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.

4

1068

1-00

0 –

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

BioMatrix BioMatrix FlexBioMatrix II

Biodegradable Polymer and Primer Coating

FUTURE 1 and 2 STEALTH FIM

BEACON Registry

STEALTH PK LEADERS

Matrix: Polylactic AcidMatrix: Polylactic Acid Matrix: Polylactic Acid

Primer: ParylenePrimer: Parylene No Primer

StentStentStent

Source: S. Windecker, PCR 2008

6

107

17-0

00

– R

ev.0

1

7

1o endpoint: CV death, MI, clinically-indicated TVR (9 month)2o endpoints: Death, CV death, MI, TLR, TVR

Stent thrombosis according to ARC Angiographic study: In-stent % diameter stenosis

Late loss, binary restenosis

BESBioMatrix Flex N=850

SESCypher Select N=850

Trial DesignStable and ACS Patients Undergoing PCI

N=1700 Patients

1:3 Randomisation

Clinical F/UN=640

Angio F/UN=210

Clinical F/UN=640

Angio F/UN=210

Assessor-blind 1:1 Randomisation

DAPT recommended for 12 month

8

0

5

10

15

0 1 2 3 4 5 6 7 8 9

Months of Follow-up

Cum

ulat

ive

Inci

denc

e (%

)

SES 10.5%

BES 9.2%

Pnon-inferiority = 0.003

Primary EndpointCardiac Death, MI and TVR @ 9 Months2

BES reached its primary endpoint2Windecker S. et al., The Lancet 2008; 372 No. 9644: 1163-1173

-12%

9

MACE

MACE = Cardiac Death, MI, or Clinically-Indicated TVR

%

Number at risk

BES 857 804 795 777 760 742 731 725 716

SES 850 791 786 771 747 727 712 707 694

Months

13.0%

15.4%

2-year HR0.84 [0.65 to 1.08]

P = 0.18*

Δ 2.4%12.1%

10.7%

1-year HR0.88 [0.66 to 1.17]

P = 0.37*

Δ 1.4%

0

5

10

15

20

0 3 6 9 12 15 18 21 24

* P values for superiority

BESSES

10

Cardiac Death or MI

Months

%

1-year HR1.01 [0.70 to 1.45]

P = 0.95*

6.9%

6.9% Δ0%

8.3%

9.1%

2-year HR0.92 [0.66 to 1.27]

P = 0.59*

Δ0.8%

0

2

4

6

8

10

0 3 6 9 12 15 18 21 24

BESSES

Number at risk

BES 857 804 797 788 780 772 764 760 752

SES 850 801 798 793 779 770 758 755 742

*P values for superiority

11

Superior Strut Coverage and Stent Apposition3

•Lesions with at least 5% uncovered struts

3.6

39.4

0

10

20

30

40

50

BES (N=26) SES (N=20)

•Lesions with at least 5% malapposed struts

p = 0.005

10 x10 x

N strut = 6476 N strut = 4592

0.3

6.7

012345678

BES (N=26) SES (N=20)

p = 0.04

20 x20 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

3Di Mario C., TCT 2008

% %

12

Very Late Stent Thrombosis

Signs of Safety Benefits Beyond One Year

0.0

0.5

1.0

1.5

2.0

2.5

3.0

0 3 6 9 12 15 18 21 24

Definite ST through 2 years%

2.0%

2.0%

2.2%

2.5%

+0.2%

Zoom at 1% scale

+0.5%BESSES

14

Advantage in Complex Patients

15

Complex Patients – STEMI12 Month MACE

6.7

4.4

2.21.5

15.7

10

56.4

0

2

4

6

8

10

12

14

16

18

Cardiac death MI ci-TVR MACE

BES

SES

Buszman, P., PCR 2009

Superior clinical outcomes for the BES vs. SES up to 12 months

%

p=0.04 p= 0.22

p=0.07 p=0.02

-57%

-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

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

0 10 20 30 40 50

Cu

mu

lativ

e R

ele

ase

(%

)

Time (Hrs)

Biolimus A9 Elution from Stents

(MEDIUM: PBS pH 7.4/Tween, 37°C)

Biomatrix

Polymerless

4 Month Late Lumen Loss

P= 0.002

P< 0.0001

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.

Rue de Lausanne 29 – 1110 MORGES – SwitzerlandTel. (41) 0 21 804 80 00 – Fax (41) 0 21 804 80 01customer@biosensors.com