1. The Bio-Freedom Surface Etching Polymer-Free
Ron Waksman, MD, FACC, FSCAI Professor of Medicine, (Cardiology) Georgetown University
Director, Cardiovascular Research Advanced Education
MedStar Heart &Vascular Institute, Washington DC

2. Ron Waksman, MD

3. Novelty of Polymer Free stent design
Biofreedom
Novelty of Polymer Free stent design
Release kinetics: within 28 days 98% of BA9 would be transferred to the tissue of vessel wall; after that essentially a BMS
120 micron thick corrugated ring strut
Luminal surface: stainless steel bare metal surface
BA9, a very high lipophilic limus drug, allowing sustained high tissue concentration for neo-intimal suppression
Abluminal surface: “polymer-free” micro-structured crevices harboring Biolimus drug (BA9)
BioFreedom Stent

4. Pre-clinical Efficacy Evaluation
Standard Dose BioFreedom
Low Dose BioFreedom
Sirolimus-eluting stents
Bare metal stents
Tada et al., Circ Cardiovasc Interv 2010;3;

5. BioFreedom FIM Design BioFreedom FIM 4-month Angio FU
182 patients
First Cohort
Second Cohort
4-month Angio FU
75 patients
12-month Angio FU
107 patients
ANGIO FU 92%
12 MONTH CLINICAL FU 99%
ANGIO FU 92%
BioFreedom
standard dose
(BFD SD)
N=25
BioFreedom
Low dose
(BFD LD)
N=26
TAXUS® Liberté ®
N=24
BioFreedom
standard dose
(BFD SD)
N=35
BioFreedom
Low dose
(BFD LD)
N=36
TAXUS® Liberté ®
N=36
Enrollment Period Sept 2008 – Jan 2009
Enrollment Period Jan 2009 – Jun 2009

6. Median in-Stent LLL at 12-month Follow-up 2nd Cohort – Primary Endpoint
P = 0.001* (p=0.11**)
P = 0.21* (p=0.55**)
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

7. BioFreedom FIM - 60-month Outcomes All Patients – 1st and 2nd Cohorts (95.8%)
Event
BFD SD
N = 60
BFD LD
N = 62
TAXUS
MACE
(All Death, MI, Emergent Bypass or TLR)
14 (23.8%)
16 (26.4%)
12 (20.3%)
All Death
5 (8.5%)
7 (11.6%)
4 (6.9%)
Cardiac Death
3 ( 5.2%)
2 (3.6%)
0 (0.0%) MI
3 (5.3%)
2 (3.3%)
2 (3.5%)
Q Wave MI
1 (1.8%)
Non-Q Wave MI
1 (1.7%)
Emergent Bypass
0(0.0%)
TLR
6 (10.8%)
9(15.1%)
7(11.9%)
Definite / Probable Stent Thrombosis (ARC)
Stephen WL LEE
All p-values are non-significant.
Tests were performed for BFD SD vs. TAXUS and BFD LD vs. TAXUS.
Grube E., poster presentation, Jacc interfvention 2015

8. Longitudinal Sequential OCT Assessments: The EGO-BioFreedom Study
The first establishment of early healing profile & 9-month outcomes of a new “polymer-free” Biolimus-A9 drug-coated-stent by
Longitudinal Sequential OCT Assessments:
The EGO-BioFreedom Study
Stephen WL LEE; Kelvin KW CHAN; Simon CC LAM; Shun-Ling KONG; Frankie CC TAM; Michael KL Wong; Anthony YT WONG; Arthur SY YUNG; Catherine P SHEA; Li-Wei ZHANG; Yui Ming LAM; Gary Mintz*, Akiko Maehara*
Division of Cardiology, University of Hong Kong, Queen Mary Hospital, Hospital Authority, Hong Kong
* Columbia University Medical Center, Cardiovascular Research Foundation, New York, USA

9. EGO BIOFREEDOM STUDY Aims, Design & Methods
Prospective single center
N = 100 (20:20:20:20:20) patients
29% diabetic cases
Real world, all-comers except STEMI
EGO BIOFREEDOM STUDY
Aims, Design & Methods
Aims: To examine the benefits of the polymer-free BA9 Drug Coated Stent: -
Early (1-5M) strut coverage: healing profile & guiding DAPT
9M OCT follow-up: neointimal metrics and morphology as a DES
Clinical outcomes (12 months)
Method: 3 Longitudinal sequential OCT assessments to monitor (a) progression of strut coverage and (b) morphological changes of neointima.
* NIT, NIA, NIV denote neointimal thickness, area & volume by OCT

