1. Update on the BioMatrix Program
John E Shulze, CTO
Biosensors International Inc. 1

2. My conflicts of interest are:
Chief Technology Officer
and a shareholder of
Biosensors International Inc.

3. Biolimus is a semi-synthetic sirolimus analogue with 10x higher lipophilicity and similar potency as sirolimus.
Biolimus is immersed at a concentration of 15.6 g/mm into a biodegradable polymer, polylactic acid, and applied solely to the abluminal stent surface by a fully automated process.
Biolimus is co-released with polylactic acid and completely desolves into carbon dioxide and water after a 6-9 months period.
The stainless steel stent platform has a strut thickness of 120 m with a quadrature link design.

4. Biolimus A9™
Released from a PLA Biodegradable polymer abluminal coating, BA9 shows sustained safety and efficacy independent from stent platform!
BioMatrixTM
BioMatrixTM Flex
BioFreedomTM
AXXESSTM
Nobori
(Terumo)
Custom NXTM (XTENT)
Stainless Steel
Balloonexpandable
Abluminal biodegradable polymer
Polymer Free
Nitinol
Self-expandable
Designed for Bifurcations SS
BA9/PLA
Cobalt-Chrome
PRODUCTS NOT AVAILABLE
FOR SALE IN USA

6. LEADERS ‘all-comers’ Trial Design
1o endpoint: MACE: Cardiac death, MI, clinically-indicated TVR (9 mo)
2o endpoints: Death, CV death, MI, TLR, TVR
Stent thrombosis according to ARC Angiographic study: In-stent % diameter stenosis (9 mo)
Late loss, binary restenosis
DAPT recommended for 12 months
BioMatrix Flex™ (BES) N=850
Cypher® Select™ (SES) N=850
Stable and ACS Patients Undergoing PCI
N=1700 Patients
10 European centers
1:3 Randomisation
Clinical F/U
N=640
Angio F/U
N=210
Assessor-blind
1:1 Randomisation 6

7. Patient Demographics BES SES 857 Patients 850 Patients
Age in years 65   11
Male gender 75% 75%
Arterial hypertension 74% 73%
Diabetes mellitus 26% 23%
- insulin-dependent 10% 9%
Hypercholesterolemia 65% 68%
Family history of CAD 40% 44%
Smoking 24% 25%
Previous MI 32% 33%
Previous PCI 36% 37%
- with drug-eluting stent 12% 14%
Previous CABG 11% 13%

8. Patient Flow - Clinical
SES (N=850)
Randomized
(N=1,707)
BES (N=857)
1-year follow-up
(N=1,669; 97.8%)
BES (N=839)
SES (N=830)
2-year follow-up
(N=1,657; 97.1%)
BES (N=819)
BES (N=832)
SES (N=825)
3-year follow-up
(N=1,636; 95.8%)
SES (N=817)
BES (N=838)
4-year follow-up
(N=1,663; 97.4%)
5-year follow-up
(N=1,647; 96.5%)
BES (N=833)
SES (N=814)
24 Lost to FU
8 lost to FU and alive
16 lost to FU and vital status unknown
12 withdrew
13 Lost to FU
2 lost to FU and alive
11 lost to FU and vital status unknown
11 withdrew
Serruys et al., oral abstract presentation, TCT 2012

9. MACE (Cardiac Death, MI and ci-TVR)
Number at risk
SES
850
774
738
718
701
676
655
640
616
589
572
BES
857
780
749
733
723
710
697
675
657
635
618
MACE = cardiac death, MI, or clinically-indicated TVR
* p-value for superiority
Serruys et al., oral abstract presentation, TCT 2012

10. Patient Oriented Composite Endpoint (All-cause Death, Any MI, All Revascularization)
Number at risk
SES
850
729
661
637
618
594
569
551
530
504
491
BES
857
749
689
672
654
639
619
597
579
557
540
POCE = all death, MI, any revascularization (includes adjudicated and non-adjudicated events)
* p-value for superiority
Serruys et al., oral abstract presentation, TCT 2012

11. Definite Stent Thrombosis (ARC)
Number at risk
SES
850
816
801
787
776
759
749
732
717
696
678
BES
857
819
804
792
780
775
757
747
730
* p-value for superiority
Serruys et al., oral abstract presentation, TCT 2012

12. Effect of DAPT Discontinuation
Overall Population
Patient who d/c DAPT
P = 0.062*
P = 0.030*
P = 0.020* %
N=22/857
N=36/850
N=0/160
N=6/165
N=2/595
N=10/572
* p-value for superiority (Fisher Exact Test) Serruys et al., oral abstract presentation, TCT 2012

13. Räber L et al., JAMA. 2012; 308(8):

14. COMFORTABLE AMI Trial Räber L et al., JAMA. 2012; 308(8): 777-87
1161 Patients with STEMI
4 pts provided preliminary but refused definite consent
1:1 randomization
Biolimus-eluting stent (BES)
575 Patients with 633 lesions
Bare-metal stent (BMS)
582 Patients with 649 lesions
11 lost to follow-up
4 refused follow-up
11 lost to follow-up
5 refused follow-up
560 patients followed-up
at 1 year (97.4%)
566 patients followed-up
at 1 year (97.2%)

