1. Medtronic Non-Polymeric DES Development: Update on the Drug Filled Stent
Josiah N. Wilcox, Ph.D. Vice President and Resident Scholar Science and Technology Medtronic CardioVascular

2. Disclosures I am a full time employee of Medtronic CardioVascular
I will be talking about products and product concepts that are currently not approved for use in the USA
Resolute, DFS, S10/CoreWire

3. 1Internal Bench Test Data on file at Medtronic, Inc.
Integrity BMS
Superior Deliverabilty1
129% trackability improvement vs Biotronik PRO-Kinetic Energy
116% trackability improvement vs Abbott Multi-link Vision
Conformability
Excellent post-deployed wall apposition with minimal vessel straightening
Radial Strength
No compromise – equivalent to leading competitive stents
Add radial strength?
Hong Kong, Nov. 2009
1Internal Bench Test Data on file at Medtronic, Inc.

4. Continuous Sinusoid Technology A New Standard in Stent Design & Manufacturing
Conventional Stent Design
Medtronic Modular Design
vs.
Slotted Tube
Modular Design
Medtronic’s Continuous Sinusoid Technology
Drug Filled Stent is made possible by Continuous Sinusoid Technology, a new revolution in stent design & manufacturing from Medtronic
Sinusoidal Formed Wire
Helical Wrap
Laser Fused 4 4

6. Continuous Sinusoid Technology
Continuous sinusoid technology allow greater stent flexibility
Stiff
Flex
Separate stiff and flexible segments limit range of motion
Flex
Continuous sinusoid technology will flex continually 6

7. Continuous Sinusoid Technology The Next Revolution in Stent Technology
Drug-Filled Stent
Enabling designs that could not be attempted in the past
Bare Metal Stents
Drug-Eluting Stents
Resolute Integrity
Integrity
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.
Core Wire
New Alloys
Platforms for next gen DES coatings
BioLinx (Resolute)
PC Technology (Endeavor)
Bioabsorbable polymer
Nanoporous
Product concepts not currently approved for us in the USA

8. Continuous Sinusoidal Technology Core Wire and New Alloy Stents
Program Targets
Maintain / extend Medtronic lead in stent technology
Enhance performance w/o compromising strength & opacity
Create a backbone for DES coating technologies
0.0038"
Cobalt Chromium
0.0034"
Core Wire
0.0030"
0.0025"
New alloys
0.0020"
Product concepts not currently approved for us in the USA

9. Continuous Sinusoidal Technology Core Wire Stents
0.0345’’
Integrity
0.0404’’
Visibility with “old” lab equipment:
>20% thinner struts, yet more opaque
Integrity (same as Driver)
Core Wire vs. Integrity
(3.5 x 18mm size)
15% reduction in crossing profile
22% thinner stent struts
45% improvement in flexibility
25% improvement in trackability
Increased visibility
Core Wire
Product concepts not currently approved for us in the USA

10. Drug Filled Stent (DFS) Technology Polymer Free Drug Delivery
Innovative DES design
Essentially a BMS surface
No drug carrier issues such as
Polymer biocompatibility
Inflammation upon polymer degradation
Surface coating durability
Allows for controlled, prolonged, and tailored elution profiles
Has not been achievable with other non-polymeric approaches
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
Product concepts not currently approved for us in the USA

11. DFS R&D Process (abbreviated)
Stent Forming
Welding
Hole Drilling
De-Coring
Drug Filling
Finishing
Drug Extraction
Pre-Clinical Proof
Product concepts not currently approved for us in the USA 11

12. Drug Filled Stent (DFS) Technology Core Wire Construction
Core Material
Co Alloy Shell
Product concepts not currently approved for us in the USA

13. Drug Filled Stent (DFS) Technology Elution Hole Drilling
Product concepts not currently approved for us in the USA

14. Laser Hole Drilling Facilitate drug filling and elution
500 – 5000 holes per stent (18 mm)
Variable hole diameter and shape
Automation
Throughput
Reliability
Product concepts not currently approved for us in the USA

15. Drug Filled Stent (DFS) Technology Elution Hole Drilling – Most Recent
Product concepts not currently approved for us in the USA

16. Drug Filled Stent (DFS) Technology Elution Hole Drilling – The Future
Product concepts not currently approved for us in the USA

17. Drug Filled Stent (DFS) Technology De-Coring Process
Etching Gas + Sacrificial Core
Vapor Phase Etched Core (sublimates)
Etching Gas
Sacrificial
Core
Vapor
Sacrificial
Core
Vapor
Product concepts not currently approved for us in the USA

18. Drug Filled Stent (DFS) Technology De-Coring Process
X-Ray with Core
X-Ray without Core
Product concepts not currently approved for us in the USA

19. Drug Filled Stent (DFS) Technology Radial Strength Structural Analysis
Calculated moment of inertia (I) for various drug channel sizes on a percent basis.
The “strength” of a stent comes from the stiffness of its struts, and their resistance to bending. Based on a simple beam in bending analogy, the stiffness of a stent strut is directly proportional to the moment of inertia (I) of the strut. For a round cross-section, like that of the Integrity stent, the moment of inertia (I) of a strut is directly proportional to the radius of the strut to the fourth power. In the case of the drug filled stent, the radius of the inner lumen does decrease the moment of inertia (I) of the strut; however, due to the proportionality of the radius being to the fourth power, the moment of inertia is dominated by the outer radius of the strut.
Product concepts not currently approved for us in the USA

20. Drug Filled Stent (DFS) Technology Radial Strength Structural Analysis
Radial Crush Test – Stent is placed in an iris that decreases the diameter during which the force being measured is the outward force of the stent against the iris. The graph show Force rising as the stent diameter is reduced (from left to right along x-axis).
Hollow stents appears higher than the solid wire (implying greater radial strength), but in this case it is due to the different diameters of the hollow wire stent and solid wire (Integrity) stent being tested. The hollow wire has a thickness of ” and the solid wire Integrity is ”.
Product concepts not currently approved for us in the USA

21. Drug Filled Stent (DFS) Technology Possible Elution Mechanism
Here we provide one theory for how the drug can elute, namely diffusion. It is also likely that dissolution and convection play a part of the drug release from the drug filled stent.
First we are showing how the concentration changes over time. The concentration will continuously move from the higher to lower concentration. In this example the concentration would most likely not reach a 50/50 equilibrium as the drug is the tissue is being used up by the cells or diffusing farther away from the strut causing the concentration to remain lower than in the strut itself.
(upon click) Fick’s 2nd law of diffusion appears, which is the governing equation that describes how the concentration changes with time.
Product concepts not currently approved for us in the USA

22. DFS Prototype Elution Comparison
Drug Filled Stent (DFS) Technology Controllable Elution
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
Elution can be controlled by the size of the holes and the number of holes in each strut.
Testing suggests a variety of elution profiles possible
Product concepts not currently approved for us in the USA

23. Drug Filled Stent (DFS) Technology In Vitro Elution into Agar Gel
Product concepts not currently approved for us in the USA

24. Design Comparisons Elution
Product concepts not currently approved for us in the USA

25. Percent Drug In Tissue – DFS vs Resolute
Product concepts not currently approved for us in the USA

26. THANK YOU!