1. The SYNERGY™ Biodegradable Program & EVOLVE Clinical Trials
Ian T. Meredith
Professor and Director of MonashHEART,
Southern Health, Monash Medical Centre
and Monash University Clayton, Victoria, Australia
February 6, 2012
The SYNERGY stent is an investigational device. Not for sale.

2. Ian T Meredith, MD, PhD Honoraria: Abbott Vascular
Boston Scientific Corporation
Medtronic, Inc.

3. Desired Features of Next Generation DES
Next Generation DES Desired Attributes
SYNERGY™ Stent Attributes and Design Goals
Acute Performance
Stent & Delivery System
Deliverable
Visible
Trackable
Conformable
PtCr Stent Platform
Thinner Struts
Modified Cell Geometry
Improved Deliverability
Efficacy
Low Drug Load
Good Clinical Outcomes
Low TLR
Low Clinical Symptom Recurrence
Drug Load = PROMUS™/Xience™
Release kinetics similar to PROMUS™/Xience™
Safety
Reduced Polymer Load
Bioabsorbable Polymer
BMS within 4mo
Abluminal Polymer Coating
Low Polymer Mass
No Stent Thrombosis
Shortened DAPT Requirement
Safer for DAPT Interruption
Presented by Ian Meredith, MBBS PhD, TCT 2011 The SYNERGY Stent System is an investigational device limited by law for investigational use. Not for sale.

4. Stent Design Progression: Platform
Material
SSTL
CoCr / CoNi
PtCr
Architecture
Strength
Flexibility
Coverage
Optimization
Closed Cell
Open Cell
Hybrid
Strut Thickness
3rd Generation
2nd Generation
1st Generation
4th Generation
The SYNERGY™ Stent is an investigational device and not for sale.
The SYNERGY™ Stent is an investigational device and not for sale.

5. Platinum Chromium (PtCr) Stent Material
Biocompatibility
Radial Strength
Bench Test Data
Newtons/mm
CoCr
CoNi
SSTL
SSTL
PtCr
Flexibility
Radiopacity
PtCr
CoCr
CoNi
SSTL
SSTL
Data on file. Stent Performance Summary April mm Stents. PROMUS Element™ Stent n=15. TAXUS™ Liberté™ Stent n=10. Cypher™ Stent n=3. Endeavor™ Stent n=7. Xience V™ Stent n=10. Bench test results may not necessarily be indicative of clinical performance. Images taken by Boston Scientific. 3.0 mm Stents. 4.0 mm CU Phantom

6. PROMUS™ (Xience V™) Stent (n=762)
PLATINUM Workhorse Less bail-out stenting with PtCr stents due to improved lesion coverage
Overall Rate
Cited Reason for Bail-out Stent
P=0.004
P=0.36
P=0.01
P=0.06
Incidence Rate (%)
PROMUS™ (Xience V™) Stent (n=762)
PROMUS Element™ Stent
(n=768)
Presented by Gregg W. Stone, MD, ACC PROMUS Stent is a private-labeled Xience V Everolimus Eluting Coronary Stent System manufactured by Abbott and distributed by Boston Scientific Corporation. Xience V is a registered trademark of Abbott Cardiovascular Systems, Inc.

7. Stent Design Progression: Drug Delivery
Anti-Restenotic Agents
BMS
DES
Everolimus
Polymer Coating
Biostable Conformable
Polymer
Bioabsorbable Abluminal

8. Importance of Continued DES Innovation
DAPT Considerations
Patient Perspective
Quality of life
Side effects
Other therapies
Cost
Piece of mind
Physician Perspective
Concerns with VLST
Bleeding complications
Non-compliance
DAPT interruption
DAPT responsiveness
DES vs. BMS
Delayed healing
VLST
Longer DAPT vs. BMS
Discontinuation #1 ST Risk

9. SYNERGY™ Stent Abluminal Bioabsorbable Polymer Current Durable Polymer
Bioabsorbable polymer (PLGA)
Applied only to the abluminal surface (rollcoat)
Thin strut PtCr Stent
Current Durable Polymer
Abluminal Bioabsorbable Polymer
Durable Permanent Polymer +
Drug
360° Around Stent
PLGA Bioabsorbable Polymer +
Everolimus on Abluminal Side of Stent
Presented by Ian Meredith, MBBS, PhD at TCT 2011.  The SYNERGY™ Stent is an investigational device and not for sale.

10. Bioabsorbable Abluminal
SYNERGY™ Stent Abluminal Bioabsorbable Polymer Thickness in Perspective 60
50-120µm 50 40
Micron (µm) 30 20
14µm
12-14µm 10
6-8µm
4µm
Bioabsorbable Abluminal
Polymer
(Thickness)
Red Cell
(Diameter)
TAXUS™ Liberté™
Polymer
(Thickness)
Neutrophil
(Diameter)
Human Hair
(Thickness)
The SYNERGY stent is an investigational device limited by law for investigational use. Not for sale.

