1. Boston Scientific Corporation: DES Bioabsorbable Technologies
Keith Dawkins MD FRCP FACC FSCAI
Global Chief Medical Officer
Executive Vice President
Boston Scientific Corporation

2. Conflicts of Interest Boston Scientific Corporation Employee
Stockholder

3. DES Polymer Considerations
Purpose of the Polymer
Provides mechanically stable matrix for drug
Modulates drug release into vessel wall
Polymer has no function after drug release is complete
All polymer coatings have potential to be damaged
Damaged durable polymers are permanent

4. Safety Efficacy Potential Issues with Durable Polymer DES
Late / very late stent thrombosis
Higher risk in certain patient populations
Potentially require long-term DAPT
Chronic inflammation with neoatherosclerosis
Constant irritant may lead to late restenosis
Diminished efficacy in diabetic populations

5. SYNERGY™ Stent: Design Characteristics
Element Stent Platform
Bioerodable PLGA polymer is only applied to the abluminal surface of the stent
Abluminal delivery of Everolimus
Maximum abluminal coating thickness 4μm
Drug and Polymer gone ~ 3 months
Enhanced Stent geometry
Reduced Stent Profile
Laser-cut hypotube
SYNERGY
Everolimus
PLGA
Ultrathin Abluminal, Bioerodable Polymer (Rollcoat Technology)
Element Stent

6. SYNERGY™ Stent Platform
Stent Architecture
Visibility
PROMUS Element™ 81µm
PROMUS Element™
SYNERGY™
SYNERGY™ 74µm
PROMUS Element & SYNERGY Stent Designs
Platinum Chromium
(PtCr) Alloy
Radial Strength & Visibility
Similarities
SYNERGY Design Modifications
Strut Thickness
Connector Angle
Peak Radius
Additional End Connectors
Crimping Profile
Flexibility
Conformability
Longitudinal Robustness
Improvements

7. Comparative Strut Thickness
SYNERGY (360 days)
Strut Thickness (µm)
BVS
150µm
BioMatrix
Flex
120µm
Resolute
Integrity
89µm
PROMUS
Element 81µm
XIENCE V
81µm
SYNERGY 74µm
Thinner struts are associated with more rapid healing

8. Relative Drug & Polymer Weight//
Bare Metal Stent
SYNERGY
RESOLUTE Integrity
BioMatrix Flex
XIENCE/PROMUS
BVS / /
I I I I I I I I
I I I
7, , ,900
Coat Weight (µg) per 16 mm Stent

9. SEM of coating (x5000 magnification)
SYNERGY Stent Polymer Coating Microstructure
PLGA Polymer
Everolimus Drug
Stent Strut
SEM of coating (x5000 magnification)
BSC Internal Data

10. Time Course for Drug & Polymer Dissolution3 6
Drug
Polymer 6 6 9 10 12 3
Time (Months)

11. Vascular Response in Healthy Swine Model
Similar vascular response to SYNERGY™ & OMEGA™ (BMS)
OMEGA™ Stent SYNERGY™ Stent
30 Days
90 Days
180 Days
360 Days
Wilson GJ: J Am Coll Cardiol 2011;57:E1661

12. Cellular Response to Platinum Chrome
Platinum Chrome vs. PVDF
Less Platelet Adhesion
Less Platelet Aggregation
More Strut Coverage
More mature & functioning Endothelium
Inflammatory potential similar between Platinum Chrome & PVDF
Garanich JS: J Am Coll Cardiol 2011;58:B126
Tellez A: J Am Coll Cardiol 2012;60:B187

13. SYNERGY Stent: Clinical Trials
EVOLVE FHU
First Human Use Trial. 291 patients. PROMUS Element vs. SYNERGY vs. SYNERGY Half-Dose (1:1:1). Primary Endpoint: 6 month Late Loss + Composite 30 days
Enrolling
EVOLVE II
Global IDE Trial patients, 150 sites, 19 countries . PROMUS Element Plus vs. SYNERGY (1:1) single-blind trial. Primary Endpoint: 12 month TLF
EVOLVE II QCA
Quantitative Angiography. 100 Patient Registry, sites (Australia, Japan, New Zealand, Singapore).
Primary Endpoint: 9 month in-stent Late Loss
EVOLVE China
China regulatory approval trial (SFDA). 400 patients, up to 15 sites. PROMUS Element vs. SYNERGY (1:1) Primary Endpoint: 9 month Late Loss
EVOLVE DAPT
Prospective, Multi-center, Global, double-blind RCT: 3 months vs. 12 months DAPT patients.
Primary Endpoint: Cardiac Death/ MI

