutschland GmbH Bonn, Germany Steering Committee: Prof. Dr. S. Silber, Munich, Germany Dr. Suryapranata, Zwolle, Netherlands Dr. B. Chevalier, Saint-Denis, France QCA Core Lab: Bio-Imaging Technologies Leiden, The Netherlands Data Safety Monitoring Committee / Clinical Events Committee Dr. Marcus Lins, Kiel, Germany Prof. Dr. Blanchard, France Jan Bart Hak, Netherlands (Chairman) Sponsor: BIOTRONIK GmbH & Co. KG

11. Study Design Prospective, Randomized, Multi-Center European Study Lesions  25 mm in length, 2.5 – 3.5 mm diameter 303 Patients at 18 Centers UniStar™ Coronary Stent (Control Group) N = 151 CoStar ™ Paclitaxel-eluting Stent N = 152 Randomized 1:1 Antiplatelet Therapy: Clopidogrel 300 mg loading dose, 75 mg QD for  6 months Aspirin 100 mg QD for 6 months, and daily ASA indefinitely EuroSTAR II

12. Study Endpoints Primary In-segment binary angiographic restenosis at 8 months Secondary Angiographic Endpoints –In-stent late lumen loss at 8 months –In-stent and in-lesion minimum lumen diameter (MLD) Clinical Endpoints –MACE at 30 days and 8 months –Target lesion revascularization (TLR) and target vessel revascularization (TVR) at 8 months EuroSTAR II

13. Statistical Assumptions Assumptions: –5% in treatment group –15% in control group –  = 0.05 and  = 0.2 110 patients needed to provide 80% power to detect a difference in the primary endpoint of in-segment binary restenosis A total of 150 patients will be needed in each group due to an assumed 25% lost to follow-up EuroSTAR II

14. Key Inclusion Criteria Up to two discrete de-novo lesions in two native coronary arteries Stenosis between 50-99% (visual estimate) Reference vessel diameter (RVD) 2.5 – 3.5 mm Lesion length  25 mm TIMI flow 1 or higher EuroSTAR II

15. Study Investigators Investigator Investigator Site Name and Location Prof. Dr. D. Andresen Prof. Dr. D. Andresen Vivantes Klinikum Am Urban, Berlin, D Vivantes Klinikum Am Urban, Berlin, D Prof. Dr. S. Behrens Prof. Dr. S. Behrens Vivantes GmbH Reinickendorf, Berlin, D Vivantes GmbH Reinickendorf, Berlin, D Prof. Dr. H. Darius Prof. Dr. H. Darius Vivantes Klinikum Neukölln, Berlin, D Vivantes Klinikum Neukölln, Berlin, D Prof. Dr. H. D. Glogar Prof. Dr. H. D. Glogar AHK, Wien, A AHK, Wien, A Dr. S. Hoffmann Dr. S. Hoffmann Vivantes Friedrichshain, Berlin, D Vivantes Friedrichshain, Berlin, D Dr. M. Jereczek Dr. M. Jereczek Vivantes Klinikum Spandau, Berlin, D Vivantes Klinikum Spandau, Berlin, D Prof. Dr. A. Jeron Prof. Dr. A. Jeron PD Dr. B. Lauer, PD Dr. B. Lauer, Universitätsklinik, Regensburg, D Universitätsklinik, Regensburg, D Zentralklinik, Bad Berka, D Zentralklinik, Bad Berka, D Dr. K. M. J. Marques Dr. K. M. J. Marques Vu Medisch Centrum, Amsterdam, NL Vu Medisch Centrum, Amsterdam, NL Prof. Dr. C. Nienaber Prof. Dr. C. Nienaber Universitätsklinik, Rostock, D Universitätsklinik, Rostock, D Prof. Dr. G. Richardt Prof. Dr. G. Richardt Kliniken GmbH, Bad Segeberg, D Kliniken GmbH, Bad Segeberg, D Prof. Dr. S. Silber Prof. Dr. S. Silber Cardiology Practice and Hospital, Munich, D Cardiology Practice and Hospital, Munich, D Dr. T. Slagboom Dr. T. Slagboom OLVG Amsterdam, NL OLVG Amsterdam, NL Dr. H. Suryapranata Dr. H. Suryapranata Isala Klinicken Zwolle, NL Isala Klinicken Zwolle, NL Dr. M. J. Suttorp Dr. M. J. Suttorp Antonius Zh Nieuwegein, NL Antonius Zh Nieuwegein, NL Prof. Dr. W. Voelker Prof. Dr. W. Voelker Universitätsklinik, Würzburg, D Universitätsklinik, Würzburg, D Dr. M. Wiemer Dr. M. Wiemer Herzzentrum NRW, Bad Oeynhausen, D Herzzentrum NRW, Bad Oeynhausen, D Dr. B. Witzenbichler Dr. B. Witzenbichler Campus Benjamin Franklin, Berlin, D Campus Benjamin Franklin, Berlin, D EuroSTAR II