11. SYNERGY™ Stent Designed for polymer resorption within 4 months
Polymer Mass Remaining (%)
Time (Days)
PLGA mass assessed in explanted stent and adjacent tissue
The SYNERGY stent is an investigational device limited by law for investigational use. Not for sale.

12. SYNERGY™ Stent Release Kinetics60 50
In vitro KDR
PROMUS Stent (in vivo) 40
In vivo release
In vivo release
Everolimus Cumulative Release (g) 30
SYNERGY Stent ½ Dose
In vitro KDR 20 10 10 20 30 40 50 60
Time (days)
Presented by Ian Meredith, MBBS, PhD at TCT 2010  The SYNERGY stent is an investigational device. Not for sale in the EEA. 12 12

13. SYNERGY™ Stent Design Attributes in Perspective Stent
Strut Thickness (mm)
Coating
Approximate Coating Thickness (mm)
Approximate Drug Load μg/mm
SYNERGY™ 74
Abluminal 4 6
PROMUS™ / Xience™ 81
Conformal 8
Resolute Integrity™ 91 10
BioMatrix™ Flex
112 16
The SYNERGY stent is an investigational device limited by law for investigational use. Not for sale.

14. EVOLVE FHU (SYNERGY™ Stent) Study Design
Patients with de novo native coronary lesions
≤28 mm in length, RVD ≥2.25 mm ≤3.5, %DS>50
(excluded LM disease, CTO, AMI or recent MI)
Randomized 1:1:1 at 29 sites (EU, Australia, New Zealand)
PROMUS Element™ N=98
SYNERGY N=94
SYNERGY ½ Dose N=99
Single-blind, noninferiority design
Primary Clinical Endpoint: TLF (TV-CD, TV-MI, or TLR) at 30 days
Primary Angiographic Endpoint: In-stent late loss at 6 months
Presented by Ian Meredith, MBBS, PhD at TCT 2011.  The SYNERGY™ Stent is an investigational device and not for sale.

15. Sample Size & Power Calculation
Primary Angiographic Endpoint: 6-month in-stent Late Loss
Expected rate for both groups = 0.14 ± 0.47 mm*
Non-inferiority margin (Δ) = 0.20
Test significance level () = (1-sided)
Power (1) = approximately 0.85
Expected rate of attrition = 20%
N = 291 patients (97 per group at 1:1:1 ratio)
Natfile06\depts\Clinical\Clinical Communications\Projects\IC\SYNERGY\Protocol\EVOLVE FHU\EVOLUTION FHU Protocol_Final_02Feb2010.doc Page 10
If the P value from the one-sided Student test is <0.048, it will be concluded that SYNERGY is non-inferior to PROMUS Element
* From SPIRIT III (9-month endpoint)

16. EVOLVE Trial Support Ian Meredith Melbourne, Australia Stefan Verheye
Co-Principal
Investigators
Ian Meredith
Melbourne, Australia
Stefan Verheye
Antwerp, Belgium
Core Labs
Angio:
CardioVascular Institute at BIDMC
IVUS:
MedStar Health Research Institute
Clinical Events
Committee
Joseph Kannam (Chair)
Germano DiSciascio
Claude Hanet
Goran Stankovic
Data Monitoring
Committee
W. Douglas Weaver (Chair)
David Parker Faxon
Steven R. Bailey
David J. Molitemo
Jan G. P. Tijssen
Adam Greenbaum

17. EVOLVE FHU (SYNERGY™ Stent) Target Lesion Failure
30 Days
6 Months
P=0.49
P=1.00
P=0.25
P=0.72
Patients, %
Patients, %
PROMUS Element™
SYNERGY
SYNERGY ½ Dose
PROMUS Element
SYNERGY
SYNERGY ½ Dose
Intent-to-treat; P values are versus PROMUS Element (Fisher exact test)
Presented by Ian Meredith, MBBS, PhD at TCT 2011.  The SYNERGY™ Stent is an investigational device and not for sale.

18. EVOLVE FHU (SYNERGY™ Stent) Late Loss at 6 Months
Difference and 95.2% UCB
Noninferiority
Threshold
P=0.19*
P=0.56*
SYNERGY
P<0.001
Difference (SYNERGY – PROMUS Element)
Late loss, mm
SYNERGY ½ Dose
P<0.001
PROMUS Element™
SYNERGY
SYNERGY ½ Dose
Noninferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents
Intent-to-treat; *P values for superiority comparison
Presented by Ian Meredith, MBBS, PhD at TCT 2011.  The SYNERGY™ Stent is an investigational device and not for sale.

