As presented by

Patrick W. Serruys, MD, PhD, FACCPrincipal Investigator

Thoraxcentre - Erasmus UniversityRotterdam, The Netherlands

PISCESPaclitaxel In-Stent Controlled Elution Study

4 and 12-Month Results

Bridge ElementsBridge Elements ReservoirsReservoirs Ductile HingesDuctile Hinges

CoStar™ Stent Design

CoStar™ Paclitaxel-Eluting Coronary Stent System Clinical Trials

A Stent Designed Specifically for Controlled and Targeted Drug DeliveryA Stent Designed Specifically for Controlled and Targeted Drug Delivery

Conor Stainless Steel and Cobalt Chromium Stents

Characteristic MedStent*

Stainless Steel

CoStar™

Cobalt Chromium

Design 576 Reservoirs

(17mm stent)

492 Reservoirs

(17mm stent)

Alloy 316L Stainless Steel L605 Cobalt Chromium

Strut Thickness 0.0051 inch 0.0035 inch

Crossing Profile

(3.0mm Stent)

0.046 inch 0.039 inch

Radiopacity Excellent Excellent

Polymer Type 85/15 PLGA 85/15 PLGA

Polymer Volume 515 µg 347 µg

* MedStent was the study stent for the PISCES trial* MedStent was the study stent for the PISCES trial

PISCES – Paclitaxel In-Stent Controlled Elution Study

Study Purpose:

To evaluate safety and performance of the Conor MedStent™ and determine optimal dosing of Paclitaxel in a prospective, multi-center, sequentially enrolled study involving 6 different release formulations. The proposed intended use of the MedStent is to improve and maintain arterial lumen diameter in patients with ischemic heart disease in native coronary arteries with de novo lesions.

PISCES TrialStudy Design & Patient Follow-Up

** Bi-Directional = direction of paclitaxel elution is both mural and luminal Bi-Directional = direction of paclitaxel elution is both mural and luminal+ 12 Month Angiography w/ QCA and IVUS was optional+ 12 Month Angiography w/ QCA and IVUS was optional

D 1D 110 10 µg / 5 daysµg / 5 days

Bi-Directional* ReleaseBi-Directional* ReleaseN = 30 patientsN = 30 patients

D 2D 210 µg / 10 days10 µg / 10 daysMural ReleaseMural ReleaseN = 30 patientsN = 30 patients

D 3D 310 µg / 10 days10 µg / 10 days

Bi-Directional* ReleaseBi-Directional* ReleaseN = 29 patientsN = 29 patients

D 4D 410 µg / 30 days10 µg / 30 daysMural ReleaseMural ReleaseN = 39 patientsN = 39 patients

D 5D 530 µg / 30 days30 µg / 30 daysMural ReleaseMural ReleaseN = 29 patientsN = 29 patients

D 6D 630 µg / 10 days30 µg / 10 days

Bi-Directional* ReleaseBi-Directional* ReleaseN = 30 patientsN = 30 patients

Tre

atm

ent

Arm

sT

reat

men

t A

rms

1 Month Clinical1 Month Clinical

4 Month Clinical4 Month Clinical

4 Month Angiographic4 Month Angiographicwith QCA & IVUSwith QCA & IVUS

1 Year Clinical1 Year Clinical

Baseline Angiography Baseline Angiography

1212 Month Angiographic Month Angiographicwith QCA & IVUSwith QCA & IVUS++

Do

se

Ra

ng

ing

Stu

dy

Do

se

Ra

ng

ing

Stu

dy

PISCES TrialStudy Endpoints

Safety Endpoint: A composite of MACE at 4 months

Efficacy Endpoints: Late Loss by QCA within the stent% Stent Volume Obstruction by IVUS Rate of Binary Restenosis

The data is presented as “intent to treat”.

