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

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

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.

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

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

Patient Demographics BES SES 857 Patients 850 Patients Age in years 65  11 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%

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

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

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

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

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

Räber L et al., JAMA. 2012; 308(8): 777-87

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%)

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 (0.30-0.80) P=0.004 Clinical outcomes were adjudicated by an independent and blinded CEC Räber L et al., JAMA. 2012; 308(8): 777-87.

2nd Endpoint – Cardiac Death 10 1 yr HR 0.81 (0.42-1.56) 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): 777-87.

2nd Endpoint – TV-Reinfarction 10 1 yr HR 0.20 (0.06-0.69) 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): 777-87.

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): 777-87.

(death, reinfarction, any revascularization) Patient oriented 2nd EP (death, reinfarction, any revascularization) 15 1 yr HR 0.68 (0.47-0.98) 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): 777-87.

ARC Definite Stent Thrombosis 5 1 yr HR 0.42 (0.15-1.19) 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): 777-87.

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

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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

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

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

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