BIOSENSORS-CLINICAL UPDATE “LEADERS AND BEYOND” John E Shulze, CTO BIOSENSORS INTERNATIONAL GROUP Jan 29, 2010

MY CONFLICTS OF INTEREST ARE: EMPLOYEE AND SHAREHOLDER OF BIOSENSORS INTERNATIONAL

Biosensors Research: There is an unmet market need for DES that have a high effectiveness for suppression on NH combined with a low incidence of late stent thrombosis upon cessation of antiplatelet therapies. Development of Acute & SubAcute Thrombosis in stents is multifactorial and we should expect that higher risk patients/procedures will result in more early thrombosis and perhaps greater needs for antiplatelet therapy. However, Rapid healing, leading to complete endotheliazation and return of normal endothelial function inside the stent we believe to be the most important factors in reducing risk of VLST and maybe LST. Both PLA biodegradable coating technology and “polymer free” coating technologies developed by Biosensors are intended to provide faster healing of the stent, 6-9 months in the case of BioMatrix and similar to a bare stent in the case of the Biofreedom Stent.

– Rev.01 BioMatrix™ The abluminal biodegradable polymer DES PLA biodegradation and BA9™ elution Abluminal biodegradable coating absorbed after 6-9 months * * Data on file - molecular weight<10kDa

BioMatrixBioMatrix Flex BioMatrix II Biodegradable Polymer and Primer Coating FUTURE 1 and 2 STEALTH FIM BEACON Registry STEALTH PK LEADERS Matrix: Polylactic Acid Primer: Parylene No Primer Stent Source: S. Windecker, PCR 2008

– Rev.01

7 1 o endpoint: CV death, MI, clinically-indicated TVR (9 month) 2 o endpoints:Death, CV death, MI, TLR, TVR Stent thrombosis according to ARC Angiographic study:In-stent % diameter stenosis Late loss, binary restenosis BES BioMatrix Flex N=850 SES Cypher Select N=850 Trial Design Stable and ACS Patients Undergoing PCI N=1700 Patients 1:3 Randomisation Clinical F/U N=640 Angio F/U N=210 Clinical F/U N=640 Angio F/U N=210 Assessor-blind 1:1 Randomisation DAPT recommended for 12 month

Months of Follow-up Cumulative Incidence (%) SES 10.5% BES 9.2% P non-inferiority = Primary Endpoint Cardiac Death, MI and 9 Months 2 BES reached its primary endpoint 2 Windecker S. et al., The Lancet 2008; 372 No. 9644: % MACE %

9 MACE MACE = Cardiac Death, MI, or Clinically-Indicated TVR % Number at risk BES SES Months 13.0% 15.4% 2-year HR 0.84 [0.65 to 1.08] P = 0.18* Δ 2.4% 12.1% 10.7% 1-year HR 0.88 [0.66 to 1.17] P = 0.37* Δ 1.4% * P values for superiority BES SES

10 Cardiac Death or MI Months % 1-year HR 1.01 [0.70 to 1.45] P = 0.95* 6.9% Δ0%Δ0% 8.3% 9.1% 2-year HR 0.92 [0.66 to 1.27] P = 0.59* Δ0.8% BES SES Number at risk BES SES *P values for superiority

11 Superior Strut Coverage and Stent Apposition 3 Lesions with at least 5% uncovered struts Lesions with at least 5% malapposed struts p = x N strut = 6476 N strut = 4592 p = x N strut = 6476 N strut = 4592 BES with an abluminal biodegradable polymer achieved a 10 x better strut coverage and a 20 x better stent apposition vs. SES with a symmetric durable polymer at 9 months 3 Di Mario C., TCT 2008 % %

12 Very Late Stent Thrombosis Signs of Safety Benefits Beyond One Year

Definite ST through 2 years % 2.0% 2.2% 2.5% +0.2% Zoom at 1% scale +0.5% BES SES

14 Advantage in Complex Patients

15 Complex Patients – STEMI 12 Month MACE Buszman, P., PCR 2009 Superior clinical outcomes for the BES vs. SES up to 12 months % MACE p=0.04 p= 0.22 p=0.07 p= % -77%

BIOSENSORS PRODUCT PIPELINE Changes to stent platform, stent delivery catheter, coating methods, and connector design, for the Biomatrix Flex design….. BioFreedom: complete elimination of polymer, Use of Surface texturing, yields more rapid drug clearance to enhance healing: BioMatrix BioMatrix Flex Enhance flexibility Increase stent retention

4 Month Late Lumen Loss Late Loss mm (median) P= P< In-segment P= 0.09 P = 0.32 P = 0.35 P = 0.09 P = 0.89 P = 0.99 P = 0.77 P = 0.19 P = 0.37 P = 0.71

Conclusions The biodegradable PLA polymer with complete release of drug and polymer within 6-9 months differentiates the Biolimus eluting stents from other DES with limus drugs eluted from durable polymers The abluminal surface coating manufacturing technology reduces the polymer exposure compared with symmetric coatings

Conclusions The clinical trial program demonstrates that Biolimus A9 released from a biodegradable PLA coating is a safe antiproliferative combination for use in DES. The clinical studies in both simple and complex lesions have consistently achieved or exceeded clinical endpoints compared to BMS and other approved DES with: -low MACE at various clinical endpoints up to and including 4 years -low %DS & late loss -no very late Thrombosis Clinical Trial data is currently available in the Biolimus program in over 4000 patients, and during 2010, additional >5000 patients (e-BioMatrix). Ongoing and planned clinical trials in an additional >5000 patients will evaluate the durability of the BioMatrix results in large populations and in a wide range of more complex patients and lesion subsets incl AMI.

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