Participating Investigators & Centers

31RotterdamP.W. Serruys

1KreuzlingenM. Pieper

23EindhovenH. Bonnier

12Rotterdam ZuidA. G. de Vries

7CaracasJ. A. Condado

191Total

8Buenos AiresJ. Belardi

10AntwerpS. Verheye

11New ZealandD. McClean

26BredaP. den Heijer

62Sao PaoloJ. E. Sousa / A. Abizaid

Patients EnrolledSite LocationInvestigator

Risk Factors per Dose

D1 D2 D3 D4 D5 D6 TotalDose/Duration/Direction 10/5/b 10/10/m 10/10/b 10/30/m 30/30/m 30/10/b

N=30 N=31 N=30 N=31 N=39 N=30 N=191

DM, % 16 16 23 16 10 33 19

HT, % 40 65 63 55 36 63 53

Dyslip, % 67 65 73 65 62 67 66

Prior MI, % 40 42 33 29 41 43 38

Prior PCI, % 7 7 10 16 15 16 12

D1 D2 D3 D4 D5 D6 TotalDose/Duration/Direction 10/5/b 10/10/m 10/10/b 10/30/m 30/30/m 30/10/b

N=30 N=31 N=30 N=31 N=39 N=30 N=191

DM, % 16 16 23 16 10 33 19

HT, % 40 65 63 55 36 63 53

Dyslip, % 67 65 73 65 62 67 66

Prior MI, % 40 42 33 29 41 43 38

Prior PCI, % 7 7 10 16 15 16 12

Release Direction: b = bi-directional, m = mural

Number of Patients 191 Patients

Total Lesions Treated 187 Lesions

Total Number of CoStar™ Stent Implanted 209 Stents

Average Number of Stents per Patient 1.1

Average Number of Stents per Lesion 1.1

Direct Stenting per Lesion 51.0%

Procedural Success 92.7%

Device / Technical Success 95.3%

PISCES TrialProcedural Data

N = 191 Patients

Age in Years (mean ± SD) 59.1 ± 9.2

Gender (% Male) 70.2 (134)

History of Smoking 76.0% (145)

Diabetes Mellitus 18.8% (36)

Hypertension 52.9% (101)

Dyslipidemia 66.0% (126)

Prior MI 38.2% (73)

Prior CABG 2.6% (5)

Prior PCI 12.0% (23)

PISCES TrialBaseline Patient Demographics

N = 187 Lesions

Target Lesion Location

LAD

RCA

LCX

46.0% (86)

31.6% (59)

22.6% (42)

Reference Vessel Diameter 2.72 + 0.43 mm

Lesion Length (visual) 11.6 + 2.71 mm

Percent Diameter Stenosis (visual) 80.0% + 13.0%

ACC Classification

A

B1 / B2

C

26.2% (49)

72.1% (135)

1.6% (3)

PISCES TrialBaseline Lesion Demographics

C

Proximal

D

5 mm17 mm 5 mm

In-Stent

Peri-Stent

Total Vessel

Side Branch

Side Branch

Distal

vessel

QCA Analysis - Methodology

In-Stent Binary Restenosis at 4 Months

%%

N=26N=26N=38N=38N=43N=43 N=29N=29 N=28N=28N=28N=28 N=29N=29

11.611.610.310.3 10.710.7

3.63.6

6.96.9

00

3.83.8

00

55

1010

1515

D0D0 D1D1 D2D2 D3D3 D4D4 D5D5 D6D6

10/5/b10/5/b 10/10/b10/10/bBareBare 10/10/m10/10/m 10/30/m10/30/m30/10/b30/10/b 30/30/m30/30/m

0

5

10

15

D0 D1 D2 D3 D4 D5 D6

In-Stent Binary Restenosis at 4 and 12 Months

Cumulative

%%

00 00

5.65.6

N=18N=18N=32N=32

5.65.6

10/30/m10/30/m 30/30/m30/30/m

0.88

0.720.67

0.48

0.380.30

0.70

0

0.2

0.4

0.6

0.8

1

D0 D1 D2 D3 D4 D5 D6

In-Stent Late Loss at 4 Months(m

m)

(mm

)

N=26N=26N=38N=38N=43N=43 N=29N=29 N=28N=28N=28N=28 N=29N=29

10/5/b10/5/b 10/10/b10/10/bBareBare 10/10/m10/10/m 10/30/m10/30/m30/10/b30/10/b 30/30/m30/30/m

0

0.2

0.4

0.6

0.8

1

D0 D1 D2 D3 D4 D5 D6

(mm

)In-Stent Late Loss at 4 and 12 MonthsSerial Analysis

0.400.40

0.320.32

0.520.52

0.360.36

p=0.01p=0.01 p=0.53p=0.53

N=32N=32 N=18N=18

Late loss of patients undergoing TLR at 4 months (D5=0, D6=1) is

imputed as the value of late loss at 12 months.