16. Study Investigators Investigator Investigator Site Name and Location Prof. Dr. D. Andresen Prof. Dr. D. Andresen Vivantes Klinikum Am Urban, Berlin, D Vivantes Klinikum Am Urban, Berlin, D Prof. Dr. S. Behrens Prof. Dr. S. Behrens Vivantes GmbH Reinickendorf, Berlin, D Vivantes GmbH Reinickendorf, Berlin, D Prof. Dr. H. Darius Prof. Dr. H. Darius Vivantes Klinikum Neukölln, Berlin, D Vivantes Klinikum Neukölln, Berlin, D Prof. Dr. H. D. Glogar Prof. Dr. H. D. Glogar AHK, Wien, A AHK, Wien, A Dr. S. Hoffmann Dr. S. Hoffmann Vivantes Friedrichshain, Berlin, D Vivantes Friedrichshain, Berlin, D Dr. M. Jereczek Dr. M. Jereczek Vivantes Klinikum Spandau, Berlin, D Vivantes Klinikum Spandau, Berlin, D Prof. Dr. A. Jeron Prof. Dr. A. Jeron PD Dr. B. Lauer, PD Dr. B. Lauer, Universitätsklinik, Regensburg, D Universitätsklinik, Regensburg, D Zentralklinik, Bad Berka, D Zentralklinik, Bad Berka, D Dr. K. M. J. Marques Dr. K. M. J. Marques Vu Medisch Centrum, Amsterdam, NL Vu Medisch Centrum, Amsterdam, NL Prof. Dr. C. Nienaber Prof. Dr. C. Nienaber Universitätsklinik, Rostock, D Universitätsklinik, Rostock, D Prof. Dr. G. Richardt Prof. Dr. G. Richardt Kliniken GmbH, Bad Segeberg, D Kliniken GmbH, Bad Segeberg, D Prof. Dr. S. Silber Prof. Dr. S. Silber Cardiology Practice and Hospital, Munich, D Cardiology Practice and Hospital, Munich, D Dr. T. Slagboom Dr. T. Slagboom OLVG Amsterdam, NL OLVG Amsterdam, NL Dr. H. Suryapranata Dr. H. Suryapranata Isala Klinicken Zwolle, NL Isala Klinicken Zwolle, NL Dr. M. J. Suttorp Dr. M. J. Suttorp Antonius Zh Nieuwegein, NL Antonius Zh Nieuwegein, NL Prof. Dr. W. Voelker Prof. Dr. W. Voelker Universitätsklinik, Würzburg, D Universitätsklinik, Würzburg, D Dr. M. Wiemer Dr. M. Wiemer Herzzentrum NRW, Bad Oeynhausen, D Herzzentrum NRW, Bad Oeynhausen, D Dr. B. Witzenbichler Dr. B. Witzenbichler Campus Benjamin Franklin, Berlin, D Campus Benjamin Franklin, Berlin, D EuroSTAR II 18 Sites in 3 European States

