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John E Shulze, CTO
Biosensors 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™ DRUG
RAPAMYCIN 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
10810-0
00-E
N –
Rev.0
1
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 restenosis
DAPT recommended for 12 month
N=1700
Patients
SES
Cypher Select N=850
BES
BioMatrix Flex N=850
Clinical F/U
N=640
Angio F/U
N=210
Clinical F/U
N=640
Angio F/U
N=210
1:3 Randomisation
Stable and ACS Patients Undergoing PCI
3-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
BES
SES
3630
15.7%
19.0%
3-year HR0.82 [0.65 to 1.03]
P = 0.09*
*P values for superiority
MACE = Cardiac Death, MI, or Clinically-Indicated TVR
Serruys, P. W., oral presentation ,TCT 2010
Definite ST through 3 years
1.0
2.0
3.0
% 2.2%
2.9%
BES
SES
0 6 12 18 24 3630Months
2.2%
2.5%
2-year HR
0.90 [0.48 to 1.67
P = 0.73*
2.0%
2.0%
1-year HR
0.99 [0.51 to 1.94]
P = 0.98*
3-year HR
0.78 [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 superiority
Serruys 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 HR
0.69 [0.46 to 1.04]
P = 0.08*
25High 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 HR
0.79 [0.53 to 1.16]
P = 0.22*
25
16.0%
24.1%
3-year HR
0.65 [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 superiority
Windecker, 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 Period
Jan 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 Period
Sept 2008 – Jan 2009
Angio FU 92%
12 Month Clinical FU 99%
Angio FU 92%
12 Month Angiographic FUIn-Stent Late Lumen Loss: 2nd Cohort
0.17[0.09, 0.39]
0.22[0.17, 0.66]
0.35[0.22, 0.57]
0.0
0.1
0.2
0.3
0.4
BFD SD BFD LD Taxus
P = 0.001
P = 0.21
Non – inferiority
P values
(mm
)
N = 31 N = 31N = 35
Primary Endpoint
Grube E., oral presentation, TCT 2010
All values are presented as median [IQR]
12 Month MACEAll Patients (1st + 2nd Cohorts)
BFD SD
N = 60
BFD LD
N = 62
Taxus
N = 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 pts
Both
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-Set
1:1:1 randomization
Sparrow DES: Sparrow BM:
Micro-Driver/Driver BM
14 Centers
IVUS sub-study (n = 120 @ 7
centers)
2 Arm Sub-Set
1:1 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
FlexBioFreedom
TMAXXESS
TMPlus Sparrow-DES Nobori
(Terumo)
Custom
NXTM
(XTENT)
Stainless SteelBalloonexpandable
Abluminal
biodegradable
polymer
Stainless SteelBalloonexpandable
Polymer Free
Nitinol
Self-expandable
Abluminal
biodegradable
polymer
Designed for
Bifurcations
Nitinol
Self-
expandable
Sirolimus*/PLA
Designed for
small vessels
SS
BA9/PLA
Cobalt-Chrome
BA9/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