John E Shulze, CTOBiosensors International Inc

Drug Application in Stent Technology:How to Diversify?

My Conflicts of interest are:

Chief Technology Officer

and a shareholder of

Biosensors International Inc.1

(1Biosensors’ development pipeline products to be discussed

in this Presentation)

BIOLIMUS A9™ DRUGRAPAMYCIN DERIVATIVE

Developed specifically for stent application by Biosensors

Potent immunosuppressive and anti-inflammatory properties

LIPOPHILICITY COMPARISON

Highest lipophilic and hydrophobic properties of commercially available limus drugs

Mainly localized effects, minimal drug release into bloodstream

BIOLIMUS A9™ DRUGBiosensors’ proprietary rapamycin derivative

Highest lypophilicity of the common limus drugs1

BIODEGRADABLE PLASimultaneous PLA biodegradation and BA9™ elution

No PLA /BA9™ coating on the stent after 6 to 9months2

The Abluminal Biodegradable Polymer DES

ABLUMINAL BIODEGRADABLE COATINGEarly BMS-like endothelial coverage1

More targeted tissue release Less systemic exposure

1 Data on file at Biosensors Intl2 In vivo testing in porcine model demonstrates abluminal coating is absorbed after 6 to 9 months - Data on file at Biosensors Intl

1081

0-00

0-E

N –

Rev

.01

Trial Design (LEADERS)

Assessor-blind 1:1 Randomisation

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

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

Late loss, binary restenosisDAPT recommended for 12 month

N=1700 Patients

SESCypher Select N=850

BESBioMatrix Flex N=850

Clinical F/UN=640

Angio F/UN=210

Clinical F/UN=640

Angio F/UN=210

1:3 Randomisation

Stable and ACS Patients Undergoing PCI3-year follow-up

(N=1,621; 95.0%)

0

5

10

15

0 1 2 3 4 5 6 7 8 9

Months of Follow-up

Cypher® Select™ 10.5%

BioMatrix Flex™ 9.2%

pnon-inferiority = 0.003

Primary EndpointMACE (Cardiac Death, MI and TVR) @ 9 Months

BioMatrix Flex™ reached its primary endpoint

Windecker S. et al., The Lancet 2008; 372 No. 9644: 1163-1173

MA

CE

%

MACE

%

Number at risk

BES 857 851 761 743 729 712 668

SES 850 846 749 732 713 686 639

Months

13.0%

15.4%

2-year HR0.84 [0.65 to 1.08]

P = 0.18*

12.1%

10.7%

1-year HR0.88 [0.66 to 1.17]

P = 0.37*

0

5

10

15

20

0 6 12 18 24

BESSES

3630

15.7%

19.0%

3-year HR0.82 [0.65 to 1.03]

P = 0.09*

*P values for superiorityMACE = Cardiac Death, MI, or Clinically-Indicated TVRSerruys, P. W., oral presentation ,TCT 2010

Definite ST through 3 years

1.0

2.0

3.0

% 2.2%

2.9%

BESSES

0 6 12 18 24 3630Months

2.2%

2.5%

2-year HR0.90 [0.48 to 1.67

P = 0.73*

2.0%

2.0%

1-year HR0.99 [0.51 to 1.94]

P = 0.98*

3-year HR0.78 [0.43 to 1.43]

P = 0.43*

0

4.0

Number at risk

BES 857 846 808 797 787 774 732

SES 850 841 801 792 779 758 715

Δ 0.0%Δ 0.3%

Δ 0.7%

*P values for superioritySerruys P.W., oral presentation, TCT 2010

PROVISIONAL STENTING USE

Micro-CT Biomatrix results

MV STENTING AFTER KISSING

MACE in Complex Patients

%

Months

8.4%

19.7%15.9%

6.8%

0

5

10

15

20

0 6 12 18 24 3630

10.0%

21.3%

3-year HR0.43 [0.23 to 0.84]

P = 0.01*

25 STEMI

%

Months

15.3%

21.8%

18.6%

12.7%

0

5

10

15

20

0 6 12 18 24 3630

17.0%

23.8%

3-year HR0.69 [0.46 to 1.04]

P = 0.08*

25 High Syntax Score (>16)

Bifurcations

%15.6%

18.9%16.4%

12.9%

0

5

10

15

20

0 6 12 18 24 3630

18.5%

23.3%

3-year HR0.79 [0.53 to 1.16]

P = 0.22*

25

16.0%

24.1%

3-year HR0.65 [0.41 to

1.03]P = 0.06*

%

15.0%

23.5%

17.1%

13.0%

0

5

10

15

20

0 6 12 18 24 3630

25

Multi-vessel

*P values for superiorityWindecker, S., oral presentation ,TCT 2010

BES

SES

BioFreedom™Selectively micro-structured surface holds drug in

abluminal surface structures

Proprietary Highly Lipophilic Limus drug

Hypothesis: Polymer-free drug release via porous-eluting stents

may reduce late events caused by polymer stent coatings.