15. Primary Endpoint – MACE
@ 1 Year 2 4 6 8 10
MACE (%)
575
543
541
540
537
534
530
BES
582
546
539
531
525
519
514
BMS
No at risk 60
120
180
240
300
365
Days since index procedure
BES 4.3 %
BMS 8.7 %
1 yr HR
0.49 ( )
P=0.004
Clinical outcomes were adjudicated by an independent and blinded CEC
Räber L et al., JAMA. 2012; 308(8):

16. 2nd Endpoint – Cardiac Death10
1 yr HR
0.81 ( )
P=0.53 8 6
Cardiac Death (%)
BMS 3.5 % 4 2
BES 2.9 % 60
120
180
240
300
365
No at risk
Days since index procedure
BMS
582
558
556
551
549
545
542
BES
575
549
547
546
544
542
538
Clinical outcomes were adjudicated by an independent and blinded CEC
Räber L et al., JAMA. 2012; 308(8):

17. 2nd Endpoint – TV-Reinfarction10
1 yr HR
0.20 ( )
P=0.01 8 6
TV-MI (%) 4
BMS 2.7 % 2
BES 0.5 % 60
120
180
240
300
365
Days since index procedure
No at risk
BMS
582
548
545
539
538
534
530
BES
575
547
545
544
542
539
535
Clinical outcomes were adjudicated by an independent and blinded CEC
Räber L et al., JAMA. 2012; 308(8):

18. 2nd Endpoint – ID-TLR 1 yr HR 0.28 (0.13-0.59) P<0.001 10 8 6
Ischemia-driven TLR (%)
BMS 5.7 % 4 2
BES 1.6 % 60
120
180
240
300
365
Days since index procedure
No at risk
BMS
582
547
540
532
526
520
515
BES
575
543
541
540
537
534
530
Clinical outcomes were adjudicated by an independent and blinded CEC
Räber L et al., JAMA. 2012; 308(8):

19. (death, reinfarction, any revascularization)
Patient oriented 2nd EP
(death, reinfarction, any revascularization) 15
1 yr HR
0.68 ( )
P=0.04
BMS 12.2 % 10
Cumulative incidence (%)
BES 8.4 % 5 60
120
180
240
300
365
Days since index procedure
No at risk
BMS
582
538
532
517
509
502
497
BES
575
536
530
525
520
515
509
Clinical outcomes were adjudicated by an independent and blinded CEC
Räber L et al., JAMA. 2012; 308(8):

20. ARC Definite Stent Thrombosis5
1 yr HR
0.42 ( )
P=0.10 4 3
Definite Stent Thrombosis (%) 2
BMS 2.1 % 1
BES 0.9 % 60
120
180
240
300
365
Days since index procedure
No at risk
BMS
582
547
545
540
538
534
481
BES
575
545
543
542
540
538
494
Clinical outcomes were adjudicated by an independent and blinded CEC
Räber L et al., JAMA. 2012; 308(8):

21. Biolimus-eluting stent (BES)
GLOBAL LEADERS
Primary endpoint: Study Treatment strategy superior to reference treatment strategy on cumulative 2 year composite of all cause mortality and new Q-wave MI
Study Treatment Strategy
Reference Treatment Strategy
All-Comers PCI Population
ACS and Elective/Stable Patients
N =16’000
1:1 Randomization, Open-Label Design
Biolimus-eluting stent (BES)
BioMatrix Flex™
ASA
Ticagrelor
Ticagrelor
ASA
Clopidogrel
12 months DAPT
ACS pts (ASA + Ticagrelor)
Elective pts (ASA + Clopidogrel)
1 month ASA + Ticagrelor
23-months monotherapy Ticagrelor
12-months monotherapy ASA

22. Biosensors’ DES Program

23. Thank you!

24. BIOFREEDOM IS CE APPROVED.
Selectively micro-structured surface holds drug in abluminal surface structures
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
BIOFREEDOM IS CE APPROVED.
Proprietary Highly Lipophilic Limus drug

25. In-Stent LLL at 12 Months FU
2nd Cohort – PRIMARY ENDPOINT
P = 0.001* (p=0.11**)
P = 0.21* (p=0.55**)
(mm)
N = 31
N = 35
N = 31
*Non-inferiority tests based on the mean. **Superiority tests.
All values are presented as median [IQR].
Grube E., oral presentation, TCT 2010

26. All patients – 1st and 2nd Cohorts (96.1%)
36-Month Outcomes
All patients – 1st and 2nd Cohorts (96.1%)
EVENT
BFD SD
N = 60
BFD LD
N = 62
TAXUS
MACE
(All Death, MI, Emergent Bypass or TLR)
7(11.9%)
11(18.1%)
6(10.0%)
All Death
3(5.1%)
2(3.3%)
1(1.7%) MI
2(3.4%)
Q Wave MI
0(0.0%)
Non-Q Wave MI
Emergent Bypass
TLR
3(5.2%)
8(13.2%)
4(6.7%)
Definite/probable stent thrombosis (ARC)
All P values are non-significant.
Tests were performed for BFD SD vs. TAXUS and BFD LD vs. TAXUS.
Grube TCT 2012

27. Biofreedom Presentation (Grube) TODAY/time: 1:30PM PALLADIAN BALLROOM