14. Late Loss Distribution
EVOLVE Trial Results (6 months)
Late Loss at 6 months
Late Loss Distribution
p=0.19
p=0.56
In-Stent Late Loss (mm)
Late Loss Distribution (%)
PROMUS
Element
SYNERGY
Half-Dose
SYNERGY
Non-inferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents
Meredith IT: J Am Coll Cardiol 2012;59:1362–1370

15. EVOLVE Trial Results (6 months)
Late Loss at 6 months
Safety & Efficacy at 6 months
p=0.19
Cardiac Death = 0% (All Groups)
Q-MI = 0% (All Groups)
Stent Thrombosis = 0% (All groups)
p=0.56
Late Loss (mm)
Patients (%)
PROMUS
Element
SYNERGY
Half-Dose
SYNERGY
Non-inferiority is proven because the upper 95.2% confidence bound of the difference in 6-month late loss is <0.20 for both SYNERGY stents
Meredith IT: J Am Coll Cardiol 2012;59:1362–1370

16. EVOLVE Trial Results (12 months)
PROMUS Element (n=98)
SYNERGY Half-Dose (n=99)
SYNERGY (n=94)
Components of TLF
Patients (%)
Verheye S: Presented at EuroPCR 2012

17. EVOLVE II Study Design SYNERGY™ Stent Pivotal Trial
1,954-2,006 patients with
atherosclerotic native coronary lesions
≤ 34 mm in length, RVD ≥2.25 mm ≤ 4.0, %DS ≥ 50
Up to 3 lesions in 2 vessels
(excludes LM disease, CTO, ISR, STEMI)
Randomized Cohort (RCT)
Up to 160 global sites PK
Substudy
PROMUS Element™
Plus Stent N=842
SYNERGY™
Stent N=842
SYNERGY™
Stent N=20-30
RCT Design
Multicenter, Noninferiority trial
Single-blind, 1:1 randomization
Primary Endpoint: TLF (CD, TV-MI, or TLR) at 12 months
Follow-up: 30d, 6m, 12m, 18m and annual 2-5 years
Diabetes Substudy
SYNERGY™
Stent N=

18. SYNERGY™ vs. BVS SYNERGY™ (BSC) BVS (ABT) Acute Performance +++ ±
Strut Thickness
Thin (74µm)
Thick (150µm)
Radial Strength +
Fracture Resistance
Visualization
Ability to Post-Dilate -
Full Matrix
Low Drug Load
Low Polymer Load
Short Time to Polymer Dissolution
Low Particulates
Normal Vessel Function ?
Shorter DAPT

19. The Burden of Stent Thrombosis...
Cost
Thrombus
Hemorrhage
DAPT

20. Relative Cost (DES Stent vs. DAPT)
7.1%
13.3%
US Dollars ($)
23.5%
60.6%
Assumptions: Cost of Aspirin 81mgs = US$ 0.05
Cost of DES = US$ 1600 (MRG Data, September 2012)
Cost of Clopidogrel 75mgs = US$ 2.80 (

21. Conclusions
Long term durable polymer exposure is potentially undesirable
The SYNERGY™ Stent is a next generation bioabsorbable polymer technology with unique properties:
Polymer gone shortly after drug elution is complete at 3 months
Parallel, synchronous drug release and polymer absorption
Ultra-thin abluminal coating and lower polymer load than previous technologies
Presence of drug in arterial tissue throughout entire course of polymer degradation to promote optimal healing
12-month safety and efficacy data from the EVOLVE Trial support positive clinical performance
Bioabsorbable polymer DES may improve late outcomes (reduce late/very late ST), minimize DAPT dependency, and enhance healing vs. durable polymer DES. Further confirmatory trials are ongoing