10/30/m10/30/m 30/30/m30/30/m

44

31 3125

1611

8

0

10

20

30

40

50

D0 D1 D2 D3 D4 D5 D6

Neo-Intimal Volume at 4 Months(m

m(m

m33 ))

N=21N=21N=37N=37N=39N=39 N=28N=28 N=27N=27N=23N=23 N=26N=26

10/5/b10/5/b 10/10/b10/10/bBareBare 10/10/m10/10/m 10/30/m10/30/m30/10/b30/10/b 30/30/m30/30/m

Neo-Intimal Volume at 4 and 12 MonthsSerial Analysis

(mm

(mm

33 ))

111199

18181414

p=0.0004p=0.0004 p=0.29p=0.29

N=15N=15N=30N=30

0

10

20

30

40

50

D0 D1 D2 D3 D4 D5 D6

10/30/m10/30/m 30/30/m30/30/m

In-Stent % Volume Obstruction at 4 Months

26

2220

17

12

85

0

10

20

30

D0 D1 D2 D3 D4 D5 D6

%%

N=21N=21N=37N=37N=39N=39 N=28N=28 N=27N=27N=23N=23 N=26N=26

10/5/b10/5/b 10/10/b10/10/bBareBare 10/10/m10/10/m 10/30/m10/30/m30/10/b30/10/b 30/30/m30/30/m

In-Stent % Volume Obstruction at 4 and 12 MonthsSerial Analysis

0

10

20

30

D0 D1 D2 D3 D4 D5 D6

%%77 66

1212

88

p=0.0004p=0.0004 p=0.31p=0.31

N=15N=15N=30N=30

10/30/m10/30/m 30/30/m30/30/m

MACE at 4 and 12 Months

%%

0

5

10

15

20

25

D0 D1 D2 D3 D4 D5 D6

8

17.2

20.7

6.7

13.3

6.7

10

2.6

5.13.4

6.9

Between 4 and 12 months, 1 non Q-wave MI occurred in D5 in a non-Between 4 and 12 months, 1 non Q-wave MI occurred in D5 in a non-target vessel and 1 Q-wave MI (total occlusion of target lesion) in D6.target vessel and 1 Q-wave MI (total occlusion of target lesion) in D6.

16.7

10/5/b10/5/b 10/10/b10/10/bBareBare 10/10/m10/10/m 10/30/m10/30/m30/10/b30/10/b 30/30/m30/30/m

N=29N=29N=39N=39N=50N=50 N=30N=30 N=30N=30N=29N=29 N=30N=30

TLR at 4 and 12 Months

%%

0

5

10

15

D0 D1 D2 D3 D4 D5 D6

10/30/m10/30/m

N=29N=29N=39N=39N=50N=50 N=30N=30 N=30N=30N=29N=29 N=30N=30

6.96.9

3.43.400 00

30/30/m30/30/m

Proximal and Distal Edge Late Loss at 4 and 12 Months - Serial Analysis

0.07

0.33

0.120.12

0

0.2

0.4

0.6

0.8

1

proximal distal

p=0.44p=0.44 p=0.97p=0.97

p=0.10p=0.10 p=0.69p=0.69

D5D5

D6D6

0.220.27

0.110.10

0

0.2

0.4

0.6

0.8

1

proximal distal

Conclusions

This study represents one of the most comprehensive analyses of pharmacokinetic releases ever performed in a FIM Study.

The safety profile of this system - using an erodable polymer and delivering 100% of the drug is within the accepted standards.

Protocol called for 6 months Plavix therapy. There were no reported cases of delayed stent thrombosis in the interval period.

Although the doses used were substantially less than paclitaxel-coated stents, the inhibition of neo-intimal hyperplasia was similar.

Conclusions

In the 2 long release (most effective) formulations the TLR and MACE rates remained low at 12 months.

In D5, there was 0% in stent restenosis at both 4 and 12 months and in D6 the restenosis rate remained 5.6%.

There was a modest but statistically significant increase in neo-intimal volume, % in-stent obstruction and late loss between 4 months and 12 months in D5 but not in D6. The TLR and restenosis rates in the D6 group were not as good as in D5.

These 2 pharmacokinetic profiles are currently under investigation in the Eurostar trial with a thin strut cobalt chromium stent and 33% less polymer volume.