17. UniStar n = 151 CoStar n = 152 Age, years Age, years 65.7 ± 9.4 64.4 ± 9.2 Male, % Male, %68.974.3 Angina, % Angina, %87.484.2 Stable Angina, % Stable Angina, %74.277.3 Prior MI, % Prior MI, %27.227.0 Prior CABG, % Prior CABG, %8.62.0 Prior PCI, % Prior PCI, %31.136.8 History of Stroke or TIA, % History of Stroke or TIA, %2.74.61 Diabetes Melitus, % Diabetes Melitus, %22.526.3 Insulin Dependent, % Insulin Dependent, %41.237.5 History of Smoking, % History of Smoking, %42.446.7 History of Hyperlipidemia, % History of Hyperlipidemia, %61.661.2 History of Hypertension, % History of Hypertension, %72.265.8 LVEF, % LVEF, % 61.1 ± 12.9 62.2 ± 13.0 EuroSTAR II Demographics and Clinical Characteristics

18. QCA Analysis UniStarCoStarp-value Pre-Procedure: Pre-Procedure: RVD, mm RVD, mm 2.73 ± 0.48 2.74 ± 0.51 NS Lesion Length, mm Lesion Length, mm 15.16 ± 7.69 15.12 ± 7.58 NS MLD, mm MLD, mm 1.05 ± 0.30 1.12 ± 0.37 NS % DS, mm % DS, mm 60.93 ± 10.45 59.41 ± 0.51 NS 8-Month Follow-up: 8-Month Follow-up: MLD In-stent, mm MLD In-stent, mm 1.77 ± 0.57 2.16 ± 0.65 <0.0001 MLD In-segment, mm MLD In-segment, mm 1.69 ± 0.52 1.99 ± 0.66 0.0004 % DS In-stent % DS In-stent 36.95 ± 16.93 23.79 ± 16.33 <0.0001 % DS In-segment % DS In-segment 39.56 ± 15.04 30.18 ± 17.39 <0.0001 EuroSTAR II

19. 8-Month Binary Angiographic Restenosis 29/10312/13222/12527/89 Primary Endpoint 41.9% Reduction EuroSTAR II p=0.0002p=0.0327

20. Late Loss at 8 Months EuroSTAR II 0.81 ± 0.49 0.41 ± 0.48 0.64 ± 0.49 0.29 ± 0.50 p<0.0001

21. MACE at 30-Days EuroSTAR II MACE defined as composite of TVR, new Q- or non-Q-wave MI attributed to target vessel, or cardiac death attributed to target vessel p=NS for all comparisons

22. MACE at 8 Months EuroSTAR II p=0.0214p=0.0079p=0.0465 p=NS

23. Stent Thrombosis: Definitions per Protocol Subacute: –Abrupt vessel closure of the treatment site that results in clinical manifestations of ischemia and occlusion occurring after the patient left the cath lab but with 30 days of index procedure MI attributed to target vessel ACS with angiographic evidence of thrombus Death within 30 days that cannot be attributed to other obvious cause Late: –MI attributable to the target vessel, with angiographic documentation or thrombus or total occlusion at the target lesion 31-120 days post-procedure EuroSTAR II

