1. A Unique Approach to Creating a Polymer Free Stent The Medtronic Drug Filled Stent Program
Josiah N. Wilcox, Ph.D.
Chief Scientific Officer
Coronary and Renal Denervation
Medtronic CardioVascular
CRT 2013
February 25, 2013

2. Major Stock Shareholder/Equity
Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Major Stock Shareholder/Equity
Full Time Employee
Medtronic, Inc.
Medtronic CardioVascular

3. Integrity™ and Resolute Integrity™ A New Standard in Stent Design and Manufacturing
Conventional Stent Design
Medtronic Modular Design
Vs.
Slotted Tube
Modular Design
Medtronic’s Continuous Sinusoid Technology
Sinusoidal Formed Wire
Helical Wrap
Laser Fused 3

4. Sinusoidal Formed Wire
Integrity Platform Continuous Flexibility Due to Unique Sinusoidal Design
Flex
DES:
Stiff
Stiff
“Box Car” or Coupler
Promus
Element
Flex
Stiff
Stiff
Xience Prime
Continuous Sinusoid
Flex
Integrity
115° Bend
Sinusoidal Formed Wire
Helical Wrap
Laser Fused 4

5. Resolute Integrity Improves Deliverability
Average Push Force (gf)
Promus Element DES
2.50 mm x 20 mm
Xience Prime DES
2.50 mm x 18 mm
Resolute Integrity DES
DES 10 20 30 40 50 60 70 80 90
100 86
Superior Deliverability* 69
Lower is Better
* Based on 3D tracking bench test data on file at Medtronic, Inc.

6. Continuous Sinusoid Technology The Next Revolution in Stent Technology
Bare Metal Stents
Integrity
Drug-Filled Stent
Enabling designs that could not be attempted in the past
Drug-Eluting Stents
Resolute Integrity
S10 DES
It would not be possible to create a thinner strut cobalt alloy stent (< 0.003”) without compromising radiopacity. That’s where Core Wire and New alloys allow stent designs that would not otherwise be possible without major compromise.
S10/Core Wire
New Alloys
Platforms for next gen DES coatings
BioLinx (Resolute)
PC Technology (Endeavor)
Bioabsorbable polymer
Nanoporous
CAUTION: Design concepts not approved for sale or clinical use

7. Core wire design featuring thinner struts than Resolute Integrity
S10 DES
Core wire stent with enhanced deliverability, radiopacity, and size matrix
Attribute
Description
Deliverability
Targeted 10-15% Improvement over Resolute Integrity
Radiopacity
Increased due to core wire technology
Expanded Size Matrix
New 2.0, mm diameters and long length (34 and 38 mm) sizes at diameters
Integrity
S10
Omega (Element)
ML-8 (Xience)
Improved Deliverability
and Radiopacity
Is midpoint between Integrity radiopacity and element good enough?
Core wire design featuring thinner struts than Resolute Integrity
CAUTION: Design concepts not approved for sale or clinical use

8. Deliverability – Animal Model
3.0 x 18mm blinded, pairwise testing
Bench testing also showed a 27% improvement in trackability

9. Drug Filled Stent (DFS) Technology Polymer Free Drug Delivery
Innovative DES design
Essentially a BMS surface
Designed to address drug carrier issues such as:
Polymer biocompatibility
Inflammation upon polymer degradation
Surface coating durability
Enables use of new drugs without extensive development efforts
With CST, Medtronic is working to bring a new concept in DES – a polymer-free Drug Filled Stent
Drug is contained in a small diameter hollow core running the length of the stent and elutes in a controlled fashion via tiny holes
This design is not possible with laser cut technology
From the start, it has a bare metal surface with no durability, biocompatibility, or inflammation issues associated with durable or bioabsorble polymers
Elution rates can be controlled by mechanical means – the size (diameter) and number of the holes
Elution Holes
CAUTION: Design concepts not approved for sale or clinical use

10. Drug Filled Stent (DFS) Technology Core Wire Construction is sacrificial
Core Material
Co Alloy Shell
CAUTION: Design concepts not approved for sale or clinical use

11. Laser Hole Drilling Facilitate drug filling and elution
500 – 5000 holes per stent (18 mm)
Variable hole diameter and shape
Automation
Throughput
Reliability
CAUTION: Design concepts not approved for sale or clinical use

12. Drug Filled Stent (DFS) Technology Elution Hole Drilling – The Present and Future
CAUTION: Design concepts not approved for sale or clinical use

13. Drug Filled Stent (DFS) Technology De-Coring Process
Etching Gas + Sacrificial Core
Vapor Phase Etched Core (sublimates)
CAUTION: Design concepts not approved for sale or clinical use

14. Drug Filled Stent (DFS) Technology Radial Strength Structural Analysis
CAUTION: Design concepts not approved for sale or clinical use

15. Drug Filled Stent (DFS) Technology Radial Strength Structural Analysis
CAUTION: Design concepts not approved for sale or clinical use

16. Drug Filled Stent (DFS) Technology
Stress Distribution Structural Analysis
Driver
Drug Filled Stent
CAUTION: Design concepts not approved for sale or clinical use

17. Drug Filled Stent (DFS)
CAUTION: Design concepts not approved for sale or clinical use

18. DFS Deliverability Performance
Summary- 3.0x18mm Size
Track gain over Resolute Integrity
Push gain over Resolute Integrity
Sub 1mm Crossing Profile
CAUTION: Design concepts not approved for sale or clinical use

19. Radiopacity DFS, no drug BMS
CAUTION: Design concepts not approved for sale or clinical use

20. Drug Filled Stent (DFS) Technology Possible Elution Mechanism
CAUTION: Design concepts not approved for sale or clinical use

21. DFS Prototype Elution Comparison
Drug Filled Stent (DFS) Technology Controllable Elution – In Vitro
Standard non-polymeric elution
DFS Prototype Elution Comparison
70%
60%
50%
40%
30%
20%
10% 0%
% Eluted
Time
Design 1
Design 2
Design 3
Design 4
Design 5
Design 6
Resolute
In vitro testing suggests a variety of elution profiles possible
CAUTION: Design concepts not approved for sale or clinical use

22. Multiple Elution Profiles Possible
Pre-Clinical Elution
% Drug Remaining In Stent
Resolute
Xience
CAUTION: Design concepts not approved for sale or clinical use

23. Multiple Elution Profiles Possible
Pre-Clinical Elution
% Drug Remaining In Stent
CAUTION: Design concepts not approved for sale or clinical use

24. Distribution of drug in the artery wall DFS vs Resolute in porcine coronary arteries
CAUTION: Design concepts not approved for sale or clinical use

25. Drug Filled Stent 28 day histology porcine coronary arteries
DFS (No Drug)
DFS-1
CAUTION: Design concepts not approved for sale or clinical use

26. Drug-Filled Stent – Morphometric Data
28-Day Porcine Coronary Arteries
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CAUTION: Design concepts not approved for sale or clinical use 26

27. Conclusions Extended drug elution can be achieved in a polymer free stent
Variable elution kinetics possible in vivo
Clinically relevant drug in tissue levels remain constant for days after implantation depending on protypes chosen
DFS implants result in a significant inhibition of neointimal development compared to BMS controls
DFS show excellent healing by 28 days
Low inflammation (equivalent to BMS)
Residual fibrin was found associated with DFS with drug only (marker for drug action)
100% endothelialization
Growth of SMC into the DFS drug lumen
The lack of inflammation and complete healing suggests DFS may be appropriate for a wide variety of patients with potential for enhanced safety and outcomes
CAUTION: Design concepts not approved for sale or clinical use