10. Study Flow Charts & Status BioFreedom Stent Implantation
106 lesions (128 stents)
Mean stent length = 25.0±10.2mm
Mean stent diameter = 3.05±0.49mm
Study Flow Charts & Status
BioFreedom Stent Implantation
Baseline OCT for best stent optimization
Baseline: 100 Patients
1 month: 20 Patients
2 months: 20 Patients
Patients randomly assigned to 5 groups (1:1:1:1:1 ) Early OCT assessment for early healing profile
3 months: 20 Patients
4 months: 20 Patients
5 months: 20 Patients
100% OCT FU rate
4 ISR (TLR rate 4%)
9 months: 100 Patients
9-month OCT assessment for neointima metrics
Study Status: 100% OCT FU rate; study completed, pending core lab QCA results

11. 6 Category Coverage Classification (CRF Core Lab
6 Category Coverage Classification (CRF Core Lab., frame by frame analysis)
To ensure consistency & accuracy of visual assessment of early strut coverage !!
A = Definitely uncovered. Strut not covered by tissue and both sides appear square.
B = Uncovered with abnormal in-stent tissue (AIST). Strut covered by irregular tissue or fibrin, and both sides appear square.
C = Partially uncovered. Strut partially covered by tissue but only one side has a smooth continuous shoulder.
D = Covered (protruding). Strut covered by thin continuous tissue on both sides but still extending into the lumen.
E = Covered (embedded). Strut covered by continuous tissue or neointima, and not interrupting the smooth lumen contour.
F = Covered (proliferative). Strut covered with excessive growth of neointima with thickness > 0.3mm.

12. Early Healing Curve (1-5 months Coverage %)
EGO-BioFreedom Study
Early Healing Curve (1-5 months Coverage %)
Percentage strut coverage (Cat. D, E, F) increased progressively from 48.16% (minimum) at 1M to 97.14% (median) at 5M. In each group (20 patients) the variations of coverage were much higher in the earlier phases (1-2M), which were largely replaced by near complete coverage in the later months.
Early coverage is rapid with BF stents.

13. Representative cases EGO-BioFreedom Study
Varying degree of coverage and changing neointimal morphology Longitudinal Sequential OCT Assessments
Worse scenario (Group 2) 2 BF stents
Optimal baseline apposition
2M: some early coverage with minor positive remodeling
9M: still inadequate coverage with unhealthy neointima
Optimal scenario (Group 2) 1 BF stent
Optimal baseline apposition with some thrombi
2M: good early coverage with young tissue
9M: fully covered struts with healthy neointima

14. BioFreedom US IDE Feasibility Trial
Prospective, multi-center
De novo stenotic lesions in native coronary arteries
Reference vessel diameter 2.25 mm to 4.0 mm PI: Ron Waksman
Up to 100 patients at 13 centers in the USA
Angiographic and IVUS follow 9-month
BioFreedom™ DCS
Clinical Follow-up
1 mo
3 mo
4 mo
6 mo
9 mo
1 yr
2 yrs
3 yrs
4 yrs
5 yrs
Primary safety endpoint: MACE (composite of cardiac death, MI, TLR) and ARC definite stent thrombosis at 9 months
Primary efficacy endpoint: In-stent late lumen loss at 9 months
DAPT treatment: 3-month only
ClinicalTrials.gov Identifier: NCT

15. ClinicalTrials.gov Identifier: NCT02131142
Trial Structure
PI:
Ron Waksman (MedStar Washington Hospital Center)
Sponsor:
Biosensors Research USA, Inc.
CRO:
MedStar ACRO
Enrollment and 9 months follow-up completed
Results will be available in late first quarter 2016
ClinicalTrials.gov Identifier: NCT

16. Enrolling Sites Site Number Site Name Principal Investigator
Research Coordinator
Total Enrolled
001
MedStar Washington Hospital Center
Dr. Ron Waksman
Shreejana Pokharel 13
003
St. Joseph Medical Center/Berks Cardiologists
Dr. Guy Piegari
Kim Petersheim 20
004
Mercy St. Vincent Medical Center
Dr. Ameer Kabour
Elizabeth Urrutia
005
Cardiac & Vascular Research Center of Northern Michigan
Dr. Louis Cannon
Jennifer Lalonde 11
006
NC Heart & Vascular Research
Dr. George Adams
Danielle Matthews 3
007
The Lindner Center for Research & Education at The Christ Hospital
Dr. Dean Kereiakes
Kathleen Buszek 1
011
MedStar Union Memorial Hospital
Dr. John Wang
Mary Park 7
002
Emory University Hospital
Dr. Habib Samady
Beth Holloway
016
MedStar Southern Maryland Hospital Center
Dr. Roy Leiboff
Meseret Deressa
022
Jewish Hospital Kentucky One Health
Dr. Naresh Solankhi
Stephanie Copeland 2
008
Columbia University Medical Center
Dr. Kumar Kalapatapu
Matthew Brinkman
017
Our Lady of Lourdes Medical Center
Dr. Anthony Smeglin
Danielle Connors
010
Baptist Cardiac & Vascular Institute
Dr. Ramon Quesada
Claudia Hodgson

17. BioFreedom™ Clinical Trial Overview
EGO BioFreedom is a physician initiated trial.

18. Thank you for your attention