24. Stent Thrombosis EuroSTAR II p=NS for all comparisons

25. The four Studies with the Cobalt-Chromium CoStar™ Stent releasing Paclitaxel 10µg/30 days (in-vitro) COSTAR I COSTAR II EUROSTAR I EUROSTAR II Principal Investigator Principal Investigator U. Kaul India M. W. Krucoff USA K. D. Dawkins UK S. Silber Germany Study Design Study DesignRegistryRandomized vs. Taxus RegistryRandomized vs. BMS Patients (Paclitaxel) Patients (Paclitaxel) n = 40 n = 989 n = 145 n = 152 RVD, mm RVD, mm 2.46 ± 0.41 2.77 ± 0.47 2.62 ± 0.54 2.74 ± 0.51 Lesion Length, mm Lesion Length, mm 15.94 ± ? 15.35 ± 6.48 10.9 ± 5.19 15.12 ± 7.58 6 - 8 Months Angiographic Results: 6 - 8 Months Angiographic Results: In-Segment RR, % In-Segment RR, %0,0 16.9 (18.7) 5.817.6 In-Stent Late Loss, mm In-Stent Late Loss, mm 0,55 ± 0,38 0.62 (0.64) 0.28 ± 0.42 0.41 ± 0.48 8 - 12 Months Clinical Results: 8 - 12 Months Clinical Results: TLR, % TLR, %1.86.62.815.1 MACE, % MACE, %7.511.08.319.7 Stent Thrombosis, % Stent Thrombosis, %00.60.70

26. The four Studies with the Cobalt-Chromium CoStar™ Stent releasing Paclitaxel 10µg/30 days (in-vitro) COSTAR II EUROSTAR II Principal Investigator Principal Investigator M. W. Krucoff USA S. Silber Germany Study Design Study Design Randomized vs. Taxus Randomized vs. BMS Patients (Paclitaxel) Patients (Paclitaxel) n = 989 n = 152 RVD, mm RVD, mm 2.77 ± 0.47 2.74 ± 0.51 Lesion Length, mm Lesion Length, mm 15.35 ± 6.48 15.12 ± 7.58 6 - 8 Months Angiographic Results: 6 - 8 Months Angiographic Results: In-Segment RR, % In-Segment RR, % 16.9 (18.7) 17.6 In-Stent Late Loss, mm In-Stent Late Loss, mm 0.62 (0.64) 0.41 ± 0.48 8 - 12 Months Clinical Results: 8 - 12 Months Clinical Results: TLR, % TLR, % 6.6 15.1 MACE, % MACE, % 11.0 19.7 Stent Thrombosis, % Stent Thrombosis, % 0.6 0 different release kinetics ?

27. The four Studies with the Cobalt-Chromium CoStar™ Stent releasing Paclitaxel 10µg/30 days (in-vitro) COSTAR II EUROSTAR II Principal Investigator Principal Investigator M. W. Krucoff USA S. Silber Germany Study Design Study Design Randomized vs. Taxus Randomized vs. BMS Patients (Paclitaxel) Patients (Paclitaxel) n = 989 n = 152 RVD, mm RVD, mm 2.77 ± 0.47 2.74 ± 0.51 Lesion Length, mm Lesion Length, mm 15.35 ± 6.48 15.12 ± 7.58 6 - 8 Months Angiographic Results: 6 - 8 Months Angiographic Results: In-Segment RR, % In-Segment RR, % 16.9 (18.7) 17.6 In-Stent Late Loss, % In-Stent Late Loss, % 0.62 (0.64) 0.41 ± 0.48 8 - 12 Months Clinical Results: 8 - 12 Months Clinical Results: TLR, % TLR, % 6.6 15.1 MACE, % MACE, % 11.0 19.7 Stent Thrombosis, % Stent Thrombosis, % 0.6 0 Angiography routinely performed at primary angiographic endpoint of 8 months Angiography 1 month after the primary clinical endpoint at 8 months

29. Conclusions EuroSTAR II is a positive trial, having reached its primary endpoint. The CoStar™ Paclitaxel-eluting stent had a significantly lower angiographic restenosis rate and a significantly lower late loss than the identically designed bare UniStar™. With comparable vessel size and comparable lesion length in the TAXUS-IV trial, in-stent late loss of the CoStar™ Paclitaxel-eluting stent in the EuroSTAR II trial was in the range of the Taxus stent. TLR, TVR and MACE were also significantly reduced. No early or late stent thromboses were seen with the CoStar™ stent. The reservoir technology combined with a completely absorbable polymer offers a great potential for further development using different drugs with modifiable optimization of release kinetics, specifically taylored to the patients’ needs. EuroSTAR II