19. EVOLVE FHU (SYNERGY™ Stent) Revascularization and ST at 6 Months
PROMUS Element™
SYNERGY ½ Dose
SYNERGY
All P=N.S.
Patients, %
TVR
TLR
Non-TLR TVR
Stent Thrombosis
Intent-to-treat; P values are versus PROMUS Element (Fisher exact test)
Presented by Ian Meredith, MBBS, PhD at TCT 2011.  The SYNERGY™ Stent is an investigational device and not for sale.

20. Clinical Trial Plan for the SYNERGY™ Stent
EVOLVE Clinical Trials
Clinical Trial Plan for the SYNERGY™ Stent
EVOLVE FHU
291 patients
Control Device
PROMUS Element™
Primary Endpoint
30D TLF
6M Late Loss
TCT 2011
EVOLVE II
1684 patients
Control Device
PROMUS Element™ Plus
Primary Endpoint
12M TLF
2014
Planned
Pre-Approval
EVOLVE QCA/PK
EVOLVE China
EVOLVE India
Post-Approval
EVOLVE DAPT
The SYNERGY stent is an investigational device limited by law for investigational use. Not for sale. 20 20

21. Where Will the SYNERGY™ Stent Sit in the DES Landscape?
Concerns with DES
Late ST
DAPT Compliance
DAPT Interruption
SYNERGY™ Stent Design
Reduced Polymer Load
Minimal Drug Burden
Short Term Polymer Exposure
Desired Outcomes
Improve late events
Reduce DAPT duration
Reduce risk w/DAPT interruption
Although DES have significantly improved restenosis outcomes compared with BMS, issues such as late ST and DAPT compliance remain a concern
Minimizing polymer and/or drug burden may be key to improving late events or reducing risk associated with DAPT interruption for DES
The next generation SYNERGY stent utilizes the proven PtCr stent platform, a proven dose of everolimus, and a bioabsorbable polymer designed to leave a bare metal stent within 4 months of implantation
This stent is currently being evaluated in the EVOLVE randomized, controlled clinical trial
BSC data on file. The SYNERGY stent is an investigational device limited by law for investigational use. Not for sale.

22. Thank You

23. DES Drug and Polymer Weight
SYNERGY™ Stent*
BioMatrix™ Stent
Xience ™ (PROMUS™) Stent
BVS Stent + Coating
Bare-Metal Stent
½ X Dose
1X Dose //
l l l l l l l l l l l
,700 7,800 7,900
Coating Weight (µg, 16 mm Stent)
Data on file Boston Scientific Corporation. Coating weights for BioMatrix is estimates for a 16mm stent based on published coat weights for 3.0x18mm stents. The SYNERGY stent is an investigational device limited by law to investigational use. Not for sale. 23 23 23

24. EVOLVE FHU (SYNERGY™ Stent) Baseline Demographics
PROMUS Element™ N=98
SYNERGY N=94
P value
SYNERGY ½ Dose N=99
P value
Age, years
62.1 ± 10.0
64.9 ± 11.0
0.07
62.9 ± 10.2
0.61
Male
79.6%
69.9%
0.12
69.7%
0.11
Hypertension
69.4%
61.3%
0.24
71.7%
0.72
Hyperlipidemia
70.4%
68.5%
0.77
72.4%
0.75
Diabetes*
22.4%
17.2%
0.36
18.2%
0.46
Insulin-treated
8.2%
6.5%
0.65
4.0%
0.23
Current smoker
27.8%
21.7%
0.33
20.6%
Prior MI
34.4%
32.3%
0.76
34.7%
0.96
Unstable angina
21.1%
22.6%
0.80
30.6%
0.13
Intent-to-treat; P values are versus PROMUS Element; *medically treated
Presented by Ian Meredith, MBBS, PhD at TCT 2011.  The SYNERGY™ Stent is an investigational device and not for sale. 24

25. SYNERGY™ Stent Physical and Chemical Changes Drug released over 3 months Polymer resorbed within 4 months
Schematic
Drug
Burst release
Sustained release
Drug release is completed
Polymer
Hydration & polymer molecular weight reduction begins
Significant reduction in molecular weight & polymer absorption begins
Molecular weight continues to drop & remaining polymer is absorbed
Vessel Wall
Vessel Wall
Vessel Wall
Lactic & Glycolic Acid
H2O
Lactic & Glycolic Acid
Everolimus
H2O
H2O
Everolimus
Stent Surface
Stent Surface
Stent Surface
BSC data on file. The SYNERGY stent system is an investigational device limited by law for investigational use. Not for sale. 25 25