Potential advantage

• Avoid long term late adverse effects that might be attributable to the polymer

• Improved surface integrity since there is no polymer to be sheared or peeled away from the stent struts

• Possible shorter need of dual antiplatelet therapy

Grube E., oral presentation, TCT 2010

BioFreedom FIM Design

BioFreedom FIM182 patients

12 Month Angio FU107 patients

BioFreedom standard

dose(BFD SD)

N=35

BioFreedom low

dose(BFD LD)

N=36

TAXUS® Liberté ®

N=36

Second Cohort

Enrollment PeriodJan 2009 – Jun 2009

BioFreedom standard

dose(BFD SD)

N=25

BioFreedom low

dose(BFD LD)

N=26

TAXUS® Liberté ®

N=24

4 Month Angio FU75 patients

First Cohort

Enrollment PeriodSept 2008 – Jan 2009

Angio FU 92%

12 Month Clinical FU 99%

Angio FU 92%

12 Month Angiographic FUIn-Stent Late Lumen Loss: 2nd Cohort

BFD SD BFD LD Taxus0.0

0.1

0.2

0.3

0.4

0.17[0.09, 0.39]

0.22[0.17, 0.66]

0.35[0.22, 0.57]

P = 0.001P = 0.21

Non – inferiority P values

(m

m)

N = 31 N = 31N = 35

Primary Endpoint

Grube E., oral presentation, TCT 2010All values are presented as median [IQR]

12 Month MACEAll Patients (1st + 2nd Cohorts)

BFD SD N = 60

BFD LDN = 62

TaxusN = 60

MACE*(All Death, MI, Emergent Bypass or TLR)

3 (6.1%) 7 (11.6%) 3 (5.5%)

All Death 1 (1.8%) 0 (0.0%) 0 (0.0%)

MI 1 (1.8%) 1 (1.6%) 0 (0.0%)

Q Wave MI 0 (0.0%) 0 (0.0%) 0 (0.0%)

Non-Q Wave MI 1 (1.8%) 1 (1.6%)** 0 (0.0%)

Emergent Bypass 0 (0.0%) 0 (0.0%) 0 (0.0%)

TLR 1 (1.8%) 6 (10.0%) 3 (5.5%)

All p values are non significant.Tests were performed for BFD SD vs. Taxus and BFD LD vs. Taxus.

*Time to first event**In-hospital MI

No ST event out to 12 months: ARC defined Definite, Probable or Possible!

AXXESS

The AXXESS stent

The AXXESS stent is a dedicated bifurcation stent• Nitinol self explandable stent• Using PLA/BA9™ abluminal coating technology• 4 references: 3.0 and 3.5 mm in diameter; 11

and 14 mm in lengths• 2 models: bifurcation and LM (difference in

sizes of the conical shape)

The AXXESS stent is associated to a clinical program• AXXESS Plus and DIVERGE for de novo

bifurcation• AXXENT for LM lesion

THE AXXESS stent received CE mark in August 2010• Indication: bifurcation

Restenosis in DIVERGE

Any in-Bifurcation restenosis: 6.4% (9/140 at 9 months)

Lowest restenosis rates ever reported in a bifurcation

study of any kind

Parent Vessel RS

3 pts

Side Branch RS

4pts

2 ptsBoth

What is next?

• The smallest profile drug-eluting stent system in the world

• 60% smaller than the nearest available coronary stent system.

• limus drug with a biodegradable polymer matrix

• Self-expanding ultra-thin Nitinol stent

• 0.014-inch guidewire delivery system

• unique “stent-on-the-wire” construction

• BMS System CE Marking 3/2010

Sparrow™ Microstent: designed for small vessels

Non-Sterile,

reusable, hand-held

Power Supply

Sterile,

Disposable

Adapter

Delivery

System

Stent

Lead Connection/

Wire Extension

CARE II RCT4:4:3 (80:80:60)

Total N=220 + roll in

3 Arm Sub-Set1:1:1 randomization

Sparrow DES: Sparrow BM: Micro-Driver/Driver BM

14 CentersIVUS sub-study (n = 120 @ 7

centers)

2 Arm Sub-Set1:1 randomization

Sparrow DES: Sparrow BM 4 Centers

Sparrow - BM(N=20)

Sparrow – DES(~6 ug/mm Sirolimus)

(N=20)

Sparrow DES= 80 Sparrow BM = 80 Micro-Driver/Driver = 60

Sparrow - BM(N=60)

Micro-Driver/Driver(N=60)

Sparrow – DES(~6ug/mm Sirolimus)

(N=60)

CARE II DESIGN

Primary Endpoint:In Stent Late lumen loss @ 8 mo

CARE II 8 month QCA

SES Sparrow Stent demonstrated superior in-stent LLL -

CARE II Primary Endpoint met

% CMI-SES CMI-BMS Driver

Mean (mm) 0.29±0.45 0.86±0.54 0.94±0.39

Range (mm) -0.59-1.28 -0.20-1.89 0.44-2.11

p 0.0001 < 0.0001

n 30 31 25

-10

0

10

20

30

40

CMI-SES

(n=30)

(%)

CMI-BMS

(n=31)

Driver

(n=25)

P=0.0012

Binary Restenosis(in Lesion)

6.7 4445.2

P=.00006

Abiziaid A.C. et al., TCT 2010

BA9 shows sustained Safety and Efficacy – Independent from stent platform or method of drug delivery!

Take-home message

BioMatrixTM

BioMatrixTM FlexBioFreedomTM AXXESSTM Plus Sparrow-DES Nobori

(Terumo)

Custom NXTM

(XTENT)

Stainless SteelBalloonexpandableAbluminal biodegradable polymer

Stainless SteelBalloonexpandablePolymer Free

NitinolSelf-expandableAbluminal biodegradable polymer

Designed for Bifurcations

NitinolSelf-expandableSirolimus*/PLA

Designed for small vessels

SSBA9/PLA

Cobalt-ChromeBA9/PLA

*BA9 application under development

BioMatrix Flex™ Drug Eluting Coronary Stent System is CE approvedNot available for sale in the United States and certain other countries

BioMatrix Flex, Biolimus A9 and BA9 are trademarks or registered trademarks of Biosensors International group, Ltd. in the United States and other countries

All cited trademarks are the property of their respective owners

© 2011 Biosensors International Group, Ltd. All rights reserved